Recent Scientific Abstracts of Acne Treatment

[Hidradenitis suppurativa] [Article in Norwegian] Tolaas E, Knudsen CW, Sviland L, Tønseth KA. Tidsskr Nor Laegeforen. 2009 May 14;129(10):992-6.

BACKGROUND: Hidradenitis suppurativa is a chronic inflammatory skin disease
characterized by recurrent tender nodules and boils, usually in the armpits and
groins. Draining fistulas and hypertrophic scarring are hallmarks of more severe
disease. The objective of this article is to review the clinical presentation,
diagnostic considerations and treatment of the disease. MATERIAL AND METHODS: The
article is based on a non-systematic literature search in PubMed, review of
dermatology textbooks and the author’s personal clinical experience. RESULTS:
Hidradenitis suppurativa, also known as acne inversa, is a follicular occlusion
disease that can severely reduce quality of life. Staphylococci and other
pathogenic bacteria frequently colonize the lesions, but the disease is not
primarily a bacterial infection. Smoking and obesity can worsen disease activity.
Moderate and severe disease is usually treated with excisional surgery.
Antibiotics, often tetracyclines, are indicated for mild disease and as an
adjunct to surgery in more severe disease. Antibiotics, however, are not
curative. New treatment options, such as TNF-alpha inhibitors and zinc gluconate
should still be considered experimental. INTERPRETATION: Hidradenitis suppurativa
is probably underdiagnosed. The disease is often recalcitrant to treatment. The
effect of medical treatment is not supported by high quality evidence.

New insights into the management of acne: an update from the Global Alliance to Improve Outcomes in Acne group. Thiboutot D, Gollnick H, Bettoli V, Dréno B, Kang S, Leyden JJ, Shalita AR, Lozada VT, Berson D, Finlay A, Goh CL, Herane MI, Kaminsky A, Kubba R, Layton A, Miyachi Y, Perez M, Martin JP, Ramos-E-Silva M, See JA, Shear N, Wolf J Jr; Global Alliance to Improve Outcomes in Acne. J Am Acad Dermatol. 2009 May;60(5 Suppl):S1-50.

The Global Alliance to Improve Outcomes in Acne published recommendations for the
management of acne as a supplement to the Journal of the American Academy of
Dermatology in 2003. The recommendations incorporated evidence-based strategies
when possible and the collective clinical experience of the group when evidence
was lacking. This update reviews new information about acne pathophysiology and
treatment-such as lasers and light therapy-and relevant topics where published
data were sparse in 2003 but are now available including combination therapy,
revision of acne scarring, and maintenance therapy. The update also includes a
new way of looking at acne as a chronic disease, a discussion of the changing
role of antibiotics in acne management as a result of concerns about microbial
resistance, and factors that affect adherence to acne treatments. Summary
statements and recommendations are provided throughout the update along with an
indication of the level of evidence that currently supports each finding. As in
the original supplement, the authors have based recommendations on published
evidence as much as possible.

Spironolactone versus placebo or in combination with steroids for hirsutism and/or acne. Brown J, Farquhar C, Lee O, Toomath R, Jepson RG. Cochrane Database Syst Rev. 2009 Apr 15;(2):CD000194.

BACKGROUND: Hirsutism is the presence of excessive hair growth in women and is an
important cosmetic condition often resulting in severe distress. The most common
cause is by increased production of male sex hormones (androgens). It is also
affected by increased sensitivity to androgens in the hair follicles, and
secretory glands around hair follicles (sebaceous glands). Spironolactone is an
antiandrogen and aldosterone antagonist used to treat hirsutism. OBJECTIVES: The
objective was to investigate the effectiveness of spironolactone and/or in
combination with steroids (oral contraceptive pill included) in reducing excess
hair growth and/or acne in women. SEARCH STRATEGY: The Cochrane Menstrual
Disorders and Subfertility Group (MDSG) trials register was searched (April
2008). The Cochrane MDSG register is based on regular searches of MEDLINE,
EMBASE, CINAHL, PsycINFO and CENTRAL, handsearching of 20 relevant journals and
conference proceedings, and searches of several key grey literature sources. In
addition, all reference lists of relevant trials were searched and drug companies
contacted for details of unpublished trials. SELECTION CRITERIA: All randomised
controlled comparisons of spironolactone versus: placebo, steroids (oral
contraceptive pill included), spironolactone of varying dosages, or
spironolactone and steroids versus steroids alone when used to reduce hair growth
and acne in women. DATA COLLECTION AND ANALYSIS: Nine trials were included in the
review, eight trials were excluded. Two other trials are awaiting assessment.
Only one trial studied acne as an outcome, the remainder were concerned with
hirsutism. Major outcome measures include the following: subjective observations,
Ferriman and Gallwey hair scores, hormonal and biochemical parameters, side
effects, sebum production measurement. MAIN RESULTS: In the two trials that
compared 100 mg of spironolactone with placebo significant differences were
reported for subjective improvements in hair growth (OR 7.18, 95% CI 1.96 to
26.28), although not the Ferriman-Galwey score (WMD 7.20, 95% CI -10.98 to
-3.42)). Data could not be otherwise pooled as only one trial reported an
outcome. AUTHORS’ CONCLUSIONS: From the studies included in this review, there is
some evidence to show that spironolactone is an effective treatment to decrease
the degree of hirsutism but there was no evidence for effectiveness for the
treatment of acne vulgaris. Studies in this area are scarce and small. Individual
study data indicates some superiority of spironolactone over other drugs but
results cannot be generalised.

Changing the face of acne therapy. Ghali F, Kang S, Leyden J, Shalita AR, Thiboutot DM. Cutis. 2009 Feb;83(2 Suppl):4-15.

Many innovations in acne therapy have evolved since the discovery in 1949 that
vitamin A derivatives affected epidermal proliferation. Approval of topical
tretinoin solution in 1971 was followed by modifications in the formulation to
improve tolerability and provide flexibility in dosing. Identification of
retinoid receptors led to research that resulted in 2 receptor-selective
synthetic retinoids: adapalene and tazarotene. Today, topical retinoids are one
of the cornerstones of acne therapy and are recommended as first-line therapy for
all but the most severe forms of acne. They are used as monotherapy in mild
comedonal acne; for inflammatory acne, topical retinoids are used in combination
with benzoyl peroxide (BPO) and antibiotics (topical or oral) and/or hormonal
therapy for females. Because of the high prevalence of antibiotic-resistant
strains of Propionibacterium acnes, topical antibiotics should no longer be used
as monotherapy. Topical retinoid monotherapy is recommended for maintenance
because it prevents formation of microcomedones, the precursor lesions in acne.
Combination topical retinoid/antimicrobial therapy has become the current
recommended standard of care for the management of patients with acne.
Combination therapy can target multiple pathogenic factors: abnormal follicular
keratinization, P acnes proliferation, inflammation, and increased sebum
production. A number of fixed-combination products are available. These products
are effective, generally well-tolerated, and more convenient for patients than
multiple individual agents. By reducing the number of medications and
applications, fixed-combination products have the potential to improve patient
adherence, thereby improving treatment outcomes.

[Evaluation of therapeutic effect and safety for clinical randomized and controlled trials of treatment of acne with acupuncture and moxibustion] [Article in Chinese] Li B, Chai H, Du YH, Xiao L, Xiong J. Zhongguo Zhen Jiu. 2009 Mar;29(3):247-51.

OBJECTIVE: To evaluate the therapeutic effect and safety of acupuncture and
moxibustion for treatment of acne, and to analyze the current situation of
clinical studies at present. METHODS: Retrieve PubMed, Cochrane library, CBM
databank, CNKI databank, etc., and collect the randomized and controlled trials
of treatment of acne with acupuncture and moxibustion, and select clinical trials
conforming with the enrolled criteria, and conduct evaluation of quality with
Cochrane systematic manual 5.0, and RevMan 4.2.8 was used for statistical
analysis. RESULTS: Seventeen papers, including 1,613 cases, conformed with the
enrolled criteria. Seventeen studies adopted the cured rate as the evaluation
index, Meta-analysis showed treatment of acne by acupuncture and moxibustion with
routine western medicine as control, significant difference for inter-group
comparison [combined RR (random efficacy model) = 2.96, 95% CI (1.63, 4.91),
Z=4.08. P<0.0001]; comprehensive acupuncture and moxibustion therapy was
controlled with single acupuncture moxibustion therapy, significant difference
for inter-group comparison [combined RR (fixed efficacy model) = 2.51, 95% CI
(1.76, 3.57), Z=5.11, P<0.00001]. CONCLUSION: Acupuncture-mox ibustion is safe
and effective for treatment of acne, and it is possibly better than routine
western medicine, and the comprehensive acupuncture-moxibustion therapy is better
than single acupuncture-moxibustion therapy. The conclusion has not been
determined yet, because lower quality of a part of literature enrolled.

Photodynamic therapy: off-label and alternative use in dermatological practice. Buggiani G, Troiano M, Rossi R, Lotti T. Photodiagnosis Photodyn Ther. 2008 Jun;5(2):134-8. Epub 2008 May 6.

Photodynamic therapy (PDT) is a treatment technique that permits the clearance of
different skin lesions with high success rates in many dermatological diseases.
Worldwide recognized uses for PDT in dermatology include non-melanoma skin
cancer, actinic keratoses, acne vulgaris, photorejuvenation, and hidradenitis
suppurativa. In the European Union, and in the USA, its indication is for the
treatment of nonhyperkeratotic actinic keratoses (AKs) of the face and scalp, for
basal cell carcinoma and for Bowen’s disease. However, due to its intriguing
mechanism of action, many dermatologists have begun to look at the use of PDT in
photorejuvenation, acne vulgaris and hidradenitis suppurativa. Moreover,
clinicians have to learn how to maximize this kind of therapy to treat other
dermatologic entities, and many anecdotic reports can already be found in the
literature. This paper aims to briefly but critically review these reports to
give the dermatologist a useful guide to what could be the future experiences in
PDT and how to target their efforts in clinics and research.

Sustained remission of SAPHO syndrome with pamidronate: a follow-up of fourteen cases and a review of the literature. Colina M, La Corte R, Trotta F. Clin Exp Rheumatol. 2009 Jan-Feb;27(1):112-5.

OBJECTIVE: To evaluate the efficacy of intravenous (i.v.) pamidronate in patients
with SAPHO syndrome refractory to first line treatments and to review the
available literature on pamidronate for this indication. METHODS: We report 14
cases of SAPHO syndrome refractory to non-steroideal anti-inflammatory drugs
(NSAIDs), glucocorticoids and disease modifying anti-rheumatic drugs (DMARDs)
treated with i.v. pamidronate. All patients received i.v. 60 mg pamidronate/day
for 3 consecutive days. The primary evaluation criterion was the disappearance of
bone pain, considered as the reduction in the visual analogic scale for pain
(VAS) greater than 50%. RESULTS: Ten patients were females and 4 were males. The
mean age at onset was 40.4 years old. Ten patients presented a
relapsing-remitting course, while in 4 cases the disease followed a prolonged
course. In all cases anterior chest wall involvement occurred early in the
disease. In 2 cases there was also a peripheral monoarthritis. Eleven patients
experienced several flares of palmo-plantar pustulosis, while severe acne was
present in 2. In one case there was no cutaneous involvement. Twelve of the 14
patients had a good response after 3 infusions and in 8 of these patients a
sustained remission was observed. The recurrence of skin manifestations does not
seem to be influenced by pamidronate. CONCLUSIONS: Pamidronate appears to be an
effective treatment in the osteo-articular manifestations of SAPHO syndrome. As
far as cutaneous lesions are concerned, evidence of efficacy is not so
impressive.

Hidradenitis suppurativa: a comprehensive review. Alikhan A, Lynch PJ, Eisen DB. J Am Acad Dermatol. 2009 Apr;60(4):539-61; quiz 562-3.

Hidradenitis suppurativa, also known as acne inversa, is a chronic, often
debilitating disease primarily affecting the axillae, perineum, and inframammary
regions. Prevalence rates of up to 4% have been estimated. Our understanding of
the disease has changed over time. It is now considered a disease of follicular
occlusion rather than an inflammatory or infectious process of the apocrine
glands. Clinically, the disease often presents with tender subcutaneous nodules
beginning around puberty. The nodules may spontaneously rupture or coalesce,
forming painful, deep dermal abscesses. Eventually, fibrosis and the formation of
extensive sinus tracts may result. The location of the lesions may lead to social
embarrassment and the failure to seek medical treatment. Therapies in the past
have consisted of long-term antibiotics, antiandrogens, and surgery. New
treatments like tumor necrosis factor-alfa inhibitors have given clinicians more
options against this difficult disease.

Concomitant therapy for acne in patients with skin of color: a case-based approach. Alexis AF, Lamb A. Dermatol Nurs. 2009 Jan-Feb;21(1):33-6.

Acne affects individuals of all races and ethnicities. Patients with skin of
color present a unique challenge, particularly due to the potential for
post-inflammatory hyperpigmentation. Concomitant therapy is an appropriate
strategy for this population, as demonstrated in the following case.

Hidradenitis suppurativa. Buimer MG, Wobbes T, Klinkenbijl JH. Br J Surg. 2009 Apr;96(4):350-60.

BACKGROUND: Hidradenitis suppurativa is a chronic, recurrent, suppurative
cutaneous disease. Despite its incidence, optimal medical or surgical treatment
remains unclear. This review describes the disease, ranging from pathogenesis to
treatment and prognosis. METHODS: Articles were sourced from PubMed and Medline,
using the MeSH terms ‘hidradenitis suppurativa’ and ‘acne inversa’. Selection of
articles was based on peer review, journal, relevance and English language.
RESULTS AND CONCLUSION: On the basis of histological findings, the disease is now
considered inflammatory and originating from the hair follicle; therefore, the
term ‘acne inversa’ is favoured by some experts. The exact aetiology remains
obscure but smoking seems to be a major triggering factor. Treatment should be
individualized according to the site and extent of the disease. Absolute
cessation of smoking is essential in the treatment of hidradenitis. Management
with antibiotics or other medications may relieve early symptoms, but radical
surgery may be necessary for control and to prevent recurrence. (c) 2009 British
Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

[Management of acne in women over 25 years of age] [Article in Spanish] Rivera R, Guerra A. Actas Dermosifiliogr. 2009 Jan-Feb;100(1):33-7.

Acne is one of the most widespread skin diseases in the general population and
among adolescents in particular. However, it is becoming increasingly common in
patients over 25 years of age, and particularly in women. We distinguish 2 types
of post adolescent acne: persistent acne–the most frequent such acne–is an
extension of acne that began in adolescence and continues into adulthood, and
late-onset acne, which first appears in those over 25 years. We review the
clinical characteristics of these types of acne in women, the causes, the
recommended complementary tests, and the particulars of treatment in order to
adequately manage this condition.

Bioactive peptides: signaling the future. Fields K, Falla TJ, Rodan K, Bush L. J Cosmet Dermatol. 2009 Mar;8(1):8-13.

Natural processes within the body are modulated almost exclusively by the
interaction of specific amino acid sequences, either as peptides or as
subsections of proteins. With respect to skin, proteins and peptides are involved
in the modulation of cell proliferation, cell migration, inflammation,
angiogenesis, melanogenesis, and protein synthesis and regulation. The creation
of therapeutic or bioactive peptide analogs of specific interactive sequences has
opened the door to a diverse new field of pharmaceutical and active cosmetic
ingredients for the skincare industry. Here, we describe the origin of such
sequences, their role in nature, their application to dermatology, as well as the
advantages and challenges posed by this new technology.

Facial seborrheic dermatitis: a report on current status and therapeutic horizons. Bikowski J. J Drugs Dermatol. 2009 Feb;8(2):125-33.

Seborrheic dermatitis, characterized by erythema and/or flaking or scaling in
areas of high sebaceous activity, affects up to 5% of the US population and often
appears in conjunction with other common skin disorders, such as rosacea and
acne. Despite ongoing research, its etiology is puzzling. Increased sebaceous and
hormonal (androgenic) activity is thought to play a part. Recent evidence
suggests an important role for individual susceptibility to irritant metabolites
of the skin commensal Malassezia, most probably M globosa. Current approaches
thus include agents with antifungal as well as antikeratinizing, and
anti-inflammatory activity. Azelaic acid, which has all 3 properties, may be a
useful addition to first-line management, which now comprises of topical
steroids, the immunosuppressant agents tacrolimus and pimecrolimus, azoles and
other antifungals, and keratolytic agents. A recent exploratory study supports
the efficacy and safety of azelaic acid 15% gel in seborrheic dermatitis. Azelaic
acid may be especially valuable in this application because of its efficacy in
treating concomitant rosacea and acne.

[Oral contraception - doses and way of administration] [Article in German] Thaler C, Kuhl H, Mueck A, Birkhäuser M, Braendle W, Neulen J, Keller PJ, Kiesel L. Ther Umsch. 2009 Feb;66(2):93-9.

Since the correlation between the amount of Ethinylestradiol (EE) and the
thromboembolic risk has been recognized, the development of new oral
contraceptives (OC) has been characterized by a constant lowering of the EE
dosage. The consecutive decrease of ovulation inhibition has been compensated by
the introduction of potent progestagens. Therefore, the contraceptive safety has
been maintained in presence of less side-effects. The effect of ultra-low-dose OC
on acne and seborrhea remains beneficial. The effect of ultra-low-dose OC on bone
is contradictory. Because there are fundamental differences between Estradiol and
EE, the thromboembolic risk is not decreased by the parenteral administration of
EE. In users of the contraceptive patch, it is even increased. EE is not bound at
SHBG. Because of its Ethinyl group, the inactivation of EE occurs slowly.
Therefore, EE reaches the liver in a low but constant concentration where it
modifies many estrogen-dependent hepatic parameters significantly. One of these
is hemostasis. It is generally accepted that such changes are responsible for the
increased thromboembolic risk of the contraceptive patch and vaginal ring. A
reduction of the hormone-free interval of the pill to 5 or 4 days results in a
complete suppression of the ovarian function, a reliable ovulation inhibition and
an increase of the contraceptive efficacy in spite of a reduction of the EE
dosage to 20 microg or 15 microg.

Acne in the adult. Ascenso A, Marques HC. Mini Rev Med Chem. 2009 Jan;9(1):1-10.

This paper is a general overview that contributes for the knowledge
systematization concerning the characteristics of the acne in the adult, its
prevalence, causes, diagnosis, classification and drugs available for treatment.
The reference therapy is the combination between topical retinoids and oral
antibiotics. Oral isotretinoin is still the only available therapy that may
modify the different acne physiopathologic factors and therefore it is the
standard treatment for severe acne. The importance of the acne treatment in the
adult should be enhanced as it can also lead to symptoms of serious depression
and anxiety.

[Dermatoses in obesity: sick skin over the adipose tissue] [Article in German] Krause W. MMW Fortschr Med. 2008 Nov 13;150(46):45-7.

Moisturizers for the treatment of inflammatory skin conditions. Lynde C. J Drugs Dermatol. 2008 Nov;7(11):1038-43.

The maintenance of normal hydration is an important function of the skin. The
stratum corneum provides an antimicrobial, antioxidant, and UV barrier and plays
an integral role in maintaining skin hydration. Environmental factors and disease
states may compromise the barrier function of the stratum corneum, leading to
excessively dry skin. Evidence supports the use of moisturizers in the treatment
of various skin conditions, and a wide variety of these products are currently
available. The presence of moisturizing agents in a compound, however, may not
guarantee optimal moisturization effects. Pharmacologic and physiologic (eg,
concentration, bioavailability, and proper determination of moisturization
effects), as well as patient-based considerations, can potentially influence the
effects of moisturizer ingredients. While moisturizers as adjunctive therapy have
proven benefits in enhancing the management of certain dermatologic conditions,
the incorporation of moisturizing ingredients into topical treatments may not
translate into clinical benefit, particularly in the enhancement of skin barrier
function.

Continuing medical education article-skin treatment: Photodynamic therapy: indications and treatment. Gold MH. Aesthet Surg J. 2008 Sep-Oct;28(5):545-52; quiz 553-5.

[Management of acne vulgaris: focus on clindamycin and zinc] [Article in German] Korting HC, Schöllmann C. Hautarzt. 2009 Jan;60(1):42-7.

Topical antibiotics, especially clindamycin, are well-accepted in the treatment
of mild to moderate acne. Combinations of clindamycin and other agents such as
benzoyl peroxide, retinoids or zinc, are possibly superior to clindamycin
monotherapy regarding efficacy and tolerability with the combination 1%
clindamycin/5% benzoyl peroxide being particularly well-supported by evidence.
Moreover, a recent study has shown that patients themselves prefer a complex of
zinc acetate/clindamycin phosphate.

Outcome measures in acne vulgaris: systematic review. Barratt H, Hamilton F, Car J, Lyons C, Layton A, Majeed A. Br J Dermatol. 2009 Jan;160(1):132-6. Epub 2008 Dec 5.

BACKGROUND: Clinical trials require valid and reliable outcome measures to
facilitate the interpretation and communication of results, and the secondary use
of data for systematic reviews. There are numerous tools available to assess the
severity of acne vulgaris in clinical trials, and extensive debate about the
merits of these. OBJECTIVES: To review the literature about investigator-assessed
outcome measures used in clinical trials for acne vulgaris; and to evaluate the
measurement properties of these tools. METHODS: A systematic literature review
was conducted of articles outlining and evaluating investigator-assessed outcome
measures for acne. RESULTS: Thirty-one papers met the criteria for inclusion in
the literature review, including nine papers proposing a novel means of assessing
acne, and five evaluating existing outcome measures. Variable attempts had been
made to evaluate these tools. CONCLUSIONS: The array of evaluation tools used in
acne trials prohibits good secondary analysis of trial data, and complicates the
interpretation of study results, potentially compromising clinical care. Existing
outcome measures need to be assessed further and agreement reached about which
should be used more widely. Other innovative methods of assessing acne should
also be explored.

Behçet’s syndrome. Yurdakul S, Yazici H. Best Pract Res Clin Rheumatol. 2008 Oct;22(5):793-809.

Recent epidemiological work suggests that genetic background overrides
environmental factors in the pathogenesis of Behçet’s syndrome (BS). There are at
least two clusters of disease expression. The first is the cluster of superficial
vein thrombosis, deep vein thrombosis and dural sinus thrombi; the second cluster
is that of acne, arthritis and enthesitis. The association of antibodies to
anti-Saccharomyces cerevisiae antibodies and the presence of inflammatory bowel
disease is perhaps another such cluster. The presence of such clusters suggests
that there might be more than one disease mechanism operative in this complex
disorder. There is a recent trend to classify BS with the autoinflammatory
disorders. However, practically all autoinflammatory conditions are recurrent
fever syndromes of children, and are genetically linked to well-defined loci;
none of this is true for BS. Recent guidelines from the European League Against
Rheumatism are quite useful for the management of the disease in organ systems
other than the vascular, neurological and gastrointestinal systems, because of
the lack of controlled studies related to these latter pathologies.

Corticotropin-independent cushing syndrome in a child with an ovarian tumor misdiagnosed as nonclassic congenital adrenal hyperplasia. Gupta P, Goyal S, Gonzalez-Mendoza LE, Noviski N, Vezmar M, Brathwaite CD, Misra M. Endocr Pract. 2008 Oct;14(7):875-9.

OBJECTIVE: To describe a patient with corticotropin-independent Cushing syndrome
previously diagnosed and treated as congenital adrenal hyperplasia (CAH).
METHODS: We describe the initial manifestations, clinical investigations, and
postoperative follow-up of the patient and review similar cases in the
literature. RESULTS: A 5 and 9/12-year-old girl who was initially diagnosed and
treated as having CAH and was noncompliant with glucocorticoid therapy presented
with weight gain, hypertension, and a mass in the lower abdomen. On physical
examination, she was a cushingoid-appearing girl with proximal muscle weakness
and notable facial acne. Laboratory findings included elevated serum
testosterone, 17-hydroxyprogesterone, dehydroepiandrosterone sulfate,
androstenedione, estradiol, and cortisol, as well as elevated urinary cortisol
and cortisone. Serum corticotropin was undetectable. She had normal serum
electrolytes and plasma renin activity. Computed tomography scan of the abdomen
and pelvis showed a cystic mass with a focal enhancing solid component arising
from the right ovary, which was subsequently determined to be a steroid cell
tumor not otherwise specified. CONCLUSION: Although ovarian steroid cell tumors
typically secrete gonadal steroids, the rare steroid cell tumors not otherwise
specified can secrete both glucocorticoids and gonadal steroids and are an
unusual cause of Cushing syndrome.

Optimizing use of oral antibiotics in acne vulgaris. Del Rosso JQ, Kim G. Dermatol Clin. 2009 Jan;27(1):33-42.

Oral antibiotics are commonly used to treat acne vulgaris, primarily in patients
presenting with moderate to severe facial or truncal disease severity. These
agents are most appropriately used in combination with a topical regimen
containing benzoyl peroxide and a topical retinoid. The most common oral
antibiotics for treating acne vulgaris are the tetracycline derivatives, although
macrolide agents such as erythromycin have also been used extensively. Over the
past 4 decades, as the sensitivity of Propionibacterium acnes to several oral and
topical antibiotics has decreased, the efficacy of oral tetracycline and
erythromycin has markedly diminished, leading to increased use of doxycycline,
minocycline, and other agents, such as trimethoprim/sulfamethoxazole.

Topical antibiotics in dermatology: emerging patterns of resistance. Elston DM. Dermatol Clin. 2009 Jan;27(1):25-31.

Resistance to topical antibiotics is increasingly relevant in dermatology. This
article discusses emerging patterns of resistance and the implications for
clinical practice. Emergence of resistance is complicating decolonization of the
skin and nares in patients infected with methicillin-resistant Staphylococcus
aureus. In the setting of acne treatment, adding topical benzoyl peroxide has
been shown to reduce the emergence of strains resistant to topical antibiotics.
Other agents, such as zinc salts, are promising in this regard. This article
discusses alternatives to antibiotics and mechanisms to stem the emergence of
resistance.

A current review of topical benzoyl peroxide: new perspectives on formulation and utilization. Tanghetti EA, Popp KF. Dermatol Clin. 2009 Jan;27(1):17-24.

Benzoyl peroxide (BPO) is the most widely used topical acne treatment, with
significant antibacterial, antikeratolytic, and comedolytic activity. It has been
shown to be extremely effective as monotherapy and in combination with
antibiotics or retinoids for managing comedonal and inflammatory acne lesions. As
numerous clinical studies have shown, the combination of BPO plus a topical
antibiotic is not only more effective but also is often better tolerated than
either agent alone. Unlike antibiotics, no bacterial resistance has been noted.
Adding BPO to any long-term antibiotic regimen in acne is generally recommended
to help reduce populations of drug-resistant variants. Although effective
combinations of BPO and antibiotics or retinoids are used, BPO monotherapy can
also be extremely effective in treating mild to moderate acne with no resistance
issues.

Clinical considerations in the treatment of acne vulgaris and other inflammatory skin disorders: a status report. Leyden JJ, Del Rosso JQ, Webster GF. Dermatol Clin. 2009 Jan;27(1):1-15.

This article reviews the anti-inflammatory and nonantimicrobial effects of
antibiotics in acne and other diseases and examines issues relating to the
emergence of decreased bacterial sensitivity to antibiotics and how these issues
relate to clinical practice. It includes an overview of the inflammatory
activities of some antibiotic agents and their potential for use in various
dermatologic and nondermatologic diseases. It demonstrates that P.
acnes-resistant organisms may be associated with therapeutic failure in some
patients with acne, and that the prudent use of antibiotics is necessary to
ensure that we can continue to use these drugs to combat disease effectively. It
concludes that there are treatment strategies that can effectively minimize the
potential for development of resistant P. acnes organisms.

Topical retinoids in acne vulgaris: update on efficacy and safety. Thielitz A, Gollnick H. Am J Clin Dermatol. 2008;9(6):369-81. doi: 10.2165/0128071-200809060-00003.

Topical retinoids represent a mainstay of acne treatment because they expel
mature comedones, reduce microcomedone formation, and exert anti-inflammatory
effects. The first-generation retinoid tretinoin (all-trans retinoic acid) and
the synthetic third-generation polyaromatics adapalene and tazarotene are
approved for acne treatment by the US FDA, whereas topical tretinoin,
isotretinoin (13-cis retinoic acid), and adapalene are accredited in Canada and
Europe. Topical retinoids have a favorable safety profile distinct from the
toxicity of their systemic counterparts. Local adverse effects, including
erythema, dryness, itching, and stinging, occur frequently during the early
treatment phase. Their impact varies with the vehicle formation, skin type,
frequency and mode of application, use of moisturizers, and environmental factors
such as sun exposure or temperature. The broad anti-acne activity and safety
profile of topical retinoids justifies their use as first-line treatment in most
types of non-inflammatory and inflammatory acne. They are also suitable as
long-term medications, with no risk of inducing bacterial resistance, for
maintenance of remission after cessation of initial combination therapy.

Talarozole, a selective inhibitor of P450-mediated all-trans retinoic acid for the treatment of psoriasis and acne. Geria AN, Scheinfeld NS. Curr Opin Investig Drugs. 2008 Nov;9(11):1228-37.

Talarozole, being developed by Barrier Therapeutics Inc under license from
Johnson & Johnson, is a potent and selective inhibitor of cytochrome P450
26-mediated breakdown of endogenous all-trans retinoic acid for the treatment of
psoriasis and acne. Phase II clinical trials of an oral formulation of talarozole
in patients with psoriasis and with acne, and a phase I clinical trial of a
topical formulation have been completed. At the time of publication, Barrier
Therapeutics had suspended the development of talarozole as part of a series of
cost-cutting initiatives; the company had also been acquired by Stiefel
Laboratories Inc. No formal announcement had been made regarding the further
development of talarozole.

Drugs for acne, rosacea and psoriasis. [No authors listed] Treat Guidel Med Lett. 2008 Nov;6(75):75-82.

Guidelines for topical photodynamic therapy: update. Morton CA, McKenna KE, Rhodes LE; British Association of Dermatologists Therapy Guidelines and Audit Subcommittee and the British Photodermatology Group. Br J Dermatol. 2008 Dec;159(6):1245-66. Epub 2008 Oct 13.

Multicentre randomized controlled studies now demonstrate high efficacy of
topical photodynamic therapy (PDT) for actinic keratoses, Bowen’s disease (BD)
and superficial basal cell carcinoma (BCC), and efficacy in thin nodular BCC,
while confirming the superiority of cosmetic outcome over standard therapies.
Long-term follow-up studies are also now available, indicating that PDT has
recurrence rates equivalent to other standard therapies in BD and superficial
BCC, but with lower sustained efficacy than surgery in nodular BCC. In contrast,
current evidence does not support the use of topical PDT for squamous cell
carcinoma. PDT can reduce the number of new lesions developing in patients at
high risk of skin cancer and may have a role as a preventive therapy. Case
reports and small series attest to the potential of PDT in a wide range of
inflammatory/infective dermatoses, although recent studies indicate insufficient
evidence to support its use in psoriasis. There is an accumulating evidence base
for the use of PDT in acne, while detailed study of an optimized protocol is
still required. In addition to high-quality treatment site cosmesis, several
studies observe improvements in aspects of photoageing. Management of
treatment-related pain/discomfort is a challenge in a minority of patients, and
the modality is otherwise well tolerated. Long-term studies provide reassurance
over the safety of repeated use of PDT.

Pyoderma gangrenosum following isotretinoin therapy for acne nodulocystic. Tinoco MP, Tamler C, Maciel G, Soares D, Avelleira JC, Azulay D. Int J Dermatol. 2008 Sep;47(9):953-6.

A 19-year-old man with nodulocystic acne on baseline was treated with
isotretinoin therapy. After 1 month on the medication, he developed pyoderma
gangrenosum on his pubis area, arms and legs, and pathergy on a puncture site.
Possible underlying diseases were excluded. The patient was started on steroids
(prednisone 1 mg/kg/d) and isotretinoin therapy was withdrawn. Later the
prednisone was tapered and dapsone 100 mg/daily was initiated. After 10 months of
follow-up all lesions had healed and no underlying diseases developed.

Antibiotic use in acne vulgaris and rosacea: clinical considerations and resistance issues of significance to dermatologists. Del Rosso JQ, Leyden JJ, Thiboutot D, Webster GF. Cutis. 2008 Aug;82(2 Suppl 2):5-12.

Antibiotics are commonly prescribed in dermatology practice for a variety of
disorders, including acne vulgaris and rosacea. Importantly, they often are used
long-term for these inflammatory dermatoses. Changes in bacterial ecology related
to antibiotic prescribing have led to the decreased sensitivity of some bacterial
organisms, such as Propionibacterium acnes, to antibiotics commonly prescribed by
dermatologists. The potential clinical outcomes of altered bacterial
sensitivities may vary among specific disease states and include decreased
therapeutic response and the need to alter approaches in disease management.
Additionally, changing patterns of antibiotic sensitivity and the emergence of
more virulent pathogens, such as community-acquired methicillin-resistant
Staphylococcus aureus, macrolide-resistant staphylococci and streptococci, and
mupirocin-resistant S aureus, have led to marked changes in how clinicians use
antibiotics in clinical practice. This article reviews antibiotic prescribing in
dermatology practice and provides important clinical perspectives and
recommendations to preserve the therapeutic value of antibiotics based on a
thorough review of current literature and clinical experience.

Beyond first-line treatment: management strategies for maintaining acne improvement and compliance. Yan AC, Treat JR. Cutis. 2008 Aug;82(2 Suppl 1):18-25.

The management of acne vulgaris is a long-term process that must be
individualized to each patient. Relevant factors influencing treatment include
the age and gender of the patient, the severity and extent of disease, the
efficacy and tolerability of prior interventions, and the degree of compliance
with recommended therapies. The follow-up phase of acne management requires a
framework for approaching treatment modification that may include concepts such
as up-titration, add-on, or switching of available agents to improve efficacy and
tolerability. Whenever oral antibiotics are used, abrupt discontinuation in favor
of topical maintenance therapy rather than gradual tapering is recommended.
Strategies for assessing and optimizing medical adherence are reviewed.

Addressing patient variability: clinical challenges in the initiation of acne treatment. Tschen E. Cutis. 2008 Aug;82(2 Suppl 1):9-17.

Aligning an acne diagnosis with a therapeutic strategy is the cornerstone of acne
management. The challenges associated with treatment selection include the type
and severity of the patient’s acne as well as the mechanism of action of each
medication and its ability to address one or more of the pathogenic factors of
acne. Beyond the efficacy of treatment, the clinician must be able to address a
number of factors that also will influence treatment success, the most important
being compliance. The characteristics of treatment (e.g., tolerability profiles,
dosing, vehicle) have a profound effect on compliance. In addition, patient
characteristics, such as level of expectation, acne treatment knowledge, and
willingness to be treated, impact a clinician’s approach to management.
First-line treatment sets the tone in the overall management of acne; thus,
medication choice, patient education, and communication are critical to treatment
success.

Clinical presentation and diagnosis of acne: patient-centric considerations. Cook-Bolden FE. Cutis. 2008 Aug;82(2 Suppl 1):4-8.

Acne is a common dermatologic condition that primarily affects adolescents and
young adults. Advances in research have led to more in-depth understanding of the
pathophysiology of this condition and the development of new therapeutic
interventions. Acne is now recognized as a multifactorial disease requiring a
multifaceted approach to therapy. Acne can affect individuals of either gender,
any ethnicity, and any age group. Nuances in the underlying pathophysiology,
distribution, clinical presentation, and differential diagnosis are important to
appreciate, as they may substantially contribute to the choice of therapy.

A review of adapalene in the treatment of acne vulgaris. Irby CE, Yentzer BA, Feldman SR. J Adolesc Health. 2008 Nov;43(5):421-4.

Topical retinoids help address the early lesions of acne vulgaris. Consensus
guidelines advocate the use of topical retinoids as the primary treatment for
most forms of acne vulgaris. However, all topical retinoid preparations may be
irritating, and this may contribute to underutilization in clinical practices.
Topical adapalene fosters topical retinoid treatment of acne with less
irritation. Adapalene is a more stable molecule than tretinoin. Adapalene can be
used without concern for photo-deactivation. Because of its chemical stability,
adapalene can be used in combination with benzoyl peroxide products. The
availability of a stable topical retinoid associated with little irritation may
facilitate meeting acne treatment consensus guidelines.

What every physician should know about polycystic ovary syndrome. Rosenfield RL. Dermatol Ther. 2008 Sep-Oct;21(5):354-61.

Polycystic ovary syndrome (PCOS) is the most common endocrine cause of hirsutism,
acne, and pattern alopecia. It is a heterogeneous syndrome of hyperandrogenic
anovulation that is typically due to intrinsic ovarian dysfunction, which is
often aggravated by insulin-resistant hyperinsulinemia with its risks of diabetes
mellitus and metabolic syndrome and their complications. Because there are many
pitfalls to androgen assays, evaluation for hyperandrogenemia is suggested in
women with moderate or severe hirsutism or hirsutism equivalents, menstrual
irregularity, acanthosis nigricans, or intractable obesity. An endocrinologic
work-up is necessary to rule out other hyperandrogenic disorders that require
specific therapy (e.g., virilizing tumors, nonclassic congenital adrenal
hyperplasia, hyperprolactinemia, and Cushing’s syndrome). Ultrasonography helps
in the differential diagnosis and may demonstrate the polycystic ovaries that
have recently been vetted as an alternative to oligo-anovulation as a diagnostic
criterion. Management of PCOS is determined by symptomatology. For those women
not desiring pregnancy, the most common therapies are oral contraceptive pills,
antiandrogens (contraindicated in the absence of adequate contraception), and
insulin-lowering treatments (which have little effect on hirsutism).

Advances in plasma skin regeneration. Foster KW, Moy RL, Fincher EF. J Cosmet Dermatol. 2008 Sep;7(3):169-79.

Plasma skin regeneration (PSR) is a novel method of resurfacing that uses plasma
energy to create a thermal effect on the skin. PSR is different from lasers,
light sources, and ablative lasers in that it is not chromophore dependent and
does not vaporize tissue, but leaves a layer of intact, desiccated epidermis that
acts as a natural biologic dressing and promotes wound healing and rapid
recovery. Histological studies performed on plasma resurfacing patients have
confirmed continued collagen production, reduction of elastosis, and progressive
skin rejuvenation beyond 1 year after treatment. PSR has received US Food and
Drug Administration 510 (k) clearance for treatment of rhytides of the body,
superficial skin lesions, actinic keratoses, viral papillomata, and seborrheic
keratoses. PSR also has beneficial effects in the treatment of other conditions
including dyschromias, photoaging, skin laxity, and acne scars. The safety
profile of PSR is excellent, and there have been no reports of demarcation lines
in perioral, periorbital, or jawline areas, as can sometimes be observed
following CO2 resurfacing. PSR is effective in improving facial and periorbital
rhytides and can be used on nonfacial sites, including the hands, neck, and
chest. Numerous treatment protocols with variable energy settings allow for
individualized treatments and provide the operator with fine control over the
degree of injury and length of subsequent recovery time.

Superficial chemical peels and microdermabrasion for acne vulgaris. Kempiak SJ, Uebelhoer N. Semin Cutan Med Surg. 2008 Sep;27(3):212-20.

Superficial chemical peels and microdermabrasion are used for many dermatologic
conditions. A common condition treated with these modalities is acne vulgaris. In
this review, we discuss the theory behind the technique of these procedures and
describe the application and complications of each of these procedures in the
office setting. The evaluation of patients before proceeding with the procedure
and discuss pre- and postpeel regimens used for patients is discussed. We also
analyze studies on both of these in-office procedures and comparative studies
between the 2 most commonly used superficial chemical peeling agents, glycolic
and salicylic acid.

Evidence for laser- and light-based treatment of acne vulgaris. Munavalli GS, Weiss RA. Semin Cutan Med Surg. 2008 Sep;27(3):207-11.

Acne is a very prevalent skin disorder, affecting more than 85% of adolescents
and often continuing into adulthood. Active acne and its sequelae, especially
permanent scarring, may cause longstanding psychological or emotional harm in
patients. Novel and promising treatments with laser/light devices (such as blue
light, red light, pulsed dye laser, infrared lasers, light-emitting diodes, and
pulsed light) have been reported to have varying degrees of efficacy for
treatment. The authors compiled a summary of evidence-based literature on
laser/light treatment for acne to assist clinicians to more appropriately
identify treatment options, should they choose to supplement current medical
antiacne therapies.

Preventing and managing the side effects of isotretinoin. Brelsford M, Beute TC. Semin Cutan Med Surg. 2008 Sep;27(3):197-206.

Isotretinoin (13-cis-retinoic acid) is widely used for the treatment of severe
acne as well as for disorders of conification, for psoriasis, and for skin cancer
prevention. As a member of the retinoid family, it has a wide spectrum of side
effects, including reproductive, cutaneous, ocular, neurological,
musculoskeletal, and hepatic. As long as patients are able to tolerate these side
effects, it can be a very effective treatment option. This article examines both
the most common and the most concerning side effects as well as ways in which
providers and patients may best manage them to be able to benefit from
isotretinoin treatment.

Hormonal therapy for acne. George R, Clarke S, Thiboutot D. Semin Cutan Med Surg. 2008 Sep;27(3):188-96.

Acne affects more than 40 million people, of which more than half are women older
than 25 years of age. These women frequently fail traditional therapy and have
high relapse rates even after isotretinoin. Recent advances in research have
helped to delineate the important role hormones play in the pathogenesis of acne.
Androgens such as dihydrotestosterone and testosterone, the adrenal precursor
dehydroepiandrosterone sulfate, estrogens, growth hormone, and insulin-like
growth factors may all contribute to the development of acne. Hormonal therapy
remains an important part of the arsenal of acne treatments available to the
clinician. Women dealing with acne, even those without increased serum androgens,
may benefit from hormonal treatments. The mainstays of hormonal therapy include
oral contraceptives and antiandrogens such as spironolactone, cyproterone
acetate, or flutamide. In this article, we discuss the effects of hormones on the
pathogenesis of acne, evaluation of women with suspected endocrine abnormalities,
and the myriad of treatment options available.

Antibiotic treatment for acne vulgaris. Webster GF, Graber EM. Semin Cutan Med Surg. 2008 Sep;27(3):183-7.

Although topical therapies alone can be very effective for milder acne, there are
often cases for which oral antibiotics are needed to control disease. Through
both antibacterial and antiinflammatory effects, oral antibiotics in combination
with other drugs such as retinoids and benzoyl peroxide can be highly effective
in the treatment of more severe disease. Patients and their parents often have
many questions regarding the safety and efficacy of long-term antibiotic use. It
is important for the physician to have a thorough understanding of the
antibiotics at their disposal as well as their side effects. Through careful
discussion, antibiotic compliance can be optimized and side effects minimized
ultimately resulting in treatment success.

Topical retinoids in the treatment of acne vulgaris. Zaenglein AL. Semin Cutan Med Surg. 2008 Sep;27(3):177-82.

Topical retinoids are highly effective in the treatment of both comedonal and
inflammatory lesions of acne and are a vital part of almost any acne regimen. A
better understanding of the structure and function of this class of medications
has led to better outcomes in treatments of patients with acne. In this article,
the structure and function of retinoids is first reviewed. Then, the clinical
effectiveness and tolerability of each of the available topical retinoid
formulations is summarized.

Effective over-the-counter acne treatments. Bowe WP, Shalita AR. Semin Cutan Med Surg. 2008 Sep;27(3):170-6.

Acne is the most common disease of the skin, yet only a fraction of acne
sufferers are treated with prescription products by physicians. There is,
however, a large and expanding market for over-the-counter (OTC) medications,
many of which are not only effective but also well tolerated and cosmetically
elegant. Given the presence of OTC acne medications on the television, the
Internet, and store shelves, patients will be acutely aware of these OTC remedies
and will have questions. Patients will expect dermatologists to advise them
regarding products to use either as a sole therapy or in combination with
prescription drugs. Recently, combinations of OTC acne medications in treatment
regimens or “kits” have gained popularity and appear to have increased patient
compliance. Quality-of-life outcomes from OTC medication use, in at least one
study, have demonstrated good benefit. The most common OTC ingredients include
benzoyl peroxide, a potent antibacterial agent, and salicylic acid, a mild
comedolytic and antiinflammatory medication. Other, less-common OTC ingredients
include sulfur, sodium sulfacetamide, and alpha hydroxy acids. Zinc, vitamin A,
tea tree oil, and ayurvedic therapies also are available OTC for acne. Additional
and better studies are needed to clarify the benefit of these latter medications.

Vaccine therapy for P. acnes-associated diseases. Nakatsuji T, Rasochova L, Huang CM. Infect Disord Drug Targets. 2008 Sep;8(3):160-5.

Recent studies have afforded abundant evidences showing that Propionibacterium
acnes (P. acnes) is involved not only in acne vulgaris, but also in many
diseases, including endocarditis, endophthalmitis, osteomyelitis, joint, nervous
system, cranial neurosurgery infections, and implanted biomaterial contamination.
In spite of a range of P. acnes pathogenicity, its vaccine therapies have been
studied much less intensively than antibiotic therapies which have been mainstay
of treatment for P. acnes-associated diseases. Therefore, we have recently
developed effective vaccines for P. acnes-associated inflammatory acne,
consisting of a cell wall-anchored sialidase of P. acnes or killed-whole organism
of P. acnes. Our data strongly show that immunization of ICR mice with the
vaccines provides in vivo protective immunity against P. acnes challenge and
decreases P. acnes-induced elevation of cytokine production. This review
highlights the potential functions of killed P. acnes- and sialidase-based
vaccines as novel treatments for P. acnes-associated diseases.

The role of antimicrobial peptides in human skin and in skin infectious diseases. Schittek B, Paulmann M, Senyürek I, Steffen H. Infect Disord Drug Targets. 2008 Sep;8(3):135-43.

Antimicrobial peptides or proteins (AMPs) represent an ancient and efficient
innate defense mechanism which protects interfaces from infection with pathogenic
microorganisms. In human skin AMPs are produced mainly by keratinocytes,
neutrophils, sebocytes or sweat glands and are either expressed constitutively or
after an inflammatory stimulus. In several human skin diseases there is an
inverse correlation between severity of the disease and the level of AMP
production. Skin lesions of patients with atopic dermatitis show a diminished
expression of the beta-defensins and the cathelicidin LL-37. Furthermore, these
patients have a reduced amount of the AMP dermcidin in their sweat which
correlates with an impaired innate defense of human skin in vivo. In addition,
decreased levels of AMPs are associated with burns and chronic wounds. In
contrast, overexpression of AMPs can lead to increased protection against skin
infections as seen in patients with psoriasis and rosacea, inflammatory
skin-diseases which rarely result in superinfection. In other skin diseases, e.g.
in patients with acne vulgaris, increased levels of AMPs are often found in
inflamed or infected skin areas indicating a role of these peptides in the
protection from infection. These data indicate that AMPs have a therapeutical
potential as topical anti-infectives in several skin diseases. The broad spectrum
of antimicrobial activity, the low incidence of bacterial resistance and their
function as immunomodulatory agents are attractive features of AMPs for their
clinical use.

The use and safety of doxycycline hyclate and other second-generation tetracyclines. Sloan B, Scheinfeld N. Expert Opin Drug Saf. 2008 Sep;7(5):571-7.

Tetracyclines have long been used to treat a wide variety of medical conditions,
especially in the field of dermatology. Unfortunately, safety concerns,
especially gastrointestinal (GI), have always been present. Other safety concerns
have included tooth development in children, candidiasis, vestibular concerns,
photosensitivity/phototoxicity, and more unusual adverse effects such as
uncontrolled hypertension. This article first discusses the pharmacological
development of the tetracyclines from the first to the second generation versions
with an emphasis on the safety concerns, especially with regards to doxycycline
hyclate (DH). Second, the adverse effects of the tetracyclines are discussed.
Third, the favorable side effect profile of DH delayed release capsules (Doryx)
is compared with DH powder contained in tablets (Vibramycin). Fourth, the
increased use with a continued favorable safety profile is also discussed
concerning the subantimicrobial dosing of DH for acne. Fifth, the safety of
periodontic uses of DH is discussed. Last, the favorable safety profiles of the
2006 approved uses of an anti-inflammatory dose of 40 mg doxycycline for rosacea
and an extended-release minocycline tablet for acne are also discussed.

EGFR inhibitor-associated acneiform folliculitis: assessment and management. Duvic M. Am J Clin Dermatol. 2008;9(5):285-94.

Treatment with epidermal growth factor receptor (EGFR) inhibitors is associated
with cutaneous adverse events, including acneiform folliculitis, dry skin, and
nail disorders. Acneiform folliculitis is a class effect of EGFR inhibitors that
is thought to be a direct result of EGFR blockade in the hair follicle. The
folliculitis is typically mild to moderate in severity and reversible without
scarring upon treatment completion. Dose modification or treatment
discontinuation is rarely necessary, except in severe cases. Standard acne
treatments (e.g. benzoyl peroxide, oral or topical antibacterials, retinoic acid)
may provide some benefit, based on anecdotal reports. Clinicians should be aware
of the possibility of superinfection with Staphylococcus aureus, in some cases
involving meticillin-resistant strains, which may require treatment with oral
antibacterials. Further study is needed to determine how the presence and
severity of acneiform folliculitis are related to clinical outcomes, and which
patients taking EGFR inhibitors are more likely to develop this disorder.

Can we define acne as a chronic disease? If so, how and when? Gollnick HP, Finlay AY, Shear N; Global Alliance to Improve Outcomes in Acne. Am J Clin Dermatol. 2008;9(5):279-84.

There is widespread misunderstanding of acne amongst both the medical and lay
community, who often perceive the condition to be a simple, self-limited
affliction of adolescents. Because many think that the disease “will go away on
its own,” they do not feel an urgency to aggressively treat acne. However, very
often the reality is that acne treatment can be quite difficult. Furthermore,
acne can be a devastating disease for the patient, since it manifests on visible
body parts and in children near puberty, who are vulnerable both socially and
psychologically. Most typically, acne is not an acute disease but rather a
condition that continuously changes in its distribution and severity. Usually,
acne treatment is necessary for many months and sometimes years. Despite
treatment, acne may cause scarring and associated negative psychological effects.
It is important for both patients and physicians to be aware that very effective
treatments are available. It is also important to realize that new studies have
proven the benefit of maintenance therapy with topical retinoids; these agents
can minimize the potential for relapse, which is part of the natural history of
acne. This article reviews the evidence suggesting that acne is a chronic disease
in at least a subset of individuals. The members of the Global Alliance to
Improve Outcomes in Acne believe that acne should be recognized and investigated
as a chronic disease. This will change expectations of clinical trial design and
treatment and will highlight gaps in the knowledge of acne epidemiology. The
result should be an improvement in patient outcomes.

Non-contraceptive benefits of oral contraceptives. Huber JC, Bentz EK, Ott J, Tempfer CB. Expert Opin Pharmacother. 2008 Sep;9(13):2317-25.

BACKGROUND: There is increasing awareness of the opportunity that many
contraceptive interventions may provide for additional health benefits. However,
treatment of medical problems with oral contraceptives (OCs) is often an
‘off-label’ practice. OBJECTIVE: The aim of this review is to summarize available
data on non-contraceptive benefits of OCs. METHODS: Review of the literature.
RESULTS: OCs have been shown to reduce the risk of ovarian, endometrial, and
colorectal cancer. It has been suggested that OCs may be used in treatment of
endometriosis, menorrhagia, and uterine leiomyomas. Pelvic inflammatory disease,
dysmenorrhea, premenstrual syndrome, and acne have been shown to improve under
OCs. CONCLUSION: OCs are important for global and female health. Besides
contraception, non-contraceptive effects of OCs are evidence based, well
established, and commonly used in clinical practice.

Acne through the ages: case-based observations through childhood and adolescence. Tom WL, Fallon Friedlander S. Clin Pediatr (Phila). 2008 Sep;47(7):639-51.

Acne vulgaris is a common disorder that affects more than 17 million individuals
in the United States. Knowledge of the disease is an important part of clinical
practice, particularly for the pediatric practitioner. Contrary to common belief,
acne is not a disease limited to adolescents and young adults but can occur at
any stage of life. This article is a case-based review of acne during childhood
and adolescence. Workup is based on age and concurrent physical findings, whereas
therapy depends on the type of skin lesions along with patient characteristics
and preferences.

Acne scarring: a review and current treatment modalities. Rivera AE. J Am Acad Dermatol. 2008 Oct;59(4):659-76. Epub 2008 Jul 26.

Acne is a prevalent condition in society and often results in secondary damage in
the form of scarring. Of course, prevention is the optimal method to avoid having
to correct the physically or emotionally troublesome scars. However, even with
the best efforts, scars will certainly arise. This article attempts to give a
broad overview of multiple management options, whether medically, surgically, or
procedurally based. The hope is that a general knowledge of the current available
alternatives will be of value to the physician when confronted with the difficult
task of developing a treatment plan for acne-scarred individuals, even in
challenging cases.

Adolescent female acne: etiology and management. Olutunmbi Y, Paley K, English JC 3rd. J Pediatr Adolesc Gynecol. 2008 Aug;21(4):171-6.

Acne vulgaris, a multifactorial condition often conferring significant
psychosocial morbidity, affects an estimated 40 million people in the United
States. The majority of these individuals are adolescents and young adults. The
pathophysiology of the condition is still not fully known, but it is believed to
be related in part to excess sebum production, follicular hyperkeratinization,
microbial colonization by P acnes, and inflammation. Prior to initiating
treatment in a female patient, a hyperandrogenic state must be considered and
ruled out through history, physical exam, and laboratory evaluation if necessary.
Treatment options are vast and include hormonal therapy among others. Hormonal
therapies have long been noted to reduce acne lesions and offer a valuable
adjuvant to standard therapy. Hormonal agents are thought to improve acne by
blocking the androgen receptor and/or decreasing circulating androgens which
leads to decreased sebum production. Hormonal treatment options include
spironolactone, other antiandrogens, and oral contraceptives. The use of these
agents to effectively treat acne has been demonstrated in several randomized,
placebo-controlled clinical trials. Optimal results are often achieved with
combination therapy with the goal of targeting multiple pathogenic pathways in
acne development.

Novel topical drug delivery systems and their potential use in acne vulgaris. Taglietti M, Hawkins CN, Rao J. Skin Therapy Lett. 2008 Jun;13(5):6-8.

A vast spectrum of topical anti-acne agents has emerged in response to new
insights that have been gained through the understanding of disease
pathophysiology and the need for clinicians to adopt an individualized
therapeutic approach. Because topical agents are most commonly used for acne
management, this article reviews some novel vehicle delivery advances that are
poised to further enhance the efficacy of topical acne formulations, and/or offer
the possibility of simplified dosing regimens that may improve treatment
outcomes.

Novelties in the multifaceted miconazole effects on skin disorders. Quatresooz P, Vroome V, Borgers M, Cauwenbergh G, Piérard GE. Expert Opin Pharmacother. 2008 Aug;9(11):1927-34.

BACKGROUND: Miconazole nitrate is a time-honored antifungal of the imidazole
class. OBJECTIVE: To revisit the various aspects of action of the drug in a
dermatologic setting. METHOD: Review of the current peer-reviewed publications.
RESULTS/CONCLUSION: Miconazole essentially inhibits 14alpha-demethylase, an
enzyme required for the biosynthesis of ergosterol, which is the main sterol
constituent of fungal cell membranes. Hence, toxic methylated sterols accumulate.
Synthesis of triglycerides and phospholipids is also affected. In addition,
miconazole also exhibits other ancillary mechanisms of action that probably
participate in the therapeutic efficacy of the drug. The oxidative and
peroxidative enzyme activities are altered leading to an intracellular build up
of a toxic concentration of hydrogen peroxide. This may contribute to the
deterioration of subcellular organelles and to cell necrosis. Farnesol synthesis
is stimulated in Candida spp. leading to the prevention of yeast-to-mycelium
formation. Overall, miconazole is fungistatic through its effect on ergosterol
biosynthesis, but it may also have a fungicidal effect against a number of fungal
species due to its effect on hydrogen peroxide accumulation. In addition,
miconazole is active against a series of Gram-positive bacteria and has been
shown to help the repair of the skin barrier function and to help mitigate some
inflammatory cell reactions (such as in acne). To conclude, miconazole exerts
multi-pronged effects both against pathogenic fungi and on skin physiology.

New insights into adolescent acne. Tom WL, Barrio VR. Curr Opin Pediatr. 2008 Aug;20(4):436-40.

PURPOSE OF REVIEW: Acne vulgaris remains one of the most common conditions
affecting adolescents. The pediatric practitioner is the first to evaluate
adolescent acne, making familiarity with the condition and its management
essential. This review covers some of the recent literature regarding acne to
help practitioners stay current on the issues regarding this topic. RECENT
FINDINGS: The pathogenesis of acne is multifactorial and complex, but recent
advances in molecular genetics have provided additional information on the
actions of Proprionibacterium acnes. Nutritional studies have reevaluated a
possible role for diet and lifestyle factors in acne development. Many therapies
are available to control acne and to limit associated scarring. Their appropriate
use requires an understanding of not only the benefits but also the possible
risks and adverse effects involved. Recent concerns regarding the use of
antibiotics and isotretinoin will be addressed. SUMMARY: This study reviews the
recent literature regarding teenage acne, focusing on pathogenesis, associations,
and controversies and considerations in therapy.

South African herbal teas: Aspalathus linearis, Cyclopia spp. and Athrixia phylicoides–a review. Joubert E, Gelderblom WC, Louw A, de Beer D. J Ethnopharmacol. 2008 Oct 28;119(3):376-412. Epub 2008 Jun 22.

Rooibos (Aspalathus linearis (Brum.f) Dahlg.) and honeybush (Cyclopia Vent.
species) are popular indigenous South African herbal teas enjoyed for their taste
and aroma. Traditional medicinal uses of rooibos in South Africa include
alleviation of infantile colic, allergies, asthma and dermatological problems,
while a decoction of honeybush was used as a restorative and as an expectorant in
chronic catarrh and pulmonary tuberculosis. Traditional medicinal uses of
Athrixia phylicoides DC., or bush tea, another indigenous South African plant
with very limited localised use as herbal tea, include treatment of boils, acne,
infected wounds and infected throats. Currently rooibos and honeybush are
produced for the herbal tea market, while bush tea has potential for
commercialisation. A summary of the historical and modern uses, botany,
distribution, industry and chemical composition of these herbal teas is
presented. A comprehensive discussion of in vitro, ex vivo and in vivo biological
properties, required to expand their applications as nutraceutical and
cosmeceutical products, is included, with the main emphasis on rooibos. Future
research needs include more comprehensive chemical characterisation of extracts,
identification of marker compounds for extract standardisation and quality
control, bioavailability and identification of bio-markers of dietary exposure,
investigation of possible herb-drug interactions and plant improvement with
regards to composition and bioactivity.

Clinical considerations on the use of concomitant therapy in the treatment of acne. Alexis AF. J Dermatolog Treat. 2008;19(4):199-209.

Acne is a disease that affects millions of people worldwide and requires prompt
and effective management of both the physical and psychological sequelae that an
individual may experience. The ultimate goal of treatment is to address as many
of the pathogenic factors of acne as possible while minimizing side effects.
Numerous therapeutic options are available; however, most current treatment
options address only one or two of these factors. For this reason, combining
single therapies has been the practice since the mid-1970s, beginning with the
concomitant use of treatments such as topical vitamin A with systemic
tetracyclines or topical benzoyl peroxide. As additional therapeutic options have
emerged, dermatologists have also begun to utilize these treatments concomitantly
based on their synergistic and multifactorial effects on the different pathogenic
factors of acne. This review provides an update of recent advances and data
regarding the concomitant use of various anti-acne agents.

In the clinic. Acne. Bershad SV. Ann Intern Med. 2008 Jul 1;149(1):ITC1-1-ITC1-16.

Rhinophyma: diagnosis and treatment options for a disfiguring tumor of the nose. Sadick H, Goepel B, Bersch C, Goessler U, Hoermann K, Riedel F. Ann Plast Surg. 2008 Jul;61(1):114-20.

Rhinophyma is a benign dermatologic disease of the nose affecting primarily
Caucasian men in their fifth to seventh decades of life. It is characterized by a
slowly progressive enlargement with irregular thickening of the nasal skin and
nodular deformation. It is assumed to be the end stage of chronic acne rosacea.
Main reasons that urge the patients to seek help are plastic cosmetic and
functional impairments such as nasal obstruction. Surgical removal of the
hyperplastic tumor mass is the treatment of choice for rhinophyma. In a
retrospective review, the authors describe the pros and cons of the main
treatment modalities that have been described in literature and present their own
clinical experience.

Congenital adrenal hyperplasia in adolescents: diagnosis and management. Lin-Su K, Nimkarn S, New MI. Ann N Y Acad Sci. 2008;1135:95-8.

Adolescent females who have irregular menstrual periods may have the nonclassical
form of congenital adrenal hyperplasia due to a mild deficiency of steroid
21-hydroxylase (NC 21-OHD). Hyperandrogenic signs such as acne, frontal hair
loss, hirsutism, and irregular menstrual periods should alert the physician to
the diagnosis of NC 21-OHD. An ACTH stimulation test in which serum hormone
concentrations of 17-OHP, Delta(4)-androstenedione, and testosterone are
determined will assist in the diagnosis of NC 21-OHD, but the definitive
diagnostic test is an analysis of the mutations in the CYP21A2 gene. Typical
mutations in the CYP21A2 gene in patients with NC 21-OHD are an exon 7 or an exon
1 mutation. Once the genotype establishes the diagnosis of NC 21-OHD, treatment
should be initiated. Typical treatment is dexamethasone, 0.25 mg HS, which
generally reverses the hyperandrogenic signs.

Practical considerations in acne treatment and the clinical impact of topical combination therapy. Krakowski AC, Stendardo S, Eichenfield LF. Pediatr Dermatol. 2008 Jun;25 Suppl 1:1-14.

Acne vulgaris is a highly prevalent, multifactorial disease process affecting the
pilosebaceous units of the dermis. The effects of acne are profound both
physically and psychosocially across all age groups and ethnicities; therefore,
prompt recognition and appropriate treatment are critical. Pharmacotherapeutic
approaches range from simple monotherapy to multimodal treatments with a variety
of topical and systemic agents. Optimal patient outcomes in acne management,
however, are based both on treatment efficacy as well as overall patient
satisfaction. In an effort to comprehensively address these key clinical
considerations in acne management, we examine the diverse nature of acne
patients, the factors in optimizing treatment outcomes, and the clinical impact
of current medications, particularly topical combination therapy.

Local antibiotics in dermatology. Gelmetti C. Dermatol Ther. 2008 May-Jun;21(3):187-95.

Although the vast majority of skin infection must be treated with systemic
antibiotics, topical antibiotics are used overwhelmingly in the world, often as
self-prescribed medications without taking into account the sensitivity of the
presumed bacteria. Dermatologists are aware that different types of topical
antibiotics kill different species of bacteria and tend to be more specific in
their prescriptions. At present local antibiotics are advised to treat minor
superficial uncomplicated skin infections (e.g., impetigo) and to prevent
bacterial infections caused into minor cuts, scrapes, and burns. The role of
topical antibiotics in the management of acne and atopic dermatitis is
controversial. Retapamulin, a novel topical antibacterial agent, will probably
replace the use of the old mupirocin and fusidic acid.

[How I treat... acne by isotretinoin] [Article in French] Piérard-Franchimont C, Nikkels AF, Piérard GE. Rev Med Liege. 2008 Mar;63(3):115-8.

Acne benefits from a series of treatments. The introduction of isotretinoin was a
therapeutic breakthrough which considerably improved both the evolution and the
prognosis of the disease. Indications of this retinoid kept changing over the
past twenty years. New clinical conditions emerged including the management of
disease recurrences. The daily dosages must be selected according to the type of
acne, the gender of the patient and the pharmaco-economical implications.
Teratogenicity must never be neglected as it represents the dreadful adverse
event of the drug. A European Directive currently marks out the way to use this
retinoid.

Procedures offered in the medical spa environment. Taub AF. Dermatol Clin. 2008 Jul;26(3):341-58, v.

Medical spas’ menus of services vary widely and depend greatly on the medical
director or owner’s experience and predilection. Core services include:
microdermabrasion, mild chemical peels, medical facials, laser hair removal,
photorejuvenation, botulinum toxin, and injectable fillers. Common procedures
include cellulite reduction, tissue tightening, and acne treatments. Less common
procedures that are more likely to be performed in medical spas with direct
on-site daily involvement of the medical director include: laser resurfacing,
laser-assisted lipoplasty, sclerotherapy, photodynamic therapy, and cosmetic
surgery. Multisite spas often use multi-platform devices to assist with
uniformity in menu offerings and training.

Clindamycin phosphate 1.2%- tretinoin 0.025% gel: vehicle characteristics, stability, and tolerability. Del Rosso JQ, Jitpraphai W, Bhambri S, Momin S. Cutis. 2008 May;81(5):405-8.

An aqueous gel formulation containing solubilized clindamycin phosphate 1.2% and
a stable combination of both solubilized and crystalline tretinoin 0.025%
(clin/tret) has been evaluated in 3 pivotal phase 3 studies, among other studies
including a 52-week trial. The pivotal studies enrolled 4550 participants 12
years and older with mild, moderate, and severe acne vulgaris. The combination
clin/tret gel was effective in reducing both inflammatory and noninflammatory
lesions and was well-tolerated. This article reviews important vehicle
characteristics of the combination gel as well as formulation stability and
tolerability data that are potentially clinically relevant.

[Drug therapy of acne] [Article in German] Ochsendorf FR, Degitz K. Hautarzt. 2008 Jul;59(7):579-89; quiz 590.

Acne is treated according to the clinical picture and the pathophysiologically
relevant mechanisms, such as seborrhea, follicular hyperkeratosis, P. acnes
colonisation,and inflammation. In mild forms of acne, topical therapy is most
appropriate. Comedonal acne can be treated with topical retinoids; papulopustular
acne with a combination of retinoids and topical antimicrobial substances
(benzoyl peroxide, antibiotics, or azelaic acid). Moderate forms or those with
extrafacial involvement can be treated with oral antibiotics combined with
topical retinoids or benzoyl peroxide. Acne conglobata and other severe
manifestations are treated with oral isotretinoin. Women are also treated with
oral contraceptives containing anti-androgenic progestins. If inflammation is
prominent, initial short term treatment with oral glucocorticoids is helpful.
Second-line agents include oral zinc or dapsone. Following successful treatment,
topical retinoids are suitable for maintenance therapy.

Novel vesicular and particulate drug delivery systems for topical treatment of acne. Castro GA, Ferreira LA. Expert Opin Drug Deliv. 2008 Jun;5(6):665-79.

BACKGROUND: The efficacy of the antiacne topical drugs is well established. The
local side effects, however, mainly cutaneous irritation, erythema, dryness,
peeling and scaling, remain major problems. Novel vesicular and particulate drug
delivery systems have been proposed to reduce the side effects of drugs commonly
used in the topical treatment of acne. OBJECTIVE: This review focuses on the
development and evaluation of antiacne drug-loaded vesicular and particulate
delivery systems (liposomes, polymeric microspheres and solid lipid
nanoparticles) for topical treatment, their advantages and challenges. METHODS:
All the literature available was reviewed to highlight the potential of these
novel systems for the topical treatment of acne. CONCLUSION: The encapsulation of
antiacne drugs in vesicular and particulate delivery systems represents an
innovative alternative to minimize side effects, while preserving their efficacy.
This can be obtained by the capacity of these systems to provide controlled
release or to improve the drug penetration into skin or even into the
pilosebaceous unit.

Use of calcium hydroxylapatite (Radiesse) for facial augmentation. Jacovella PF. Clin Interv Aging. 2008;3(1):161-74.

Radiesse (Bioform Inc, USA) is a sterile, latex-free, non-pyrogenic, semi-solid,
cohesive subdermal, injectable implant, whose principal component is synthetic
calcium hydroxylapatite, a biocompatible material with over 20 years of use in
medicine. The semi-solid nature of the product is created by suspending calcium
hydroxylapatite microspheres of 25-45 microns diameter in a gel carrier of
carboxymethylcellulose. The product has FDA approval for esthetic facial
augmentation in the US. Such approval includes the long-lasting correction of
moderate to severe facial wrinkles and folds and the treatment of facial fat loss
due to immunodeficiency virus infection. Diverse facial regions can be injected
in order to ameliorate or enhance some features: glabellar lines, subdermal
support of the brows, malar and buccal fat pads, tear troughs, nasolabial folds,
nose, lips, perioral region, marionette lines, oral commisures and chin among
others, as well as saucerized acne scars. Other medical indications include
nipple projection for nipple areolar reconstruction, urinary incontinence,
vesicoureteral reflux, vocal cord augmentation, and use as a radiographic tissue
marker. The average lasting result is from 12 to 18 months. Radiesse can be
considered an effective soft-tissue filler for overall longevity,
biocompatibility, and low rate of side effects.

Selected applications of technology in the pediatric dermatology office. Ducharme EE, Silverberg NB. Semin Cutan Med Surg. 2008 Mar;27(1):94-100.

The pediatric dermatologist is equipped with several diagnostic and therapeutic
tools that can be used in the office. The Wood’s lamp, introduced nearly a
century ago, continues to be a safe, noninvasive diagnostic tool used today for
diagnosing cutaneous infections, pigmentary disorders, and porphyrias. The pulsed
dye laser is the treatment of choice for vascular lesions and has an expanding
list of other applications, such as warts, which are extremely common in the
pediatric population. Dermoscopy has emerged as an effective adjunctive tool in
the in vivo examination of pigmented skin lesions and early diagnosis of
cutaneous malignant melanoma. Other uses are also being explored including
diagnosis of scabies. Future directions of technology in the pediatric
dermatology office include implementation of electronic medical record systems
and treatment of conditions such as molluscum, warts, and acne vulgaris with
photodynamic therapy.

Photodynamic therapy in dermatology: an update on applications and outcomes. MacCormack MA. Semin Cutan Med Surg. 2008 Mar;27(1):52-62.

Photodynamic therapy is a relatively new and rapidly evolving therapeutic option
in dermatology. Initially used for the treatment of actinic damage and
nonmelanotic skin cancer, more recent work indicates efficacy in the treatment of
a wide range of conditions, such as acne, infectious processes, cutaneous T-cell
lymphoma, and photorejuvenation, among others. This article provides a
comprehensive review of applications and outcomes that use topical photodynamic
therapy in the treatment of dermatologic disease.

Topical retinoids in acne–an evidence-based overview. [Article in English, German] Thielitz A, Abdel-Naser MB, Fluhr JW, Zouboulis CC, Gollnick H. J Dtsch Dermatol Ges. 2008 Dec;6(12):1023-31. Epub 2008 May 13.

Topical retinoids are important tools in the management of acne because they act
against comedones and microcomedones and have direct anti-inflammatory effects.
The substances approved for acne treatment comprise tretinoin (all-trans-retinoic
acid), isotretinoin (13-cis retinoic acid) as well as the synthetic
third-generation polyaromatic retinoids adapalene and tazarotene, the latter
being approved for acne treatment in the US only. Retinaldehyde is used in
cosmetic preparations against acne. All topical retinoids are effective as single
agents in mild to moderate acne but differ in efficacy and tolerability.
Tazarotene 0.1% is more effective than tretinoin 0.025% or 0.1% microsphere gel
or adapalene 0.1% gel or cream (EBM-level 2c). Adapalene 0.1% is equally
effective to tretinoin 0.025% or tretinoin microsphere 0.1% gel or tretinoin
0.05% cream or isotretinoin 0.05% gel (EBM-level 2c). Adapalene 0.1% gel is
significantly better tolerated than tazarotene 0.1% gel, tretinoin 0.025% and
tretinoin 0.05% gel, tretinoin 0.05% cream, tretinoin microsphere 0.1% gel or
isotretinoin 0.05% gel (EBM-level 2c). The safety profile of topical retinoids
differs from their systemic counterparts and is related mainly to local adverse
effects, such as erythema, dryness, itching and stinging. The currently available
evidence justifies the use of topical retinoids in most types of acne and during
maintenance treatment.

A primer on topical antibiotics for the skin and eyes. Noah S. J Drugs Dermatol. 2008 Apr;7(4):409-15.

A thorough knowledge of all topical antibiotics treatment options is important as
more pathogens become resistant to standard therapies. As resistance to mupirocin
increases, it seems that triple antibiotic ointments and retapamulin (the newest
FDA-approved agent) will have greater roles in treating impetigo and skin
infections. Awareness of all these agents provides a dermatologist additional
tools with which to treat skin infections. As a wide variety of topical
antibiotics, combination antibiotics, and combination anti-inflammatory
preparations used by ophthalmologists are not part of the therapeutic
armamentarium of most dermatologists, this review will provide the knowledge
needed to rationally use such ophthalmologic preparations. Finally, information
related to the topical nadifloxacin for acne and skin infections, which is in
clinical use in Japan, is summarized.

[Is acne caused by colonization with the "wrong" strain of Propionibacterium acnes? A review of the role of Propionibacterium acnes in acne] [Article in Danish] Lomholt HB, Kilian M. Ugeskr Laeger. 2008 Apr 7;170(15):1234-7.

Acne is still a major problem, and treatment options are far from ideal. A number
of studies suggest that the species Propionibacterium acnes plays an important
role in the pathogenesis, and new data point towards molecular mechanisms by
which the organism is able to trigger the host inflammatory response. The current
knowledge on P. acnes in relation to acne is reviewed.

Clindamycin/benzoyl peroxide gel (BenzaClin): a review of its use in the management of acne. McKeage K, Keating GM. Am J Clin Dermatol. 2008;9(3):193-204.

Clindamycin 1%/benzoyl peroxide 5% (BenzaClin) is a combination gel indicated for
use twice daily, or as directed by a physician, for the topical treatment of
inflammatory and noninflammatory lesions of acne vulgaris. In well designed
clinical trials in patients with mild to moderately severe acne, the efficacy of
once- or twice-daily clindamycin/benzoyl peroxide in the reduction of
inflammatory lesion counts was greater than that of benzoyl peroxide alone,
clindamycin alone, or tretinoin plus clindamycin, and not significantly different
from that of erythromycin/benzoyl peroxide. In the reduction of noninflammatory
lesion counts, the efficacy of once- or twice-daily clindamycin/benzoyl peroxide
was greater than that of clindamycin alone, but not significantly different to
that observed with benzoyl peroxide, tretinoin plus clindamycin, or
erythromycin/benzoyl peroxide. Clindamycin/benzoyl peroxide has a fairly rapid
onset of action, with acne improvement usually recorded within 2-4 weeks. Despite
widespread use, bacterial resistance is not associated with clindamycin/benzoyl
peroxide. The product is generally well tolerated, and the main treatment-related
adverse events in clinical trials were application-site dryness, irritation,
peeling, and erythema. Thus, clindamycin/benzoyl peroxide is an effective and
well tolerated option for the management of mild to moderately severe acne.

A survey of treatment of acne by acupuncture. Nie Y, Wang C. J Tradit Chin Med. 2008 Mar;28(1):71-4.

New developments in topical antimicrobial therapy for acne. Leyden J. J Drugs Dermatol. 2008 Feb;7(2 Suppl):s8-11.

Benzoyl peroxide (BPO) has been an important component of the acne treatment
armamentarium for decades. A number of characteristics contribute to its success
in acne, including its lipophilicity, potent antibacterial activity, and ability
to suppress antibiotic-resistant strains of Propionibacterium acnes. With some
commercially available products in which BPO comprises crystals in suspension,
aggregation of BPO can occur on the skin surface in large clumps, resulting in
poor penetration of sebaceous follicles. In addition, the poor water solubility
of BPO, coupled with its chemical instability in other solvents, presents
challenges with respect to formulating topical products with optimal
bioavailability, stability, and tolerability. Several products and vehicle
systems have evolved in attempts to improve on the benefits of BPO in treating
acne. A new acne treatment has been developed that contains 5% solubilized BPO
consisting of small-size particles. This new product exhibits enhanced follicular
penetration of BPO, improved P acnes kill rates and clinical efficacy, and good
consumer acceptance relative to existing formulations.

Emerging topical antimicrobial options for mild-to-moderate acne: a review of the clinical evidence. Del Rosso J. J Drugs Dermatol. 2008 Feb;7(2 Suppl):s2-7.

Topical antimicrobial agents are commonly used as first-line agents for the
management of mild to moderate acne vulgaris. Agents with antibacterial activity
(eg, benzoyl peroxide and clindamycin), reduce counts of Propionibacterium acnes,
while also decreasing the numbers of inflammatory and noninflammatory lesions. In
order to optimize efficacy, topical antibiotics are most commonly used in
combination with benzoyl peroxide, an approach which also reduces the emergence
of strains of P acnes that are less sensitive to antibiotics. Other topical
antiacne options include retinoids (with or without an antimicrobial agent),
sulfacetamide, sulfacetamide-sulfur, and azelaic acid. Certain formulations of
benzoyl peroxide offer improved tolerability, while a new micronized form may
enhance efficacy by optimizing follicular penetration. This wide array of options
allows dermatologists to tailor topical treatments to the needs of individual
patients.

Photodynamic therapy in dermatology–an update 2008. [Article in English, German] Klein A, Babilas P, Karrer S, Landthaler M, Szeimies RM. J Dtsch Dermatol Ges. 2008 Oct;6(10):839-45, 839-46. Epub 2008 Apr 9.

SUMMARY: Photodynamic therapy (PDT) is used for the prevention and treatment of
non-melanoma skin cancer. Until recently, clinically approved indications have
been restricted to actinic keratoses, nodular and superficial basal cell
carcinoma, and–since 2006–Bowen disease. However, the range of indications has
been expanding continuously. PDT is also used for the treatment of non-malignant
conditions such as acne vulgaris and leishmaniasis, as well as for treating
premature skin aging due to sun exposure. Here, PDT is used for the stimulation
of immunomodulatory effects in contrast to the induction of necrosis and
apoptosis as produced in the treatment of skin tumors. The porphyrin precursor
5-aminolevulinic acid (ALA) or its methyl ester (MAL, so far the only approved
formulation in Europe) is applied topically as photosensitizer to exclude
systemic reactions. Possible light sources include lasers as well as incoherent
light sources; irradiation with incoherent light sources is cheaper and more
appropriate for large treatment areas. The main advantages of PDT in comparison
to other treatment modalities are its excellent cosmetic results and its high
remission rates despite low invasiveness.This article provides up-to-date
information about PDT with focus on recently published studies.

Depression and suicidal behavior in acne patients treated with isotretinoin: a systematic review. Marqueling AL, Zane LT. Semin Cutan Med Surg. 2007 Dec;26(4):210-20.

Isotretinoin (13-cis retinoic acid) is an effective treatment for severe cystic
or recalcitrant acne vulgaris; however, concerns have been raised regarding its
potential association with depression and suicidal behavior. We sought to explore
the proposed relationship between isotretinoin use and the risk of depression and
attempted and completed suicide in patients with acne vulgaris by performing a
systematic literature search for studies reporting primary data on depression and
suicidal behavior in patients treated with isotretinoin for acne vulgaris. Nine
studies met the qualifying criteria for our analysis. Rates of depression among
isotretinoin users ranged from 1% to 11% across studies, with similar rates in
oral antibiotic control groups. Overall, studies comparing depression before and
after treatment did not show a statistically significant increase in depression
diagnoses or depressive symptoms. Some, in fact, demonstrated a trend toward
fewer or less severe depressive symptoms after isotretinoin therapy. This
decrease was particularly evident in patients with pretreatment scores in the
moderate or clinical depression range. No correlation between isotretinoin use
and suicidal behavior was reported, although only one retrospective study
presented data on this topic. Although the current literature does not support a
causative association between isotretinoin use and depression, there are
important limitations to many of the studies. The available data on suicidal
behavior during isotretinoin treatment are insufficient to establish a meaningful
causative association.

[Recent advances in laser therapy and other technologies] [Article in Spanish] Boixeda P, Calvo M, Bagazgoitia L. Actas Dermosifiliogr. 2008 May;99(4):262-8.

Laser technology and other energy sources are rapidly finding a place in
dermatology clinics. In the field of skin rejuvenation by fractional
photothermolysis, although few controlled studies have been undertaken, several
devices have emerged in recent years that appear less effective than laser
ablation techniques but that are safer. The aim of this short article is to
provide an introduction, though not treat in depth, the different emerging
technologies in dermatology. We will focus particularly on lasers and light
sources in improving applications such as the treatment of vascular lesions,
acne, and encapsulated ink tattoos; light-emitting diodes; developments in the
treatment of cellulitis; photodynamic therapy; suction methods; scarring; and
finally the recent and doubtlessly future introduction of home devices for use in
a range of dermatologic applications (depilation, rejuvenation, treatment of
acne, etc).

[Hereditary systemic autoinflammatory diseases. Part II: cryopyrin-associated periodic syndromes, pediatric systemic granulomatosis and PAPA syndrome] [Article in Spanish] Aróstegui JI, Yagüe J. Med Clin (Barc). 2008 Mar 29;130(11):429-38.

Hereditary systemic autoinflammatory diseases result from a genetically-based
dysregulated inflammatory process, and are clinically characterized by recurrent
or persistent systemic inflammatory episodes, which typically occur in the
absence of infectious, neoplastic or autoimmune etiology. Elucidation of their
molecular basis has enabled the use of genetic analyses to achieve an accurate
and definitive diagnosis, and to establish a tailored treatment. The present
review is the second and last part of an updated and comprehensive overview of
hereditary systemic autoinflammatory diseases, and will introduce persistent,
non-periodic autoinflammatory diseases, such as: a) the group of
cryopyrin-associated periodic syndromes (CAPS), which includes familial
cold-induced autoinflammatory syndrome (FCAS), Muckle-Wells syndrome, and
CINCA-NOMID syndrome; b) the group of pediatric systemic granulomatosis, which
includes both Blau syndrome and early-onset sarcoidosis, and c) the pyogenic
sterile arthritis, pyoderma gangrenosum and acne (PAPA) syndrome.

New and emerging treatments in dermatology: acne. Katsambas A, Dessinioti C. Dermatol Ther. 2008 Mar-Apr;21(2):86-95.

Topical retinoids, benzoyl peroxide, azelaic acid, and topical and oral
antibiotics remain the milestone of treatment for mild to moderate acne vulgaris.
Oral isotretinoin is useful for the treatment of severe nodular acne,
treatment-resistant acne, and acne with a risk of physical or psychological
scarring. Hormonal treatment in female acne is useful in resistant or late-onset
acne. With increasing concerns regarding teratogenicity of isotretinoin and
increasing antibiotic resistance, there is a clear need for therapeutic
alternatives to these long-used treatments. Research in the pathogenesis of acne
has allowed for new therapies and future perspectives regarding acne to evolve.
They include low-dose long-term isotretinoin regimens, insulin-sensitizing
agents, 5alpha-reductase type 1 inhibitors, topical photodynamic therapy, new
combination formulations, dietary interventions, and antiinflammatory agents such
as lipoxygenase inhibitors.

Drospirenone/ethinyl estradiol. Rapkin AJ, Sorger SN, Winer SA. Drugs Today (Barc). 2008 Feb;44(2):133-45.

Drospirenone 3 mg/ethinyl estradiol 20 microg (24/4) is a new unique oral
contraceptive formulation that combines in a novel dosing regimen the lowest
dosage of ethinyl estradiol commonly used today with drospirenone, an innovative
progestin. Drospirenone is a compound closely resembling progesterone, but with
the antimineralocorticoid and antiandrogenic properties of a related therapeutic
agent, the diuretic, antihypertensive and androgen receptor antagonist,
17alpha-spironolactone. The prolongation of hormonally active pills in the
monthly drospirenone/ethinyl estradiol cycle from 21 days to 24 days, followed by
4 days of inactive pills, is an interesting variant of the recently developed
extended pill regimens (1). Recent contraceptive research has focused on
improving side effect profiles and providing noncontraceptive health and
lifestyle advantages. Many of these benefits are now supported with
evidence-based medicine (2). Most available oral contraceptives improve cycle
regularity, menstrual pain, excessive menstrual flow and acne. However, weight
gain, bloating, food cravings, breast tenderness and mood alterations (especially
irritability and depression and the complex of affective, behavioral and somatic
symptoms of premenstrual syndrome [PMS] and the severe form of PMS, premenstrual
dysphoric disorder [PMDD]) are not generally improved with the traditional oral
contraceptive formulations (3). Drospirenone/ethinyl estradiol 24/4 is currently
the only hormonally based contraceptive regimen with large, randomized,
controlled trials demonstrating efficacy for PMDD. It has received U.S. Food and
Drug Administration (FDA) indications not only for the prevention of pregnancy
but also for PMDD and for moderate acne vulgaris in women who choose oral
contraception for birth control (4, 5). Copyright 2008 Prous Science, S.A.U. or
its licensors. All rights reserved.

Pharmacotherapy of acne. Degitz K, Ochsendorf F. Expert Opin Pharmacother. 2008 Apr;9(6):955-71.

BACKGROUND: Acne results from the interplay of several pathophysiologic factors,
in particular seborrhoea, follicular hyperkeratosis, propionibacteria and
inflammation. Recently, it has become clear that inflammatory events are
important not only in the course, but also in the initiation of the disease.
OBJECTIVE: The study undertook an evaluation of the effectiveness of currently
available pharmacotherapeutic treatment options for acne. METHODS: After a
Medline-based literature search, this article critically reviewed substances used
topically (among others, retinoids, antimicrobials, salicylic acid and azelaic
acid) and systemically (antibiotics, isotretinoin, hormones and zinc) as well as
their combinations with respect to pharmacology, clinical efficacy and side
effects. RESULTS: Modern acne pharmacotherapy provides substances that antagonize
one or more of the major pathophysiologic factors of acne. When the clinical
picture but also patients’ motivation and wishes are appropriately considered,
current pharmacotherapy of acne is rational and effective.

[Recommendations of good clinical practice on the treatment of acne] [Article in French] AFSSAPS. Ann Dermatol Venereol. 2008 Jan;135 Suppl 2:S73-136.

Diagnosis and management of autoinflammatory diseases in childhood. Gattorno M, Federici S, Pelagatti MA, Caorsi R, Brisca G, Malattia C, Martini A. J Clin Immunol. 2008 May;28 Suppl 1:S73-83. Epub 2008 Mar 27.

INTRODUCTION: Autoinflammatory diseases are a group monogenic inflammatory
conditions characterized by an early onset during childhood. DISCUSSION: Under
the term “periodic fevers” are gathered some monogenic diseases (familial
Mediterranean fever, mevalonate kinase deficiency, and tumor necrosis factor
receptor-associated syndrome) characterized by periodic or recurrent episodes of
systemic inflammation causing fever often associated with rash, serositis
(peritonitis, pleuritis), lymphadenopathy, arthritis, and other clinical
manifestations. Systemic reactive (AA) amyloidosis may be a severe long-term
complication. Cryopyrinopathies are a group of conditions associated to mutations
of the gene Cryopyrin that are responsible for a spectrum of diseases (familial
cold autoinflammatory syndrome, Muckle-Wells syndrome, and chronic infantile
neurological cutaneous and articular syndrome) characterized by a chronic or
recurrent systemic inflammation variably associated with a number of clinical
features, such as urticarial-like rash, arthritis, sensorineural deafness, and
central nervous system and bone involvement. Other disorders are dominated by the
presence of sterile pyogen abscesses prevalently affecting the skin, joints, and
bones (pyogenic disorders). These include pyogenic sterile arthritis, pyoderma
gangrenosum, and acne syndrome, and Majeed syndrome. Finally, some diseases, such
as Blau’s syndrome, are characterized by the appearance of typical noncaseating
granulomatous inflammation affecting the joints, skin, and uveal tract
(granulomatous disorders). In the present review, we will focus on the clinical
presentation of these disorders in childhood and report on the available
therapeutic strategies.

Autoinflammatory diseases: clinical and genetic advances. Farasat S, Aksentijevich I, Toro JR. Arch Dermatol. 2008 Mar;144(3):392-402.

We conducted a literature review to investigate the recent advances in genetics,
molecular biology, clinical manifestations, and therapy of 7 inherited diseases
that are characterized by seemingly unprovoked inflammation. These
autoinflammatory diseases include familial Mediterranean fever; tumor necrosis
factor receptor-associated periodic syndrome; hyperimmunoglobulinemia D with
periodic fever syndrome; pyogenic arthritis, pyoderma gangrenosum, and acne
syndrome; and the 3 cryopyrinopathies: neonatal-onset multisystem inflammatory
disease/chronic infantile neurologic cutaneous and arthropathy syndrome, familial
cold autoinflammatory syndrome, and Muckle-Wells syndrome. Recent identification
of the susceptibility genes for autoinflammatory diseases has broadened the
clinical spectrum as well as the molecular basis of these diseases. The
cryopyrinopathies represent a continuum of diseases associated with mutations in
the cold-induced autoinflammatory syndrome 1 (CIAS1) gene that encodes cryopyrin.
Cryopyrin and pyrin (protein mutated in familial Mediterranean fever) belong to
the family of PYRIN domain-containing proteins. Pyogenic arthritis, pyoderma
gangrenosum, and acne syndrome is associated with mutations in the gene that
encodes for CD2-binding protein 1 (CD2BP1), which binds pyrin. Recent studies
have shown that activation of the interleukin 1beta pathway is a common mechanism
in the pathogenesis of autoinflammatory diseases, further unifying these
diseases. Recent advances in genetics and molecular biology have advanced our
understanding of the pathogenesis of autoinflammatory diseases. Understanding
autoinflammatory diseases will further our knowledge of cutaneous as well as
systemic inflammation. Anakinra, a recombinant human interleukin 1 receptor
antagonist, is a promising new biologic agent for the treatment of
cryopyrinopathies as well other autoinflammatory diseases, such as tumor necrosis
factor receptor-associated periodic syndrome and hyperimmunoglobulinemia D with
periodic fever syndrome.

[Acne, pregnant women and zinc salts: a literature review] [Article in French] Dréno B, Blouin E. Ann Dermatol Venereol. 2008 Jan;135(1):27-33. Epub 2008 Jan 18.

BACKGROUND: Acne in adult women is a common reason for dermatological
consultation. Dermatologists are occasionally confronted with the problem of
treating acne in women who are either pregnant or seeking to become pregnant, or
in breast-feeding women, in whom zinc salts are the only form of systemic
treatment that may be envisaged. PATIENTS AND METHODS: The purpose of our study
was to provide an overview of existing data concerning the use of the zinc salts
in pregnant and breast-feeding women based on a literature review, a survey of
prescription of zinc gluconate by French dermatologists, and finally, analysis of
French pharmacovigilance data. RESULTS: There are many studies involving the use
of zinc supplements during pregnancy. In these studies, more than 2500 pregnant
women were given zinc at different doses. None of these studies described any
abnormalities, congenital malformation, harmful effects or risk for the foetus
associated with the use of zinc during pregnancy at doses below 75 mg/day.
Although there are fewer studies of the use of zinc supplements in breast-feeding
women, no abnormalities associated with use of zinc during breast-feeding have
been reported. According to the results of the prescription survey, around 10,000
pregnant women and 2000 breast-feeding women are treated each year for acne using
zinc gluconate, with only four serious adverse events involving zinc being
reported since the initial introduction of the product, and with zinc having a
doubtful causal relationship. DISCUSSION: Zinc plays a key role in our body’s
physiology, since it is involved in the activities of many enzymes. In addition,
zinc requirements increase during pregnancy, mainly because of its utilisation
during embryogenesis and fetal development. This literature review shows that use
of zinc salts in pregnant women is beneficial in those with zinc deficiency but
that it has no harmful effects in those without zinc deficiency.

Tailoring individualized treatment plans for acne. Harper JC. Cutis. 2008 Jan;81(1 Suppl):23-5.

Because acne is a complex multifactorial disorder, combination treatment may be
required to target its various pathogenic factors. Combination treatments also
offer the most improvement over the shortest time. Oral contraceptives (OCs) are
an excellent treatment, and clinicians should consider them a first-line option
as part of combination therapy in women with acne.

Hormonal contraceptives for acne management. Rich P. Cutis. 2008 Jan;81(1 Suppl):13-8.

Acne vulgaris affects 42 million people, more than half of whom are women older
than 25 years. Treatment for acne includes oral and topical antibiotics,
retinoids, and hormonal therapy in the form of oral contraceptives (OCs). OCs
reduce acne lesions by increasing estrogen levels and sex hormone-binding
globulins, and by decreasing free testosterone and androgen levels. Several
studies have shown that drospirenone, a progestin available in certain OCs,
minimizes the potential negative effect the progestin has on acne. Women with
moderate acne vulgaris who seek contraception and teenagers with acne who refuse
antibiotics or in whom topical antibiotics are ineffective might be candidates
for drospirenone-containing OCs.

Pharmacology of hormonal contraceptives and acne. O’Connell K, Westhoff C. Cutis. 2008 Jan;81(1 Suppl):8-12.

Higher free testosterone levels in women are a function of lower levels of sex
hormone-binding globulins (SHBG), higher levels of total testosterone, or both.
When free testosterone levels are decreased, sebum production, a pathogenic
feature of acne vulgaris, is also decreased. Oral contraceptives (OCs) decrease
free testosterone levels by reducing testosterone production by the ovaries and
adrenal glands, increasing SHBG, and inhibiting conversion of free testosterone
to dihydrotestosterone. Studies have shown that the progestin component of OCs
lowers androgen levels, which are directly associated with the development of
acne lesions. Currently, 3 OCs have received approval for acne from the US Food
and Drug Administration. For patients with acne who are already benefiting from
OC treatment, there is no need to change the OC; however, when an OC proves
insufficient against sebum production, switching to a formulation that is
approved for acne is recommended.

Overview of acne and its treatment. Thiboutot DM. Cutis. 2008 Jan;81(1 Suppl):3-7.

Acne affects more than 85% of teenagers in the United States and often continues
into adulthood. The most deleterious form can result in permanent scarring on the
face, chest, and back. Although the pathogenic features of acne are well known,
the initiating factor remains unknown. Isotretinoin is effective against all of
the pathogenic features of acne but is contraindicated in pregnant women and has
been associated with elevations in triglyceride levels. Combination regimens
appear to be effective, but physicians should avoid prescribing complicated
treatment regimens. Hormone therapy has been found to improve acne in some women
and should be considered in appropriate candidates. Although the list of
available and effective agents appears to be extensive, several are
contraindicated in pregnant women, and long-term use of antibiotics to target
inflammation has been linked to agranulocytosis and Stevens-Johnson syndrome.
Further investigation into agents that can reduce sebum production is warranted.

Diagnosis and management of primary cicatricial alopecia: part II. Wu WY, Otberg N, McElwee KJ, Shapiro J. Skinmed. 2008 Mar-Apr;7(2):78-83.

The second part of this 2-part article reviews clinical features, histology,
management, and treatment of neutrophilic primary cicatricial alopecias
(folliculitis decalvans and dissecting folliculitis) and mixed primary
cicatricial alopecias (acne keloidalis, acne necrotica, and erosive pustular
dermatosis).

Acne counseling to improve adherence. Thiboutot D, Dréno B, Layton A. Cutis. 2008 Jan;81(1):81-6.

Acne causes substantial social, emotional, and psychological effects in both
adolescents and adults. Although current therapies can effectively treat the
disease and its related effects, adherence to these treatment regimens often is
poor. Misconceptions about the cause of acne, unrealistic treatment expectations,
the chronic and partially asymptomatic nature of the disease, difficulty
incorporating treatment into daily activities, and the need for long-term therapy
contribute to overall adherence. To improve adherence, physicians must counter
these factors with skilled counseling; consideration of the patient’s
perspective; effective means of educating the patient; and simple, effective,
tolerable regimens that are compatible with the patient’s lifestyle.

Retinoid-mediated regulation of mood: possible cellular mechanisms. O’Reilly K, Bailey SJ, Lane MA. Exp Biol Med (Maywood). 2008 Mar;233(3):251-8.

Vitamin A and its derivatives, the retinoids, have long been studied for their
ability to alter central nervous system (CNS) development. Increasingly, it is
recognized that sufficient levels of retinoids may also be required for adult CNS
function. However, excess dietary vitamin A, due to the consumption of
supplements or foods rich in vitamin A, has been reported to induce psychosis. In
addition, 13-cis-retinoic acid (13-cis-RA, isotretinoin), the active ingredient
in the acne treatment Accutane, has been reported to cause adverse psychiatric
events, including depression and suicidal ideation. Nevertheless, epidemiological
studies have reported no consistent link between Accutane use and clinical
depression in humans. Using an animal model, we have recently shown that
13-cis-RA induces an increase in depression-related behavior. Impairments in
spatial learning and memory have also been demonstrated following 13-cis-RA
treatment in mice. This review focuses on the behavioral and possible cellular
effects of retinoid deficiency or excess in the adult brain in relation to
altered mood. Specifically, we discuss the effect of retinoids on
depression-related behaviors and whether norepinephrinergic, dopaminergic, or
serotonergic neurotransmitter systems may be impaired. In addition, we consider
the evidence that adult neurogenesis, a process implicated in the pathophysiology
of depression, is reduced by retinoid signaling. We suggest that 13-cis-RA
treatment may induce depression-related behaviors by decreasing adult
neurogenesis and/or altering the expression of components of serotonergic
neurotransmitter system, thereby leading to impaired serotonin signaling.

The pharmacoeconomics of acne treatment: where are we heading? Inglese MJ, Fleischer AB Jr, Feldman SR, Balkrishnan R. J Dermatolog Treat. 2008;19(1):27-37.

INTRODUCTION: The increasing recognition of the finite nature of health care
resources has prompted the evaluation of the economic impact and value of medical
interventions through pharmacoeconomic analysis. Despite the relevance and
importance of pharmacoeconomics to dermatologic practice, there is a paucity of
available literature on this topic. The purpose of this paper is to assess the
number and quality of pharmacoeconomic studies applied to acne therapy as well as
to provide a basic understanding of pharmacoeconomic analysis, its application to
acne therapy, and the complex factors affecting the study of acne
pharmacoeconomics. METHODS: A Medline search using the keywords acne, economics,
cost-effectiveness, and pharmacoeconomics as well as a search of articles cited
as references in the literature was used to identify pharmacoeconomic analyses
for acne therapy. The quality of the studies was then evaluated by a standard
model for evaluating the quality of cost-effectiveness studies. RESULTS: Only six
studies using a formal pharmacoeconomic evaluation of acne therapy were found in
the literature. All were graded either good or excellent in quality. DISCUSSION:
There is a very limited amount of pharmacoeconomic data regarding acne therapy
albeit good in quality thus far. Conducting further pharmacoeconomic studies
could help maximize health care resources for the treatment of acne.

Versatility of azelaic acid 15% gel in treatment of inflammatory acne vulgaris. Thiboutot D. J Drugs Dermatol. 2008 Jan;7(1):13-6.

Azelaic acid (AzA) 15% gel is approved for the treatment of rosacea in the US,
but also has approval for the treatment of acne vulgaris in many European
countries where it has demonstrated success. Two randomized, multicenter,
controlled clinical trials compared the effects of AzA 15% gel with those of
topical benzoyl peroxide 5% or topical clindamycin 1%, all using a twice-daily
dosing regimen. The primary endpoint in the intent-to-treat analysis was a
reduction in inflammatory papules and pustules. AzA 15% gel resulted in a 70% to
71% median reduction of facial papules and pustules compared with a 77% reduction
with benzoyl peroxide 5% gel and a 63% reduction with clindamycin. AzA 15% gel
was well-tolerated. In addition, a 1-year European observational study conducted
by dermatologists in private practice evaluated the safety and efficacy of AzA
15% gel used as monotherapy or in combination with other agents in more than 1200
patients with acne. Most physicians (81.9%) described an improvement in patients’
symptoms after an average of 34.6 days, and 93.9% of physicians reported patient
improvement after an average of 73.1 days. Both physicians and patients assessed
AzA 15% gel to be effective with 74% of patients being “very satisfied” at the
end of therapy. AzA 15% gel was considered “well-tolerated” or “very
well-tolerated” by 95.7% of patients. The majority of patients were more
satisfied with AzA than with previous therapies. AzA 15% gel represents a new
therapeutic option for the treatment of acne vulgaris.

Newborn skin: Part I. Common rashes. O’Connor NR, McLaughlin MR, Ham P. Am Fam Physician. 2008 Jan 1;77(1):47-52.

Rashes are extremely common in newborns and can be a significant source of
parental concern. Although most rashes are transient and benign, some require
additional work-up. Erythema toxicum neonatorum, acne neonatorum, and transient
neonatal pustular melanosis are transient vesiculopustular rashes that can be
diagnosed clinically based on their distinctive appearances. Infants with unusual
presentations or signs of systemic illness should be evaluated for Candida,
viral, and bacterial infections. Milia and miliaria result from immaturity of
skin structures. Miliaria rubra (also known as heat rash) usually improves after
cooling measures are taken. Seborrheic dermatitis is extremely common and should
be distinguished from atopic dermatitis. Parental reassurance and observation is
usually sufficient, but tar-containing shampoo, topical ketoconazole, or mild
topical steroids may be needed to treat severe or persistent cases.

Evidence-based review of lasers, light sources and photodynamic therapy in the treatment of acne vulgaris. Haedersdal M, Togsverd-Bo K, Wulf HC. J Eur Acad Dermatol Venereol. 2008 Mar;22(3):267-78. Epub 2008 Jan 23.

Background There is a considerable need for effective and safe treatment for acne
vulgaris. Objective In a systematic review with an evidence-based approach to
assess the effects of optical treatments for acne vulgaris. Methods Original
publications of controlled clinical trials were identified through searches in
PubMed and the Cochrane Library. Results A total of 16 randomized controlled
trials (RCT) and 3 controlled trials (CT) were identified, involving a total of
587 patients. Interventions included photodynamic therapy (PDT; 5 RCTs), infrared
lasers (4 RCTs), broad-spectrum light sources (3 RCTs, 1 CT), pulsed dye lasers
(PDL; 2 RCTs, 1 CT), intense pulsed light (IPL; 1 RCTs, 2 CTs), and potassium
titanyl phosphate laser (1 RCT). The randomization method was mentioned in 6 of
16 RCTs, and one trial described adequate allocation concealment. Most trials
were intraindividual trials (12 of 19), which applied blinded response
evaluations (12 of 19) and assessed a short-term efficacy up to 12 weeks after
treatment (17 of 19). Based on the present best available evidence, we conclude
that optical treatments possess the potential to improve inflammatory acne on a
short-term basis with the most consistent outcomes for PDT [up to 68%
improvement, aminolevulinic acid (ALA), methyl-aminolevulinic acid (MAL) and red
light]. IPL-assisted PDT seems to be superior to IPL alone. Only two trials
compare optical vs. conventional treatments, and further studies are needed.
Side-effects from optical treatments included pain, erythema, oedema, crusting,
hyperpigmentation, pustular eruptions and were more intense for treatments
combined with ALA or MAL. Conclusion Evidence from controlled clinical trials
indicates a short-term efficacy from optical treatments for acne vulgaris with
the most consistent outcomes for PDT. We recommend that patients are
preoperatively informed of the existing evidence, which indicates that optical
treatments today are not included among first line treatments.

Omiganan pentahydrochloride in the front line of clinical applications of antimicrobial peptides. Melo MN, Dugourd D, Castanho MA. Recent Pat Antiinfect Drug Discov. 2006 Jun;1(2):201-7.

Ribosomally synthesized antimicrobial peptides have very wide killing spectra and
bacterial resistance to these peptides seems to be a rare phenomenon. Indolicidin
is a ribosomally synthesized antimicrobial peptide that served as a template to
omiganan, which is in development for the prevention of catheter-related
bloodstream infections; clinical trials also proved its efficiency against acne
vulgaris. Omiganan is the most advanced molecule in the front line of clinical
applications of antimicrobial peptides. The mode and site of action of omiganan
are not yet settled although its interaction with membranes is known to play a
fundamental role. The biochemical and biophysical foundations for the action of
indolicidin and its analogues are reviewed in this paper, as well as the clinical
application of omiganan. The in vitro efficiency tests and the outcome of
clinical trials are addressed. Altogether, despite the very specific use of
omiganan as a topical antibiotic, it has the potential of being a pioneer of a
new generation of antibiotics that carry the promise of ending the
multi-resistance problem.

Tetracyclines and pulmonary inflammation. Rempe S, Hayden JM, Robbins RA, Hoyt JC. Endocr Metab Immune Disord Drug Targets. 2007 Dec;7(4):232-6.

Tetracycline and its derivatives, such as chlortetracycline, oxytetracycline,
minocycline, doxycycline, methacycline and lymecycline, are naturally occurring
or semi-synthetic polyketide compounds that exhibit a well known broad-spectrum
antibacterial activity that interferes with prokaryotic protein synthesis at the
ribosome level. In addition to this well known antibacterial activity these
compounds also exhibit a variety of additional, less well known properties. Among
them are separate and distinct anti-inflammatory properties. Tetracycline and
related compounds have been shown to be effective chemotherapeutic agents in a
wide variety of chronic inflammatory diseases and conditions. These include
periodontitis, rosacea, acne, auto-immune diseases such as rheumatoid arthritis
and protection of the central nervous system against trauma and neurodegenerative
diseases such as stroke, multiple sclerosis and Parkinson disease. Tetracycline
and related compounds appear to be beneficial for treatment of several chronic
inflammatory airway diseases. Among them are asthma, bronchiectasis, acute
respiratory distress syndrome, chemical induced lung damage and cystic fibrosis.
The clinical use of tetracycline-type drugs in treatment of chronic airway
inflammation is becoming a topic of intense interest. Recent findings in this
area have led to an understanding of the myriad physiological, cellular and
molecular mechanisms of the inflammatory response and how this response may be
controlled to limit damage to host cells and tissues. This review presents a
brief summary of the recent research in the area of tetracycline and its
derivatives in control of pulmonary inflammation.

Polycystic ovary syndrome (PCOS) and other androgen excess-related conditions: can changes in dietary intake make a difference? Liepa GU, Sengupta A, Karsies D. Nutr Clin Pract. 2008 Feb;23(1):63-71.

Polycystic ovary syndrome (PCOS) is a condition that involves the excess
production of androgens. It affects up to 10% of all American women and can lead
to the development of acne, hirsutism, and infertility. It has also been
associated with coronary heart disease, diabetes, and metabolic syndrome. Over
half of the women who are diagnosed with PCOS are overweight or obese.
Recommendations are made for overweight/obese women to lose weight via diet and
exercise. Women with PCOS should also consider maintaining a diet that is
patterned after the type 2 diabetes diet. This diet includes an increase in fiber
and a decrease in refined carbohydrates, as well as a decrease in trans and
saturated fats and an increase in omega-3 and omega-9 fatty acids. Foods that
contain anti-inflammatory compounds (fiber, omega-3 fatty acids, vitamin E, and
red wine) should also be emphasized. Evidence is provided for the impact of these
dietary changes on improvements in the androgen profile of PCOS patients.

Newer topical therapies for the treatment of acne vulgaris. Del Rosso JQ. Cutis. 2007 Nov;80(5):400-10.

Newer topical therapies approved by the US Food and Drug Administration (FDA) for
the treatment of acne vulgaris are dapsone gel 5% and clindamycin phosphate 1.2%
and tretinoin 0.025% combination gel. Both are formulated in aqueous-based gel
vehicles. These newer topical acne products have been shown to be effective and
safe in pivotal 12-week phase 3 trials and long-term studies completed over 12
months. This article reviews applicable pharmacokinetic, efficacy, and safety
data reported with both products.

Mood and sexual function in polycystic ovary syndrome. Janssen OE, Hahn S, Tan S, Benson S, Elsenbruch S. Semin Reprod Med. 2008 Jan;26(1):45-52.

Women with polycystic ovary syndrome (PCOS) fail to conform with societal norms
for outer appearance. Many PCOS patients thus feel stigmatized in the sense of a
loss of “feminine identity.” In addition to somatic impairment, mood disturbances
such as depression and limitations in emotional well-being, quality of life, and
life satisfaction, the diagnosis of PCOS also has a negative impact on sexual
self-worth and sexual satisfaction. Both obesity and hirsutism are major
determinants of the physical component of quality of life in affected women.
However, its psychological aspect appears to be inherent and specific for PCOS.
Confirmation of the diagnosis and provision of detailed information to affected
women, together with the availability of interdisciplinary treatment aimed at
improving PCOS-related symptoms, such as hirsutism, obesity, menstrual
irregularity, and infertility, will also reduce psychological distress and
improve sexual self-worth. New treatment options, including insulin sensitizers,
psychological counseling, and participation in a PCOS support group, are likely
to further improve life satisfaction and coping of affected women.

Recent advances in acne vulgaris research: insights and clinical implications. Wang KC, Zane LT. Adv Dermatol. 2008;24:197-209.

Understanding of acne vulgaris has taken major steps forward over the past few
years. The renewed interest in the effect of dietary interventions on acne, the
elucidation of the involvement of TLR and MMPs in acne pathogenesis, and a more
detailed functional understanding of various treatment modalities at the
molecular level are all promising indications that advances in therapeutics are
sure to follow. Health utilities will serve not only as powerful outcome measures
of treatment effects but also as clinical decision-making aids in everyday
practice. It is hoped that future advances will further uncover additional
molecular and cellular details of pathophysiology, leading to rational targeted
design of medications, and advance clinical management through improved
understanding of the psychosocial impact of acne on patients.

Toll-like receptors in skin. Miller LS. Adv Dermatol. 2008;24:71-87.

TLRs have emerged as a major class of PRRs that are involved in detecting
invading pathogens in the skin and initiating cutaneous immune responses. TLRs
are expressed on many different cell types in the skin, including keratinocytes
and Langerhans cells in the epidermis. Each TLR can recognize a different
microbial component and there are differences among the TLR signaling pathways,
which lead to distinct immune responses against a given pathogen. Certain TLRs
have been implicated in the pathogenesis of skin diseases, such as atopic
dermatitis, psoriasis, and acne vulgaris. In addition, TLRs have been shown to be
important in cutaneous host defense mechanisms against common bacterial, fungal,
and viral pathogens in the skin, such as S aureus, C albicans, and HSV. Since the
discovery that topical TLR agonists promote antiviral and antitumor immune
responses, there has been considerable interest in the development of TLR-based
therapies for skin diseases, skin cancer, and infections. Future research
involving TLRs in skin will hopefully provide new insights into host defense
against skin pathogens and novel therapeutic targets aimed at treating skin
disease and skin cancer.

Acne inversa. [Article in English, German] Meixner D, Schneider S, Krause M, Sterry W. J Dtsch Dermatol Ges. 2008 Mar;6(3):189-96. Epub 2007 Dec 17.

Acne inversa is a chronic inflammatory skin disease featuring cutaneous and
subcutaneous nodular inflammation, fistula formation and discharge of
foul-smelling secretions. The disease can lead to functional impairment and
psychological problems. There is inflammation of the terminal hair follicles in
intertriginous regions, especially perianal, axillary and inguinal areas. Less
often there is submammary, periumbilical, retroauricular or nuchal involvement.
Without treatment the disease is chronic and progressive. The causes of acne
inversa are multifactorial and pathogenesis is still not well understood. Besides
a positive family history, obesity and cigarette smoking are trigger factors.
Early diagnosis and therapy of acne inversa saves the patient years of suffering.
The most effective treatment is undoubtedly the radical wide excision of the
affected areas. Local measures such as radiotherapy, photodynamic therapy and
cryotherapy have provided little benefit; the same is true for systemic
antibiotic treatment or hormonal therapy with anti-androgens. TNF-alpha
antagonists seem to have a promising influence on the disease. Further studies
investigating the effect of these substances on acne inversa are warranted.

Tumor necrosis factor-alpha inhibitor-induced psoriasis or psoriasiform exanthemata: first 120 cases from the literature including a series of six new patients. Wollina U, Hansel G, Koch A, Schönlebe J, Köstler E, Haroske G. Am J Clin Dermatol. 2008;9(1):1-14.

Tumor necrosis factor-alpha (TNFalpha) inhibition is effective in the treatment
of moderate-to-severe psoriasis. We report on 120 patients from the literature
including six new patients (three women and three men) who developed pustular
lesions during treatment with TNFalpha inhibitors. We identified 72 women and 36
men (several papers did not specify the gender of patients) with an age range of
13-78 years (mean 42.3 years). The primary diagnoses were rheumatoid arthritis (n
= 61), ankylosing spondylitis (n = 21), psoriasis (n = 10), Crohn disease (n =
8), SAPHO (synovitis acne pustulosis hyperostosis osteitis) syndrome (n = 3),
psoriatic arthritis (n = 2), and other diagnoses (n = 15). Psoriasis (except
palmoplantar pustular type) was the most common adverse effect during
anti-TNFalpha treatment (n = 73), followed by palmoplantar pustular psoriasis (n
= 37) and psoriasis of the nail (n = 6), sometimes combined in the same patient.
Palmoplantar pustulosis and psoriasiform exanthema was the diagnosis in ten
patients each. A positive personal history of psoriasis was recorded in 25
patients. A positive family history was noted in eight patients. No data about
personal (n = 7) or family history (n = 46) were available in a number of
patients. Newly induced psoriasis was diagnosed in 74 patients whereas an
exacerbation or aggravation of a pre-existing psoriasis was noted in another 25
patients. All three TNFalpha inhibitors available on the market were involved:
infliximab (63 patients), etanercept (37 patients), and adalimumab (26 patients).
Several patients were treated with more than a single TFNalpha inhibitor. The
timing of cutaneous adverse effects (psoriasis and psoriasiform rash) varied
considerably among patients, ranging from after a single application to a delayed
response of up to 63 months after initiation of treatment. The mean time to
appearance of the cutaneous adverse effect for all TNFalpha inhibitors was 9.5
months. Cessation of the responsible TNFalpha inhibitor was carried out in 47
patients either alone or in association with adjuvant anti-psoriatic therapy
(mostly topical). This resulted in complete remission in 21 patients, partial
remission in 20 patients, and stable disease in another three patients; in the
other three patients, the outcome was not reported. TNFalpha inhibition was
continued in 47 patients but anti-psoriatic adjuvant therapy was introduced. The
outcome in this group was complete remission in 22 patients, partial remission in
25 patients, and stable disease in 2 patients. The response rate (complete
remission plus partial remission) was 93.2% and 95.9%, respectively, in each
group. In six patients, switching from one TNFalpha inhibitor to another one
immediately after cutaneous adverse effects occurred resulted in an improvement
in five patients. In nine patients, a second TNFalpha inhibitor was initiated
after a break in TNFalpha inhibition. The response to a second or third drug in
these patients was mixed. The underlying pathomechanisms of induction of
psoriasis or psoriasiform exanthemata by TNFalpha inhibitors remain elusive but
there is reason to assume that induction of such adverse events has more than one
pathophysiology.

Skin lightening preparations and the hydroquinone controversy. Draelos ZD. Dermatol Ther. 2007 Sep-Oct;20(5):308-13.

Skin lightening preparations are widely used in dermatology by persons of all
Fitzpatrick skin types. Fitzpatrick skin types I-III require local pigment
lightening for the treatment of hormonally induced melasma and postinflammatory
hyperpigmentation caused by acne and trauma. Fitzpatrick skin types IV and darker
have an even greater need for skin lightening for social reasons, as well as
pigmentary changes that occur around the eyes, in the intertriginous areas,
following dermatitis, or with acne and trauma. The gold standard dermatologic
agent for skin lightening was hydroquinone, until regulatory agencies in Japan,
Europe, and most recently in the United States questioned the safety of this
substance. This has encouraged research into alternative agents to inhibit skin
pigmentation such as retinoids, mequinol, azelaic acid, arbutin, kojic acid,
aleosin, licorice extract, ascorbic acid, soy proteins, and N-acetyl glucosamine.
The efficacy and safety of each of these ingredients is examined as possible
topical alternatives to hydroquinone.

Acne vulgaris: lasers, light sources and photodynamic therapy–an update 2007. Gold MH. Expert Rev Anti Infect Ther. 2007 Dec;5(6):1059-69.

Inflammatory acne vulgaris remains one of the most common dermatologic disorders
seen in clinical practice. Medical therapy remains the gold standard for therapy
but recent advances have shown that a variety of lasers and light sources may be
useful in the treatment of inflammatory acne vulgaris. In addition, the use of
20% 5-aminolevulinic acid has found a useful niche in the treatment of
moderate-to-severe inflammatory acne vulgaris.

Sphingosine-1-phosphate signaling and the skin. Herzinger T, Kleuser B, Schäfer-Korting M, Korting HC. Am J Clin Dermatol. 2007;8(6):329-36.

Sphingolipids have long been viewed as rather passive structural components of
cellular membranes. More recently, it has become evident that metabolism of
sphingomyelin yields several lipid mediators that evoke diverse and specific
responses in different cell types. One sphingomyelin derivate,
sphingosine-1-phosphate (S1P), has attracted particular attention for its effect
on epidermal cells, which differs from those on most other cell types. S1P
inhibits keratinocyte proliferation and induces keratinocyte differentiation and
migration, suggesting a role for S1P in the re-epithelialization of wounds. The
migratory response involves the phosphorylation and activation of Smad3. In
epithelial tumors, S1P signaling has been linked with potential oncogenic
effects, but has also been found to inhibit metastasis in a mouse melanoma model.
S1P promotes endothelial cell survival, acts as a chemoattractant for vascular
cells, and exerts a protective effect on the endothelial barrier. Conversely, S1P
receptor knockout leads to embryonic lethality mainly due to impaired vascular
maturation. S1P presumably modulates peripheral T-lymphocyte levels by
stimulating their egress from lymphoid organs rather than by promoting T-cell
proliferation. The S1P analog FTY720 (fingolimod) acts as a functional antagonist
by inhibiting lymphocyte egress, and thus holds great promise as an
immunosuppressant drug for the prevention of allograft rejection and treatment of
T-lymphocyte-driven inflammatory skin diseases, such as lupus erythematosus,
psoriasis, and atopic dermatitis. Topical use of S1P and other sphingosine
compounds is also under investigation, particularly for the treatment of acne
vulgaris.

Photodynamic therapy update 2007. Gold MH. J Drugs Dermatol. 2007 Nov;6(11):1131-7.

The use of photodynamic therapy (PDT) in the US has shown record growth in 2007
with more clinicians utilizing PDT for more clinical entities than ever before.
Research endeavors utilizing PDT in published clinical manuscripts have been slow
in 2007 and yet the use continues to rise significantly. This manuscript will
highlight the state of PDT in the US as 2007 comes to a close and focus on the
future of PDT as we move toward 2008.

Fractionated delivery systems for difficult to treat clinical applications: acne scarring, melasma, atrophic scarring, striae distensae, and deep rhytides. Taub AF. J Drugs Dermatol. 2007 Nov;6(11):1120-8.

Fractional resurfacing or laser therapy (FLT) represents a technology that seeks
to address the limitations of both ablative resurfacing and nonablative
treatments. Many companies now offer versions of fractionated erbium or carbon
dioxide lasers. The purpose of this paper is to examine FLT for difficult to
treat applications such as melasma, acne scarring, atrophic scarring, striae
distensae, and deep rhytides. Fractional laser therapy is a truly novel approach
to many conditions, especially those with dermal pathology. Although published
peer review data is limited, the ability to effectively and safely treat these
conditions in all skin types appears to have been significantly enhanced with
this new modality. We are early in our scientific explorations of what is
possible with FLT.

Side-effects of topical androgenic and anabolic substances and steroids. A short review. Wollina U, Pabst F, Schönlebe J, Abdel-Naser MB, Konrad H, Gruner M, Haroske G, Klemm E, Schreiber G. Acta Dermatovenerol Alp Panonica Adriat. 2007 Sep;16(3):117-22.

There is an increasing interest, including androgenic and anabolic substances
(AAS). The uncritical use may be associated with severe adverse effects. We
observed five patients with different patterns of adverse reaction to AAS: two
females and three males, they were identified when seeking medical help and
advice. The following adverse effects from of AAS have been observed: deepening
of the voice due to topical use of AAS in an anti-cellulite cream; circumscribed
hypertrichosis and late onset acneiform eruptions due to testosterone replacement
therapy after ovariectomy; homolateral gynecomastia and infertility, acne and
striae distensae in males using injectable AAS. CONCLUSIONS: ASS can trigger
significant adverse effects. An interdisciplinary approach may be necessary for
evaluation. The dermatologists should be familiar with the adverse effects.

Efficacy of tetracyclines in the treatment of acne vulgaris: a review. Simonart T, Dramaix M, De Maertelaer V. Br J Dermatol. 2008 Feb;158(2):208-16. Epub 2007 Nov 6.

BACKGROUND: Oral tetracyclines are routinely used for the management of
inflammatory acne. However, there is a lack of evidence-based data on their
relative effectiveness and appropriate dosages. OBJECTIVES: To assess the
relative effectiveness and the optimal dosage of tetracyclines for the treatment
of inflammatory acne. METHODS: We designed a systematic review of the clinical
trials (1962-2006) investigating oral tetracyclines for the treatment of
inflammatory acne. We obtained data from MEDLINE, PubMed, Current Contents,
reference lists and specialist textbooks. RESULTS: There was substantial
heterogeneity in the design of the trials. We identified only seven randomized
trials which were set up to compare the efficacy of tetracyclines in reducing
acne lesion counts. These showed no evidence of superiority of one tetracycline
over another. Overall, there was also no significant difference between the
available tetracyclines in terms of improvement in inflammatory (32 trials,
P=0.898) and noninflammatory (23 trials, P=0.429) lesions. In the range of
investigated dosages, the antibiotic dosage had no impact on efficacy in
inflammatory (P=0.609) and noninflammatory (P=0.654) lesions. There was no
decrease in efficacy during the study period. CONCLUSIONS: There is insufficient
evidence to support one tetracycline rather than another in terms of efficacy. In
the range of investigated dosages, the antibiotic dosage seems to have no impact
on efficacy. Despite increased resistance to antibiotics, oral tetracycline
formulations displayed no change in efficacy during the study period. Further
studies are, however, required to determine if the anti-inflammatory properties
of tetracyclines are sufficient in managing acne.

The contraceptive implant. Hohmann H, Creinin MD. Clin Obstet Gynecol. 2007 Dec;50(4):907-17.

Contraceptive implants provide long-acting, highly effective reversible
contraception. Currently, the only subdermal implant available to women in the
United States is the single rod etonogestrel implant, Implanon (N.V. Organon,
Oss, the Netherlands) approved by the Food and Drug Administration in July 2006.
Implanon is currently approved for 3 years of use, provides excellent efficacy
throughout its use, and is easy to insert and remove. Similar to other
progestin-only contraceptives, Implanon can cause irregular vaginal bleeding.
Implanon has been shown to be safe to use during lactation, may improve
dysmenorrhea, and does not significantly affect bone mineral density, lipid
profile, or liver enzymes.

The ectopeptidases dipeptidyl peptidase IV (DP IV) and aminopeptidase N (APN) and their related enzymes as possible targets in the treatment of skin diseases. Thielitz A, Ansorge S, Bank U, Tager M, Wrenger S, Gollnick H, Reinhold D. Front Biosci. 2008 Jan 1;13:2364-75.

Skin cells express dipeptidyl peptidase IV (DP IV) and aminopeptidase N (APN) and
their related molecules of the DP IV-like family DP2, DP6, DP8, DP9 and
fibroblast activation protein (FAP), as well as the cytoplasmic alanyl
aminopeptidase (cAAP). The inhibitors of DP IV-like activity,
Lys(Z(NO2))-thiazolidide (LZNT) and Lys(Z(NO2))-pyrrolidide (LZNP), and the APN
inhibitors actinonin and bestatin affect proliferation, differentiation and
cytokine production in sebocytes and keratinocytes, which are involved in the
initiation of acne. Furthermore, they suppress proliferation of Propionibacterium
acnes-stimulated T cells ex vivo and induce an anti-inflammatory cytokine
profile. In the mouse tail model of psoriasis they have a pro-differentiative
effect. In addition, these inhibitors suppress skin fibroblast proliferation,
whereas only inhibition of DP IV-like activity decreases TGF-beta1 expression and
abrogates the TGF-beta1 mediated stimulatory effects on TGF-beta1 and fibronectin
production, collagen synthesis and matrix deposition in these cells. Targeting
enzyme activity of DP IV and APN and their related molecules might be a novel
approach for the treatment of acne, psoriasis or keloids.

Prospective teratology of retinoic acid metabolic blocking agents (RAMBAs) and loss of CYP26 activity. McCaffery P, Simons C. Curr Pharm Des. 2007;13(29):3020-37.

All-trans retinoic acid (atRA) is the transcriptionally active product of vitamin
A and induces gene expression via specific receptors at nM concentrations.
Essential enzymes that regulate the local levels of atRA are the CYP26 members of
the cytochrome P450 family, which catabolize atRA. Compounds that have been
designed to inhibit these enzymes are known as Retinoic Acid Metabolic Blocking
Agents (RAMBAs). Treatment with these compounds will raise endogenous atRA levels
and may be therapeutic for the treatment of diseases that respond to high atRA
concentrations, including several types of cancer as well as skin conditions such
as psoriasis and acne. This review describes the mechanism of action of the
RAMBAs and discusses the potential side effects of these compounds. atRA is
highly teratogenic and the potential teratogenicity of the RAMBAs is described by
comparison with the abnormalities resulting from null mutation of individual
CYP26 genes. The possible effects of RAMBAs on the adult brain are also described
that have the potential for harm but, in the right circumstances, may also be
beneficial.

Ilium osteitis as the main manifestation of the SAPHO syndrome: response to infliximab therapy and review of the literature. Moll C, Hernández MV, Cañete JD, Gómez-Puerta JA, Soriano A, Collado A, Sanmartí R. Semin Arthritis Rheum. 2008 Apr;37(5):299-306. Epub 2007 Oct 31.

OBJECTIVE: To analyze the clinical efficacy of anti-tumor necrosis factor
(TNF)-alpha therapy in the SAPHO (synovitis, acne, pustulosis, hyperostosis,
osteitis) syndrome. We describe 2 new cases with ilium osteitis as the main SAPHO
syndrome feature and review reported cases treated with anti-TNF-alpha. METHODS:
A literature search of SAPHO syndrome cases treated with TNF-alpha blocking
therapy with special emphasis on osteoarticular and skin responses was performed.
RESULTS: Eighteen cases were identified: 17 SAPHO syndrome and 1 chronic
recurrent multifocal osteomyelitis, a juvenile variant of SAPHO syndrome. Sixteen
were reported cases and 2 were nonreported cases seen in our arthritis unit.
Sixteen patients received infliximab and 2 received etanercept, with an early,
sustained clinical improvement in most cases. CONCLUSIONS: Anti-TNF-alpha
therapies are effective treatment for patients with refractory SAPHO syndrome,
not only for cutaneous lesions but also for persistent bone lesions such as
osteitis.

Yaz (3 mg drospirenone/20 microg ethinyl estradiol). Scheinfeld NS. Skinmed. 2007 Nov-Dec;6(6):289.

Differin (adapalene) Gel, 0.3%. Abramovits W, Gupta A. Skinmed. 2007 Nov-Dec;6(6):287-8.

Drug-induced skin, nail and hair disorders. Valeyrie-Allanore L, Sassolas B, Roujeau JC. Drug Saf. 2007;30(11):1011-30.

Drug eruptions are among the most common adverse drug reactions, affecting
approximately 3% of hospitalised patients. Although the rate of severe cutaneous
adverse reactions to medications is low, these reactions can affect anyone who
takes medication, and can result in death or disability. Two general patterns can
be distinguished, depending on the type of onset of these cutaneous adverse drug
reactions: acute or chronic. Acute-onset events are usually rather specific
cutaneous ‘syndromes’ that constitute emergencies and should therefore be
promptly recognised and treated, while chronic-onset events often present as
dermatological diseases. The challenge is therefore to recognise the drug
aetiology in front of a ‘classical’ dermatosis such as acne, lichen or pemphigus.
Therefore, clinicians should carefully evaluate the signs or symptoms of all
adverse reactions thought to be drug related, and discontinue the offending agent
when feasible. Erythematous drug eruptions are the most frequent and less severe
acute immune drug-induced rashes, and are sometimes difficult to differentiate
from viral eruptions. On the other hand, acute urticaria and angioedema are
sometimes life-threatening eruptions for which a drug aetiology must be
investigated. Photosensitivity, vasculitis and skin necrosis belong to the acute
onset reactions, which are not always drug-induced, in contrast to fixed drug
eruptions. The early recognition of acute generalised exanthematous pustulosis,
DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome,
Stevens-Johnson syndrome and toxic epidermal necrolysis are of high importance
because of the specific mechanisms involved and the different prognosis of each
of these diseases. Chronic onset drug-induced disorders include pigmentary
changes, drug-induced autoimmune bullous diseases, lupus, pseudo lymphoma and
acneiform eruptions; these are discussed, along with specific data on
drug-induced hair and nail disorders. As the disorders are numerous, the
mechanisms and the drugs involved in the development of these various reactions
are multiple. The list of drugs discussed in relation to the different disorders
are as accurate as possible at the time of preparation of this review, but will
need updating as new drugs emerge onto the market. We emphasize the clinical
recognition, pathophysiology and treatment of skin, hair and nail adverse drug
reactions, and the role of each doctor involved in the management of these
patients in the notification of the adverse drug reaction to health authorities,
using the minimal requirement for notification proposed.

Combination topical therapy in the treatment of acne. Del Rosso JQ. Cutis. 2006 Aug;78(2 Suppl 1):5-12.

Many medications are available for the management of acne. The armamentarium
includes topical retinoids (ie, adapalene, tazarotene, tretinoin), antimicrobial
and antibacterial agents (ie, benzoyl peroxide, clindamycin, erythromycin,
sulfacetamide with or without sulfur), oral antibiotics (ie, doxycycline,
minocycline, tetracycline), hormonal agents (ie, oral contraceptives,
spironolactone), and systemic retinoids (ie, isotretinoin). Acne usually is
treated with combination therapy to address its multifactorial pathophysiology.
The combination of clindamycin 1%-benzoyl peroxide 5% gel, available as a stable
formulation in a single tube, is efficacious and well-tolerated. The product’s
excipients, glycerin and dimethicone, minimize treatment-related irritation,
thereby increasing patient compliance. Clindamycin-benzoyl peroxide may be
well-tolerated when applied with topical retinoids, creating a more targeted and
complete treatment strategy.

Non-contraceptive health benefits of oral contraceptives. Maia HJ, Casoy J. Eur J Contracept Reprod Health Care. 2008 Mar;13(1):17-24.

The use of combined oral contraceptives (COCs) is associated with a reduced risk
of developing endometriosis, myomas, and endometrial and ovarian carcinoma. The
mechanisms involved are multiple; next to ovulation suppression, a reduction in
inflammation in the genital tract is involved. This is accomplished through
inhibition of the endometrial expression of enzymes related to the biosynthesis
of prostaglandin and oestrogen, particularly cyclooxygenase type II (Cox-2) and
aromatase. The blockade of these enzymatic systems by COCs explains the
beneficial effects of these compounds in treating the symptoms, and halting the
progression of myomas, endometriosis and adenomyosis, all of which are
characterized by increased inflammation. Inhibition of aromatase and Cox-2
expression in the endometrium by COCs may explain their efficacy in controlling
the pain and excessive uterine bleeding caused by these pathologies. The
reduction of inflammation in the endometrium may also be the mechanism behind the
lower incidence of endometrial carcinoma in COC users. The blockade of ovulation
and ovarian steroidogenesis, on the other hand, may explain the lesser incidence
of ovarian cancer and the improvement of acne in users. In conclusion,
inflammation appears to play a pivotal role in the development of various benign
and malignant gynecological diseases. COCs reduce inflammation in the female
genital tract by blocking enzymes such as Cox-2 and aromatase.

Hidradenitis suppurativa (acne inversa): management of a recalcitrant disease. Lam J, Krakowski AC, Friedlander SF. Pediatr Dermatol. 2007 Sep-Oct;24(5):465-73.

Hidradenitis suppurativa is a chronic relapsing disorder of follicular occlusion
that is often recalcitrant to therapy. Topical and systemic antibiotics, hormonal
therapies, oral retinoids, immunosuppressant agents, and surgical treatment are
some of the therapeutic alternatives used for this often recalcitrant and
frequently troublesome disorder. This article reviews the pathophysiology of
hidradenitis suppurativa, an evidence-based analysis of standard treatments, and
recent advances in the therapy of this disorder.

Recently approved systemic therapies for acne vulgaris and rosacea. Del Rosso JQ. Cutis. 2007 Aug;80(2):113-20.

Until recently, with the exception of oral isotretinoin for the treatment of
severe recalcitrant nodular acne, systemic therapy for acne vulgaris and rosacea
has been based on anecdotal support, clinical experience, and small clinical
trials. Tetracycline derivatives are the predominant systemic agents that have
been used for both disease states, prescribed in dose ranges that produce
antibiotic activity. Anti-inflammatory dose doxycycline, a controlled-release
(CR) 40-mg capsule formulation of doxycycline that is devoid of antibiotic
activity when administered once daily, was US Food and Drug Administration
(FDA)-approved for the treatment of inflammatory lesions (papules and pustules)
of rosacea, based on large-scale phase 3 pivotal trials and long-term
microbiologic and safety data. Also, an extended-release (ER) tablet formulation
of minocycline was approved by the FDA for the treatment of inflammatory lesions
of moderate to severe acne vulgaris in patients 12 years and older based on
large-scale phase 3 clinical trials that evaluated efficacy and safety,
dose-response analysis, and long-term data. This article discusses the studies
and clinical applications related to the use of these agents.

Dehydroepiandrosterone for systemic lupus erythematosus. Crosbie D, Black C, McIntyre L, Royle PL, Thomas S. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD005114.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic inflammatory,
multisystem autoimmune condition. Dehydroepiandrosterone (DHEA) is a naturally
occurring inactive steroid which may possess disease activity modifying
properties as well as the ability to reduce flares and steroid requirements.
OBJECTIVES: To assess the effectiveness and safety of dehydroepiandrosterone
compared to placebo in the treatment of people with systemic lupus erythematosus.
SEARCH STRATEGY: We searched The Cochrane Library (Issue 2, 2006), MEDLINE, Pub
Med, EMBASE, Science Citation Index and ISI Proceedings as well as searching web
sites of Genelabs, FDA and EMEA. (Searches undertaken in June 2006 unless
otherwise specified). SELECTION CRITERIA: We included randomised controlled
trials of at least three months duration comparing DHEA to a placebo in people
with SLE. DATA COLLECTION AND ANALYSIS: Two review authors assessed quality and
extracted data. MAIN RESULTS: From the seven RCTs identified (842 participants)
to date there is ‘gold’ ranking evidence (www.cochranemsk.org) that DHEA: had
little clinical effect on disease activity in those with mild/moderate disease
(measured by SLEDAI or SLAM) but one study demonstrated evidence of stabilisation
or improvement in 8.3% more patients than those treated with placebo; had a
modest but clinically significant improvement in health related quality of life
measured by Patient Global Assessment, estimated as 11.5% (11.5 mm on a 100 mm
scale) by meta-analysis; resulted in a greater number of patients experiencing
adverse events, particularly androgenic effects such as acne where patients risk
was doubled when compared to placebo (RR 2.2; 95% CI 1.65 to 2.83) AUTHORS’
CONCLUSIONS: Studying effectiveness of DHEA for SLE is difficult, reflecting the
problems of studying any treatment for a disease as complex as SLE. From the
seven RCTs to date, there was evidence that DHEA had a modest but clinically
significant impact on health related quality of life in the short term. Impact on
disease activity was inconsistent, with DHEA showing no benefit over placebo in
terms of change in SLEDAI in all but one of the 6 studies reporting this outcome.
Long term outcomes and safety remain unstudied.

Retinoic acid metabolism blocking agents (RAMBAs): a new paradigm in the treatment of hyperkeratotic disorders. [Article in English, German] Verfaille CJ, Borgers M, van Steensel MA. J Dtsch Dermatol Ges. 2008 May;6(5):355-64. Epub 2007 Oct 16.

Synthetic vitamin A derivatives, retinoids,have long been the mainstay of
treatment for several disorders of keratinization, notably the ichthyoses and
severe acne. Some forms of psoriasis also respond well. Their considerable power
comes at a price.They have dose-limiting side effects and can be highly
teratogenic, limiting their use in women of childbearing age.Thus, retinoids are
used less often than their potential would warrant. However, the recent
development of compounds that block the catabolism of endogenous vitamin A,
called Retinioic Acid Metabolism Blocking Agents or RAMBAs, offers new
possibilities. With these drugs, retinoid effects with less side effects and a
reduction of the post-treatment teratogenicity period due to their favourable
pharmacokinetic profile might be expected. In this review, we discuss how
retinoids work, how they are metabolized and how RAMBAs influence this process.We
also review the presently available data from clinical trials with RAMBAs.

Common and alternate oral antibiotic therapies for acne vulgaris: a review. Amin K, Riddle CC, Aires DJ, Schweiger ES. J Drugs Dermatol. 2007 Sep;6(9):873-80.

Acne vulgaris is an extremely common disorder affecting many adolescents and
adults throughout their lifetimes. The pathogenesis of acne is multifactorial and
is thought to involve excess sebum, follicular hyperkeratinization, bacterial
colonization, and inflammation. Many therapeutic options exist for treating acne,
including topical benzoyl peroxide, topical and oral antibiotics, topical and
oral retinoids, and oral contraceptives. Oral antibiotics have been a mainstay in
the treatment of acne for decades and function by exerting an antibacterial
effect by reducing the follicular colonization of Propionibacterium acnes.
Systemic antibiotics also have anti-inflammatory and immunomodulatory properties.
This article reviews the English language literature on the efficacy of various
systemic antibiotics for treating acne vulgaris, including second-line and less
historically used medications. We discuss the tetracyclines, including
subantimicrobial dose doxycycline, macrolides (notably azithromycin),
trimethoprim-sulfamethoxazole, cephalosporins, and fluoroquinolones as treatment
options for acne vulgaris.

New developments in hormonal therapy for acne. Tan JK. Skin Therapy Lett. 2007 Sep;12(7):1-3.

Oral contraceptives (OCs) are a valuable option for the treatment of women with
acne. The use of OCs can be considered across the spectrum of acne disease
severity in women. In Canada, three preparations are approved for
mild-to-moderate acne, and a fourth is indicated for severe acne. These
formulations contain estrogen in the form of ethinyl estradiol and a progestin.
In Canada, the most recently approved OC is ethinyl estradiol 0.03 mg and
drospirenone 3mg (Yasmin, Bayer). With the accumulating evidence on the efficacy
and safety of drospirenone-containing hormonal preparations, this formulation
provides dermatologists with a new treatment option for acne and other
hyperandrogenic disorders.

Topical clindamycin in the management of acne vulgaris. Guay DR. Expert Opin Pharmacother. 2007 Oct;8(15):2625-64.

A small cadre of antimicrobials are commonly used and regarded as effective and
safe, as systemic and topical treatments of acne vulgaris. These include oral
tetracycline, doxycycline, minocycline and topical clindamycin and erythromycin.
Topical antimicrobials work via both antimicrobial and non-antimicrobial
mechanisms: the former due to suppression of the growth of propionibacterial
species (especially Propionibacterium acnes and P. granulosum). Clindamycin
appears to be superior in efficacy compared with erythromycin and tetracycline.
However, the emergence and spread of resistance among propionibacteria to both
erythromycin and clindamycin calls into question their long-term viability as
topical anti-acne therapies. Only through judicious use of combination topical
therapies (e.g., topical retinoid, benzoyl peroxide or azelaic acid plus
clindamycin or erythromycin) and the practice of effective infection control
(i.e., handwashing between seeing patients in the clinic) can both clindamycin’s
and erythromycin’s widespread utility be preserved in this disorder.

[Individualization of low-dose oral contraceptives. Pharmacological principles and practical indications for oral contraceptives] [Article in Italian] Cianci A, De Leo V. Minerva Ginecol. 2007 Aug;59(4):415-25.

The contraceptive pill has been a revolution of the last 40 years. In Italy,
however, it is much less widely used than in other countries. Explanations for
this phenomenon range from religious implications and customs to misinformation
and word-of-mouth communication of negative experiences. The oral contraceptive
pill is often used to correct menstrual disorders, leading to poor results and
side-effects. Recent advances in oral contraception have led to a substantial
reduction in doses and side-effects. Low-dose pills contain minimal doses of
progesterones and estrogens and ensure good control of the menstrual cycle.
Although reduction of ethinyl estradiol (EE) concentrations has reduced the
incidence of negative systemic side effects such as water retention, edema and
swollen breasts, the low estrogen dose may be associated with spotting and
hypomenorrhea or amenorrhea in the long term, as well as dyspareunia due to
reduced vaginal trophism, which may induce women to suspend use of the drug. It
is also true that only one type of estrogen is used in the pill, albeit at
different doses, whereas the progesterone may differ and in many cases is the
cause of common side-effects. The choice of progesterone therefore involves not
only its effect on the endometrium in synergy with estrogen, but also possible
residual androgenic activity which may have negative metabolic repercussions.
Indeed, addition of a progesterone, especially androgen-derived, attenuates the
positive metabolic effects of estrogen. Two new monophasic oral contraceptives
were recently released. They contain 30 microg (Yasmin) or 20 muicrog
(Yasminelle) EE and a new progesterone, drospirenone, derived from spirolactone,
which has antiandrogenic and antimineralcorticoid activity similar to endogenous
progesterone. Like progesterone, the drospirenone molecule is an aldosterone
antagonist and has a natriuretic effect that opposes the sodium retention effect
of EE. It may, therefore, help to prevent the water retention, weight gain and
arterial hypertension often associated with oral contraceptive use. Recent
comparative studies recorded weight loss that stabilized after 6 months of
treatment with drospirenone/EE. Overweight women may therefore benefit from the
formulation with 20 microg EE, whereas the formulation with at least 30 microg EE
should be more appropriate for underweight women. Women with slight to moderate
acne, the formulation with 30 microg EE has been found to be as effective as 2 mg
cyproterone acetate combined with 35 micrig EE (Diane). Menstrual cycle
characteristics, however, remain the main factor determining the choice of
formulation. Randomised control studies comparing the new formulation with others
containing second or third generation progesterones have found similar efficacy
in cycle control and incidence of spotting. From this point of view, it is not
advisable to prescribe more than 30 microg EE (Yasmin or Yasminelle) for women
with normal menstrual cycles, whereas in cases of hypomenorrhea and/or amenorrhea
at least this dose of EE plus drospirenone may be used. Women with hypermenorrhea
run the risk of spotting if an inappropriate drug is chosen. A solution is to use
30 microg EE/drospirenone from day 5 of the cycle. To control so-called minor
side-effects, the dose of EE must be appropriate. In women with premenstrual
tension a dose of at least 30 microg EE associated with drospirenone reduces or
even prevents symptoms. On the other hand, in cases of chronic headache or
headache as a side-effect of oral contraceptive use, a lower dose of estrogen is
beneficial, and doses below 20 microg may be used. Although the progesterone
component is not considered to affect headache, good results have been obtained
with drospirenone, the antimineralcorticoid effects of which reduce blood
pressure and improve symptoms. Formulations with 20 microg EE and drospirenone
are particularly indicated in women with pre-existing mastodynia, fibrocystic
breast manifestations or who develop mastodynia as a side-effect of oral
contraceptive use. Since high plasma concentrations of androgens have been
recorded in these women, a progesterone with antiandrogen and antiedema activity
can be beneficial. Finally, it is worth recalling that monophasic pills with low
estrogen doses, such as the formulations mentioned above, ensure good mood
control, reducing the depressive symptoms often associated with oral
contraceptive use. In conclusion, formulations containing drospirenone are a
valid alternative to conventional oral contraceptives for the personalisation of
these drugs.

The role of anaerobic bacteria in cutaneous and soft tissue abscesses and infected cysts. Brook I. Anaerobe. 2007 Oct-Dec;13(5-6):171-7. Epub 2007 Sep 6.

This review presents the aerobic and anaerobic microbiological aspects and
management of cutaneous and soft tissue abscesses, paronychia, anorectal,
pilonidal, and perirectal abscesses, infected epidermal cysts, hidradenitis
suppurativa, and pustular acne lesions. These infections often occur in different
body sites or in areas that have been compromised or injured by foreign body,
trauma, ischemia, malignancy or surgery. In addition to group A beta-hemolytic
streptococci and Staphylococcus aureus, the indigenous aerobic and anaerobic
cutaneous and mucous membranes local microflora usually is responsible for these
generally polymicrobial infections. These infections may occasionally lead to
serious potentially life-threatening local and systemic complications. The
infections can progress rapidly and early recognition and proper medical and
surgical management is the cornerstone of therapy.

Acne on pigmented skin. Poli F. Int J Dermatol. 2007 Oct;46 Suppl 1:39-41.

Acne on pigmented skin occurs in Africans and their descendants, as well as in
patients with a skin phototype above IV. Acne is common in Africans and is often
the primary reason for consulting a dermatologist. Acne on pigmented skin is
principally inflammatory acne. The sequelae in terms of pigmentation are often
the main reason for consulting a dermatologist, and take precedence over the acne
itself. Research is needed into cosmetic acne and steroid-induced dermatitis,
which are common in users of skin bleaching products. The treatment for acne in
pigmented skin involves the same medicines as used in acne in white skin. Of the
available topical treatments, benzoyl peroxide is particularly effective for the
inflammatory component. Retinoids act on both the retentional and inflammatory
components of acne and have skin bleaching properties. Tetracyclines are
essential on initiation of treatment, regardless of severity. They prevent an
inflammatory episode at the onset of acne and rapidly improve the inflammatory
component. Minocycline should not be prescribed in African patients. Fatal cases
of hypersensitivity have been described, with a particular frequency in this
population. Doxycycline is effective, but has photosensitizing properties.
Lymecycline is well tolerated. Isotretinoin is indicated for nodular acne. The
same precautions for use should be followed as in all cases of acne. The skin
bleaching effects are considerable. Photoprotection should generally be imposed,
but, in patients with black skin, photoprotective agents are often not applied.
The administration of a cosmetic containing a skin bleaching agent combined with
a photoprotective agent for application in the morning, instead of hydrating
cream, is acceptable to patients, improves compliance, and is effective.

Dermatological conditions in young adults (20-35 years)–part 1. Makhado DA. SADJ. 2007 May;62(4):188-9.

Health-related quality of life measurement in women with polycystic ovary syndrome: a systematic review. Jones GL, Hall JM, Balen AH, Ledger WL. Hum Reprod Update. 2008 Jan-Feb;14(1):15-25. Epub 2007 Sep 28.

The symptoms typically associated with polycystic ovary syndrome (PCOS) such as
acne, hirsutism, irregular menses, amenorrhoea, obesity and subfertility are a
major source of psychological morbidity and can negatively affect quality of life
(QoL). We systematically searched the literature to identify the impact of
symptoms and treatments for PCOS on health-related QoL (HRQoL) and to report on
the types and psychometric properties of the instruments used. Papers were
retrieved by systematically searching four electronic databases and hand
searching relevant reference lists and bibliographies. Nineteen papers used a
standardized questionnaire to measure health status; of these 12 (63.2%) used
generic tools and 8 (42%) used the disease-specific PCOS questionnaire. Although
a meta-analysis was not possible, it appears that weight concerns have a
particular negative impact upon HRQoL, although the role of body mass index in
affecting HRQoL scores is inconclusive from the available evidence. Acne is the
area least reported upon in terms of its impact upon HRQoL. With the exception of
three studies, most of the research has focused upon adult women with PCOS.
Despite the benefits of HRQoL measures in research, few are being used to
evaluate the outcomes of treatment for PCOS upon the subjective health status of
women with the condition.

The management of postacne scarring. Goodman GJ, Baron JA. Dermatol Surg. 2007 Oct;33(10):1175-88.

BACKGROUND: Therapeutic intervention for postacne scarring has historically been
limited by the considerable morbidity of most treatments for only marginal
disease improvement. Within the past decade, however, a greater understanding of
the pathogenesis of acne scarring has led to the development of techniques that
offer more favorable risk-benefit profiles. OBJECTIVE: The aims of this article
are to highlight a number of newer techniques and to assign their appropriateness
to particular grades of acne scarring. MATERIALS AND METHODS: Current modalities
are discussed as they relate to disease process and specific acne scar types.
Techniques are presented in order of most effectual therapeutic interventions for
defined grades of acne scarring. Acne scarring grades have been described
previously in terms of disease load, severity, and lesion morphologies. RESULTS:
A comprehensive discussion of updated therapeutic techniques and their biologic
rationales in the treatment of acne scarring is presented. These include targeted
interventions of inflammatory and postinflammatory processes, angiogenesis,
immunologic processes, dermal and subcutaneous fibrosis, hypertrophy, and keloid
scarring. DISCUSSION: A requirement for developing successful treatments for
postacne scarring is a greater understanding of its pathogenesis, variability
among afflicted individuals, and the inflammatory mediators and immunology of the
scarring process. Many innovative techniques introduced in the past decade
attempt to counteract these pathologic processes while keeping the procedural and
postoperative risks to a minimum.

Nonablative cutaneous remodeling using radiofrequency devices. Alster TS, Lupton JR. Clin Dermatol. 2007 Sep-Oct;25(5):487-91.

In recent years, several new radiofrequency devices have been introduced for
treatment of a variety of skin conditions, particularly, skin wrinkling and
laxity. These nonsurgical systems induce tissue tightening and contour changes
through dermal collagen remodeling without disruption of the overlying epidermis,
obviating a significant recovery period or risk of serious adverse sequelae. As
such, radiofrequency-based systems have been used successfully for nonablative
skin rejuvenation, atrophic scar revision, and treatment of unwanted hair,
vascular lesions, and inflammatory acne.

Fractional resurfacing. Tannous Z. Clin Dermatol. 2007 Sep-Oct;25(5):480-6.

Fractional resurfacing produces a distinctive thermal damage pattern by creating
discrete columns of thermal damage referred to as microthermal treatment zones.
It characteristically spares the tissue surrounding each microthermal treatment
zone leading to fast epidermal repair. Fractional resurfacing has been
successfully used in treating a variety of skin conditions including melasma,
dyschromia, lentigenes, wrinkles, and acne scars with minimal downtime. It is
safer to use off the face and in darker skin types.

Masers to magic bullets: an updated history of lasers in dermatology. Houk LD, Humphreys T. Clin Dermatol. 2007 Sep-Oct;25(5):434-42.

Laser therapy is one of the fastest expanding and most exciting fields in
dermatology. From its theoretical beginnings in Einstein’s imagination, lasers
have come to be used in treatments for conditions ranging from skin malignancy
and acne to hirsutism and photoaging. We will briefly review the evolution of
laser treatment, with a focus on the recent developments surrounding the new
millennium.

Utilizing combination therapy for ethnic skin. Taylor SC. Cutis. 2007 Jul;80(1 Suppl):15-20.

A major issue in treating acne in individuals of color is the need to treat and
prevent postinflammatory hyperpigmentation (PIH), which is common in this
population. This subset analysis reports the pigmentary changes in subjects of
color with acne who were enrolled in a community-based trial comparing 3
different topical therapeutic regimens. All subjects received combination
clindamycin 1%-benzoyl peroxide (BPO) 5% topical gel containing glycerin and
dimethicone. Subjects were randomized to receive this combination therapy in
addition to either a tretinoin microsphere (RAM) gel at concentrations of either
0.04% or 0.1% or adapalene (AP) gel 0.1%. There was a trend toward better
resolution of hyperpigmentation in the subjects receiving the clindamycin-BPO
topical gel in combination with RAM gel 0.04%.

The impact and importance of resistance. Tanghetti E. Cutis. 2007 Jul;80(1 Suppl):5-9.

Bacterial resistance to antibiotics began to emerge soon after their
introduction. Beginning in the 1970s, Propionibacterium acnes also began to show
decreased sensitivity to the antibiotics typically used in acne management.
Clinically, this trend has translated to decreased efficacy and even nonresponse
to therapy. A variety of recommendations regarding optimum use of antibiotics in
acne management have been developed to preserve the utility of these drugs. Most
important is the use of combination therapy with benzoyl peroxide (BPO) to help
minimize the development of resistance. Retinoids also are recommended in acne
therapeutic regimens because these agents are active against most acne
pathogenetic mechanisms, but they have no apparent activity preventing antibiotic
resistance when used in combination with a topical antibiotic.

Polycystic ovary syndrome. Homburg R. Best Pract Res Clin Obstet Gynaecol. 2008 Apr;22(2):261-74. Epub 2007 Sep 5.

Polycystic ovary syndrome (PCOS) is the most common female endocrinopathy,
affecting 5-10% of the female population. It involves overproduction of ovarian
androgens leading to a heterogeneous range of symptoms including hirsutism, acne,
anovulation and infertility. Hyperinsulinaemia, exacerbated by obesity, is often
a key feature. Treatment depends on the presenting symptoms, which may often be
ameliorated by weight loss where relevant. Anti-androgen preparations are used
for hyperandrogenic symptoms, and clomiphene citrate (CC) is the first-line
treatment for anovulation and infertility. Aromatase inhibitors are being
investigated as an alternative to CC. Failure to conceive with CC can be treated
in a number of ways, including the addition of insulin-lowering agents (mainly
metformin), low-dose gonadotrophin therapy or surgically by laparoscopic ovarian
drilling. Although the exact aetiology of PCOS is not known, the therapeutic
alternatives provide reasonably successful symptomatic treatment.

Consensus guidelines for the management of radiation dermatitis and coexisting acne-like rash in patients receiving radiotherapy plus EGFR inhibitors for the treatment of squamous cell carcinoma of the head and neck. Bernier J, Bonner J, Vermorken JB, Bensadoun RJ, Dummer R, Giralt J, Kornek G, Hartley A, Mesia R, Robert C, Segaert S, Ang KK. Ann Oncol. 2008 Jan;19(1):142-9. Epub 2007 Sep 4.

BACKGROUND: Radiation dermatitis occurs to some degree in most patients receiving
radiotherapy, with or without chemotherapy. Patients with squamous cell carcinoma
of the head and neck (SCCHN) who receive radiotherapy in combination with
epidermal growth factor receptor (EGFR) inhibitors, such as cetuximab, may
develop a characteristic acne-like rash in addition to dermatitis. Design: An
advisory board of 11 experienced radiation oncologists, medical oncologists and
dermatologists discussed the management options for skin reactions in patients
receiving EGFR inhibitors and radiotherapy for SCCHN. Skin toxicity was
categorised according to the National Cancer Institute-Common Terminology
Criteria for Adverse Events (version 3) grading. RESULTS: Both general and
grade-specific approaches for the management of dermatitis in this patient group
are presented. It was concluded that where EGFR inhibitor-related acne-like rash
and dermatitis coexist within irradiated fields, management should be based on
the grade of dermatitis: for grade 1 (or no dermatitis), treatment
recommendations for EGFR-related acne-like rash outside irradiated fields should
be followed; for grades 2 and above, treatment recommendations for dermatitis
were proposed. CONCLUSIONS: This paper presents comprehensive consensus
guidelines for the treatment of dermatitis in patients with SCCHN receiving EGFR
inhibitors in combination with radiotherapy.

[Chronic blepharitis. Pathogenesis, clinical features, and therapy] [Article in German] Auw-Haedrich C, Reinhard T. Ophthalmologe. 2007 Sep;104(9):817-26; quiz 827-8.

Chronic blepharitis is one of the most common diseases of the eyelids, but
surprisingly, it is not often recognized. Frequently, a skin disease such as
seborrheic dermatitis, atopic dermatitis, or acne rosacea is the underlying cause
of chronic blepharitis. Bacterial pathological lipase, cholesterylesterase
production, and bacterial lipopolysaccharides are pathogenetically relevant. Only
rarely do genuine bacterial infections play a role. Collarettes occur at the base
of the eye lashes, and the Meibomian glands show either abundant fluid secretion
or inspissated secretion with obstruction of the orifices. Chronic blepharitis
can include sequelae including dry eye and corneal and lid contour changes. The
basic treatment comprises attendance of the underlying dermatological disease and
lid hygiene. In addition, preservative-free tear film substitutes, antibiotics,
immunomodulatory agents, or even surgical intervention may become necessary.

Procedural treatments for acne vulgaris. Taub AF. Dermatol Surg. 2007 Sep;33(9):1005-26.

BACKGROUND: Simple procedural treatments such as comedone extraction and
intralesional steroids have been utilized for many years as adjunctive therapy
for acne. In the past 5 years, new technologies and procedures have become
available that present new options for the treatment of acne. OBJECTIVES: The
objective was to review, summarize, and evaluate the key studies of procedural
therapies for the treatment of acne as well as place them in perspective with
current clinical practice. METHODS: Studies selected for evaluation had at least
10 patients and clear statements of purpose, acne severity, patient selection,
follow-up evaluations, previous and concurrent medications, treatment parameters,
methods for evaluating results, and adverse effects. All studies were complete
and published (in English) in peer-reviewed journals. RESULTS AND CONCLUSIONS:
Earlier procedural therapies were adjunctive to medical therapy, such as
intralesional steroids, chemical peels, and microdermabrasion. Newer methods
include radiofrequency, light or laser, and photodynamic therapy that represent
treatment alternatives for systemic medications. Still early in their
development, these new procedures provide an important, novel set of options for
the treatment of acne. The most developed and studied therapies are blue or
blue/red light combinations, 1,450-nm diode laser, and photodynamic therapy with
5-aminolevulinic acid or indocyanine green. Review of the literature of more
up-to-date physical procedures provides a starting point for physicians seeking
to treat their acne patients safely and effectively with these new methods.

Polycystic ovary syndrome. Norman RJ, Dewailly D, Legro RS, Hickey TE. Lancet. 2007 Aug 25;370(9588):685-97.

Polycystic ovary syndrome is a heterogeneous endocrine disorder that affects
about one in 15 women worldwide. The major endocrine disruption is excessive
androgen secretion or activity, and a large proportion of women also have
abnormal insulin activity. Many body systems are affected in polycystic ovary
syndrome, resulting in several health complications, including menstrual
dysfunction, infertility, hirsutism, acne, obesity, and metabolic syndrome. Women
with this disorder have an established increased risk of developing type 2
diabetes and a still debated increased risk of cardiovascular disease. The
diagnostic traits of polycystic ovary syndrome are hyperandrogenism, chronic
anovulation, and polycystic ovaries, after exclusion of other conditions that
cause these same features. A conclusive definition of the disorder and the
importance of the three diagnostic criteria relative to each other remain
controversial. The cause of polycystic ovary syndrome is unknown, but studies
suggest a strong genetic component that is affected by gestational environment,
lifestyle factors, or both.

Oral trimethoprim/sulfamethoxazole in the treatment of acne vulgaris. Bhambri S, Del Rosso JQ, Desai A. Cutis. 2007 Jun;79(6):430-4.

Oral trimethoprim/sulfamethoxazole (TMP-SMX) is approved by the US Food and Drug
Administration for the treatment of urinary tract infections, shigellosis, acute
otitis media in pediatric patients, and Pneumocystis carinii pneumonia. TMP-SMX
has been used off label in dermatology to treat various skin conditions,
including acne vulgaris and other skin and soft tissue infections, especially
those infections caused by methicillin-resistant Staphylococcus aureus.

The neurobiology of retinoic acid in affective disorders. Bremner JD, McCaffery P. Prog Neuropsychopharmacol Biol Psychiatry. 2008 Feb 15;32(2):315-31. Epub 2007 Jul 10.

Current models of affective disorders implicate alterations in norepinephrine,
serotonin, dopamine, and CRF/cortisol; however treatments targeted at these
neurotransmitters or hormones have led to imperfect resolution of symptoms,
suggesting that the neurobiology of affective disorders is incompletely
understood. Until now retinoids have not been considered as possible contributors
to affective disorders. Retinoids represent a family of compounds derived from
vitamin A that perform a large number of functions, many via the vitamin A
product, retinoic acid. This signaling molecule binds to specific retinoic acid
receptors in the brain which, like the glucocorticoid and thyroid hormone
receptors, are part of the nuclear receptor superfamily and regulate gene
transcription. Research in the field of retinoic acid in the CNS has focused on
the developing brain, in part stimulated by the observation that isotretinoin
(13-cis retinoic acid), an isomer of retinoic acid used in the treatment of acne,
is highly teratogenic for the CNS. More recent work has suggested that retinoic
acid may influence the adult brain; animal studies indicated that the
administration of isotretinoin is associated with alterations in behavior as well
as inhibition of neurogenesis in the hippocampus. Clinical evidence for an
association between retinoids and depression includes case reports in the
literature, studies of health care databases, and other sources. A preliminary
PET study in human subjects showed that isotretinoin was associated with a
decrease in orbitofrontal metabolism. Several studies have shown that the
molecular components required for retinoic acid signaling are expressed in the
adult brain; the overlap of brain areas implicated in retinoic acid function and
stress and depression suggest that retinoids could play a role in affective
disorders. This report reviews the evidence in this area and describes several
systems that may be targets of retinoic acid and which contribute to the
pathophysiology of depression.

Ocular toxicities of epidermal growth factor receptor inhibitors and their management. Basti S. Cancer Nurs. 2007 Jul-Aug;30(4 Suppl 1):S10-6.

Epidermal growth factor receptor (EGFR) inhibitors have become an important
therapy for patients with malignant solid tumors, such as non-small cell lung,
breast, ovarian, colorectal, renal, esophageal, sarcoma, mesothelioma, prostate,
head and neck, and pancreatic cancers. Although these agents are generally well
tolerated, some adverse effects will likely occur. The most common adverse effect
associated with use of EGFR inhibitors is an acne-like rash. Less reported in the
literature are adverse ocular reactions, which occur in approximately one third
of patients and can cause significant discomfort. The ocular toxicities that may
occur with use of EGFR inhibitors can be broadly categorized as changes in the
eyelids (eg, squamous blepharitis, trichomegaly, meibomitis), changes in the tear
film (eg, dysfunctional tear syndrome), and miscellaneous changes (eg,
iridocyclitis, corneal epithelial defect). Early recognition and management of
these adverse ocular reactions are necessary to improve patient comfort, to
facilitate compliance, and to avoid interruption of therapy. This article
describes the adverse ocular effects reported to occur with use of EGFR
inhibitors and presents specific strategies to manage these effects. Mild eyelid
and tear film changes usually can be managed by the oncology and nursing staff.
More severe ocular reactions require involvement of an ophthalmologist.

DHEA: why, when, and how much–DHEA replacement in adrenal insufficiency. Allolio B, Arlt W, Hahner S. Ann Endocrinol (Paris). 2007 Sep;68(4):268-73. Epub 2007 Aug 8.

In recent years it has been demonstrated that current replacement therapy with
glucocorticoids and mineralocorticoids fails to fully restore health-related
quality of life in patients with adrenal insufficiency (AI). Accordingly,
replacement of zona reticularis function by DHEA is of considerable interest.
Available studies have demonstrated beneficial effects of DHEA on health
perception, vitality, fatigue, and (in women) sexuality. DHEA restores low
circulating androgens in women into the normal range and increases IGF-1 levels.
Side effects are mostly mild and related to androgenic activity of DHEA in women
and include increased sebum production, facial acne, and changes in hair status.
Replacement consists of a single oral dose of 25-50 mg DHEA in the morning.
However, not all investigators have found effects of DHEA on well-being, most
likely because of small sample size and short duration of treatment. Thus, to
fully explore the role of DHEA in the treatment of AI large trials for 12-24
months are still urgently needed. Until the results of such trials are available
DHEA cannot be considered part of standard replacement in AI, but compassionate
use of DHEA in individual patients with AI and impaired well-being may be
justified.

Drospirenone/ethinylestradiol 3mg/20microg (24/4 day regimen): a review of its use in contraception, premenstrual dysphoric disorder and moderate acne vulgaris. Fenton C, Wellington K, Moen MD, Robinson DM. Drugs. 2007;67(12):1749-65.

Drospirenone 3mg with ethinylestradiol 20microg (Yaz) is a low-dose combined oral
contraceptive (COC) administered in a regimen of 24 days of active tablets
followed by a short hormone-free interval (4 days; 24/4 regimen). Drospirenone,
unlike other synthetic progestogens used in COCs, is a 17alpha-spirolactone
derivative and a 17alpha-spironolactone analogue with antimineralocorticoid and
antiandrogenic properties. Drospirenone/ethinylestradiol 3mg/20microg (24/4) is
approved in the US for the prevention of pregnancy in women, for the treatment of
the symptoms of premenstrual dysphoric disorder (PMDD) and for the treatment of
moderate acne vulgaris in women who wish to use an oral contraceptive for
contraception.Drospirenone/ethinylestradiol 3mg/20microg (24/4) provided 99%
contraceptive protection over 1 year of treatment in two large studies. The same
treatment regimen over three treatment cycles also significantly improved the
emotional and physical symptoms associated with PMDD, and improved moderate acne
vulgaris over six treatment cycles in double-blind trials. It was generally well
tolerated, with adverse events generally typical of those experienced with other
COCs and which were most likely to occur in the first few cycles. Clinical trials
indicate that drospirenone/ethinylestradiol 3mg/20microg (24/4) is a good
long-term contraceptive option, and additionally offers relief of symptoms that
characterise PMDD and has a favourable effect on moderate acne vulgaris.

A comparative review of the efficacy and tolerability of retinoid-containing combination regimens for the treatment of acne vulgaris. Campbell JL Jr. J Drugs Dermatol. 2007 Jun;6(6):625-9.

Many physicians regularly prescribe combination therapy involving a retinoid for
their acne patients. The most common retinoid-containing regimens include either
oral antibiotics or topical benzoyl peroxide and antibiotic products. A fair
number of studies have been conducted to evaluate the efficacy of these
combination therapies, but there is a lack of comparative studies examining
different regimens head-to-head. Also, many of the noncomparative studies have
very similar trial designs. A review of these studies was conducted in order to
organize the available data side by side from the different regimens. Although
not derived from comparative studies, this presentation of data is expected to
provide dermatologists with valuable information from which they can easily make
their own comparisons among similarly designed trials.

Clinical safety and efficacy studies of a novel formulation combining 1.2% clindamycin phosphate and 0.025% tretinoin for the treatment of acne vulgaris. Schlessinger J, Menter A, Gold M, Leonardi C, Eichenfield L, Plott RT, Leyden J, Wortzman M; ZIANA Study Group. J Drugs Dermatol. 2007 Jun;6(6):607-15.

Clindamycin phosphate 1.2% and tretinoin 0.025% gel (CLIN/RA gel [ZIANA Gel]) is
a novel topical combination agent approved by the FDA for the treatment of acne
vulgaris in patients 12 years of age or older. A solution of clindamycin
phosphate 1.2% combined with partially solubilized and crystalline tretinoin
0.025% suspended in an aqueous-based, alcohol-free gel formulation, CLIN/RA gel
was studied in 2 randomized, vehicle-controlled trials involving more than 4,500
patients. Efficacy results from these studies showed that treatment with the
combination significantly reduced lesion counts and improved patients’ overall
appearance to a greater extent than the individual components. Individual
ingredients and the combination were well-tolerated. Among those treated with the
combination formulation, discontinuation rates due to adverse events were 1% or
less.

Pediatric acne: clinical presentations, evaluation, and management. Krakowski AC, Eichenfield LF. J Drugs Dermatol. 2007 Jun;6(6):589-93.

Acne vulgaris can be easy to diagnose yet difficult to evaluate and manage,
especially when it presents in infancy and childhood. The differential diagnosis
of acne varies by age and, in some cases, may warrant a work-up in order to rule
out underlying systemic abnormalities. Likewise, treatment strategies can be
influenced by the patient’s age. In this article, we present an overview of the
clinical presentations of acne by age, an approach to patient evaluation, and a
general strategy for management of this common and important disease.

The Propionibacterium acnes genome: from the laboratory to the clinic. Rosen T. J Drugs Dermatol. 2007 Jun;6(6):582-6.

The genome of Propionibacterium acnes, the microbe presumed to be at least
partially etiologic for the development of acne, has recently been decoded. The
genome supports long-standing concepts regarding acne pathogenesis, but also
demonstrates heretofore unknown and/or unsuspected bacterial properties, which
might play a role in disease occurrence. In turn, understanding the genome may
lead to new therapeutic avenues, as summarized in this manuscript.

[Photodynamic therapy: new indications] [Article in Spanish] Fernández-Guarino M, García-Morales I, Harto A, Montull C, Pérez-García B, Jaén P. Actas Dermosifiliogr. 2007 Jul-Aug;98(6):377-95.

Photodynamic therapy (PDT) is approved for the treatment of actinic keratoses,
superficial and nodular basal cell carcinomas, and recently, Bowen’s disease. In
the last decade the advances experienced in the study of the photodynamic
reaction have expanded the spectrum of application to other cutaneous diseases,
neoplastic as well as inflammatory and infectious ones. The experience in
psoriasis, acne, common warts and cutaneous T cell lymphoma starts to be broad
and interesting, which permits to define its use in these entities. Photodynamic
therapy is also been tested for a great variety of dermatoses with different
photosensitizers and light sources with variable results. In this paper we review
the treatment of Bowen’s disease and other indications different from non
melanoma skin cancer with PDT, providing our experience.

Pulsed dye laser: what’s new in non-vascular lesions? Karsai S, Roos S, Hammes S, Raulin C. J Eur Acad Dermatol Venereol. 2007 Aug;21(7):877-90.

BACKGROUND AND OBJECTIVE: In dermatology, the pulsed dye laser (PDL) is the
therapeutic instrument of choice for treating most superficial cutaneous vascular
lesions. In addition, clinical experience over the last decade allowed us to
treat patients with an ever increasing number of non-vascular indications. The
purpose of this report is to summarize and critically appraise the scientific
evidence that support the role of PDL in treating non-vascular skin lesions.
METHODS: A literature-based study has been conducted, including the review of
publications over the period January 1995 to December 2006, using the Medline
Database. We also included our own experience in managing non-vascular lesions
with the PDL. Four sets of preoperative and postoperative photos are presented.
RESULTS: For viral skin lesions, PDL proved to be an alternative to other therapy
options. This applies particularly to periungual warts and mollusca contagiosa.
The mechanism of PDL with inflammatory dermatoses has not yet been elucidated.
The effect seems to be better if there is a vascular component to the disease.
With most of these indications (such as psoriasis and acne), PDL currently plays
a rather minor or complementary role. Regarding collagen remodelling
(hypertrophic scars, keloids, stretch marks, and skin rejuvenation), the question
of whether a therapy makes sense or not has to be decided from case to case.
CONCLUSION: With PDL, it is possible to achieve good results with numerous,
partly less well-known indications (i.e. lupus erythematosus). With other
diseases, PDL has so far been considered to be a complementary therapy method or
to be in an experimental state.

Acne. Stollery N. Practitioner. 2007 Jun;251(1695):86-91.

Clinical considerations in the treatment of acne vulgaris and other inflammatory skin disorders: focus on antibiotic resistance. Leyden JJ, Del Rosso JQ, Webster GF. Cutis. 2007 Jun;79(6 Suppl):9-25.

Propionibacterium acnes is an anaerobic bacterium that plays an important role in
the pathogenesis of acne. Certain antibiotics that can inhibit P acnes
colonization also have demonstrated anti-inflammatory activities in the treatment
of acne, rosacea, and other noninfectious diseases. Decreased sensitivity of P
acnes to antibiotics, such as erythromycin and tetracycline, has developed and
may be associated with therapeutic failure. Benzoyl peroxide (BPO) is a
nonantibiotic antibacterial agent that is highly effective against P acnes and
for which no resistance against it has been detected to date. Retinoids are
important components in combination therapy for acne, including use with
antibiotics, and can serve as an alternative to these agents in maintenance
therapy. By increasing our understanding of the multifaceted actions of
antibiotics and the known clinical implications of antibiotic resistance,
physicians can improve their decision making in prescribing these agents.

Dermatologic manifestations of polycystic ovary syndrome. Lee AT, Zane LT. Am J Clin Dermatol. 2007;8(4):201-19.

Polycystic ovary syndrome (PCOS) affects 5-10% of reproductive-aged women and is
one of the most common endocrine disorders in women. The disorder is commonly
characterized by elevated levels of androgen and insulin. Women with PCOS may
present with a range of signs and symptoms, and face increased risks of
reproductive, metabolic, cardiovascular, psychologic, and neoplastic sequelae,
particularly if the condition is left unrecognized or untreated. The clinical
definition of PCOS has changed in recent years and includes as one of its
cardinal criteria the dermatologic manifestations of hyperandrogenism, chiefly
hirsutism, acne vulgaris, and androgenetic alopecia. Acanthosis nigricans, a
cutaneous sign of hyperinsulinemia, may also be present. These dermatologic
features may provide early clinical clues to recognition of PCOS, and treatment
of these cutaneous conditions may improve the patient’s quality of life and
psychologic well-being. The effects of androgen on pilosebaceous units in the
skin can vary by anatomic location, producing pathophysiologic effects on hair
growth and differentiation, sebaceous gland size and activity, and follicular
keratinization. Treatment modalities may include hormonal therapy intended to
modulate androgen production and action as well as non-hormonal therapies
directed toward specific dermatologic conditions.

Management of female sexual dysfunction in postmenopausal women by testosterone administration: safety issues and controversies. Braunstein GD. J Sex Med. 2007 Jul;4(4 Pt 1):859-66.

INTRODUCTION: A Food and Drug Administration advisory group has questioned the
long-term safety of testosterone administration to postmenopausal women. Although
only short-term data exist on safety from the double-blind, placebo-controlled
trials, testosterone has been used for more than 50 years. Therefore, some data
concerning the long-term safety issues must exist in the literature. AIM: To
review the published data concerning the safety of administration of testosterone
to women. METHODS: Review of published articles identified by a search of the
Ovid databases and bibliographies from articles identified as dealing with the
topics of testosterone or androgen treatment of women. RESULTS: The major adverse
reactions to exogenous androgens are the expected androgenic side effects of
hirsutism and acne. High-density lipoprotein levels may be decreased with oral
androgens. There are insufficient long-term safety data regarding breast,
endometrium, or heart safety to draw strong conclusions, although the data
available to date are reassuring. CONCLUSIONS: Testosterone administration to
postmenopausal women that result in physiological to slightly supraphysiological
serum-free testosterone levels is safe for at least 2 years.

[Management of acne in adolescents] [Article in French] Faure M. Arch Pediatr. 2007 Sep;14(9):1152-6. Epub 2007 Jul 10.

Acne is an androgen-dependant inflammatory folliculitis with non-inflammatory
lesions (open and closed comedos) and inflammatory papules, pustules and
sometimes nodules. Topical retinoïds, benzoyl peroxyde, antibiotics with
anti-inflammatory properties, antiandrogens in female acne (antiandrogens and
antiandrogenic oral contraceptives), and isotretinoin are the major drugs used in
the management of the affection. Acne has to be treated according to the type of
acne, severity, age and sex. Acne may also be the major sign of ovarian (PCOS) or
adrenal hyperandrogenism in either female teenagers or both sexes, respectively.

Comprehensive clinical management of polycystic ovary syndrome. Setji TL, Brown AJ. Minerva Med. 2007 Jun;98(3):175-89.

Polycystic ovary syndrome (PCOS) affects 6-7% of reproductive-aged women.
Although the diagnostic criteria for PCOS have been debated, it is frequently
characterized by hyperandrogenism (hirsutism, acne, male-pattern hair loss),
oligo-anovulation, and polycystic ovaries on ultrasound. The reproductive and
metabolic complications associated with the syndrome can be serious, so a
comprehensive approach to the evaluation and treatment of affected women is
important. Menstrual cycle control is necessary to prevent endometrial
hyperplasia, and this can be accomplished with hormonal contraception,
progesterone therapy, and weight loss (if overweight). In women desiring
pregnancy, commonly used ovulation induction therapies include weight loss,
clomiphene citrate, and/or metformin. Cosmetic issues such as hirsutism, acne and
male-pattern hair loss can be challenging to cope with. Treatment options include
estrogen-containing hormonal contraceptive agents, antiandrogens, and topical
agents. More permanent hair reduction can be achieved with electrolysis and laser
therapy. Evaluation of metabolic complications includes risk assessment for
diabetes, dyslipidemia, hypertension, and nonalcoholic fatty liver disease. Women
with PCOS should also be screened for sleep apnea, as this has been reported to
occur more commonly in women with PCOS. Finally, mental health issues such as
depression and eating disorders may be present. Many of the complications
associated with PCOS can be managed with therapeutic lifestyle change, including
a healthy diet, exercise, weight loss (if overweight), and psychological support.
Pharmacological therapies are also available to effectively regulate menstrual
cycles and manage cosmetic complications. This article will review the current
diagnostic and therapeutic strategies in PCOS.

Testosterone therapy in women: its role in the management of hypoactive sexual desire disorder. Abdallah RT, Simon JA. Int J Impot Res. 2007 Sep-Oct;19(5):458-63. Epub 2007 Jun 21.

Disorders of sexual dysfunction occur in nearly half of women during their life,
and hypoactive sexual desire disorder accounts for most of those complaints.
Although the relationship between low endogenous testosterone levels and sexual
desire disorders in women has not been empirically established, clinical trials
have shown that exogenous testosterone therapy improves arousability, sexual
desire and fantasy, frequency of sexual activity and orgasm, and satisfaction and
pleasure from the sexual act. Its therapeutic role in bone mineral density,
fatigue, well-being and hot flashes requires more study before specific
recommendations can be made. Potential adverse effects of testosterone therapy
include hirsutism, acne and deepening of the voice along with changes in lipid
profiles. While less well understood, concern after increased risks for breast
cancer and cardiovascular events has been raised about this therapy. Testosterone
therapy is available in various formulations; the most commonly used are oral and
transdermal, including patches, gels, creams and ointments.

Vitamin D and the skin: an ancient friend, revisited. Reichrath J. Exp Dermatol. 2007 Jul;16(7):618-25.

Most vertebrates need vitamin D to develop and maintain a healthy mineralized
skeleton. However, 1,25-dihydroxyvitamin D3 [1,25(OH)(2)D(3)], the biologically
active vitamin D metabolite, exerts a multitude of important physiological
effects independent from the regulation of calcium and bone metabolism. We know
today that the skin has a unique role in the human body’s vitamin D endocrine
system. It is the only site of vitamin D photosynthesis, and has therefore a
central role in obtaining a sufficient vitamin D status. Additionally, the skin
has the capacity to synthesize the biologically active vitamin D metabolite
1,25(OH)(2)D(3), and represents an important target tissue for 1,25(OH)(2)D(3).
In keratinocytes and other cell types, 1,25(OH)(2)D(3) regulates growth and
differentiation. Consequently, vitamin D analogues have been introduced for the
treatment of the hyperproliferative skin disease psoriasis. Recently, sebocytes
were identified as 1,25(OH)(2)D(3)-responsive target cells, indicating that
vitamin D analogues may be effective in the treatment of acne. Other new
functions of vitamin D analogues include profound effects on the immune system as
well as in various tissues protection against cancer and other diseases,
including autoimmune and infectious diseases. It can be speculated that the
investigation of biological effects of vitamin D analogues will lead to new
therapeutic applications that, besides cancer prevention, may include the
prevention and treatment of infectious as well as of inflammatory skin diseases.
Additionally, it can be assumed that dermatological recommendations on sun
protection and health campaigns for skin cancer prevention will have to be
re-evaluated to guarantee a sufficient vitamin D status.

Decreased acne symptoms as a perception of rhinoplasty success. Coban YK. Aesthetic Plast Surg. 2007 Jul-Aug;31(4):413-4.

[Photodynamic therapy: non-oncologic indications.] [Article in German] Karrer S, Szeimies RM. Hautarzt. 2007 Jul;58(7):585-96.

While efficacy of topical photodynamic therapy (PDT) for the treatment of
superficial non-melanoma skin cancer is already well-proven by several controlled
clinical trials, there are only a few controlled studies showing efficacy of PDT
for non-oncologic skin disorders. This report provides information on the use of
PDT for inflammatory skin disorders, disorders of the pilosebaceous unit,
infections of the skin, sclerotic skin diseases and cosmetic indications.

Bipolar radiofrequency for facial rejuvenation. Sadick N. Facial Plast Surg Clin North Am. 2007 May;15(2):161-7, v.

Combined approaches using light and radiofrequency represent an innovative
approach to whole body rejuvenation. Synergistic results using combined
modalities are a major advantage of this technology. In addition, by using lower
levels of light energy, darker skin phenotypes can be treated with a lower risk
for pigment dyschromia and scarring.

Development and clinical indications of cetuximab. Labianca R, La Verde N, Garassino MC. Int J Biol Markers. 2007 Jan-Mar;22(1 Suppl 4):S40-6.

Cetuximab is a chimeric immunoglobulin G1 monoclonal antibody that targets the
extracellular domain of the epidermal growth factor receptor (EGFR) with high
specificity and affinity. It competitively inhibits endogenous ligand binding and
thereby inhibits subsequent EGFR activation. The EGFR signaling pathways regulate
cell differentiation, proliferation, migration, angiogenesis and apoptosis, all
of which become deregulated in cancer cells. EGFR is an important target for
cancer therapy and many studies have demonstrated that cetuximab is active in
several types of cancer, particularly colorectal and head and neck cancer.
Cetuximab enhances the effects of many standard cytotoxic agents, including
irinotecan, and in combination with chemotherapy it can elicit antitumor
responses in tumors that previously failed to respond to that chemotherapy.
Cetuximab also enhances radiation-induced apoptosis. On the basis of a pivotal
European randomized study (the BOND study) and of 2 clinical studies conducted in
the USA, cetuximab has been approved in combination with irinotecan for patients
affected by EGFR-expressing metastatic colon cancer after failure with
irinotecan. There have only been a few small phase II trials on first-line
treatment in metastatic colorectal cancer, but the results suggest promising
activity of cetuximab together with irinotecan or oxaliplatin. There is some
evidence that additive efficacy can be achieved using EGFR inhibitors in
combination with vascular endothelial growth factor receptor inhibitors such as
bevacizumab. A correlation between response and the main toxicity (acne-like skin
reaction) has been observed but is unclear. EGFR status as a specific marker for
EGFR inhibitors is controversial. At the moment, EGFR expression does not appear
to be a predictive factor for response to EGFR inhibitors.

Safety of testosterone treatment in postmenopausal women. Braunstein GD. Fertil Steril. 2007 Jul;88(1):1-17. Epub 2007 May 10.

OBJECTIVE: To critically examine the safety of T therapy given to postmenopausal
women. DESIGN: MEDLINE literature review, cross-reference of published data, and
review of Food and Drug Administration transcripts. RESULT(S): Although some
retrospective and observational studies provide some long-term safety data, most
prospective studies have had a duration of 2 years or less. In addition, with the
exception of the female-to-male transsexuals, T was administered in conjunction
with estrogens or estrogens and progestins, which confound the interpretation of
some of the studies. The major adverse reactions are the androgenic side effects
of hirsutism and acne. There does not appear to be an increase in cardiovascular
risk factors, with the exception of a lowering of high-density lipoprotein with
oral T. There are little data on endometrial safety, and most of the experimental
data support a neutral or beneficial effect in regards to breast cancer. There
does not appear to be an increased risk of hepatotoxicity, neurobehavioral
abnormalities, sleep apnea, or fetal virilization (in premenopausal women) with
the physiologic treatment doses of T. CONCLUSION(S): Except for hirsutism and
acne, the therapeutic administration of T in physiologic doses is safe for up to
several years. However, prospectively collected long-term safety studies are
needed to provide a greater degree of assurance.

[UVA-1 phototherapy: properties and indications] [Article in French] Comte C, Picot E, Peyron JL, Dereure O, Guillot B. Ann Dermatol Venereol. 2007 Apr;134(4 Pt 1):407-15.

Pharmacotherapy of diseases mediated by 5-lipoxygenase pathway eicosanoids. Rubin P, Mollison KW. Prostaglandins Other Lipid Mediat. 2007 May;83(3):188-97. Epub 2007 Jan 17.

Inflammatory eicosanoids generated by the 5-lipoxygenase (5-LO) pathway of
arachidonic acid metabolism are now known to have at least 6 receptors: OXE,
which recognizes 5-HETE and 5-oxo-ETE; a putative receptor recognizing a potent
5-oxo-ETE metabolite, FOG(7); the LTB(4) receptors, BLT1 and BLT2; the cysteinyl
leukotriene receptors, CysLT(1) and CysLT(2), which recognize leukotrienes
LTC(4), LTD(4), LTE(4) and LTF(4). The 5-LO pathway is activated in many diseases
and invokes inflammatory responses not affected by glucocorticoids, but therapy
with selective BLT1 or CysLT(1) antagonists in asthma has met with variable
success. Studies show that 5-LO pathway eicosanoids are not primary mediators in
all cases of asthma, but may be especially important in severe persistent asthma,
aspirin- and exercise-induced asthma, allergic rhinitis, COPD, idiopathic
pulmonary fibrosis, atherosclerosis, atopic dermatitis, acne and ischemia-related
organ injury. These disorders appear to involve multiple 5-LO pathway eicosanoids
and receptor subtypes, suggesting that inhibition of the pathway at the level of
5-LO may be necessary for maximal efficacy.

[A case of acne infantum--reviews of the literature regarding therapy] [Article in Polish] Wojas-Pelc A, Sułowicz J, Brzewski P. Przegl Lek. 2006;63(9):807-9.

We report a case of a 19 month old boy that presented with acneform eruption on
his cheeks since birth. This condition was left untreated until the age of one.
At that time the lesions developed into inflammatory nodules that resolved after
topical treatment (Aknemycin fluid, cynober-sulfer pastae) and remission exist
during 6 months. Based on presented case authors describe etiopatogenesis of acne
and have done rewies of the literature regarding therapy, indications and safety
of administration of oral retinoids to children.

Azelaic acid (15% gel) in the treatment of acne rosacea. Gupta AK, Gover MD. Int J Dermatol. 2007 May;46(5):533-8.

In December of 2002, the FDA approved azelaic acid 15% gel for the topical
treatment of inflammatory papules and pustules of mild to moderate rosacea.
Azelaic acid is a saturated dicarboxylic acid, which is naturally occurring and
has been used in the treatment of rosacea, acne, and melasma. The 15% gel has a
high efficacy and is generally well tolerated, with the local irritation
(burning, stinging, itching, and scaling) being typically mild and transient.
Azelaic acid 15% gel is considered effective and safe as a therapy for
inflammatory papulo-pustular rosacea and is suitable for use on all skin types.

Drospirenone: a novel progestin. Rapkin AJ, Winer SA. Expert Opin Pharmacother. 2007 May;8(7):989-99.

Drospirenone is a novel progestin available in combined oral contraceptives and
menopausal hormonal therapy. Similar to its parent compound spirolactone, an
analog of spironolactone, drospirenone has antimineralocorticoid and
antiandrogenic activity. Combined with ethinyl estradiol in oral contraceptive
formulations, drospirenone-containing contraceptives have similar efficacy and
safety profiles to other low-dose oral contraceptives, but seem to offer improved
tolerability with regard to weight gain, mood changes, acne and treatment of a
severe form of premenstrual syndrome called premenstrual dysphoric disorder.
Combined with estradiol as a continuous hormone therapy regimen, the compound was
shown to reduce vasomotor symptoms, maintain bone mass, have a beneficial effect
on body weight and, more importantly, was shown to lower blood pressure in
postmenopausal women.

Therapeutic options in the polycystic ovary syndrome. Bhathena RK. J Obstet Gynaecol. 2007 Feb;27(2):123-9.

The polycystic ovary syndrome is the most common endocrine disorder affecting
women. It is a heterogeneous familial condition of uncertain aetiology. The
diagnosis is made by the detection of polycystic ovaries on ultrasound
examination and the occurrence of single or multiple clinical features such as
menstrual cycle disturbances, obesity, acne, hirsutism, alopecia and biochemical
abnormalities such as hypersecretion of luteinising hormone and testosterone. In
a significant number of women with this condition there is impaired insulin
metabolism. Women with the polycystic ovary syndrome are at an increased risk of
developing diabetes and possibly cardiovascular disease in later life. The
management should be symptom-orientated. Menstrual cycle regulation may be
attained with the combined oral contraceptive pill or cyclical progestogen
therapy. In obese women, with the loss of weight, the symptoms and endocrine
profile are generally improved. Short-term treatment with metformin may be useful
in women with insulin resistance. Hyperandrogenism may be treated with the
contraceptive pill containing cyproterone acetate or with short-term low-dose
anti-androgen therapy, together with effective contraception. Ovulation may be
induced with clomiphene citrate with careful monitoring, failing which low-dose
gonadotrophin therapy or laparoscopic ovarian diathermy are effective options.

Key bioavailability features of a new extended-release formulation of minocycline hydrochloride tablets. Plott RT, Wortzman MS. Cutis. 2006 Oct;78(4 Suppl):6-10.

For a long time, minocycline has been recognized as highly efficacious for the
treatment of acne vulgaris but with use-limiting acute vestibular adverse events
(AVAEs). Based on the concept that lowered overall systemic exposure to
minocycline should reduce unwanted side effects, a program was initiated to
develop a modified-release formulation for clinical testing. An extended-release
(ER) minocycline hydrochloride tablet formulation was developed that demonstrated
delayed time of maximum concentration (tmax, 3 1/2 – 4 hours) compared with a
nonmodified-release minocycline (tmax, 2 1/4 – 3 hours), and a lower maximum
concentration of drug (cmax) in the blood (90%) compared with nonmodified-release
formulations. At steady state (day 6), the ER-minocycline formulation had a 0- to
24-hour area under the curve (AUC(0-24)) and cmax of 33.32 microg x h/mL and 2.63
microg/mL, respectively, compared with 46.35 micro x h/mL and 2.92 microg/mL,
respectively, for the nonmodified-release minocycline. These studies demonstrated
that the new ER-minocycline hydrochloride formulation is not bioequivalent to the
immediate-release (IR) minocycline hydrochloride formulation currently on the
market. The favorable pharmacokinetic profile of ER minocycline also was not
affected by concomitantly ingested food, including dairy products.

Pharmacologic modulation of sebaceous gland activity: mechanisms and clinical applications. Clarke SB, Nelson AM, George RE, Thiboutot DM. Dermatol Clin. 2007 Apr;25(2):137-46, v.

Acne vulgaris is a common skin condition seen by physicians. It primarily affects
adolescents, but can continue into adulthood. A key factor in the pathogenesis of
acne is sebum production. Typical therapy includes combinations of topical
retinoids and antimicrobials for mild acne, with the addition of oral antibiotics
for moderate to severe disease. In the most recalcitrant cases or for
nodulocystic acne, oral retinoids are indicated. In women who fail to respond to
conventional treatment, hormonal therapy is often used adjunctively. Only
isotretinoin and hormonal therapy improve acne via their action on the sebaceous
glands. This article focuses on the mechanisms by which these treatment
modalities act on the sebaceous glands and their clinical use in the practice of
medicine.

Anti-inflammatory activity of tetracyclines. Webster G, Del Rosso JQ. Dermatol Clin. 2007 Apr;25(2):133-5, v.

Tetracyclines are known to exhibit multiple significant anti-inflammatory
actions. This article describes the mechanisms of this anti-inflammatory
activity, such as inhibition of chemotaxis, granuloma formation, and protease.
The article also discusses the effectiveness of tetracyclines in treating such
diseases as acne vulgaris, rosacea, bullous dermatoses, granulomatous disease,
and livedo vasculitis.

[Polycystic ovary syndrome and hair unit function disturbances in dermatological practice] [Article in Polish] Szpringer EA, Lutnicki KR, Zych IS. Wiad Lek. 2006;59(11-12):848-54.

Polycystic ovary syndrome (PCOS) is the common endocrine disorder of reproductive
age women which is characterized by hyperandrogenism, chronic anovulation, and
increased risk for infertility, endometrial cancer, developing metabolic
dysfunction (type II diabetes, dyslipidemia), hypertension and heart disease. The
syndrome is also associated with some skin disorders: hirsutismus, alopecia
androgenetica and acne. The successful dermatologic therapy requires the holistic
diagnosis of the women with skin disorders described above and use the
antiandrogenic treatment with conventional methods and laser depilation in
hirsutismus. In this paper we present literature studies and our own experiences.

[Oxytetracycline--mechanism of action and application in skin diseases] [Article in Polish] Olszewska M. Wiad Lek. 2006;59(11-12):829-33.

Oxytetracycline is a bacteriostatic antibiotic. Newly discovered, additional
mechanisms of action include antioxidant, antiinflammatory and immynosupresive
activity of oxytetracycline and other tetracyclines. These activities were the
basis for developing therapy regimens with oxytetracycline in subantimicrobial
doses. Due to its significant efficacy, limited adverse effects and low therapy
costs, oxytetracycline at the dose of 500 mg per day is presently considered as
therapy of choice in papulopustulous acne. Rosacea and perioral dermatitis are
other indications. Topical oxytetracycline shows significant efficacy in primary
and secondary skin infections with inflammatory reaction.

Current approaches to the diagnosis and treatment of polycystic ovarian syndrome in youth. Harwood K, Vuguin P, DiMartino-Nardi J. Horm Res. 2007;68(5):209-17. Epub 2007 Apr 5.

Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies in
reproductive-age women. It often presents during late adolescence but in some
cases certain features are evident even before menarche. PCOS is a spectrum of
disorders with any combination of oligo/anovulation, clinical and/or biochemical
evidence of androgen excess, obesity, insulin resistance and polycystic ovaries
on ultrasound. The pathogenesis is unknown; however, it is a complex multigenetic
disorder where disordered gonadotropin release, dysregulation of steroidogenesis,
hyperinsulinism and insulin resistance play a role. The diagnosis is based on a
typical physical exam (acne, hirsutism, obesity, and acanthosis nigricans) and
laboratory evidence of hyperandrogenism, such as elevated free testosterone,
androstenedione and dehydroepiandrosterone sulfate (DHEAS), decreased sex
hormone-binding globulin (SHBG) and increased luteinizing hormone (LH). An
ovarian ultrasound may detect the multiple cysts. Secondary causes of PCOS need
to be excluded. There are several classes of medications correcting different
parameters of PCOS that can be used alone or in combination. Oral contraceptive
therapy is used to reduce androgen and LH levels with resultant improvement in
acne and hirsutism, and the induction of regular menses. Antiandrogens are
usually required for a substantial improvement in hirsutism score. Insulin
sensitizers such as metformin are a new class of drugs utilized in treatment of
PCOS. By improving insulin sensitivity and decreasing insulin levels, they
improve the unfavorable metabolic profile of patients with PCOS. Metformin also
helps to increase SHBG, decrease androgen levels and induce ovulation. Despite
all the available medications, life-style changes are the mainstay of therapy as
weight loss and exercise improve all parameters of PCOS without the potential
side effects of medication. (c) 2007 S. Karger AG, Basel.

[Significance of dehydroepiandrosterone and dehydroepiandrosterone sulfate in different diseases] [Article in Hungarian] Bácsi K, Kósa J, Lazáry A, Horváth H, Balla B, Lakatos P, Speer G. Orv Hetil. 2007 Apr 8;148(14):651-7.

Dehydroepiandrosterone and dehydroepiandrosterone-sulfate are precursors of
androgens and estrogens, support the gonadal sexual steroid production. The
levels of dehydroepiandrosterone and dehydroepiandrosterone-sulfate are maximal
between the ages of 20 and 30 years, then start a decline of 2% per year, leaving
a residual of 10-20% of the peak production by the eight decade of life. The
age-associated decrease may lead to osteoporosis, deterioration of
lipid-metabolism, cardiovascular diseases and second type of diabetes mellitus.
Decreased levels were found in autoimmune diseases and in sexual dysfunction,
too. Intracrinology describes the formation of active hormones which exert their
action in the same cells where synthesis took place without release into the
pericellular compartment. The high local androgen and estrogen concentration may
be important in the pathomechanism of hirsutism, acne, seborrhea, breast and
prostate cancer. Administration of dehydroepiandrosterone resulted in a reduction
of postmenopausal osteoporosis, also the decreased symptoms in systemic lupus
erythematosis, psychiatric diseases and sexual disfunction. The authors summarize
the metabolism of dehydroepiandrosterone and dehydroepiandrosterone-sulfate and
their role in different diseases.

Peroxisome proliferator-activated receptors (PPARs) in skin health, repair and disease. Michalik L, Wahli W. Biochim Biophys Acta. 2007 Aug;1771(8):991-8. Epub 2007 Feb 24.

Peroxisome proliferator-activated receptors, PPARalpha, PPARbeta/delta and
PPARgamma, are fatty acid activated transcription factors that belong to the
nuclear hormone receptor family. While they are best known as transcriptional
regulators of lipid and glucose metabolism, evidence has also accumulated for
their importance in skin homeostasis. The three PPAR isotypes are expressed in
rodent and human skin. Various cell culture and in vivo approaches suggest that
PPARalpha contributes to fetal skin development, to epidermal barrier maturation
and to sebocyte activity. PPARbeta/delta regulates sebocyte differentiation,
promotes hair follicle growth and has pro-differentiating effects in
keratinocytes in normal and inflammatory conditions. In contrast, the role of
PPARgamma appears to be rather minor in keratinocytes, whereas its activity is
required for sebaceous gland differentiation. Importantly, PPARalpha and
beta/delta are instrumental in skin repair after an injury, each of them playing
specific roles. Due to their collective diverse functions in skin biology, PPARs
represent a major research target for the understanding and treatment of many
skin diseases, such as benign epidermal tumors, papillomas, acne vulgaris and
psoriasis.

[Anti-microbial therapies for acne vulgaris: anti-inflammatory actions of anti-microbial drugs and their effectiveness] [Article in Japanese] Murata K, Tokura Y. J UOEH. 2007 Mar 1;29(1):63-71.

The etiology of acne vulgaris is complicated and characterized by two aspects,
non-inflammatory and inflammatory mechanisms. The non-inflammatory aspect is
represented by follicular occlusion by sebaceous materials and resultant
formation of comedo. On the other hand, acne features the continuing occurrence
of inflammation, which yields reddish popular or nodular lesions. Therefore, acne
is not a simple infection with Propionibacterium acnes, but subsequent
inflammatory changes are the nature of acne. New quinolones, macrolides and
tetracyclines are used for the treatment of acne as topical or systemic drugs.
Recent accumulated evidence has suggested that these drugs exert their
therapeutic effects by not only bacteriocidal actions but also anti-inflammatory
or anti-immunological actions. These effects include antioxidative action toward
neutrophils, inhibition of cytokine/chemokine production and adhesion molecule
expression by keratinocytes, and suppression of the antigen-presenting ability of
Langerhans cells. Drugs possessing these anti-inflammatory capacities are
clinically beneficial for the treatment of inflammatory acne.

The characteristics and utility of solid phase porous microspheres: a review. Smith S, Morhenn V, Webster G. J Drugs Dermatol. 2006 Nov-Dec;5(10):969-74.

Topical drugs use a variety of ingredients to control the properties of the final
product. Solid phase porous microspheres (SPPM, Microsponge) have been
incorporated into several topical prescription products in an effort to improve
performance or tolerability. SPPMs provide a reservoir effect allowing more
prolonged skin exposure to the active ingredient. They are used in products for
acne vulgaris, actinic keratoses, and pigmentary changes. The differences in
clinical performance between existing formulations of these common active
ingredients and the formulations using SPPMs are compared and contrasted.

Skin rejuvenation with microthermal fractional photothermolysis. Narurkar VA. Dermatol Ther. 2007 Mar;20 Suppl 1:S10-3.

Fractional resurfacing is gaining acceptance as a preferred method for skin
resurfacing. Experience in treating photoaging, acne scars, and melasma is
reviewed.

The use of hydroxy acids on the skin: characteristics of C8-lipohydroxy acid. Saint-Léger D, Lévêque JL, Verschoore M. J Cosmet Dermatol. 2007 Mar;6(1):59-65.

The hydroxy acids are widely used in skin creams because of their exfoliating and
rejuvenating effect on photoaged skin. As a member of this family, the salicylic
acid derivative known in the literature as 2-hydroxy-5-octanoyl benzoic acid or
beta-lipohydroxy acid has also been proposed as an exfoliant and as a treatment
of photoaged skin and acne. This article reviews the effects of the hydroxy acids
and compares them to those of the salicylic acid derivative. We propose the name
C(8)-lipohydroxy acid (C8-LHA) for this derivative to differentiate it from other
related compounds. The lipophilic nature of C8-LHA and its relatively slow
penetration in the skin afford it an exfoliating effect that is efficient at low
concentrations. It appears to have antimicrobial, anti-inflammatory, and
anticomedogenic properties, which make it effective against acne. Its antifungal
and exfoliating properties are also likely to prove useful in combating dandruff.

[Paroxysmal iatrogenic acne and the epidermal growth factor receptor inhibitors (EGFR)] [Article in French] Piérard-Franchimont C, Blaise G, Paquet P, Quatresooz R, Rorive A, Piérard GE. Rev Med Liege. 2007 Jan;62(1):11-4.

Paroxysmal drug-induced acne is a peculiar condition recognized for decades in
dermatology. It can be induced by a variety of drugs. In recent years, the
epidermal growth factor receptor inhibitors used in oncology have shown this type
of adverse effects. The pathogenic mechanism is likely related to the EGF
implication in the rupture of the microcomedo wall resulting in the
perifollicular inflammatory reaction typical for acne. Other cutaneous adverse
effects have been reported with anti-EGFR drugs including paronychia and xerosis.
The dermatological treatments of these drug-induced disorders must be adequately
targeted.

Behçet’s syndrome: disease manifestations, management, and advances in treatment. Yazici H, Fresko I, Yurdakul S. Nat Clin Pract Rheumatol. 2007 Mar;3(3):148-55.

The acne lesions characteristic of Behçet’s syndrome are not sterile and are
commonly observed in combination with arthritis. The two main nodular skin
lesions–superficial thrombophlebitis and erythema nodosum–are equally frequent,
and rather difficult to distinguish. Superficial thrombophlebitis is usually
observed in combination with thrombosis in large veins, and thrombosis of the
large veins usually clusters with dural sinus thrombi, which make up
approximately 20% of all central nervous system (CNS) lesions of Behçet’s
syndrome. The remaining CNS lesions are parenchymal, mainly located in the
brainstem, and associated with a graver prognosis than dural sinus thrombi. The
presence of clinical clusters indicates that there are at least two pathogenetic
pathways in Behçet’s syndrome: a reactive arthritis pathway and a thrombophilia
pathway. Research into the pathogenesis of Behçet’s syndrome has shown that the
most consistent genetic marker of Behçet’s syndrome is HLA-B51; however, the
genetic association of this true-to-form ‘complex’ disorder with HLA-B51 is only
20%, and a whole-genome study showed associations with 16 different loci. The
severity of Behçet’s syndrome and the mortality associated with it tend to
decrease with time, and there is no associated increase in incidence of
atherosclerosis. Although treatment of skin-mucosa manifestations, eye disease
and pulmonary artery aneurysms has improved significantly in the past decades,
the treatment of CNS lesions and thrombophilia are still problematic.

Sexual hormones in human skin. Zouboulis CC, Chen WC, Thornton MJ, Qin K, Rosenfield R. Horm Metab Res. 2007 Feb;39(2):85-95.

The skin locally synthesizes significant amounts of sexual hormones with
intracrine or paracrine actions. The local level of each sexual steroid depends
upon the expression of each of the androgen- and estrogen-synthesizing enzymes in
each cell type, with sebaceous glands and sweat glands being the major
contributors. Sebocytes express very little of the key enzyme, cytochrome
P450c17, necessary for synthesis of the androgenic prohormones
dehydroepiandrosterone and androstenedione, however, these prohormones can be
converted by sebocytes and sweat glands, and probably also by dermal papilla
cells, into more potent androgens like testosterone and dihydrotestosterone. Five
major enzymes are involved in the activation and deactivation of androgens in
skin. Androgens affect several functions of human skin, such as sebaceous gland
growth and differentiation, hair growth, epidermal barrier homeostasis and wound
healing. Their effects are mediated by binding to the nuclear androgen receptor.
Changes of isoenzyme and/or androgen receptor levels may have important
implications in the development of hyperandrogenism and the associated skin
diseases such as acne, seborrhoea, hirsutism and androgenetic alopecia. On the
other hand, estrogens have been implicated in skin aging, pigmentation, hair
growth, sebum production and skin cancer. Estrogens exert their actions through
intracellular receptors or via cell surface receptors, which activate specific
second messenger signaling pathways. Recent studies suggest specific site-related
distribution of ERalpha and ERbeta in human skin. In contrast, progestins play no
role in the pathogenesis of skin disorders. However, they play a major role in
the treatment of hirsutism and acne vulgaris, where they are prescribed as
components of estrogen-progestin combination pills and as anti-androgens. These
combinations enhance gonadotropin suppression of ovarian androgen production.
Estrogen-progestin treatment can reduce the need for shaving by half and arrest
progression of hirsutism of various etiologies, but do not necessarily reverse
it. However, they reliably reduce acne. Cyproterone acetate and spironolactone
are similarly effective as anti-androgens in reducing hirsutism, although there
is wide variability in individual responses.

Vitamins as hormones. Reichrath J, Lehmann B, Carlberg C, Varani J, Zouboulis CC. Horm Metab Res. 2007 Feb;39(2):71-84.

Vitamins A and D are the first group of substances that have been reported to
exhibit properties of skin hormones, such as organized metabolism, activation,
inactivation, and elimination in specialized cells of the tissue, exertion of
biological activity, and release in the circulation. Vitamin A and its two
important metabolites, retinaldehyde and retinoic acids, are fat-soluble
unsaturated isoprenoids necessary for growth, differentiation and maintenance of
epithelial tissues, and also for reproduction. In a reversible process, vitamin A
is oxidized IN VIVO to give retinaldehyde, which is important for vision. The
dramatic effects of vitamin A analogues on embryogenesis have been studied by
animal experiments; the clinical malformation pattern in humans is known.
Retinoic acids are major oxidative metabolites of vitamin A and can substitute
for it in vitamin A-deficient animals in growth promotion and epithelial
differentiation. Natural vitamin A metabolites are vitamins, because vitamin A is
not synthesized in the body and must be derived from carotenoids in the diet. On
the other hand, retinoids are also hormones – with intracrine activity – because
retinol is transformed in the cells into molecules that bind to and activate
specific nuclear receptors, exhibit their function, and are subsequently
inactivated. The mechanisms of action of natural vitamin A metabolites on human
skin are based on the time- and dose-dependent influence of morphogenesis,
epithelial cell proliferation and differentiation, epithelial and mesenchymal
synthetic performance, immune modulation, stimulation of angiogenesis and
inhibition of carcinogenesis. As drugs, vitamin A and its natural metabolites
have been approved for the topical and systemic treatment of mild to moderate and
severe, recalcitrant acne, photoaging and biologic skin aging, acute
promyelocytic leukaemia and Kaposi’s sarcoma. On the other hand, the critical
importance of the skin for the human body’s vitamin D endocrine system is
documented by the fact that the skin is both the site of vitamin D (3)- and
1,25-dihydroxyvitamin D (3) [1, 25(OH) (2)D (3)]-synthesis and a target organ for
1,25(OH) (2)D (3). 1,25(OH) (2)D (3) is not only essential for mineral
homeostasis and bone integrity, but also for numerous further physiologic
functions including regulation of growth and differentiation in a broad variety
of normal and malignant tissues, including cells derived from prostate, breast
and bone. In keratinocytes and other cell types, 1,25(OH) (2)D (3) regulates
growth and differentiation. Consequently, vitamin D analogues have been
introduced for the treatment of the hyperproliferative skin disease psoriasis.
Other newly detected functions of vitamin D analogues include profound effects on
the immune system as well as protection against cancer and other diseases,
including autoimmune and infectious diseases, in various tissues. Current
investigation of the biological effects of vitamin D analogues are likely to lead
to new therapeutic applications that, besides cancer prevention, may include the
prevention and treatment of infectious as well as of inflammatory skin diseases.
This review summarizes existing knowledge on vitamins A and D, the major
vitamin-hormones of the skin.

Primary pigmented nodular adrenocortical disease associated with Carney complex: case report and literature review. Gonçalves FT, Feibelmann TC, Mendes CM, Fernandes ML, Miranda GH, Gouvêa AP, Jorge PT. Sao Paulo Med J. 2006 Nov 7;124(6):336-9.

CONTEXT: Carney complex (CNC), a familial multiple neoplasm syndrome with
dominant autosomal transmission, is characterized by tumors of the heart, skin,
endocrine and peripheral nervous system, and also cutaneous lentiginosis. This is
a rare syndrome and its main endocrine manifestation, primary pigmented nodular
adrenal disease (PPNAD), is an uncommon cause of adrenocorticotropic
hormone-independent Cushing’s syndrome. CASE REPORT: We report the case of a
20-year-old patient with a history of weight gain, hirsutism, acne, secondary
amenorrhea and facial lentiginosis. Following the diagnosing of CNC and PPNAD,
the patient underwent laparoscopic bilateral adrenalectomy, and she evolved with
decreasing hypercortisolism. Screening was also performed for other tumors
related to this syndrome. The diagnostic criteria, screening and follow-up for
patients and affected family members are discussed.

[Fractional photothermolysis] [Article in German] Laubach HJ, Manstein D. Hautarzt. 2007 Mar;58(3):216-8, 220-3.

Fractional photothermolysis (FP) has been recently introduced as a new concept in
dermatologic laser medicine. FP employs an array of small laser beams to create
many microscopic areas of thermal necrosis within the skin called microscopic
treatment zones (MTZ). Even though FP completely destroys the epidermis and
dermis within these MTZ, the 3-dimensional pattern of damage heals quickly and
with few side effects. FP is currently used to treat fine wrinkles, photodamaged
skin, acne scars, and melasma. Due to its clinical efficacy and limited side
effects FP has established itself in the past two years as an alternative
treatment modality to the conventional ablative and non ablative laser therapy.

Guidelines of care for acne vulgaris management. Strauss JS, Krowchuk DP, Leyden JJ, Lucky AW, Shalita AR, Siegfried EC, Thiboutot DM, Van Voorhees AS, Beutner KA, Sieck CK, Bhushan R; American Academy of Dermatology/American Academy of Dermatology Association. J Am Acad Dermatol. 2007 Apr;56(4):651-63. Epub 2007 Feb 5.

DISCLAIMER: Adherence to these guidelines will not ensure successful treatment in
every situation. Furthermore, these guidelines should not be deemed inclusive of
all proper methods of care or exclusive of other methods of care reasonably
directed to obtaining the same results. The ultimate judgment regarding the
propriety of any specific therapy must be made by the physician and the patient
in light of all the circumstances presented by the individual patient.

Polycystic ovary syndrome: diagnosis and treatment. Setji TL, Brown AJ. Am J Med. 2007 Feb;120(2):128-32.

Polycystic ovary syndrome affects 6%-7% of reproductive-aged women, making it the
most common endocrine disorder in this population. It is characterized by chronic
anovulation and hyperandrogenism. Affected women may present with reproductive
manifestations such as irregular menses or infertility, or cutaneous
manifestations, including hirsutism, acne, or male-pattern hair loss. Over the
past decade, several serious metabolic complications also have been associated
with polycystic ovary syndrome including type 2 diabetes mellitus, metabolic
syndrome, sleep apnea, and possibly cardiovascular disease and nonalcoholic fatty
liver disease. In addition to treating symptoms by regulating menstrual cycles
and improving hyperandrogenism, it is imperative that clinicians recognize and
treat metabolic complications. Lifestyle therapies are first-line treatment in
women with polycystic ovary syndrome, particularly if they are overweight.
Pharmacological therapies are also available and should be tailored on an
individual basis. This article reviews the diagnosis, clinical manifestations,
metabolic complications, and treatment of the syndrome. A table summarizing
treatment recommendations is provided.

Abuse of anabolic-androgenic steroids and bodybuilding acne: an underestimated health problem. [Article in English, German] Melnik B, Jansen T, Grabbe S. J Dtsch Dermatol Ges. 2007 Feb;5(2):110-7.

Abuse of anabolic-androgenic steroids (AAS) by members of fitness centers and
others in Germany has reached alarming dimensions. The health care system
provides the illegal AAS to 48.1 % of abusers. Physicians are involved in illegal
prescription of AAS and monitoring of 32.1 % of AAS abusers. Besides
health-threatening cardiovascular, hepatotoxic and psychiatric long-term side
effects of AAS, acne occurs in about 50 % of AAS abusers and is an important
clinical indicator of AAS abuse, especially in young men 18-26 years of age. Both
acne conglobata and acne fulminans can be induced by AAS abuse. The dermatologist
should recognize bodybuilding acne, address the AAS abuse, and warn the patient
about other potential hazards.

Metformin versus oral contraceptive pill in polycystic ovary syndrome: a Cochrane review. Costello MF, Shrestha B, Eden J, Johnson NP, Sjoblom P. Hum Reprod. 2007 May;22(5):1200-9. Epub 2007 Jan 29.

BACKGROUND: The object of this review was to compare metformin versus oral
contraceptive pill (OCP) treatment in polycystic ovary syndrome. METHODS: A
systematic review and meta-analysis employing the principles of the Cochrane
Menstrual Disorders and Subfertility Group was undertaken. RESULTS: Four
randomized controlled trials (RCTs) (104 subjects) were included. Limited data
demonstrated no evidence of a difference in effect between metformin and the OCP
on hirsutism, acne or development of type 2 diabetes mellitus. There were no
trials assessing diagnosis of cardiovascular disease or endometrial cancer.
Metformin, in comparison with the OCP, was less effective in improving menstrual
pattern [Peto odds ratio (OR) 0.08, 95% confidence interval (CI) 0.01-0.45) and
in reducing the serum total testosterone level weighted mean difference (WMD)
0.54, 95% CI 0.22-0.86] but more effective in reducing fasting insulin (WMD
-3.46, 95% CI – 5.39 to -1.52) and not increasing fasting triglyceride (WMD
-0.48, 95% CI – 0.86 to -0.09) levels. Limited data demonstrated no evidence of a
difference in effect between the two therapies on reducing fasting glucose or
total cholesterol levels and severe adverse events. CONCLUSIONS: The limited RCT
evidence to date does not show adverse metabolic risk with the use of the OCP
compared with metformin. Further long-term RCTs are required.

Insulin-sensitising drugs versus the combined oral contraceptive pill for hirsutism, acne and risk of diabetes, cardiovascular disease, and endometrial cancer in polycystic ovary syndrome. Costello M, Shrestha B, Eden J, Sjoblom P, Johnson N. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD005552.

BACKGROUND: Insulin-sensitizing drugs (ISDs) have recently been advocated as
possibly a safer and more effective long-term treatment than the oral
contraceptive pill (OCP) in women with polycystic ovary syndrome (PCOS). It is
important to directly compare the efficacy and safety of ISDs versus OCPs in the
long-term treatment of women with PCOS. OBJECTIVES: To assess the effectiveness
and safety of ISDs versus the OCP (alone or in combination) in improving
clinical, hormonal, and metabolic features of PCOS. SEARCH STRATEGY: We searched
the Cochrane Menstrual Disorders and Subfertility Group Trials Register
(September 2005), Cochrane Central Register of Controlled Trials (CENTRAL (Ovid),
third quarter 2005), MEDLINE (1966 to September 2005), CINAHL (1982 to September
2005), and EMBASE (1988 to September 2005). References of the identified articles
were handsearched, and pharmaceutical companies and experts in the field were
also contacted for additional relevant studies. SELECTION CRITERIA: Randomised
controlled trials which compared ISDs versus the OCP (alone or in combination).
DATA COLLECTION AND ANALYSIS: Performed independently by two review authors. MAIN
RESULTS: Six trials were included for analysis, four of which compared metformin
versus OCP (104 participants) and two of which compared OCP combined with
metformin versus OCP alone (70 participants). Limited data demonstrated no
evidence of difference in effect between metformin and the OCP on hirsutism and
acne. There was either insufficient or no data on the relative efficacy of
metformin or the OCP (alone or in combination) for preventing the development of
diabetes, cardiovascular disease, or endometrial cancer. Metformin was less
effective than the OCP in improving menstrual pattern (Peto odds ratio (OR) 0.08,
95% CI 0.01 to 0.45). Metformin resulted in a higher incidence of
gastrointestinal (Peto OR 7.75, 95% CI 1.32 to 45.71), and a lower incidence of
non-gastrointestinal (Peto OR 0.11, 95% CI 0.03 to 0.39), severe adverse effects
requiring stopping of medication. Metformin was less effective in reducing serum
androgen levels (total testosterone: weighted mean difference (WMD) 0.54, 95% CI
0.22 to 0.86; free androgen index: WMD 3.69, 95% CI 2.56 to 4.83). Metformin was
more effective than the OCP in reducing fasting insulin (WMD -3.46, 95% CI -5.39
to -1.52) and not increasing triglyceride (WMD -0.48, 95% -0.86 to -0.09) levels,
but there was insufficient evidence regarding comparative effects on reducing
fasting glucose or cholesterol levels. AUTHORS’ CONCLUSIONS: Up to 12-months
treatment with the OCP is associated with an improvement in menstrual pattern and
serum androgen levels compared with metformin; but metformin treatment results in
a reduction in fasting insulin and lower triglyceride levels than with the OCP.
Side-effect profiles differ between the two drugs. There is either extremely
limited or no data on important clinical outcomes such as the development of
diabetes, cardiovascular disease, or endometrial cancer. There are no data
comparing ISDs other than metformin (that is rosiglitazone, pioglitazone, and
D-chiro-inositol) versus OCPs (alone or in combination).

Combined oral contraceptive pills for treatment of acne. Arowojolu AO, Gallo MF, Lopez LM, Grimes DA, Garner SE. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD004425.

BACKGROUND: Acne is a common skin disorder among women. Although no uniform
approach to the management of acne exists, combination oral contraceptives
(COCs), which contain an estrogen and a progestin, often are prescribed for
women. OBJECTIVES: To determine the effectiveness of combined oral contraceptives
(COCs) for the treatment of facial acne compared to placebo or other active
therapies. SEARCH STRATEGY: We searched the computerized databases of the
Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE,
POPLINE, Biological Abstracts and LILACS for randomized controlled trials of COCs
and acne. We wrote to authors of identified trials to seek any unpublished or
published trials that we might have missed. SELECTION CRITERIA: All randomized
controlled trials reported in any language that compared the effectiveness of a
COC containing an estrogen and a progestin to placebo or another active therapy
for acne in women were eligible. DATA COLLECTION AND ANALYSIS: We extracted data
on total and specific (i.e., open or closed comedones, papules, pustules and
nodules) facial lesion counts; acne severity grades; global assessments by the
clinician or the participant and discontinuation due to adverse events. Data were
entered and analyzed in RevMan. MAIN RESULTS: The search yielded 23 trials: 5
placebo-controlled trials made 3 different comparisons, 17 trials made 13
comparisons between 2 different COC regimens, and 1 additional trial compared a
COC to an antibiotic. COCs reduced acne lesion counts, severity grades and
self-assessed acne compared to placebo. Differences in the comparative
effectiveness of COCs containing varying progestin types and dosages, though,
were less clear. COCs that contained chlormadinone acetate or cyproterone acetate
improved acne better than levonorgestrel, although this apparent advantage was
based on limited data. A COC with cyproterone acetate might result in better acne
outcomes than one with desogestrel; however, the three studies comparing these
COCs produced conflicting results. Likewise, levonorgestrel showed a slight
improvement over desogestrel in acne outcomes in one trial, but a second trial
found no difference between the COCs. AUTHORS’ CONCLUSIONS: The three COCs
evaluated in placebo-controlled trials are effective in reducing inflammatory and
non-inflammatory facial acne lesions. Few differences were found between COC
types in their effectiveness for treating acne. How COCs compare to alternative
acne treatments is unknown since limited data were available regarding this
question.

Autoinflammatory diseases: clinical and dermatologic features, genetics, pathogenesis and therapy. Pithukpakorn M, Aksentijevich I, Toro JR. Adv Dermatol. 2006;22:67-90.

Don’t use minocycline as first line oral antibiotic in acne. McManus P, Iheanacho I. BMJ. 2007 Jan 20;334(7585):154.

Dermatologic treatment during pregnancy: practical overview. Al Hammadi A, Al-Haddab M, Sasseville D. J Cutan Med Surg. 2006 Jul-Aug;10(4):183-92.

BACKGROUND: This article provides a practical overview of dermatologic medication
use in pregnancy. OBJECTIVE: The therapeutics of the following common dermatoses
are reviewed: acne, psoriasis, and bacterial, fungal, viral, and parasitic
infections. Antipruritic, analgesic, and topical anesthetic use in pregnancy is
reviewed as well. CONCLUSIONS: At the end, the reader is challenged with a series
of applied clinical scenarios that highlight the presented material and provide
information on additional important medications.

Acne and PDT: new techniques with lasers and light sources. Gold MH. Lasers Med Sci. 2007 Jun;22(2):67-72. Epub 2007 Jan 16.

Acne vulgaris is one of the most common dermatologic disorders encountered in
everyday practice. Treatment options for this often psychologically scarring
disease are numerous and, for many individuals, provide relief from the disorder.
However, factors such as antibiotic resistance and slow onset of action from many
topical therapies have led researchers to seek out alternative therapies,
especially for those suffering from moderate to severe inflammatory acne
vulgaris. Lasers and light sources are finding increased usage in the treatment
of inflammatory acne vulgaris. Light sources including blue lights and intense
pulsed lights are becoming regular additions to routine medical management to
enhance the therapeutic response. Finally, photodynamic therapy may change many
of the acne vulgaris paradigms, as its place is being defined in the treatment of
moderate to severe inflammatory acne vulgaris. More and more clinical trials are
showing the effectiveness of 5-aminolevulinic acid and photodynamic therapy in
the treatment of moderate to severe inflammatory acne vulgaris.

[How I treat...acne in adolescents: a strategic algorithm without antibiotic] [Article in French] Xhauflaire-Uhoda E, Goffin V, Piérard-Franchimont C, Piérard GE. Rev Med Liege. 2006 Oct;61(10):667-70.

Acne is a multifaceted disorder. Its clinical presentation differs according to
the age and gender of the subjects. Acne of the adolescent is a frequent
disorder. Some topical and oral antibiotics have proven their efficacy. However,
the risk of bacterial resistance may be a concern for the clinicians and their
patients. Hence, a therapeutic strategy without antibiotics merits to be
considered. Retinoids have a place of choice in this therapeutic strategy.
Benzoyl peroxide and miconazole are also active and valuable agents in this
therapeutic algorithm.

[Acne rosacea--diagnostic challenge] [Article in Polish] Wozniacka A, Kruk M, Robak E, Sysa-Jedrzejowska A. Przegl Lek. 2006;63(7):557-61.

Acne rosacea is a common skin disorder which affects adults, usually women.
Erythema, papules, pustules and telangiectases, the main clinical manifestations
of the disease are located on the face. Currently opinions dealing with
pathogenesis and clinical forms of rosacea are presented. As the clinical picture
might be confusing, similar to other illnesses, differential diagnosis with other
dermatoses like acne vulgaris, erysipelas, seborrhoeic and contact eczema as well
as systemic diseases like lupus erythematosus, dermatomyositis, scleroderma,
sarcoidosis and leukemia were discussed.

Can we ensure the safe use of known human teratogens?: The iPLEDGE test case. Honein MA, Lindstrom JA, Kweder SL. Drug Saf. 2007;30(1):5-15.

Minimising the public health burden of isotretinoin-induced teratogenicity has
been a challenge for 24 years, the duration of availability of isotretinoin in
the US for the treatment of severe, recalcitrant nodular acne. Although the
teratogenicity of this drug is well known and risk-management programmes had been
implemented, preventable fetal exposures continued to occur, largely as a result
of the lack of sufficient controls within the programmes themselves. The
manufacturers of isotretinoin implemented a new risk-management programme,
iPLEDGE, in March 2006. iPLEDGE is a comprehensive distribution system that
includes mandatory registration of patients, healthcare providers, pharmacies,
and wholesalers. It allows real-time linkage of pregnancy-test results for
verification prior to the dispensing of isotretinoin. Although the challenges of
implementing a closed distribution system for a very widely used medication have
been extensive, the potential public health benefits from preventing fetal
exposure to isotretinoin are substantial.

Acne vulgaris–psychosomatic aspects. [Article in English, German] Niemeier V, Kupfer J, Gieler U. J Dtsch Dermatol Ges. 2006 Dec;4(12):1027-36.

More than a cosmetic nuisance, acne can produce anxiety, depression, and other
psychological problems that affect patients’ lives in ways comparable to
life-threatening or disabling diseases. Emotional problems due to the disease
should be taken seriously and included in the treatment plan. A purely
dermatological therapy by itself may not achieve its purpose. Even mild to
moderate disease can be associated with significant depression and suicidal
ideation, and psychologic change does not necessarily correlate with disease
severity. Acne patients suffer particularly under social limitations and reduced
quality of life. Psychological comorbidities in acne are probably greater than
generally assumed. Attention should be paid to psychosomatic aspects especially
if depressive-anxious disorders are suspected, particularly with evidence of
suicidal tendencies, body dysmorphic disorders, or also in disrupted
compliance.Therefore, patients who report particularly high emotional distress or
dysmorphic tendencies due to the disease should be treated, if possible, by
interdisciplinary therapy. The dermatologist should have some knowledge of the
basics of psychotherapy and psychopharmacology, which sometimes must be combined
with systemic and topical treatment of acne in conjunction with basic
psychosomatic treatment.

[Pseudofolliculitis and acne keloid in subjects of African origin] [Article in French] Garsaud AM. Ann Dermatol Venereol. 2006 Nov;133(11):887-9.

Photodynamic therapy: other uses. Taub AF. Dermatol Clin. 2007 Jan;25(1):101-9.

Mainstream uses for photodynamic therapy (PDT) in dermatology include nonmelanoma
skin cancer and its precursors, acne vulgaris, photorejuvenation, and
hidradenitis suppurativa. Many other dermatologic entities have been treated with
PDT, including psoriasis, lichen planus, lichen sclerosus, scleroderma, cutaneous
T cell lymphoma, alopecia areata, verruca vulgaris, Darier’s disease and tinea
infections. Nondermatologic applications include anal and vulva carcinoma,
palliation of metastatic breast cancer to skin, Barrett’s esophagus, and macular
degeneration of the retina. PDT also has found to be useful in immunologic and
inflammatory disorders, neoplasias other than skin cancer, and infections. The
ability of this treatment to hone in on dysplastic epithelial and endothelial
cells while retaining viability of surrounding tissue is its key feature because
this leads to specific tumor destruction with cosmesis and function of the target
organ intact.

The use of photodynamic therapy for treatment of acne vulgaris. Nestor MS. Dermatol Clin. 2007 Jan;25(1):47-57.

Current topical and most oral therapies for acne vulgaris have limited efficacy,
especially in moderate to severe cases. Photodynamic therapy with
5-aminolevulinic acid and recently methyl aminolevulinate has been shown to be a
safe and effective modality for the treatment of acne vulgaris. Consensus
guidelines suggest that 30 to 60 minutes is sufficient 5-aminolevulinic acid
contact time before photoactivation with blue light, red light, yellow light,
broadband light, halogen, or pulsed dye laser devices. An average of three
treatment can yield significant long-term improvement.

Aminolevulinic acid photodynamic therapy for actinic keratoses/actinic cheilitis/acne: vascular lasers. Alexiades-Armenakas M. Dermatol Clin. 2007 Jan;25(1):25-33.

The combination of newer laser and light sources, the long-pulsed pulsed dye
laser (LP PDL) and intense pulsed light, with topical aminolevulinic acid
photodynamic therapy (PDT) has achieved enhanced efficacy and rapid treatment and
recovery, while diminishing unwanted side effects. In particular, LP PDL PDT has
been shown to be safe and effective in the treatment of actinic keratoses,
actinic cheilitis, photodamage, and acne vulgaris with minimal discomfort, rapid
treatment and recovery, and excellent posttreatment cosmesis.

What is the best approach to reducing birth defects associated with isotretinoin? Abroms L, Maibach E, Lyon-Daniel K, Feldman SR. PLoS Med. 2006 Nov;3(11):e483.

BACKGROUND TO THE DEBATE: Isotretinoin is an effective treatment for severe acne,
a condition which can be physically, emotionally, and socially disabling. Because
the drug is teratogenic, causing severe birth defects, women taking the drug are
directed to avoid pregnancy. In the United States, a series of risk reduction
programs have been implemented that aim to prevent pregnant women from taking the
drug and to prevent women taking it from getting pregnant. The most recent, and
most stringent, is an Internet-based, performance-linked system called iPLEDGE,
which tries to ensure that the drug is dispensed only when there is documentary
proof that the patient is not pregnant and is using two forms of birth control.
Is iPLEDGE the best way to reduce isotretinoin birth defects, or is it an
unproven and overly burdensome system?

Prasterone. Kocis P. Am J Health Syst Pharm. 2006 Nov 15;63(22):2201-10.

PURPOSE: The pharmacology, pharmacokinetics, clinical efficacy, adverse effects
and toxicities, drug interactions, dosage and administration, and safety issues
related to the use of prasterone are discussed. SUMMARY: Prasterone is a
proprietary synthetic dehydroepiandrosterone product under investigation for use
in women with systemic lupus erythematosus (SLE) who are taking glucocorticoids.
Initial trials investigated prasterone as a treatment to improve disease activity
and symptoms in women with mild to moderate SLE. The Food and Drug Administration
(FDA) did not approve prasterone’s labeling for these indications. Subsequent
trials have focused on prasterone as a treatment to limit bone loss in women who
have SLE. A study was conducted to assess bone mineral density in patients who
had been taking glucocorticoids for six months or longer. The patients in the
prasterone group showed an increase in bone mineral density, while the placebo
group demonstrated a loss. The most common adverse effects of prasterone therapy
were acne and hirsutism. Hematuria, hypertension, and serum creatinine
concentration increases have also occurred. Interactions of prasterone
potentially exist with 5-alpha reductase inhibitors and additive or antagonistic
effects could possibly occur with androgens, estrogens, oral contraceptives, and
progestins. In clinical trials, oral prasterone dosages of 100-200 mg/day were
administered. These dosages have resulted in supraphysiological hormone levels.
CONCLUSION: FDA has granted orphan drug status for the prevention of loss of bone
mineral density in SLE patients taking glucocorticoids. FDA is requesting
additional Phase III trial data for the treatment of SLE and the prevention of
loss of bone mineral density.

Clinical inquiries. What is the best treatment for mild to moderate acne? Rao S, Malik MA, Wilder L, Mott T. J Fam Pract. 2006 Nov;55(11):994-6.

For mild comedonal acne, monotherapy with topical retinoids is the treatment of
choice (strength of recommendation [SOR]: A). For moderate comedonal and mild to
moderate papulopustular acne, combination therapy with either benzoyl peroxide or
topical retinoids (adapalene [Differin], tazarotene [Tazorac], tretinoin
[Retin-A]) plus topical antibiotics (erythromycin or clindamycin) is proven most
effective (SOR: A). Six to 8 weeks should be allowed for most treatments to work
before altering the regimen (SOR: A).

Acne. Purdy S, de Berker D. BMJ. 2006 Nov 4;333(7575):949-53.

Polycystic ovary syndrome. King J. J Midwifery Womens Health. 2006 Nov-Dec;51(6):415-22.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder, affecting
between 4% and 8% of reproductive aged women. This syndrome, a complex disorder
with multiple components, including reproductive, metabolic, and cardiovascular
manifestations, has long-term health concerns that cross the life span. The
diagnostic criteria for PCOS are ovarian dysfunction evidenced by oligomenorrhea
or amenorrhea and clinical evidence of androgen excess (e.g., hirsutism and acne)
in the absence of other conditions that can cause these same symptoms. This
article reviews current knowledge about the pathophysiology, clinical
manifestations, diagnosis, and management of this disorder.

[Acne scars: epidemiology, physiopathology, clinical features and treatment] [Article in French] Chivot M, Pawin H, Beylot C, Chosidow O, Dreno B, Faure M, Poli F, Revuz J; GROUPE EXPERTS ACNE. Ann Dermatol Venereol. 2006 Oct;133(10):813-24.

[Urinary hormone analysis] [Article in German] Mohaupt MG, von Vigier RO. Ther Umsch. 2006 Sep;63(9):559-64.

Urinary hormone analysis is applied to detect an altered steroid hormone
metabolism, an elevated production of biogenic amines and to non-invasively
determine the protein hormone human beta-choriogonadotropin indicating a
pregnancy. Occasionally, these determinations need to be complemented by plasma-
or serum hormone analysis. Clinical data including current drug therapy and
urinary creatinine as reference are required to interpret any urine analysis.
Diseases to be investigated by steroid hormone analysis are excess production of
a typical or atypical mineralocorticoid active steroid hormones, the hormonal
activity of adrenal or ovarian tumors, acne of unknown origin, hirsutism, a PCO-,
an adrenogenital or a suspected Cushing syndrome. Biogenic amines should be
determined in suspected secondary or refractory arterial hypertension, in case of
pheochromocytoma- or paraganglioma-associated symptoms or if a
serotonin-producing tumor is suspected. In children genetically determined
diseases are the primary background to perform an analysis.

Polycystic ovary syndrome in adolescents: current and future treatment options. Mastorakos G, Lambrinoudaki I, Creatsas G. Paediatr Drugs. 2006;8(5):311-8.

Polycystic ovary syndrome (PCOS) is a very common disorder affecting 5-10% of
women of reproductive age. The pivotal endocrine abnormalities of this syndrome
are insulin resistance and ovarian and, to a lesser degree, adrenal
hypersensitivity to hormonal stimulation. PCOS may manifest itself as early as
the first decade of life by premature pubarche or menarche. Oligoamenorrhea in
the first postpubarchal years, although very common, may be an early symptom of
PCOS, especially in overweight girls with hirsutism or acne. Girls with low birth
weight as well as a family history of diabetes mellitus or premature
cardiovascular disease are at high risk for developing PCOS. Circulating
bioavailable testosterone levels are usually elevated, while total testosterone
may be normal due to low levels of sex hormone-binding globulin. The typical
sonographic appearance of PCOS ovaries consists of high ovarian volume (>10 mL)
and the presence of 12 or more follicles in each ovary measuring 2-9 mm in
diameter. However, this finding is not specific, since it may occur in >20% of
healthy girls. The therapeutic goals in adolescents with PCOS is first to restore
bodyweight and menses and to reduce the signs of hyperandrogenism. The reduction
of bodyweight in this young age group may require the collaboration of the
pediatrician, dietitian, and psychotherapist. The adolescent should be urged to
adopt a healthy lifestyle with the aim to maintain a normal body mass index
throughout adolescence and adult life. The choice of medical therapy depends on
the clinical presentation. Oral contraceptives are a good option when acne and
hirsutism are the principal complaints. Adolescents with isolated cycle
irregularity may be placed on a cyclical progestin regimen to induce withdrawal
bleeding. Metformin, by decreasing insulin resistance, alleviates many of the
hormonal disturbances and restores menses in a considerable proportion of
patients. It may be used alone or in combination with oral contraceptives.
Independently of medical treatment, restoration and maintenance of bodyweight
within normal range is of paramount importance.

Soft tissue augmentation. Hirsch RJ, Cohen JL. Cutis. 2006 Sep;78(3):165-72.

Recent additions to the soft tissue augmentation armamentarium have greatly
increased the dermatologic surgeon’s choices in optimizing facial contouring and
the treatment of acne scars. In this article, we review the science of fillers
and look at the future of dermal fillers.

Current concepts in acne management. Yan AC. Adolesc Med Clin. 2006 Oct;17(3):613-37; abstract x-xi.

Acne vulgaris is a nearly universal phenomenon among adolescents in the western
world and continues to remain problematic for a significant proportion of adults.
During adolescence, emotional and physical changes must be successfully
integrated into the emerging sense of self, and skin disorders such as acne,
which alter that self-image, may engender distressing feelings of embarrassment,
shame, and disgust. While most patients eventually achieve spontaneous remission,
approximately one quarter of teenagers will show evidence of permanent acne
scarring by 18 years of age. This article reviews current information regarding
the pathophysiology, clinical manifestations, differential diagnosis, and therapy
of the adolescent patient who has acne, and emphasizes recent advances in acne
management.

Acne: intervene early. Roebuck HL. Nurse Pract. 2006 Oct;31(10):24-43; quiz 44-5.

“There is no single disease which causes more psychic trauma, more maladjustment
between parents and children, more general insecurity and feelings of
inferiority, and greater sums of psychic suffering than does acne vulgaris.”

Nadifloxacin: a quinolone for topical treatment of skin infections and potential for systemic use of its active isomer, WCK 771. Jacobs MR, Appelbaum PC. Expert Opin Pharmacother. 2006 Oct;7(14):1957-66.

Nadifloxacin is a potent, broad-spectrum, quinolone agent approved for topical
use in acne vulgaris and skin infections in Japan. As exposure of pathogenic and
colonising bacteria to antibiotics results in drug resistance, it is not
desirable to use an important, broad-spectrum antibiotic, which belongs to a
class of agents widely used systemically to treat a wide variety of infections,
as a topically applied preparation. On this basis, nadifloxacin is not a good
option for topical treatment of acne when other effective non-antibiotic
treatments are available. Nadifloxacin has potential as a topical agent for
short-term treatment of skin infections. The arginine salt of its (-)-(S)-isomer
is being developed as a parenteral agent based on its potency against methicillin
and quinolone-resistant Staphylococcus aureus.

Update in retinoid therapy of acne. Thielitz A, Krautheim A, Gollnick H. Dermatol Ther. 2006 Sep-Oct;19(5):272-9.

The pathogenesis of acne, the most common skin disease, is complex and
multifactorial. Clinical experience has demonstrated that parallel targeting of
various pathogenetic factors, achieved either by mono- or combination therapy
with appropriate drugs, represents the most effective approach to treating acne.
Topical retinoids have been shown to expulse mature comedones, reduce
microcomedone formation, and exert immunomodulatory effects. They have broad
anti-acne activity without the risk of inducing bacterial resistance, which
justifies their use as first-line treatment in most types of noninflammatory and
inflammatory acne and makes them uniquely suitable as long-term medication to
maintain remission after cessation of initial combination therapy. Systemic
isotretinoin as a monotherapeutic agent strongly affects all four major
pathogenetic factors and has been, in the hand of experienced dermatologists, a
potent and safe agent for the treatment of severe and recalcitrant acne forms for
more that 20 years. However, patient counseling, careful monitoring, and
evaluation and management of adverse events are necessary. The use of
isotretinoin has experienced a drawback now that its indication has been lowered
from a first-line to a second-line medication.

Contemporary medical therapy for polycystic ovary syndrome. Lanham MS, Lebovic DI, Domino SE. Int J Gynaecol Obstet. 2006 Dec;95(3):236-41. Epub 2006 Sep 28.

Polycystic ovary syndrome is a multi-system endocrinopathy with long-term
metabolic and cardiovascular health consequences. Patients typically present due
to symptoms of irregular menstruation, hair growth, or infertility; however,
recent management options are aimed at further treating underlying
glucose-insulin abnormalities as well as androgen excess for proactive control of
symptoms. By a 2003 international consensus conference, diagnosis is made by two
out of three criteria: chronic oligoovulation or anovulation after excluding
secondary causes, clinical or biochemical evidence of hyperandrogenism (but not
necessarily hirsutism due to inter-patient variability in hair follicle
sensitivity), and radiological evidence of polycystic ovaries. Traditional
medical treatment options include oral contraceptive pills, cyclic progestins,
ovulation induction, and anti-androgenic medications (aldosterone antagonist,
5alpha-reductase antagonist, and follicle ornithine decarboxylase inhibitor).
Recent pharmacotherapies include insulin-sensitizing medications metformin and
two thiazolidinediones (rosiglitazone/Avandia and pioglitazone/Actos), a CYP19
aromatase inhibitor (letrozole/Femara), and statins to potentially lower
testosterone levels.

Systemic antibiotic therapy of acne vulgaris. [Article in English, German] Ochsendorf F. J Dtsch Dermatol Ges. 2006 Oct;4(10):828-41.

BACKGROUND: Inflammatory, medium to severe acne vulgaris is treated with systemic
antibiotics worldwide. The rationale is an effect on Propionibacterium acnes as
well as the intrinsic anti-inflammatory properties of these antibiotics. Although
there are no correlations between the number of P. acnes and the severity of the
disease, associations between the degree of humoral and cellular immune responses
towards P. acnes and the severity of acne have been reported. Exact data on
practical use of these compounds, such as differential efficacy or side effects
are unavailable. A summary of currently available studies is presented. METHODS:
The data of studies of systemic antibiotic therapy of acne vulgaris up to 1975,
the summary of literature in English up to 1999, a systematic review of
minocycline from 2002 as well as the data of randomized controlled studies
published and listed in Medline thereafter were reviewed. RESULTS: Tetracyclines
[tetracycline 1,000 mg daily, doxycycline 100 (-200) mg daily, minocycline 100
(-200) mg daily, lymecycline 300 (-600) mg] and erythromycin 1 000 mg daily are
significantly more effective than placebo in the systemic treatment of
inflammatory acne.The data for tetracycline are best founded. Clindamycin is
similarly effective. Co-trimoxazole and trimethoprim are likely to be effective.
Clear differences between the tetracyclines or between tetracycline and
erythromycin cannot be ascertained. The data for the combination with topical
treatments [topical benzoyl peroxide (BPO) or retinoids] suggest synergistic
effects.Therefore systemic antibiotics should not be used as monotherapy. In case
of similar efficacy, other criteria, such as pharmacokinetics (doxycycline,
minocycline, lymecycline have longer half-lives than tetracyclines), the rate of
side-effects (tetracycline: side effect-rate approximately 4 % mild side effects;
erythromycin: frequent gastrointestinal complaints; minocycline: rare, but
potentially severe hypersensitivity reactions; doxycycline: dose-dependent
phototoxic reactions), the resistance rate [percentage of resistant bacteria
higher with erythromycin (approximately 50 %) than with tetracycline-therapy
(approximately 20 %)], and the costs of therapy have to be taken into account.
CONCLUSIONS: The systemic antibiotic therapy of widespread papulo-pustular acne
not amenable to a topical therapy is effective and well-tolerated. In general
therapy can be carried out for 3 months and should be combined with BPO to
prevent resistance.

Persistent acne in women : implications for the patient and for therapy. Williams C, Layton AM. Am J Clin Dermatol. 2006;7(5):281-90.

Acne is traditionally regarded as a skin disorder of the teenage years. However,
recent epidemiologic studies have shown that a significant number of female
patients aged >25 years experience acne. One recent community-based UK study
estimated the prevalence of facial acne in adult women aged between 26 and 44
years to be 14%. It is not clear whether there is a true increase in acne in this
age group or whether these patients are less tolerant of their acne and/or better
informed of available therapies and so seek advice. The reasons for persistent
acne are not fully understood. External factors such as use of certain cosmetics,
ingestion of drugs, and endocrine abnormalities should all be considered when
managing these patients. Post-adolescent acne in females can be divided into
‘persistent acne’, which represents a continuation of acne from adolescence into
adult life, and ‘late-onset’ acne, which describes significant acne occurring
sometimes for the first time after the age of 25 years. The clinical picture of
each of these forms of acne in adult females can differ slightly from
conventional adolescent disease. The course of each form is more indolent.
Because of these variations, the approach to investigation and management of
these cases may have subtle differences when compared with that for teenage
disease. Acne treatment should aim to reduce sebum, comedogenesis,
propionibacteria population, and inflammation. Treatment selection will depend on
the acne grade and site as well as the patient’s preference and ability to comply
with therapy. Maintenance therapy plays an important role in managing this group
of patients. As the response to treatment is inevitably slow, patients must be
encouraged to adhere to the chosen treatment regimen. This article reviews the
literature on persistent acne in women in terms of clinical presentation and
possible etiologic factors, and outlines principles of therapy related to
managing these cases.

Psychological problems in the acne patient. Fried RG, Wechsler A. Dermatol Ther. 2006 Jul-Aug;19(4):237-40.

Acne is a ubiquitous affliction that can leave physical and emotional scars that
can persist throughout the life of the affected individual. Recent studies have
substantiated the psychological impact and support a causal, and at times
reciprocal, link between acne and the emotional and functional status of the
patient. The present article will examine the recent data substantiating the
emotional and functional impact of acne on the affected individual. Criteria to
identify high-risk patients are provided. High-risk patients are those at
increased risk for psychological and functional impairment or self-injurious
behavior.

Tricks for improving compliance with acne therapy. Baldwin HE. Dermatol Ther. 2006 Jul-Aug;19(4):224-36.

Adherence to a medical regimen is the most important aspect of therapeutic
efficacy. It goes without saying that a drug that is not used will not be
effective. Reasons for noncompliance can be related to the specific disease
state, to characteristics of the drugs chosen, to patient personality traits, and
to effectiveness of the clinician in dealing with the individual patient.
Recognizing, confronting, and improving noncompliant behavior are all part of an
effective doctor-patient relationship.

Diagnosis and management of the dermatologic manifestations of the polycystic ovary syndrome. Lowenstein EJ. Dermatol Ther. 2006 Jul-Aug;19(4):210-23.

Polycystic ovary syndrome (PCOS) is a complex phenotypic spectrum of primarily
hyperandrogenic signs and symptoms. PCOS is the most common endocrine disturbance
to affect women of reproductive years. Although patients affected are often very
disturbed by the cutaneous manifestations, including acne, hirsutism, alopecia,
obesity, and acanthosis nigricans, the clinical manifestations of PCOS ramify far
beyond the skin. PCOS frequently causes menstrual abnormalities and infertility.
Insulin resistance is both pathogenic and a cause of numerous serious health
consequences. The accurate diagnosis and recognition of cutaneous
hyperandrogenism in PCOS are discussed. The differential diagnosis is reviewed.
The work-up and approach to evaluation of patients with PCOS is presented.
Although no uniform treatment approach for the management of the cutaneous
manifestations of PCOS has been agreed upon, the data on various treatment
options and the author’s treatment approach to these patients are presented.

Childhood acne: evaluation and management. Cantatore-Francis JL, Glick SA. Dermatol Ther. 2006 Jul-Aug;19(4):202-9.

Acne is a disease that can be seen in the first year of life, early childhood,
prepubertal age, and puberty. The purpose of this article is to review the
clinical presentation and pathogenesis of the various forms of prepubertal acne
and to propose guidelines regarding its evaluation and treatment. The early
clinical recognition of the disease and prompt initiation of therapy in these age
groups will help prevent the sequelae of emotional distress and severe scarring
in both the child and parents.

Pediatric rosacea. Kroshinsky D, Glick SA. Dermatol Ther. 2006 Jul-Aug;19(4):196-201.

Rosacea is a condition most commonly associated with adults; however, various
forms exist in the pediatric population and need to be considered when a child
presents with a facial rash. Acne rosacea, steroid rosacea, granulomatous
periorificial dermatitis, and other variants of rosacea are presented here and
are distinguished from their numerous mimickers. Various topical and systemic
therapeutic options exist for the treatment of rosacea with several adjustments
and considerations that must be taken into account when treating a child.

Antibiotic resistance in Propionibacterium acnes. Microbiological and clinical aspects. Nord CE, Oprica C. Anaerobe. 2006 Oct-Dec;12(5-6):207-10. Epub 2006 Sep 26.

Pharmacological management of SAPHO syndrome. Olivieri I, Padula A, Palazzi C. Expert Opin Investig Drugs. 2006 Oct;15(10):1229-33.

The SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome (SaS)
includes different skeletal manifestations such as recurrent multifocal
osteomyelitis, osteitis and arthritis, which are frequently associated with
different forms of skin pustulosis (palmoplantar pustulosis, pustular psoriasis
and severe acne). This syndrome is strictly related to the spondyloarthopathies
(particularly to psoriatic arthritis) and many SaS cases fulfil the
classification criteria for the spondyloarthopathies. Because SaS is an uncommon
disease, current knowledge regarding its therapy is based on limited experiences
gained by treating mainly small groups of patients. As a consequence, its
treatment is still empiric. Several drugs (including NSAIDs, corticosteroids,
sulfasalazine, methotrexate, ciclosporin, leflunomide, calcitonin and so on) have
been administered and obtained conflicting results. The use of antibiotics, due
to the isolation of Propionibacterium acnes from the bone biopsies of several
subjects with SaS, has not represented a turning point in therapy, although some
patients are responsive to this treatment. Initial reports concerning the
administration of bisphosphonates (pamidronate and zoledronic acid) and of an
anti-TNF-alpha agent (infliximab) are very promising for the future. In any case,
larger, multi-centre, controlled, double-blind studies are required to emerge
from the present pioneering phase.

Treatment considerations for inflammatory acne: clinical evidence for adapalene 0.1% in combination therapies. Thiboutot DM, Gollnick HP. J Drugs Dermatol. 2006 Sep;5(8):785-94.

Acne vulgaris is an exceptionally common, chronic, and recurring disease. It
involves multiple etiological factors including follicular hyperkeratinization,
increased sebum production, Propionibacterium acnes proliferation, and
inflammation. Presently, oral isotretinoin is the only single agent that is
effective against all 4 major pathophysiologic features. However, this drug is
also responsible for several serious side effects, including teratogenicity.
Therefore, it should be used in only the most severe cases and alternative
treatment approaches for inflammatory acne, such as initial combination therapy,
should be considered first. Combination therapy in inflammatory acne
simultaneously targets multiple pathogenic factors. Current guidelines recommend
early initiation of combination therapy with a topical retinoid and
antimicrobials for mild to moderate inflammatory acne and topical retinoids with
oral antibiotics (with or without the use of benzoyl peroxide) for moderate to
severe cases of acne, followed by maintenance therapy with topical retinoids.
This review evaluates the rationale and clinical evidence for the use of
adapalene in combination therapy for inflammatory acne.

Photodynamic therapy: practical cosmetic applications. Alster TS, Surin-Lord SS. J Drugs Dermatol. 2006 Sep;5(8):764-8.

Photodynamic therapy (PDT) has been used in the treatment of a variety of benign
and malignant cutaneous conditions. More recently, it has been used to enhance
the results of skin rejuvenation procedures. The purpose of this article is to
review the current practical applications of PDT in a cosmetic practice.

Defining criteria used to evaluate response to treatment of acne vulgaris. Del Rosso JQ. Cutis. 2006 Aug;78(2):117-21.

Results from controlled studies form the basis of overall perceptions regarding
the efficacy and safety of specific treatments. In acne vulgaris, determining
statistical significance related to mean percentage reduction in inflammatory and
noninflammatory lesion counts, investigator global assessment, and patient
(subject) global assessment have formed the basis of most studies. Results may be
impacted by several mitigating factors related to inclusion and exclusion
criteria and variations in study “power.” Recently, standards for evaluation of
response to acne treatment have been reconsidered, with new methodologies
suggested throughout the approval process. For example, the standard of “complete
clearance” has been introduced. How the new methodologies compare with previous
standards, and how new criteria will impact the reporting and interpretation of
trial results are reviewed in this article. Specific study outcomes, including
those reported in more recent trials with topical adapalene, are utilized as
illustrative examples.

Skin disorders with arthritis. Levin J, Werth VP. Best Pract Res Clin Rheumatol. 2006 Aug;20(4):809-26.

Many inflammatory, metabolic and infectious diseases affect the skin and joints.
Most of these, such as rheumatoid arthritis and systemic lupus erythaematosus,
are considered to be rheumatic conditions with secondary skin involvement.
However, several primary cutaneous diseases are associated with arthritis and may
even present with joint symptoms prior to cutaneous lesions. Common skin
disorders, such as acne and psoriasis, have well-known musculoskeletal
manifestations. Other less common conditions, such as dermatomyositis,
multicentric reticulohistiocytosis, pyoderma gangrenosum, Sweet’s syndrome and
various cutaneous vasculitides, also have frequent joint involvement. This review
will discuss the clinical presentation, both cutaneous and musculoskeletal,
diagnosis and management of these disorders.

Acne vulgaris. Purdy S. Clin Evid. 2006 Jun;(15):2183-201.

Zinc in skin pathology and care. Bibi Nitzan Y, Cohen AD. J Dermatolog Treat. 2006;17(4):205-10.

OBJECTIVES: To assess the significance of zinc in the etiology of various
dermatological conditions and examine the role of zinc as a mode of treatment for
a wide range of dermatoses. METHODS: Review of existing literature through
searches using the PubMed site with zinc and the dermatosis in question as search
words. RESULTS: Severe zinc deficiency states such as acrodermatitis
enteropathica are associated with a variety of skin manifestations, such as
perioral, acral and perineal dermatitis. These syndromes can be reversed with
systemic zinc repletion. In addition to skin pathologies which are clearly
zinc-dependent, many dermatological conditions (e.g. dandruff, acne and diaper
rash) have been associated and treated with zinc. Success rates for treatment
with zinc vary depending on the disease, mode of application and zinc salt used.
Usually, alternative modes of treatment are superior to zinc. CONCLUSIONS:
Generally, it seems that with the exception of systemic deficiency states, there
is very little evidence to convincingly demonstrate the efficacy of zinc as a
first-line treatment for any dermatological conditions. Further research is
needed in order to establish the indications for zinc treatment in dermatology,
optimal mode of delivery, type of compound and therapeutic indexes.

Current and future treatment options for acne. van de Kerkhof PC, Kleinpenning MM, de Jong EM, Gerritsen MJ, van Dooren-Greebe RJ, Alkemade HA. J Dermatolog Treat. 2006;17(4):198-204.

Acne is a frequent skin disease with abnormalities in the process of
keratinization, sebaceous gland functioning and inflammation. In this review, our
understanding of the pathogenesis of acne has been updated. An overview of
efficacy and side effects of available anti-acne treatments is presented. Based
on the present overview a recommendation for the treatment of various
manifestations of acne is provided, also reconciling beneficial combinations of
treatments. It is attractive to speculate that the increased insight into the
pathogenesis of acne will create new treatment options. Challenging new options
comprise blue light, photodynamic therapy, retinoic acid metabolism blocking
agents and inhibitors of Th-1 cytokines.

The skin and the mind. Chuh A, Wong W, Zawar V. Aust Fam Physician. 2006 Sep;35(9):723-5.

BACKGROUND: The intimate relationship of the skin and the mind illustrates the
importance of a holistic approach in caring for patients with skin problems.
Habits related to psychological problems may lead to skin problems such as lichen
simplex chronicus and acne excoriée. Emotional stress may affect skin diseases
such as atopic dermatitis, perioral dermatitis, pompholyx, and plaque psoriasis.
OBJECTIVE: This article describes the relationship between the mind and skin
disease. DISCUSSION: Skin disease can exert a profound effect on the psychosocial
dimension of a patient’s life. Its effect on quality of life can be objectively
assessed and documented by validated tools specific for the skin. Patient rated
measures should be taken into account when evaluating the efficacy and adverse
effects of treatments for skin disease.

Managing acne vulgaris effectively. Goodman G. Aust Fam Physician. 2006 Sep;35(9):705-9.

The management of acne is a gratifying experience. Available treatments are
effective, relatively nontoxic and generally safe. However, there is no quick
fix. Antibiotics, hormone therapies and topical therapies are maintenance
treatments. Isotretinoin can induce remission, as can some of the newer physical
modalities of lights, lasers and radiofrequency devices. Effective management of
acne often requires using a combination of treatments that act on different parts
of the pathogenic process of acne development.

Expert committee recommendations for acne management. Zaenglein AL, Thiboutot DM. Pediatrics. 2006 Sep;118(3):1188-99.

In 2003, an international committee of physicians and researchers in the field of
acne, working together as the Global Alliance to Improve Outcomes in Acne,
developed consensus guidelines for the treatment of acne. These guidelines were
evidence based when possible but also included the extensive clinical experience
of this group of international dermatologists. As a result of the evaluation of
available data and the experience, significant changes occurred in the management
routines for acne. The greatest change arose on the basis of improved
understanding of acne pathophysiology. The recommendation now is that acne
treatments should be combined to target as many pathogenic factors as possible. A
topical retinoid should be the foundation of treatment for most patients with
acne, because retinoids target the microcomedo, the precursor to all acne
lesions. Retinoids also are comedolytic and have intrinsic antiinflammatory
effects, thus targeting 2 pathogenic factors in acne. Combining a topical
retinoid with an antimicrobial agent targets 3 pathogenic factors, and clinical
trials have shown that combination therapy results in significantly faster and
greater clearing as opposed to antimicrobial therapy alone. Oral antibiotics
should be used only in moderate-to-severe acne, should not be used as
monotherapy, and should be discontinued as soon as possible (usually within 8-12
weeks). Because of their effect on the microcomedo, topical retinoids also are
recommended as an important facet of maintenance therapy.

Photodynamic therapy in dermatology. Babilas P, Landthaler M, Szeimies RM. Eur J Dermatol. 2006 Jul-Aug;16(4):340-8.

Currently, topical photodynamic therapy (PDT) has received approval for the
treatment of dermato-oncologic conditions like actinic keratoses, Bowen’s
disease, in-situ squamous cell carcinoma and basal cell carcinoma in many
countries all over the world. For many non-neoplastic dermatological diseases
like localized scleroderma, acne vulgaris and viral warts a therapeutical benefit
of PDT is evident, too. Unlike the formerly used, only systemically-applicable
haematoporphyrin derivates, the recently developed topical photosensitizers
5-aminolevulinic acid (ALA) or its methyl ester (MAL) induce photosensitizing
porphyrins. Moreover, the latter do not induce strong generalized cutaneous
photosensitization. Due to the easy accessibility of skin to light activation,
incoherent lamps or LED arrays are suitable for PDT. The production of reactive
oxygen intermediates like singlet oxygen depends on the applied light dose as
well as the concentration and localization of the photosensitizer in the diseased
tissue. Either cytotoxic effects resulting in tumor destruction or
immunomodulatory effects improving inflammatory skin conditions are induced.
Treating superficial non-melanoma skin cancer, PDT has been shown to be highly
efficient despite the low level of invasiveness. The excellent cosmetic results
after treatment are beneficial, too.

Factitial dermatoses in children. Shah KN, Fried RG. Curr Opin Pediatr. 2006 Aug;18(4):403-9.

PURPOSE OF REVIEW: Factitial skin diseases are characterized by unusual patterns
of skin lesions that do not conform to any known dermatologic condition and that
are consciously or subconsciously fabricated by the patient. This review
summarizes the current literature regarding the diagnosis and management of
factitial dermatoses in children. RECENT FINDINGS: Neurotic excoriations, acne
excoriee and trichotillomania are the most common factitial skin diseases seen in
children. Dermatitis artefacta is also seen in children, but is less common. In
many cases, the development of factitial skin disease is associated with a
comorbid psychiatric condition or identifiable psychosocial stressor. With regard
to the management of factitial dermatoses in children, it is of paramount
importance for the clinician to establish an appropriate physician-patient-family
relationship. Although controlled studies in children are lacking, pharmacologic
and/or nonpharmacologic adjunctive therapy can be helpful in the treatment of
these difficult conditions. SUMMARY: The diagnosis and management of factitial
skin diseases in children is a challenge. Clinicians caring for children should
be able to recognize the common factitial dermatoses that are seen in the
pediatric population. The conveyance of support and acceptance by the physician
is essential to the treatment process. Both psychotherapy and psychopharmacology
can be important adjunctive treatments.

Extensive clinical experience: nonclassical 21-hydroxylase deficiency. New MI. J Clin Endocrinol Metab. 2006 Nov;91(11):4205-14. Epub 2006 Aug 15.

CONTEXT: Nonclassical congenital adrenal hyperplasia (CAH) owing to steroid
21-hydroxylase deficiency (NC21OHD) is the most frequent of all autosomal
recessive genetic diseases, occurring in one in 100 persons in the heterogeneous
New York City population. NC21OHD occurs with increased frequency in certain
ethnic groups, such as Ashkenazi Jews, in whom one in 27 express the disease.
NC21OHD is underdiagnosed in both male and female patients with hyperandrogenic
symptoms because hormonal abnormalities in NC21OHD are only mild to moderate, not
severe as in the classical form of CAH. Unlike classical CAH, NC21OHD is not
associated with ambiguous genitalia of the newborn female. MAIN OUTCOME MEASURES:
The hyperandrogenic symptoms include advanced bone age, early pubic hair,
precocious puberty, tall stature, and early arrest of growth in children;
infertility, cystic acne, and short stature in both adult males and females;
hirsutism, frontal balding, polycystic ovaries, and irregular menstrual periods
in females; and testicular adrenal rest tissue in males. CONCLUSIONS: The signs
and symptoms of hyperandrogenism are reversed with dexamethasone treatment.

Is minocycline overused in acne? [No authors listed] Drug Ther Bull. 2006 Aug;44(8):60-2.

Patients with moderate or severe acne vulgaris, or an inadequate response to
topical treatments, are often treated with oral antibacterials, in particular,
tetracyclines. Minocycline is one of the most commonly prescribed tetracyclines
in acne, the predominant use for this drug. In 2005, around 2.5 million
prescriptions for oral tetracyclines were dispensed in England at a cost to the
NHS of over pound 21 million, and minocycline accounted for 40% of this
expenditure. The drug is often recommended with claims that it is more effective,
less likely to cause bacterial resistance, and easier to take than other
tetracyclines. Here we consider the use of minocycline for acne.

Pharmionics in dermatology: a review of topical medication adherence. Lee IA, Maibach HI. Am J Clin Dermatol. 2006;7(4):231-6.

The objective of this article was to review patient adherence to topical
medications and its relationship to health outcomes in dermatologic disease. To
this end, MEDLINE searches from January 1966 through June 2006 and EMBASE
searches from January 1974 through June 2006 were conducted. Relevant human
efficacy studies, including randomized controlled trials, observational studies,
and case-control studies, were selected on the basis of the key words
‘compliance,’ ‘adherence,’ ‘pharmionics,’ ‘topical,’ ‘medication,’ or
‘dermatology.’ Studies were included and reviewed on the basis of their
experimental design, controls, and statistical analysis. Analysis revealed that
suboptimal adherence to topical medications is a common cause of minimal response
or lack of response to drugs and is linked with poor dermatologic outcomes in
diseases such as psoriasis, atopic dermatitis, and acne. It is concluded that
non-adherence to topical medications is as common as non-adherence to oral
medications, and its relationship to poor health outcomes is clear. Several
barriers to topical medication adherence and predictors of non-adherence are
similar to those for oral medications, while other barriers and predictors are
unique to topical medications and the nature of dermatologic disease. Further
studies of effective interventions to increase adherence are necessary to improve
health outcomes in dermatology.

Acne–natural history, facts and myths. Goodman G. Aust Fam Physician. 2006 Aug;35(8):613-6.

This article describes the epidemiology and natural history of acne and discusses
the common aetiological myths and beliefs surrounding acne. Acne is a polymorphic
disease with noninflammatory and inflammatory aspects and a wide spectrum of
severity. The severe inflammatory patterns tend to be those that most frequently
scar and therefore require early intervention. The pattern of disease, relative
severity, distribution, and patient’s social circumstances will influence
appropriate management. However, effective management also includes patient
education about acne, its natural history, and dispelling acne myths.

Acne: more than skin deep. Ayer J, Burrows N. Postgrad Med J. 2006 Aug;82(970):500-6.

Acne is one of the most prevalent skin conditions affecting teenagers. It is a
disease of the pilosebaceous unit. Blockage of sebaceous glands and colonisation
with Proionobacterium acnes leads to acne. Grading the severity of acne helps to
determine the appropriate treatment. Treatment of acne should be started as early
as possible to minimise the risk of scarring and adverse psychological effects.
It should be tailored to the individual patient, the type of acne, its severity,
the patient’s ability to use the treatment, and the psychological state. Topical
agents are the mainstay for treatment of mild acne. Moderate acne is treated with
oral antibiotics. Resistance to antibiotics may be reduced by subsequent use of
non-antibiotic topical medications. Severe acne is treated with isotretinoin, and
this can lead to permanent remission. With better education and care given by
medical profession, acne treatment could be significantly improved.

Dioxin-induced chloracne–reconstructing the cellular and molecular mechanisms of a classic environmental disease. Panteleyev AA, Bickers DR. Exp Dermatol. 2006 Sep;15(9):705-30.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is among the most toxic pollutants
known to date that serves as a prototype for a group of halogenated hydrocarbon
compounds characterized by extraordinary environmental persistence and unique
ability to concentrate in animal and human tissues. TCDD can elicit a complex
array of pleiotropic adverse effects in humans, although chloracne, a specific
type of acne-like skin disease, is the only consistent manifestation of dioxin
intoxication, thus representing a ‘hallmark’ of TCDD exposure. Chloracne is
considered to be one of the most specific and sensitive biomarkers of TCDD
intoxication that allows clinical and epidemiological evaluation of exposure
level at threshold doses. The specific cellular and molecular mechanisms involved
in pathogenesis of chloracne are still unknown. In this review, we summarize the
available clinical data on chloracne and recent progress in understanding the
role of the dioxin-dependent pathway in the control of gene transcription and
discuss molecular and cellular events potentially involved in chloracne
pathogenesis. We propose that the dioxin-induced activation of skin stem cells
and a shift in differentiation commitment of their progeny may represent a major
mechanism of chloracne development.

Pharmacologic doses of nicotinamide in the treatment of inflammatory skin conditions: a review. Niren NM. Cutis. 2006 Jan;77(1 Suppl):11-6.

Various skin disorders with an inflammatory component often have been treated
with steroids and/or oral antibiotics. However, long-term use of these agents has
drawbacks: steroids may induce numerous serious side effects such as
hypertension, immunosuppression, and osteoporosis, and overuse of oral
antibiotics may contribute to the development of bacterial resistance, as well as
to a host of nuisance side effects such as diarrhea, yeast infections, and
photosensitivity. As a result, alternative oral treatments, such as nicotinamide,
have been investigated. During the past 50 years, many clinical reports have
identified nicotinamide as a beneficial agent in the treatment of a variety of
inflammatory skin disorders; what’s more, its exceptional safety profile at
pharmacologic doses makes it a potentially ideal long-term oral therapy for
patients with inflammatory skin diseases. A recent large study evaluating
nicotinamide for the treatment of acne or rosacea has confirmed the potential
benefits of oral nicotinamide as an alternative approach to managing inflammatory
lesions associated with acne vulgaris and acne rosacea. This article reviews the
substantial number of reports published over the past 50 years that document the
clinical utility and safety of oral and topical formulations of nicotinamide for
the treatment of a variety of inflammatory skin conditions.

The mechanisms of action of nicotinamide and zinc in inflammatory skin disease. Fivenson DP. Cutis. 2006 Jan;77(1 Suppl):5-10.

Nicotinamide (niacinamide), a physiologically active form of niacin (nicotinic
acid), in combination with zinc is being assessed in clinical studies for the
treatment of inflammatory skin diseases such as acne vulgaris and bullous
pemphigoid. The basis for these investigations is the variety of potential
mechanisms of action of nicotinamide and zinc, including an anti-inflammatory
effect via inhibition of leukocyte chemotaxis, lysosomal enzyme release,
lymphocytic transformation, mast cell degranulation, bacteriostatic effect
against Propionibacterium acnes, inhibition of vasoactive amines, preservation of
intracellular coenzyme homeostasis, and decreased sebum production. Other
possible mechanisms involve suppression of vascular permeability and inflammatory
cell accumulation, as well as protection against DNA damage. The goal of this
paper is to review the pathophysiology of inflammatory skin diseases and discuss
the role, mechanisms of action, and safety of nicotinamide and zinc as
therapeutic options for these disorders.

The pH of the skin surface and its impact on the barrier function. Schmid-Wendtner MH, Korting HC. Skin Pharmacol Physiol. 2006;19(6):296-302. Epub 2006 Jul 19.

The ‘acid mantle’ of the stratum corneum seems to be important for both
permeability barrier formation and cutaneous antimicrobial defense. However, the
origin of the acidic pH, measurable on the skin surface, remains conjectural.
Passive and active influencing factors have been proposed, e.g. eccrine and
sebaceous secretions as well as proton pumps. In recent years, numerous
investigations have been published focusing on the changes in the pH of the
deeper layers of the stratum corneum, as well as on the influence of
physiological and pathological factors. The pH of the skin follows a sharp
gradient across the stratum corneum, which is suspected to be important in
controlling enzymatic activities and skin renewal. The skin pH is affected by a
great number of endogenous factors, e.g. skin moisture, sweat, sebum, anatomic
site, genetic predisposition and age. In addition, exogenous factors like
detergents, application of cosmetic products, occlusive dressings as well as
topical antibiotics may influence the skin pH. Changes in the pH are reported to
play a role in the pathogenesis of skin diseases like irritant contact
dermatitis, atopic dermatitis, ichthyosis, acne vulgaris and Candida albicans
infections. Therefore, the use of skin cleansing agents, especially synthetic
detergents with a pH of about 5.5, may be of relevance in the prevention and
treatment of those skin diseases.

Isotretinoin and the controversy of psychiatric adverse effects. Strahan JE, Raimer S. Int J Dermatol. 2006 Jul;45(7):789-99.

Isotretinoin is a synthetic oral retinoid that has great efficacy against severe,
recalcitrant, nodulocystic acne. Since its introduction to the market, it has
been associated with a variety of adverse psychiatric effects, including
depression, psychosis, mood swings, violent behavior, suicide, and suicide
attempts. A MEDLINE review was performed to compile all case reports, case
series, adverse drug event reportings, and prospective and retrospective studies
relating psychiatric adverse events to isotretinoin. In addition, literature
linking a biological mechanism for psychiatric adverse events to retinoid
signaling pathways was also reviewed. Although a variety of anecdotal and
epidemiologic studies are available, the overall lack of concrete scientific data
limits any conclusion that can be drawn about a causal relationship between
istotretinoin and psychiatric adverse events. Several lines of evidence link
retinoid signaling to theorized psychiatric pathogenesis, but are limited in
their applicability to adult neurophysiology.

Pharmacokinetics and pharmacodynamics of nonsteroidal androgen receptor ligands. Gao W, Kim J, Dalton JT. Pharm Res. 2006 Aug;23(8):1641-58.

Testosterone and structurally related anabolic steroids have been used to treat
hypogonadism, muscle wasting, osteoporosis, male contraception, cancer cachexia,
anemia, and hormone replacement therapy in aging men or age-related frailty;
while antiandrogens may be useful for treatment of conditions like acne, alopecia
(male-pattern baldness), hirsutism, benign prostatic hyperplasia (BPH) and
prostate cancer. However, the undesirable physicochemical and pharmacokinetic
properties of steroidal androgen receptor (AR) ligands limited their clinical
use. Nonsteroidal AR ligands with improved pharmacological and pharmacokinetic
properties have been developed to overcome these problems. This review focuses on
the pharmacokinetics, metabolism, and pharmacology of clinically used and
emerging nonsteroidal AR ligands, including antagonists, agonists, and selective
androgen receptor modulators.

Dermatology of androgen-related disorders. Essah PA, Wickham EP 3rd, Nunley JR, Nestler JE. Clin Dermatol. 2006 Jul-Aug;24(4):289-98.

Hyperandrogenism in women can be caused by various conditions, the most prevalent
of which is polycystic ovary syndrome. Common dermatologic manifestations of
hyperandrogenism include hirsutism, acne, acanthosis nigricans, and androgenic
alopecia. Hirsute women often have increased activity of 5 alpha-reductase, the
enzyme that converts the androgen testosterone to its active metabolite, in hair
follicles. Likewise, androgens affect the formation of acne by increasing sebum
production from sebaceous glands in the skin. The diagnosis of polycystic ovary
syndrome includes a complete history, physical examination with emphasis on
evidence of androgen excess, and appropriate laboratory investigation to exclude
other causes of hyperandrogenism. Treatments for the dermatologic conditions of
hyperandrogenism include lifestyle modification, oral contraceptives,
antiandrogens, and insulin-sensitizing medications.

[Acne vulgaris: endocrine aspects] [Article in Dutch] Dekkers OM, Thio BH, Romijn JA, Smit JW. Ned Tijdschr Geneeskd. 2006 Jun 10;150(23):1281-5.

Androgens play an important part in the development of acne vulgaris. Androgen
levels in patients with acne are higher than those in controls and people with
the androgen insensitivity syndrome do not develop acne. Local factors other than
androgen plasma levels, also play a part in the development of acne. The skin
contains enzymes that convert precursor hormones to the more potent androgens
such as testosterone and dihydrotestosterone. Androgen synthesis can therefore be
regulated locally. The effects of androgens on the skin are the result of
circulating androgens and enzyme activity in local tissues and androgen
receptors. Acne is a clinical manifestation of some endocrine diseases. The
polycystic ovary syndrome has the highest prevalence. In women with acne that
persists after puberty, in 10-200% of cases polycystic ovary syndrome is later
diagnosed. The mechanism of hormonal anti-acne therapy may work by blocking the
androgen-production (oestrogens) or by blocking the androgen receptor
(cyproterone, spironolactone).

Acne and acne scarring – the case for active and early intervention. Goodman G. Aust Fam Physician. 2006 Jul;35(7):503-4.

Acne as a disease is so common as to be considered a normal rite of passage, and
costs the community a substantial amount in resources. Yet acne is a devastating
disease striking most adolescents at their most vulnerable time when their life
long self esteem and sense of identity is being developed. This article reviews
the importance of acne to the individual and attempts to make the case for early
and aggressive treatment.

A review of drospirenone for safety and tolerability and effects on endometrial safety and lipid parameters contrasted with medroxyprogesterone acetate, levonorgestrel, and micronized progesterone. Shulman LP. J Womens Health (Larchmt). 2006 Jun;15(5):584-90.

BACKGROUND: Drospirenone, a novel synthetic progestin, possesses characteristics
more like natural progesterone than other synthetic progestins, such as
medroxyprogesterone acetate and levonorgestrel. The antiandrogenic and
antimineralocorticoid properties of drospirenone may, in the context of
menopausal management, provide potential novel benefits in its effect on lipids
and blood pressure while reducing the occurrence of water retention, acne
vulgaris, and hirsutism. METHODS: This review compares safety and tolerability
data from clinical trials of drospirenone, medroxyprogesterone acetate,
levonorgestrel, and micronized progesterone. RESULTS: Results suggest that
drospirenone possesses a generally well-accepted side effect profile and
resembles comparator oral progestogens in conferring endometrial protection with
no significant effect on weight. One study indicates that drospirenone may have a
benign effect on lipid parameters, having been seen to significantly lower total
cholesterol and lowdensity lipoprotein levels while maintaining high-density
lipoprotein and triglyceride levels. Drospirenone also differs from the other
progestogens in lowering blood pressure levels in hypertensive patients while
having a mild blood pressure-lowering effect on nonhypertensive patients.
CONCLUSIONS: Among pharmacological options for menopause management, drospirenone
may provide certain advantages over other progestogens in its effect on risk
factors for cardiovascular disease and, thus, constitutes a useful addition to
the menopausal armamentarium.

Photodynamic therapy in the treatment of microbial infections: basic principles and perspective applications. Jori G, Fabris C, Soncin M, Ferro S, Coppellotti O, Dei D, Fantetti L, Chiti G, Roncucci G. Lasers Surg Med. 2006 Jun;38(5):468-81.

BACKGROUND AND OBJECTIVES: Photodynamic therapy (PDT) appears to be endowed with
several favorable features for the treatment of infections originated by
microbial pathogens, including a broad spectrum of action, the efficient
inactivation of antibiotic-resistant strains, the low mutagenic potential, and
the lack of selection of photoresistant microbial cells. Therefore, intensive
studies are being pursued in order to define the scope and field of application
of this approach. RESULTS: Optimal cytocidal activity against a large variety of
bacterial, fungal, and protozoan pathogens has been found to be typical of
photosensitizers that are positively charged at physiological pH values (e.g.,
for the presence of quaternarized amino groups or the association with polylysine
moieties) and are characterized by a moderate hydrophobicity (n-octanol/water
partition coefficient around 10). These photosensitizers in a micromolar
concentration can induce a >4-5 log decrease in the microbial population after
incubation times as short as 5-10 minutes and irradiation under mild experimental
conditions, such as fluence-rates around 50 mW/cm2 and irradiation times shorter
than 15 minutes. CONCLUSIONS: PDT appears to represent an efficacious alternative
modality for the treatment of localized microbial infections through the in situ
application of the photosensitizer followed by irradiation of the
photosensitizer-loaded infected area. Proposed clinical fields of interest of
antimicrobial PDT include the treatment of chronic ulcers, infected burns, acne
vulgaris, and a variety of oral infections. Copyright 2006 Wiley-Liss, Inc.

An adolescent girl with tuberous sclerosis complex and acne. Keri JE, Avashia N. Pediatr Ann. 2006 Jun;35(6):433-5.

Management of truncal acne vulgaris: current perspectives on treatment. Del Rosso JQ. Cutis. 2006 May;77(5):285-9.

Acne vulgaris is one of the most common disorders encountered by dermatologists
in the clinical setting. Although it is well recognized that the back and chest
may be affected in many patients, little data exist regarding the prevalence,
grading, and treatment of truncal acne vulgaris. Results of clinical studies
suggest that as with facial acne vulgaris, combination therapy is optimal. This
article discusses clinical challenges related to the management of truncal acne
vulgaris, a system for rating disease severity, and recommendations regarding the
use of topical and systemic therapies.

Prevention of diabetes and cardiovascular disease in women with PCOS: treatment with insulin sensitizers. Sharma ST, Nestler JE. Best Pract Res Clin Endocrinol Metab. 2006 Jun;20(2):245-60.

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory
infertility in United States, affecting 6-10% of females in the reproductive age
group. Recent studies have shown that insulin resistance plays an important role
in the pathogenesis of PCOS. Traditionally, management of PCOS consisted mainly
of ovulation induction, treatment of acne and hirsutism, and prevention of
endometrial cancer. However, with mounting evidence showing that PCOS is
associated with dysmetabolic syndrome and an increased risk for developing
diabetes and heart disease, this can no longer be our sole focus. Current data
support a strong recommendation that women with PCOS should undergo comprehensive
evaluation for diabetes and recognized cardiovascular risk factors and receive
appropriate treatment as needed. Lifestyle modifications remain the first-line
therapy for all obese women with PCOS. However, many obese women with PCOS find
weight loss difficult to achieve and maintain, and this is not an option for lean
women with PCOS. For these reasons, insulin-sensitizing drugs are proving to be a
promising and unique therapeutic option for chronic treatment of PCOS.

Treatment of hirsutism and acne in hyperandrogenism. Moghetti P, Toscano V. Best Pract Res Clin Endocrinol Metab. 2006 Jun;20(2):221-34.

Hirsutism and acne are common and highly distressing complaints in women with
polycystic ovary syndrome (PCOS). Drugs are only partially effective on
terminalized hairs, and removal of these hairs is usually required. Therefore,
management of hirsutism is generally based upon a dual approach: a
pharmacological therapy to reduce androgen secretion and/or androgen action, and
removal of terminal hair already present. Ovarian suppression of androgen
secretion with oral contraceptives is widely used in these women, but its
efficacy appears limited. The most effective medical therapy for hirsutism is by
anti-androgen drugs. Electrolysis and laser photothermolysis are considered the
most effective cosmetic procedures, although the effects of these methods should
not be considered permanent. Acne may be treated with different tools, according
to the severity of the condition and other characteristics of the patient. These
tools include topical and systemic retinoids and antibiotics, topical
antibacterial agents, androgen suppression by oral contraceptives, and
anti-androgen drugs.

[Metabolic PPAR nuclear receptors and skin] [Article in Czech] Svacina S. Vnitr Lek. 2006 May;52(5):451-3.

Activators of metabolic PPAR receptors are used in diabetology and lipidology.
Many substance influancing PPAR (beta/delta) are in research. These substances
will be perhaps used in obesitology and in atherosclerosis treatment. Much
quicker is approaching the use in dermatology. The effect of receptor stimulation
will be used in wound healing and in the treatment of allergic and proliferative
diseases. Some realeted substancies influencing heterodimers with RXR or RAR
receptors are used in the treatment of acne and skin lymfomas. Dermatology will
be after internal medicine the second field where influencing of PPAR receptors
will be very important.

Extraprostatic complications of testosterone replacement therapy. Volpi R, Coiro V, Chiodera P, Saccani-Jotti G, Delsignore R. J Endocrinol Invest. 2005;28(11 Suppl Proceedings):75-7.

Testosterone therapy has been reported to be useful in the treatment of
hypogonadism and partial androgen deficiency of the aging male (PADAM) syndrome.
Testosterone administration is needed in order to maintain secondary sexual
characteristics, muscle mass, bone mineral density, cognitive function and sexual
drive. Newer testosterone-containing compounds, particularly gel preparations,
are known to produce more stable circulating testosterone levels than
im-administered drugs, with scarce side-effects and good patient compliance. All
patients treated with testosterone must undergo a careful follow-up to prevent
the development of the major side effects, such as sleep-apnea, erythrocytosis,
cardiovascular diseases and the alterations of hepatic function and plasma lipid
concentrations.

Hereditary auto-inflammatory disorders and biologics. Church LD, Churchman SM, Hawkins PN, McDermott MF. Springer Semin Immunopathol. 2006 Jun;27(4):494-508. Epub 2006 May 4.

The term auto-inflammatory disorders has been coined to describe a group of
conditions characterized by spontaneously relapsing and remitting bouts of
systemic inflammation without apparent involvement of antigen-specific T cells or
significant production of auto-antibodies. The hereditary periodic fever
syndromes are considered as the prototypic auto-inflammatory diseases, and
genetic studies have yielded important new insights into innate immunity. DNA
analysis has greatly enhanced the clinical characterization of these conditions,
and elucidation of their molecular aetiopathogenesis has suggested that therapies
may be aimed at specific targets within the immune cascade. The availability of
biologic response modifiers such as inhibitors of tumour necrosis factor (TNF)
and interleukin-1beta has greatly improved the outlook for some of these
disorders, although effective therapies remain elusive in patients with certain
conditions, including hyperimmunoglobulinaemia-D with periodic fever syndrome
(HIDS) and a proportion of those with TNF-receptor associated periodic syndrome
(TRAPS). Indeed, outstanding challenges and the unique potential to further
elucidate molecular mechanisms in innate immunity are illustrated by the dashed
early hope that TNF blockade would be a panacea for TRAPS: not only is etanercept
(Enbrel) ineffective in some cases, but there are anecdotal reports of this
condition being greatly exacerbated by infliximab (Remicade).

Anti-EGFR mechanism of action: antitumor effect and underlying cause of adverse events. Lenz HJ. Oncology (Williston Park). 2006 Apr;20(5 Suppl 2):5-13.

Overexpression of the epidermal growth factor receptor (EGFR) is correlated with
poor prognosis in many human cancers. Two main classes of anticancer agents
affect the EGFR: those targeting the extracellular ligand-binding domain and
those that block the intracellular tyrosine kinase (TK) domain. Cetuximab
(Erbitux) is a mouse/human chimeric monoclonal antibody that targets the
ligand-binding domain of the EGFR, whereas erlotinib (Tarceva) and gefitinib
(Iressa) are small-molecule TK inhibitors. Common toxicities of agents targeting
the EGFR differ from those associated with traditional chemotherapy. Given the
common pathway through which these agents work, some adverse events are similar.
Many patients treated with these agents develop an acne-like rash on the face and
upper body, most likely related to keratinocyte alterations and hair follicle
proliferation and maturation. Although clinical manifestation of this reaction
closely resembles acne vulgaris, the histology is more similar to infectious
folliculitis. Other adverse events appear to be related to a drug class or
individual agent. For example, interstitial lung disease is a rare but
potentially fatal reaction that has been reported with gefitinib. Hypomagnesemia
reported in association with cetuximab may be related to EGFR blockade in the
kidney. Anaphylactic or anaphylactoid infusion reactions are also seen with
cetuximab, as with other monoclonal antibodies.

Eosinophilic folliculitis in HIV-infected women: case series and review. Parker SR, Parker DC, McCall CO. Am J Clin Dermatol. 2006;7(3):193-200.

BACKGROUND AND OBJECTIVE: Dermatologic conditions are often presenting signs of
HIV infection and may be the sole cause of morbidity in patients who have
otherwise stable HIV disease. Eosinophilic folliculitis is a pruritic, follicular
eruption that typically manifests late in the course of HIV infection. Most
published reports of eosinophilic folliculitis have been in HIV-infected men. In
those reports, a characteristic truncal distribution was present, with
involvement of the head, neck, and upper extremities commonly seen as well. The
objective of this study was to better characterize the presentation of
eosinophilic folliculitis in women. METHODS: We conducted a retrospective chart
review of six HIV-seropositive women with eosinophilic folliculitis previously
seen in our dermatology clinics. We also reviewed the literature for cases of
eosinophilic folliculitis in women and for clinical and therapeutic aspects of
the condition, particularly in women. RESULTS: In our case series, we found that
eosinophilic folliculitis in women may predominantly affect the face and mimic
acne excoriée. A review of the literature of HIV-associated eosinophilic
folliculitis in women supports these findings. Regarding treatment, many
therapies are available, but none is uniformly effective. CONCLUSION: Given the
dramatic rise in the incidence of HIV infection in women, who now represent
nearly 50% of adults living worldwide with HIV/AIDS, a heightened awareness of
HIV-related dermatoses in women is essential. HIV-associated eosinophilic
folliculitis should be considered in the differential diagnosis of chronic,
pruritic, papular facial eruptions in females.

Development potential of rifalazil and other benzoxazinorifamycins. Rothstein DM, Shalish C, Murphy CK, Sternlicht A, Campbell LA. Expert Opin Investig Drugs. 2006 Jun;15(6):603-23.

Rifalazil and other benzoxazinorifamycins (new chemical entities [NCEs]) are
rifamycins that contain a distinct planar benzoxazine ring. Rifalazil has
excellent antibacterial activity, high intracellular levels and high tissue
penetration, which are attributes that favour its use in treating diseases caused
by the obligate intracellular pathogens of the genus Chlamydia. Recent studies
have shown that rifalazil has efficacy in the treatment of human sexually
transmitted disease caused by Chlamydia trachomatis. The extraordinary potency of
rifalazil and other NCEs, such as ABI-0043, extends to the related microorganism,
C. pneumoniae, a respiratory pathogen that can disseminate and persist
chronically in the vasculature, resulting in increased plaque formation in animal
studies. A pivotal clinical trial with rifalazil has been initiated for the
treatment of peripheral arterial disease. Other opportunities include gastric
ulcer disease caused by Helicobacter pylori and antibiotic-associated colitis
caused by infection with Clostridium difficile in the colon. The NCEs could prove
to be valuable as follow-on compounds in these indications, as rifampin
replacements in antibacterial combination therapy or as stand-alone topical
antibacterials (e.g., to treat acne). Neither rifalazil nor NCEs appear to induce
the cytochrome P450 3A4, an attribute of rifampin that can result in adverse
events due to drug-drug interactions.

Insulin-sensitizing agents in polycystic ovary syndrome. Pasquali R, Gambineri A. Eur J Endocrinol. 2006 Jun;154(6):763-75.

Insulin-sensitizing agents have been recently proposed as the therapy of choice
for polycystic ovary syndrome (PCOS), since insulin resistance and associated
hyperinsulinemia are recognized as important pathogenetic factors of the
syndrome. Moreover, since almost all obese PCOS women and more than half of those
of normal weight are insulin resistant, and therefore present some degree of
hyperinsulinemia, the use of insulin sensitizers should be suggested in most
patients with PCOS. Insulin sensitizer treatment has been associated with a
reduction in serum androgen levels and gonadotropins, and with an improvement in
serum lipids and in prothrombotic factor plasminogen-activator inhibitor type 1,
whatever the insulin sensitizer used. This therapy has also been associated with
a decrease in hirsutism and acne, and with a regulation of menses and an
improvement of ovulation and fertility. Notable improvements in all these
parameters have also been described after a change in lifestyle approach,
particularly in the presence of obesity. Lifestyle interventions should therefore
be combined with insulin sensitizers in PCOS when obesity is present.

Testosterone treatments: why, when, and how? Margo K, Winn R. Am Fam Physician. 2006 May 1;73(9):1591-8.

Testosterone treatment is controversial for men and even more so for women.
Although long-term outcome data are not available, prescriptions for testosterone
are becoming more common. Testosterone is used primarily to treat symptoms of
sexual dysfunction in men and women and hot flashes in women. Potential benefits
include improved libido, increased bone mass, and increased sense of well-being.
In individuals with human immunodeficiency virus infection or other chronic
diseases, testosterone has been shown to improve mood and energy levels, even in
patients with normal testosterone levels. Testosterone can be administered by
injection, patch, topical gel, pill, or implant. Side effects in men include
polycythemia and acne. Side effects in women include acne, hepatotoxicity, and
virilization and usually only occur when testosterone is used in supraphysiologic
doses. Long-term studies of the effects of testosterone on prostate cancer,
breast cancer, and heart disease have not been completed. Mammograms and
monitoring of prostate-specific antigen, hematocrit, and lipid levels are
recommended for patients taking testosterone.

Facial edema induced by isotretinoin use: a case and a review of the side effects of isotretinoin. Scheinfeld N, Bangalore S. J Drugs Dermatol. 2006 May;5(5):467-8.

Isotretinoin (13-cis-retinoic acid) is a retinoid that is used to treat cystic
acne, comedonal acne, and other diseases. For the treatment of acne, isotretinoin
is dosed at 0.5 to 2 mg/kg daily for 5 months with a target total dose of
approximately 120 mg/kg. Its most common side effects are mucocutaneous and
ocular in nature (ie, cheilitis, ocular sicca, and decreased dark adaptation). It
can also cause xerosis. Patients should be made aware of these side effects
before taking isotretinoin and also that utilization of moisturizers and eye
drops can help to mitigate such side effects. Sometimes, however, the dose of
isotretinoin needs to be decreased to reduce the induction of side effects.
Isotretinoin’s most significant side effect is the induction of birth defects if
a fetus is exposed to isotretinoin, which is pregnancy category X. Isotretinoin
should be used with 2 forms of birth control by fecund women. It can rarely
increase serum levels of triglycerides, which can, if very elevated, be related
to the development of pancreatitis and xanthomas. Isotretinoin’s well-documented
but rarer side effects include intracranial hypertension. It can induce bony
changes. A review of the literature demonstrates that isotretinoin is not linked
to depression and suicide. Facial swelling has been linked to isotretinoin use in
3 previous case reports. We note herein the first case of facial swelling that
occurred in an acne patient being treated with isotretinoin who at the time the
swelling developed had no cysts, comedones, pustules, or evidence of bacterial
infection. Possible reasons for the patient’s facial swelling include some type
of retinoid induced angioedema, exacerbation of inflammation by isotretinoin, and
isotretinoin induced capillary leak syndrome.

Antiandrogen therapy for skin and hair disease. Harper JC. Dermatol Clin. 2006 Apr;24(2):137-43, v.

Androgen hormones play an important role in common skin and hair conditions
including acne vulgaris, hirsutism, and androgenetic alopecia. Blocking this
androgen effect may lead to significant improvements in these conditions. Several
medications that work through a variety of different mechanisms may be prescribed
safely and effectively as antiandrogen therapies in the dermatology arena.

The utility of benzoyl peroxide in hydrophase base (Brevoxyl) in the treatment of acne vulgaris. Weinberg JM. J Drugs Dermatol. 2006 Apr;5(4):344-9.

Available for more than 5 decades, benzoyl peroxide has been a “workhorse” of
acne therapy. The benefits of this agent include reduction in Propionibacterium
acnes (P. acnes) with decrease in inflammatory lesions, efficacy as both “leave
on” and cleanser formulations and reduced emergence of antibiotic-resistant P.
acnes strains. As the effect of benzoyl peroxide on P. acnes is a direct toxic
effect rather than as a “true” antibiotic, resistance to benzoyl peroxide does
not occur and has never been reported. Benzoyl peroxide in hydrophase base
(Brevoxyl Creamy Washes and Gels) has shown significant efficacy in the treatment
of acne, with lower irritancy than other benzoyl peroxide preparations. It is
felt that the low irritancy of this product is related to a unique delivery
vehicle containing dimethyl isosorbide, which dissolves benzoyl peroxide crystals
on the skin. Clinical studies demonstrating the efficacy and safety of benzoyl
peroxide in hydrophase base will be reviewed.

[Acne therapy with topical benzoyl peroxide, antibiotics and azelaic acid] [Article in German] Worret WI, Fluhr JW. J Dtsch Dermatol Ges. 2006 Apr;4(4):293-300.

Benzoyl peroxide (BPO) was introduced in the treatment of acne in 1934. Despite
the fact that only few randomized trials have been published, BPO is considered
the standard in topical acne treatment. Anaerobic bacteria are reduced by
oxidative mechanisms and the induction of resistant strains is reduced. Topical
formulations are available at concentrations of 2.5, 5, 10 and 20 %. The effect
is dose-dependent, but the irritation increases with higher concentrations.
Usually 5 % BPO is sufficient to control acne grade I-II. Due to its strong
oxidative potential, patients should be advised that BPO may bleach colored and
dark clothing, bedding and even hair. BPO is safe for use in pregnant and
lactating females because it is degraded to benzoic acid. It is a cost-effective
treatment for acne grade I-II. Patients with papulopustular acne grade I-II,
particularly with marked inflammation, show satisfactory improvement with topical
antibiotic treatment. The following compounds are available and effective:
erythromycin, clindamycin and tetracycline (the latter being less frequently
used). A review in 1990 suggested that topical tetracycline was ineffective in
the treatment of acne. Along with eliminating Propionibacterium acnes, the main
mechanism of topical antibiotics is their antiinflammatory effect. All three
penetrate the epidermal barrier well and are similarly efficacious. Randomized
trials have shown that in concentrations of 2-4 %, their effects are comparable
to oral tetracycline and minocycline. Combination therapy with retinoids or
benzoyl peroxide (BPO) increases efficacy. Retinoids increase penetration and
reduce comedones, while topical antibiotics primarily address inflammation. One
side effect of topical antibacterial treatment is an increase in drug-resistant
resident skin flora with gram-negative microorganisms prevailing, which can lead
to gram-negative folliculitis. All three antibiotics fluoresce under black light
which may produce interesting effects in a discotheque. There are two reports of
topical clindamycin causing pseudomembranous colitis after long-term and
widespread usage. Azelaic acid has a predominant antibacterial action, although
it is not considered as an antibiotic in the classical sense. Furthermore, it
possesses a modest comedolytic effect. Burning upon application is common. Since
azelaic acid is naturally present, systemic side effects are not likely to occur,
making it safe for acne treatment during pregnancy and lactation.

Testosterone therapy in premenopausal women. Kalantaridou SN, Calis KA. Semin Reprod Med. 2006 Apr;24(2):106-14.

Testosterone therapy for postmenopausal women and women with surgical menopause,
albeit controversial, is becoming more widespread. However, only limited data are
available to support its use in premenopausal women. Androgens have important
biological roles in young women, influencing bone and muscle mass, mood and
well-being, and libido. Pathophysiological states affecting ovarian and adrenal
function or both may result in androgen deficiency in premenopausal women. Young
women with hypothalamic amenorrhea, premature ovarian failure, oophorectomy,
premenstrual syndrome, acquired immunodeficiency wasting syndrome, adrenal
insufficiency, and hypopituitarism may have testosterone deficiency. Young women
with loss of libido may also have testosterone deficiency. Medications that may
lead to testosterone insufficiency include oral estrogen, oral contraceptives,
and corticosteroids. Testosterone deficiency in young women may be underdiagnosed
because the symptoms generally are nonspecific and the measurement of total and
free testosterone is inaccurate with commonly used techniques. Only a few studies
investigating the effects of testosterone therapy have been performed thus far in
premenopausal women. Long-term trials evaluating safety and effectiveness of
testosterone therapy in premenopausal women are lacking. Common adverse effects
include hirsutism and acne, which reverse with discontinuation of treatment. The
availability of testosterone regimens specifically designed for women is expected
to help maintain testosterone levels within the normal range and clarify whether
the apparent beneficial effects of testosterone therapy are physiological or
pharmacological.

Gefitinib: an adverse effects profile. Cersosimo RJ. Expert Opin Drug Saf. 2006 May;5(3):469-79.

Gefitinib, an epidermal growth factor receptor inhibitor, is currently approved
for use in patients with advanced non-small cell lung cancer who have failed
previous chemotherapy or who are not suitable for chemotherapy in > 30 countries.
The approved dose in patients with non-small cell lung cancer is 250 mg/day. The
most common adverse effects are rash, diarrhoea, acne, dry skin, nausea and
vomiting. Most of the effects are mild-to-moderate in nature and do not require
discontinuation of therapy. The severity of many of these effects is dose-related
with grade 3-4 effects more likely at a dose > 250 mg/day. The most severe
adverse effect is interstitial lung disease (ILD), which occurs in approximately
1% of patients worldwide except for Japan where the incidence of ILD is 2%. ILD
is fatal in approximately one out of three of the cases. The most common adverse
effects associated with chemotherapy, myelosuppression and alopecia, are not
commonly seen with gefitinib monotherapy.

Clinical significance of brand versus generic formulations: focus on oral minocycline. Del Rosso JQ. Cutis. 2006 Mar;77(3):153-6.

Minocycline is an oral antibiotic widely prescribed throughout the world,
primarily for the treatment of acne vulgaris; other uses include the treatment of
rosacea and perioral dermatitis. In the United States, Propionibacterium acnes
resistance is lowest with minocycline compared with other tetracyclines and with
erythromycin. The availability of generic formulations of minocycline has created
confusion regarding the clinical significance of brand versus generic minocycline
products. This article reviews available data on minocycline use for acne
vulgaris and discusses a patented brand of minocycline versus generic
formulations, including evaluations of pharmacologic activity and safety.

Assessing quality of life in patients with acne vulgaris: implications for treatment. Dréno B. Am J Clin Dermatol. 2006;7(2):99-106.

Diagnosing acne is easy. However, treatment must be adapted to the type and
severity of acne, and must also take into account the impact of acne on patients’
quality of life. As there is not always a correlation between the severity of
acne and its impact on quality of life, it can be helpful for the dermatologist
to use a quality of life scale to determine the psychological impact of acne on
patients. Either global scales or specific scales for acne can be used. This
article reviews the different scales used for evaluation of quality of life in
patients with acne.Consideration of specific scales suggests that the Acne
Disability Index/Cardiff Acne Disability Index is the easiest scale to use in
routine dermatology practice. The Acne Quality of Life scale is particularly
useful for evaluating anxiety and depression. The Acne-Specific Quality of Life
questionnaire has been mainly validated in adult acne. The Assessment of the
Psychological and Social Effects of Acne scale has yet to be validated. Clinical
trials indicate that use of global and specific scales together has complementary
benefits.In the management of acne, evaluation of quality of life may help to
detect depression in teenagers. It may also help to enhance adherence to
treatment, which is a crucial factor for success. Finally, there are now
validated quality of life scales that are easy to use during patient
consultations (taking <2 minutes to complete) by clinicians wishing to evaluate
quality of life in patients with acne.

Acne: improving skin and self-esteem. Keri JE. Pediatr Ann. 2006 Mar;35(3):174-9.

Many safe and effective treatments are available to the acne sufferer. The
clinician is encouraged to offer treatment to the adolescent with a face full of
pimples, even if not asked for by the patient, as psychosocial underpinnings may
be present but not obvious on examination. Obvious physical benefits will result,
but psychosocial improvements also may occur.

An overview of oral contraceptives: mechanism of action and clinical use. Frye CA. Neurology. 2006 Mar 28;66(6 Suppl 3):S29-36.

Hormonal contraception is available in oral contraceptive pills and in newer
formulations, including the transdermal patch, the vaginal ring, subcutaneous
implants, and IM injections. Prevention of pregnancy is achieved by inhibiting
ovulation, fertilization, and/or implantation of an egg. Hormonal contraception
provides effective, tolerable, and reversible prevention of pregnancy. Efficacy
and safety profiles are similar for different formulations and administration
routes. Lowest expected failure (i.e., method failure) rates for hormonal
contraceptives, regardless of formulation, are <2%. Typical failure rates for
oral formulations range from <3% to 5% due to failures in compliance. The most
commonly reported adverse effects are weight gain, nausea, variations in
menstrual flow, breast changes such as tenderness, discomfort, or swelling,
depression or mood disturbances, decreased sexual desire or response, and acne.
Rare but serious potential effects include cardiovascular diseases, such as
stroke, and an increased risk for breast cancer, liver tumors, and gallbladder
disease. Hormonal contraceptive use should be avoided in women at risk for blood
clots, by heavy smokers, and in women with breast or other cancers. Use of
hormonal contraception in adolescents requires special consideration, in part
because of decreased compliance.

Fluorescence diagnosis and photodynamic therapy in dermatology from experimental state to clinic standard methods. Fritsch C, Ruzicka T. J Environ Pathol Toxicol Oncol. 2006;25(1-2):425-39.

The role of photodynamic therapy (PDT) in the treatment of in situ neoplasias and
tumors of the skin is steadily increasing. An intratumoral enriched
photosensitizer and its activation by light are the principles of photodynamic
action. Aminolevulinic acid (ALA) has been shown to be the drug with most
experimental and clinical use in the past. The highest efficacy with most
selectivity in topical PDT is postulated for methyl aminolevulinate or methyl
aminooxopenoat (MAL, MAOP, Metvix). For solar keratoses, topical PDT using MAL is
already considered to be the treatment of choice. Epithelial skin tumors such as
basal cell carcinomas also respond very well, however, a debulking procedure of
the exophytic tumor tissue is an absolute prerequisite to a successful cure. In
addition to functioning as a novel therapeutic tool, photodynamic sensitization
of skin cancer cells is increasingly used for fluorescence diagnosis (FD) (also
known as photodynamic diagnosis or PDD). The fluorescence of induced porphyrins
is effective in detecting and delineating neoplastic skin areas. Future
approaches of FD and PDT are nontumoral applications, especially psoriasis,
viral-induced diseases, or acne vulgaris. Topical PDT is well tolerated and leads
to excellent aesthetic results with only minor side effects.

The use of topical azelaic acid for common skin disorders other than inflammatory rosacea. Del Rosso JQ. Cutis. 2006 Feb;77(2 Suppl):22-4.

Topical azelaic acid (AzA) is approved for the treatment of acne vulgaris and
inflammatory (papulopustular) rosacea. Because of diverse mechanisms of action
that correlate with potential therapeutic benefit, AzA has been used to treat
several common dermatoses including acne vulgaris, inflammatory rosacea,
erythematotelangiectatic rosacea, perioral dermatitis, melasma, and
postinflammatory hyperpigmentation. This article reviews the therapeutic use of
topical AzA for the treatment of common skin disorders other than the US Food and
Drug Administration (FDA)-approved indications of acne vulgaris and inflammatory
rosacea.

The evolution of azelaic acid. Fleischer AB Jr. Cutis. 2006 Feb;77(2 Suppl):4-6.

Azelaic acid (AzA) is a naturally occurring dicarboxylic acid that has a long and
complex history in the treatment of skin disorders. We summarize research on AzA
from the past 25 years and follow its progress from a treatment of
hyperpigmentation to a therapy for acne vulgaris and inflammatory
(papulopustular) rosacea.

Anti-inflammatory activity of cationic peptides: application to the treatment of acne vulgaris. Marta Guarna M, Coulson R, Rubinchik E. FEMS Microbiol Lett. 2006 Apr;257(1):1-6.

Cationic antimicrobial peptides exhibit potent antimicrobial activity against
clinically relevant microorganisms including Propionibacterium acnes. Recent
studies showed that, in addition to the antimicrobial activity, these peptides
can exhibit an anti-inflammatory effect. These properties make cationic peptides
attractive drug candidates for the treatment of acne vulgaris, a disease with
both bacterial and inflammatory components. This review focuses on the
anti-inflammatory activity of cationic antimicrobial peptides and its application
for the treatment of acne vulgaris. The anti-inflammatory activity of cationic
peptides in acne vulgaris can be explained by their ability to both bind
proinflammatory bacterial factors (e.g. lipoteichoic acid), sequestering them
from the site of inflammation, and to inhibit the secretion of proinflammatory
cytokines (e.g. tumor necrosis factor-alpha, IL-1) by host cells. These
anti-inflammatory effects combined with potent antimicrobial activity may
translate into a novel therapeutic option for acne vulgaris.

A review of lasers and light sources in the treatment of acne vulgaris. Ortiz A, Van Vliet M, Lask GP, Yamauchi PS. J Cosmet Laser Ther. 2005 Jun;7(2):69-75.

There are various treatment modalities for acne vulgaris including topical and
oral therapy as well as microdermabrasion and chemical peels. Recently, there has
been an emergence of novel laser and light sources as a means for treating acne
vulgaris. This article will review the advances of laser and light sources in the
treatment of acne vulgaris.

Retinoic acid metabolism blocking agents (RAMBAs) for treatment of cancer and dermatological diseases. Njar VC, Gediya L, Purushottamachar P, Chopra P, Vasaitis TS, Khandelwal A, Mehta J, Huynh C, Belosay A, Patel J. Bioorg Med Chem. 2006 Jul 1;14(13):4323-40. Epub 2006 Mar 10.

The naturally occurring retinoids and their synthetic analogs play a key role in
differentiation, proliferation, and apoptosis, and their use/potential in
oncology, dermatology and a variety of diseases are well documented. This review
focuses on the role of all-trans-retinoic acid (ATRA), the principal endogenous
metabolite of vitamin A (retinol) and its metabolism in oncology and dermatology.
ATRA has been used successfully in differentiated therapy of acute promyelocytic
leukemia, skin cancer, Kaposi's sarcoma, and cutaneous T-cell lymphoma, and also
in the treatment of acne and psoriasis. However, its usefulness is limited by the
rapid emergence of acquired ATRA resistance involving multifactoral mechanisms. A
key mechanism of resistance involves ATRA-induced catabolism of ATRA. Thus, a
novel strategy to overcome the limitation associated with exogenous ATRA therapy
has been to modulate and/or increase the levels of endogenous ATRA by inhibiting
the cytochrome P450-dependent ATRA-4-hydroxylase enzymes (particularly CYP26s)
responsible for ATRA metabolism. These inhibitors are also referred to as
retinoic acid metabolism blocking agents (RAMBAs). This review highlights
development in the design, synthesis, and evaluation of RAMBAs. Major emphasis is
given to liarozole, the most studied and only RAMBA in clinical use and also the
new RAMBAs in development and with clinical potential.

Cosmetic aspects of pregnancy. Nussbaum R, Benedetto AV. Clin Dermatol. 2006 Mar-Apr;24(2):133-41.

There are a vast number of changes to the female body that occur during
pregnancy, to which any pregnant woman will attest. The changes, although
considered, for the most part, physiological and not pathological, are quite
distressing to many women. This chapter serves to review those changes and
comment on their physiological origins. Most of these changes can be definitively
or inferentially linked to the dramatic hormonal changes that take place to
support a pregnancy. Comments are also made about treatment as they pertain to
pregnant women. In addition, a brief discussion about performing cosmetic
procedures during pregnancy is included.

The use of photodynamic therapy in dermatology: results of a consensus conference. Nestor MS, Gold MH, Kauvar AN, Taub AF, Geronemus RG, Ritvo EC, Goldman MP, Gilbert DJ, Richey DF, Alster TS, Anderson RR, Bank DE, Carruthers A, Carruthers J, Goldberg DJ, Hanke CW, Lowe NJ, Pariser DM, Rigel DS, Robins P, Spencer JM, Zelickson BD. J Drugs Dermatol. 2006 Feb;5(2):140-54.

Photodynamic therapy (PDT) has significant promise in improving outcomes of
patients with a variety of cutaneous conditions. A group of experts met to review
the principles, indications, and clinical benefits of PDT with 5-aminolevulinic
acid (ALA). They also reviewed PDT with methyl aminolevulinate. The experts
established consensus statements for pretreatment, posttreatment, ALA contact
time, light sources, and numbers of sessions associated with ALA PDT for actinic
keratosis and superficial basal cell carcinoma, photorejuvenation and cosmetic
enhancement, acne, sebaceous skin, rosacea, and rhinophyma. They based consensus
recommendations on their clinical experience and the medical literature. They
also suggested future applications of ALA PDT. Experts concluded that ALA PDT is
a safe and effective modality for the treatment of conditions commonly
encountered in dermatology. Since downtime is minimal, the technique is suitable
for patients of all ages and lifestyles. Appropriate light sources are available
in many dermatology offices. The expanding clinical and financial benefits of PDT
justify the purchase of an appropriate light source.

[Sebaceous glands as transporters of vitamin E] [Article in German] Ekanayake-Mudiyanselage S, Thiele J. Hautarzt. 2006 Apr;57(4):291-6.

Human sebum is produced by sebaceous glands and reaches the skin surface via
secretion through the hair shaft. There is experimental evidence that the
sebaceous glands and sebum serve as a transport mechanism taking the lipophilic
antioxidant vitamin E from the blood to the skin surface. The highest levels of
vitamin E are found in the sebum and in the skin lipid film in sebum-rich areas
such as facial skin. Recent studies indicate that daily oral supplementation of
moderate doses of alpha-tocopherol for at least 3 weeks leads to significant
increases of vitamin E levels in human skin sites with a high density of
sebaceous glands, such as the face. Thus, the potential photoprotective and
antioxidants effects of oral vitamin E, as well as possibly other antioxidants,
are site-dependent. These findings should be considered when designing clinical
studies to assess the efficacy of oral antioxidants against oxidative stress in
the skin.

Topical and oral CAM in acne: a review of the empirical evidence and a consideration of its context. Magin PJ, Adams J, Pond CD, Smith W. Complement Ther Med. 2006 Mar;14(1):62-76. Epub 2005 Dec 15.

INTRODUCTION: Acne is one of the commonest diseases to afflict humanity.
Anecdotally, the use of CAM in acne is widespread. In this review the empirical
evidence for the efficacy of CAM modalities is examined and the context for their
use discussed. METHODS: Searches were made of the MEDLINE, EMBASE, AMED (Allied
and Complementary Medicines), Cochrane, and DARE databases using the search terms
"acne" and "acne vulgaris" together with "alternative" and "complementary".
RESULTS: The identified studies examined a broad range of CAM modalities but were
of generally poor methodological quality. Evidence suggests that many of these
therapies are biologically plausible. DISCUSSION AND CONCLUSION: Complementary
therapies in acne should be viewed in a wider context than that of the very
limited empiric evidence base that exists for their use. Further rigorously
conducted trials should be conducted to define efficacy and adverse effect
profiles of currently used CAM acne therapies.

Laser and light therapies for acne rosacea. Butterwick KJ, Butterwick LS, Han A. J Drugs Dermatol. 2006 Jan;5(1):35-9.

Acne rosacea is a multifactorial, somewhat mercurial disorder that can be a
challenge to control with standard pharmacologic agents. Laser and light sources
have been increasingly utilized, particularly for control of the generalized
erythema, flushing, and telangiectasia of rosacea. This paper will review the
clinical studies presented in the literature specifically treating patients with
rosacea. Long-pulsed dye lasers and intense pulsed light devices can offer
patients effective treatment without the purpura of short-pulsed dye lasers.
Long-term efficacy has not been studied but maintenance therapy may be necessary
to control the vascular manifestations of this disease.

Rosacea: clinical presentation and pathophysiology. Diamantis S, Waldorf HA. J Drugs Dermatol. 2006 Jan;5(1):8-12.

Acne rosacea is one of the most common diagnoses seen in the clinical
dermatologic practice. The classic presentation of rosacea, acneiform papules,
and pustules on a background of telangiectasia, is often easily identified by
primary care physicians, patients, or their similarly afflicted friends or family
members. However, rosacea actually represents a spectrum of disease from chronic
skin hypersensitivity and flushing to rhinophyma. Although the pathogenesis of
rosacea remains unknown, it is important to understand its various presentations
and possible etiologies prior to developing individualized treatment protocols.

Advances in deep chemical peels. Landau M. Dermatol Nurs. 2005 Dec;17(6):438-41.

Deep chemical peels have been used in dermatology for more than a century and
their popularity increased dramatically during the past decade. The main
indications for this procedure include photoaging, perioral wrinkling, acne
scars, and precancerous skin lesions. Deep chemical peel is a nonsurgical
procedure that compares favorably with other surgical and nonsurgical procedures
for skin rejuvenation, such as surgical face-lifting, dermabrasion, and laser
resurfacing. It is a safe and cost-effective method that provides significant
results and a high degree of patient satisfaction.

Tetracyclines: nonantibiotic properties and their clinical implications. Sapadin AN, Fleischmajer R. J Am Acad Dermatol. 2006 Feb;54(2):258-65.

Tetracyclines are broad-spectrum antibiotics that act as such at the ribosomal
level where they interfere with protein synthesis. They were first widely
prescribed by dermatologists in the early 1950s when it was discovered that they
were effective as a treatment for acne. More recently, biologic actions affecting
inflammation, proteolysis, angiogenesis, apoptosis, metal chelation,
ionophoresis, and bone metabolism have been researched. The therapeutic effects
of tetracycline and its analogues in various diseases have also been
investigated. These include rosacea, bullous dermatoses, neutrophilic diseases,
pyoderma gangrenosum, sarcoidosis, aortic aneurysms, cancer metastasis,
periodontitis, and autoimmune disorders such as rheumatoid arthritis and
scleroderma. We review the nonantibiotic properties of tetracycline and its
analogues and their potential for clinical application.

[Propionibacterium acnes infective endocarditis. Study of 11 cases and review of literature] [Article in French] Delahaye F, Fol S, Célard M, Vandenesch F, Beaune J, Bozio A, de Gevigney G. Arch Mal Coeur Vaiss. 2005 Dec;98(12):1212-8.

BACKGROUND: Propionibacterium acnes, a gram positive, anaerobic, skin commensal
bacillus, is too often considered a biologic fluid contaminant, of blood cultures
in particular. Its implication has been shown in various infections, including
brain abscess, ocular infections, osteitis, and acne. It is also the cause of
infective endocarditis (IE). METHODS: Retrospective, observational study of 11
patients with P. acnes IE, hospitalised between 1993 and 2001 at the Louis Pradel
Hospital, Lyon-Bron, and review of 20 published cases. RESULTS: P. acnes IE is
rare, though its prevalence is probably underestimated. It is most likely to
affect men (71%), and affects all ages (children 4/31 cases). An entry point,
probably cutaneous, is rarely confirmed. P. acnes IE often develops on valve
prosthesis (42%), and embolisms are common (61%). The infective site is usually
aortic (55%). The often-subtle symptoms and slow growth of the organism in vitro
complicate the diagnosis, which is often made at a late stage, when valvular and
peri-valvular destruction has become major. Despite the high sensitivity of P.
acnes to most antimicrobials, a surgical intervention is very often needed (81%).
The mortality is relatively high (15% to 27%). Examination of pathologic
specimens by polymerase chain reaction increases the sensitivity and speed of its
detection. The identification of P. acnes in a biologic specimen, valvular tissue
in particular, requires a thorough knowledge of the clinical context before
concluding to contamination, and mandates close surveillance of the patient. P.
acnes can be the cause of IE long before it has been detected.

Androgen excess disorders in women: the severe insulin-resistant hyperandrogenic syndrome, HAIR-AN. Rager KM, Omar HA. ScientificWorldJournal. 2006 Jan 24;6:116-21.

HAIR-AN syndrome (hyperandrogenism, insulin resistance, acanthosis nigricans) is
a subset of the polycystic ovary syndrome, where the patients demonstrate severe
insulin resistance. It is theorized that both genetic and environmental factors,
such as obesity, give rise to the development of HAIR-AN. Diagnosis is primarily
clinical, with laboratory values lending further support. Treatment is aimed at
decreasing insulin resistance, regulating ovulation, and decreasing acne,
acanthosis nigricans, and hirsutism.

Laser therapy for acne. Nouri K, Ballard CJ. Clin Dermatol. 2006 Jan-Feb;24(1):26-32.

Considered the most common skin disorder, acne affects millions of people every
year. This multifactorial condition of the pilosebaceous follicle is a
combination of at least four different primary pathogeneses. In recent years,
acne therapies have been improving, becoming more effective, and targeting one or
more of these causes. Many current therapies have drawbacks involving patient
compliance, systemic toxicities, and bacterial resistance. Lasers are now
established options in the armamentarium to treat acne. The 532-nm potassium
titanyl phosphate laser, 585- and 595-nm pulsed dye lasers, 1450-nm diode laser,
and 1540-nm erbium glass laser have been used with variable efficacy. Lasers may
be best used in combination with other therapies to enhance their results.
Photodynamic therapy has been successful with substances such as 5-aminolevulinic
acid and indocyanine green. Lasers remain viable alternatives for people who may
not desire or be able to use topical or systemic formulations. Drawbacks
associated with lasers include potential pain, skin discoloration, and cost of
treatment. Typically, multiple sessions are required to achieve the desired
results, with future maintenance treatments possible to maintain the outcomes.
With additional clinical trials underway, laser treatment of acne will surely
advance and continue to be optimized in the future.

Laser-mediated photodynamic therapy. Alexiades-Armenakas M. Clin Dermatol. 2006 Jan-Feb;24(1):16-25.

Photodynamic therapy (PDT) has evolved since its inception at the beginning of
the 20th century, when it was defined as an oxygen-dependent reaction between a
photosensitizing dye and light. Photosensitizers and light sources have since
been continually optimized for distinct applications and tissues. Systemic
porphyrins, such as hematoporphyrin, were the first photosensitizers to be used,
mostly to treat tumors. The first light sources used were broad-band, noncoherent
lights, such as quartz, xenon, tungsten, or halogen lamps. The wavelengths of
light chosen were based upon the absorption spectrum of porphyrins: blue because
the largest peak is at 400 nm (the Soret band) and red because of its greater
penetration depth but lesser absorption at 650 nm (a Q band). Systemic
photosensitizers caused prolonged photosensitivity, and broad-band light sources
had limitations and side effects. The development of topical photosensitizers,
such as 5-aminolevulinic acid, and the advent of lasers in recent years have
advanced PDT for cutaneous use. In the 1990s, red lasers were applied to PDT
because of their increased skin penetration despite lesser absorption by
porphyrins. Broad-band blue light and red light have been studied extensively,
the former achieving Food and Drug Administration approval in combination with
topical aminolevulinic acid for the treatment of actinic keratosis in 1997. These
lasers and light sources caused significant side effects, such as discomfort,
erythema, crusting, blistering, and dyspigmentation. The recent application of
the long-pulsed pulsed dye laser (595 nm) after topical aminolevulinic acid
greatly minimized side effects without compromising efficacy. Long-pulsed pulsed
dye laser-mediated PDT has since been shown to be effective in treatment of
actinic keratosis, actinic cheilitis, sebaceous hyperplasia, lichen sclerosus,
and, most recently, acne vulgaris. Finally, intense pulsed light sources have
been introduced to PDT for the treatment of photodamage and acne, offering
advantages of versatility in wavelengths and applications.

Acne: current treatment. Yates V. Clin Med. 2005 Nov-Dec;5(6):569-72.

A review on the treatment of acne vulgaris. Layton AM. Int J Clin Pract. 2006 Jan;60(1):64-72.

The following article reviews treatment for acne vulgaris. Selection of therapy
should be based on clinical appearance taking into account lesion type and
severity, as well as identification of acne scarring and the psychosocial
disability caused by the disease.

Low-dose flutamide-metformin therapy for hyperinsulinemic hyperandrogenism in non-obese adolescents and women. Ibáñez L, de Zegher F. Hum Reprod Update. 2006 May-Jun;12(3):243-52. Epub 2006 Jan 11.

Polycystic ovary syndrome (PCOS) is a variable disorder that is characterized in
adolescents and young women by a broad spectrum of anomalies, including
hyperandrogenemia, insulin resistance, dyslipidemia, body adiposity and low-grade
inflammation. At present, there is no approved therapy for PCOS. Recent studies
indicate that a low-dose combination of flutamide (Flu; a generic
androgen-receptor blocker) and metformin (Met; a generic insulin-sensitizer)
normalizes the adolescent PCOS spectrum more than an oral contraceptive (OC); in
young women, the PCOS spectrum was found to be more normalized by OC plus Flu-Met
than by OC alone. Within the pathophysiological cascade of PCOS, Flu-Met seems to
counter upstream anomalies like hyperinsulinemia or hyperandrogenism, thereby
preventing or reversing downstream effects. In contrast, an OC essentially masks
downstream symptoms like hirsutism, acne or irregular menses, whereas the
upstream aberrations remain unaltered or may even be worsened. The available
experience with Flu-Met is limited but promising. We emphasize that Flu-Met may
(as part of its efficacy) induce ovulation but is contra-indicated
post-conception because of potential embryotoxicity; therefore, it seems wise to
combine Flu-Met with an oral or a transdermal oestro-progestagen or with a
non-endocrine method of contraception. May this update prompt further research
into Flu-Met's therapeutic potential in patients with PCOS. Until the
abovementioned effects have been broadly confirmed, Flu-Met should not be
regarded as a standard therapy for widespread clinical practice.

Applications of photosynthetic bacteria for medical fields. Sasaki K, Watanabe M, Suda Y, Ishizuka A, Noparatnaraporn N. J Biosci Bioeng. 2005 Nov;100(5):481-8.

The medical applications of photosynthetic bacteria are summarized.
Photosynthetic bacteria can produce various types of physiological active
substance such as vitamin B(12), ubiquinone (coenzyme Q10), 5-aminolevulinic acid
(ALA), porphyrins and RNA. In particular, photosynthetic bacterial ALA was
commercially applied to cancer diagnosis and treatment. Recently, ALA has been
applied to the treatment of acne vulgaris and the suppression of the inflammatory
response to coronary and iliac injuries. In addition, the recent applications of
RNA from a marine photosynthetic bacterium as a medical supplement for immune
improvement and suppression of infection are described. Furthermore, the feasible
application of a biopolymer consisting of RNA from a photosynthetic bacterium as
a drug delivery system (DDS) to cancer treatment is described.

Adverse effects of topical glucocorticosteroids. Hengge UR, Ruzicka T, Schwartz RA, Cork MJ. J Am Acad Dermatol. 2006 Jan;54(1):1-15; quiz 16-8.

Topical corticosteroids were introduced into medicine about 50 years ago. They
represent a significant milestone in dermatologic therapy. Despite encouragement
to report observed adverse drug reactions, the clinical practice of reporting is
poor and incomplete. Likewise, adverse effects and safety of topical
corticosteroids are neglected in the medical literature. The authors provide an
updated review of their adverse-effect profile. Children are more prone to the
development of systemic reactions to topically applied medication because of
their higher ratio of total body surface area to body weight. Cutaneous adverse
effects occur regularly with prolonged treatment and are dependent on the
chemical nature of the drug, the vehicle, and the location of its application.
The most frequent adverse effects include atrophy, striae, rosacea, perioral
dermatitis, acne, and purpura. Those that occur with lower frequency include
hypertrichosis, pigmentation alterations, delayed wound healing, and exacerbation
of skin infections. Of particular interest is the rate of contact sensitization
against corticosteroids, which is considerably higher than generally believed.
Systemic reactions such as hyperglycemia, glaucoma, and adrenal insufficiency
have also been reported to follow topical application. The authors provide an
updated review of local and systemic adverse effects upon administration of
topical corticosteroids, including the latest FDA report on the safety of such
steroids in children. LEARNING OBJECTIVE: At the completion of this learning
activity, participants should be familiar with topical corticosteroids and their
proper use.

Hirsutism and the variable response of the pilosebaceous unit to androgen. Rosenfield RL. J Investig Dermatol Symp Proc. 2005 Dec;10(3):205-8.

The pilosebaceous unit (PSU) response to androgen is variable. Certain population
of PSU respond to androgen in a distinctive pattern that results in sexual hair
development in some, sebaceous gland development in others. Furthermore, androgen
excess is variably manifest in women as hirsutism, acne vulgaris, seborrhea, or
pattern alopecia. Although sebaceous cells act as intracrine cells, activating
pro-hormones to potent androgens that act within the sebocyte, hair follicle
metabolism predominantly inactivates testosterone. Androgen action in the sexual
hair follicle appears to be mediated by the dermal papilla and possibly, by
inducing expression of a specific keratin, hHa7, in the hair medulla. The data do
not clearly support a relationship between idiopathic hirsutism, the hirsutism
that occurs in the absence of androgen excess, and variations in androgen
mechanism of action. Androgens are prominent among the hormones that modulate the
biological mechanism regulating the hair cycle. However, the basis for the
variable pattern of PSU response to androgen is unclear, as is the basis for the
variable development of hirsutism in response to androgen excess and the
incomplete reversal of hirsutism by anti-androgen treatment. Improved treatment
of hirsutism awaits improved understanding of the nature of the interaction
between androgens and other determinants of hair follicle biology.

Dermatologic manifestations of HIV infection. Maurer TA. Top HIV Med. 2005 Dec-2006 Jan;13(5):149-54.

Although some dermatologic diseases have decreased markedly in frequency in the
potent antiretroviral therapy era, other conditions remain common. Among patients
with low CD4(+) cell counts who are not on or not adherent to antiretroviral
therapy, notable conditions include psoriasis, photodermatitis, prurigo
nodularis, molluscum, and adverse drug reactions. Conditions that remain
relatively common despite adequate antiretroviral therapy include eczema,
xerosis, warts, and Kaposi's sarcoma. Disorders that are associated with immune
reconstitution under potent antiretroviral therapy include acne, staphylococcal
infections, and erythema nodosum. In addition, HIV and hepatitis C virus (HCV)
coinfection is associated with a number of skin disorders.

[Systemic acne therapy] [Article in German] Thielitz A, Gollnick H. J Dtsch Dermatol Ges. 2005 May;3(5):366-78; quiz 379-80, 382.

Treating acne with oral contraceptives: use of lower doses. Huber J, Walch K. Contraception. 2006 Jan;73(1):23-9. Epub 2005 Sep 26.

Oral contraceptives (OCs) have been shown to effectively treat acne. Clinical
trials of various doses of ethinyl estradiol (EE) combined with progestins such
as levonorgestrel, desogestrel, norgestimate, gestodene, cyproterone acetate and
drospirenone in monophasic, triphasic and combiphasic formulations used to treat
acne in women are reviewed here. Open-label and comparative studies beginning in
the 1980s were the first to demonstrate objective and subjective reductions in
the incidence of acne, severity of existing acne and seborrhea.
Placebo-controlled trials have corroborated these findings with a trend toward
effective acne treatment with declining doses of EE. Significant reductions in
total, inflammatory and noninflammatory lesions compared with placebo have been
demonstrated with an OC containing the low dose of 20 microg of EE. Collectively,
these findings support the use of low-dose OCs for the treatment of acne.

Use of lasers and light-based therapies for treatment of acne vulgaris. Mariwalla K, Rohrer TE. Lasers Surg Med. 2005 Dec;37(5):333-42.

Over the last two decades, lasers and light-based therapies have been developed
to treat a wide variety of cutaneous maladies. Given the prevalence and number of
patients who suffer from refractory acne, alternatives to existing care are
constantly sought after. In this review, we discuss the evidence currently
available to justify the use of laser and light-based modalities and conclude
that in combination therapy, such approaches provide a safe and effective
treatment for acne vulgaris. (c) 2005 Wiley-Liss, Inc.

[Adjunctive treatments for acne therapy] [Article in German] Degitz K, Plewig G. J Dtsch Dermatol Ges. 2005 Feb;3(2):92-6.

The mainstays of modern acne therapy include comedolytic, antimicrobial, and
anti-inflammatory substances, as well as antiandrogens. Additionally, traditional
or newly developed therapeutic approaches may be considered, including
pharmacologic (dapsone, zinc) and physical measures (phototherapy, photodynamic
therapy, comedone extraction, abrasives). This article reviews such adjunctive
therapies with regard to efficacy and their roles in acne therapy.

[Molecular action of insulin-sensitizing agents] [Article in Polish] Kacalska O, Krzyczkowska-Sendrakowska M, Milewicz T, Zabińska-Popiela M, Bereza T, Krzysiek-Maczka G, Krzysiek J. Endokrynol Pol. 2005 May-Jun;56(3):308-13.

Atypical endometrial hyperplasia has been associated with progression to
endometrial cancer, the most common genital malignancy. There are multiple risk
factors for endometrial cancer, such as early menarche, exogenous estrogen
exposure, obesity and diabetes. Diabetics have a 3-4 fold relative risk of
endometrial cancer. Also, several studies have demonstrated an association
between insulin resistance and endometrial cancer. There is known the first
description of atypical endometrial hyperplasia resistant to progestogen therapy,
which was subsequently treated with an insulin-sensitizng agent, metformin.
Metformin is a biguanide antihyperglycemic agent used in the treatment of
adult-onset diabetes. Unlike the sulfonylureas, metformin does not act primarily
by increasing insulin secretion. In contrast, metformin lowers the rate of
gluconeogenesis in the presence of insulin. Therefore, it is considered an
insulin-sensitizer. Increased insulin sensitivity may improve the metabolic
effect of insulin and decrease its mitogenic effect by tissue-specific
mechanisms. One explanation for tissue specific differences in insulin binding
and action may be through the relative expression of the insulin receptor (IR)
isoforms. The IR isoforms IR-A and IR-D differ by 12 amino acid residues, owing
to the alternative splicing of exon. The IR-A is predominantly expressed in
malignant tissues and may lead to mitogenic effects within the cell. The relative
expressions of IR-A and IR-B in normal and malignant endometrial tissue is not
known. Besides direct effects on the IR, several additional mechanisms have been
proposed for the mitogenic effect of insulin in endometrial cancer. In addition
to the possible direct mitogenic effects of insulin through the IR-A, insulin
resistance may be associated with alterations in expression of insulin-like
growth factors (IGFs) and the IGF binding proteins (IGFBPs) or may inhibit the
protective effect of progestagens. Binding sites for IGF-1 and IGF-2 have been
confirmed in both normal and malignant endometrium. Binding of IGF-1 is
significantly higher in endometrial cancer compared to normal endometrium. In the
Ishikawa human endometrial cancer cell line IGF-1 was a more potent mitogen than
insulin or IGF-2. Insulin may increase mitogenicity by regulating the expression
of IGFBPs. The IGFBPs are a family of proteins that have both proliferative and
anti-proliferative effects. While all six high-affinity IGFBPs are expressed in
the endometrium, IGFBP-1 is the best characterized. Hyperinsulinemia can decrease
IGFBP-1 even in the presence of progesterone, perhaps inhibiting progesterone's
protective effects. Interestingly, IGFBP-1 was undetectable or minimally
expressed in endometrial cancers. Nestler discussed results of a 6-month
treatment of 100 nonebese women with PCOS, which showed a somewhat greater effect
of metformin than rosiglitazone and no benefit of administering both agents in
combination. Long-term treatment with oral contraceptives decreases endometrial
cancer, with a reduction in serum androgens and a decreases in hirsutism and
acne, but may worsen insulin resistance and lead to deteriration in glucose
tolerance. Insulin sensitizers, on the other hand, should decrease endometrial
hyperplasia by inducing regular menses, but may not be as beneficial in improving
androgen - related symptoms. Note that the Nurses Health Study (NHS) showed
increased risk of diabetes in oral contraceptive users. These considerations may
be related to the finding that women who used oral contraceptives have increased
risk of myocardial infarction. Thus, in view of the particular increase in CVD
risk among women with PCOS, one might be less likely to recommend oral
contraceptives, while insulin sensitizers may be of particular benefit,
decreasing androgens, improving ovulation and fertility, and reducing the risk of
diabetes and CVD. Theoretically, metformin, a treatment which is now widely used
to treat infertile women with PCOS, may have a role in preventing endometrial
hyperstimulation by lowering insulin concentrations and restoring ovulation.
However, the long-term effects of this drug in women with PCOS are not known and
more studies are required before suggesting its use for preventing endometrial
cancer.

Acne, lasers, and light. Ross EV. Adv Dermatol. 2005;21:1-32.

Acne guideline 2005 update. Sinclair W, Jordaan HF; Global Alliance to Improve Outcomes in Acne. S Afr Med J. 2005 Nov;95(11 Pt 2):881-92.

OBJECTIVE: The guidelines on the management of acne vulgaris have been developed
in an attempt to improve the outcomes of acne treatment in South Africa. This
extremely common condition has a major impact on the quality of life of South
African young people and it is expected that if implemented, these guidelines
will play a role in improving this situation. RECOMMENDATIONS: All health care
workers involved in the management of acne should take note of these guidelines
and endeavour to implement them in clinical practice. All treatment methods and
procedures not substantiated by evidence from the literature should be
discontinued and avoided to decrease the financial burden of acne treatment.
VALIDATION: These guidelines were developed through general consensus by a group
of about 40 internationally recognised experts in the field of acne treatment
(the Global Alliance to Improve Outcomes in Acne, see details below) and further
refined for South African circumstances by the majority of South African
dermatologists who attended a series of six discussions held in the major centres
of South Africa during 2004. GUIDELINE SPONSOR: The meetings of the Global
Alliance to Improve Outcomes in Acne as well as the South African discussion
meetings were sponsored by Galderma.

Familial Mediterranean fever and the other autoinflammatory syndromes: evaluation of the patient with recurrent fever. Samuels J, Ozen S. Curr Opin Rheumatol. 2006 Jan;18(1):108-17.

PURPOSE OF REVIEW: The aim of this article is to summarize recent clinical,
genetic and pathophysiologic findings of familial Mediterranean fever and several
of the other systemic autoinflammatory diseases, a recently recognized group of
disorders characterized by seemingly unprovoked inflammation but lacking
high-titer autoantibodies. Genetic and clinical tools are improving the ability
of the clinician to better approach patients with periodic fever and
inflammation. RECENT FINDINGS: The spectrum of reported genetic mutations and
susceptible ethnicities for the hereditary periodic fever subset of the
autoinflammatory diseases has continued to expand. At the same time, the
pathogeneses of many of these diseases are now understood to involve different
aspects of a common pathway, largely affecting inflammatory cascades related to
IL-1 or tumor necrosis factor-alpha. Three of these diseases which have been
grouped as the cryopyrin-associated periodic syndromes result from defects in the
same gene, and all three appear to respond well to anti-IL-1 therapy although
controlled trials are still in progress. In addition, cytokine-based therapies
are also now under investigation for hyperimmunoglobulinemia D with periodic
fever syndrome and pyogenic sterile arthritis, pyoderma gangrenosum, and acne
syndrome. SUMMARY: The identification of the genes and proteins mutated in many
of the autoinflammatory diseases has broadened our understanding of the
regulation of inflammation and the immune system, and provided the basis for the
use of targeted therapies in these syndromes. We propose an algorithm for the
evaluation of a patient with periodic fever, taking into account the patient's
age, ethnicity, symptoms and signs, and results from laboratory and genetic
testing.

Inhibition of IFN-gamma as a method of treatment of various autoimmune diseases, including skin diseases. Skurkovich B, Skurkovich S. Ernst Schering Res Found Workshop. 2006;(56):1-27.

We pioneered anticytokine therapy (ACT) for autoimmune diseases (ADs). In 1974,
we proposed that hyperproduced interferon (IFN) can bring AD and anti-IFN can be
therapeutic. In 1989, we proposed removing tumor necrosis factor (TNF)-alpha
together with certain types of IFN to treat various ADs. We found IFN in patients
with different ADs and conducted the first clinical trial of ACT in 1975.
Anti-IFN-gamma and anti-TNF-alpha work in similar ways, but the latter brings
serious complications in some patients. We obtained good, sometimes striking,
therapeutic effects treating many different Th-1-mediated ADs with
anti-IFN-gamma, including rheumatoid arthritis, multiple sclerosis (MS), corneal
transplant rejection, and various autoimmune skin diseases such as psoriasis,
alopecia areata, vitiligo, acne vulgaris, and others. Anti-IFN-gamma was in some
ways superior to anti-TNF-alpha, which was ineffective in MS. Anti-IFN-gamma
therapy holds great promise for treating many Th-1 ADs, especially skin diseases.

Enhancing the care and treatment of skin of color, part 1: The broad scope of pigmentary disorders. Taylor SC. Cutis. 2005 Oct;76(4):249-55.

Scientific research and technologies related to skin pigmentation and
dyschromias, which are often key skin concerns for patients of color, have led to
recent developments in skin care and treatment. Differences and similarities
between skin of color and white skin and current issues in the treatment of
ethnic skin are reviewed. Recent research findings, such as the elucidation of
the protease-activated receptor 2 (PAR-2) pathway and its role in pigmentation,
and areas for further investigation, such as the pathogenesis of
pseudofolliculitis barbae (PFB), also are discussed. Awareness of this
information within the wider community of dermatologists, primary healthcare
providers, and the media will help to accomplish the objective of stimulating new
prospective research.

Prophylaxis for and treatment of uncomplicated skin and skin structure infections in laser and cosmetic surgery. Nestor MS. J Drugs Dermatol. 2005 Nov-Dec;4(6 Suppl):s20-5.

Complications of laser resurfacing include infections, scarring,
hyperpigmentation, hypopigmentation, and delayed healing. Postoperative
infections cause pain, prolonged healing, and can result in scarring. Ablative
laser techniques cause partial- or full-thickness wounds, whereas so-called
"nonablative procedures" may cause "spotty" epidermal wounds. Antibiotic
prophylaxis is necessary when the risk for postoperative infection is significant
or when the risk of infection is moderate but the consequences of infection are
significant. Prophylactic antibiotic agents should have a broad spectrum of
activity, be well-tolerated and be safe. The most appropriate choice is a
broad-spectrum agent such as cefdinir, even for patients allergic to penicillin.
Additionally, all patients should be treated prospectively with antivirals to
prevent activation and dissemination of herpes simplex virus type I. Treatment of
infections in patients who have and have not received prophylactic antibiotics
requires identification of the causative factor and appropriate treatment.
Nonablative treatments such as photodynamic therapy do not usually require
antibiotic prophylaxis, although a few patients treated for acne may acquire a
secondary bacterial infection that should be treated.

Safety of doxycycline and minocycline: a systematic review. Smith K, Leyden JJ. Clin Ther. 2005 Sep;27(9):1329-42.

OBJECTIVE: The goal of this review was to summarize the available literature
covering the safety profiles of oral doxycycline and minocycline. METHODS:
Scientific literature published between 1966 and August 2003 was searched using
the MEDLINE, EMBASE, and Biosis databases (search terms: minocycline or
doxycycline, each paired with adverse reaction, adverse event, and side effect,
and doxycycline or minocycline with the limits English language, human, and
clinical trials). Safety information was collected from case reports and clinical
trials. Adverse event (AE) rates in the United States were calculated by
comparing data from the MedWatch AE reporting program used by the US Food and
Drug Administration (FDA) with the number of new prescriptions dispensed for each
drug from January 1998 to August 2003. RESULTS: Between 1966 and 2003, a total of
130 and 333 AEs were published in case reports of doxycycline and minocycline,
respectively. In 24 doxycycline clinical trials (n = 3833) and 11 minocycline
trials (n = 788), the ranges in incidence of AEs were 0% to 61% and 11.7% to
83.3%, respectively. Gastrointestinal AEs were most common with doxycycline;
central nervous system and gastrointestinal AEs were most common with
minocycline. From January 1998 to August 2003, the FDA MedWatch data contained
628 events for doxycycline and 1099 events for minocycline reported in the United
States. Approximately 47,630,000 doxycycline and 15,234,000 minocycline new
prescriptions were dispensed in the United States during that period, yielding
event rates of 13 per million for doxycycline and 72 per million for minocycline,
based on FDA data. CONCLUSIONS: Between 1998 and 2003, doxycycline was prescribed
3 times as often as minocycline. The incidence of AEs with either drug is very
low, but doxycycline had fewer reported AEs. Although more head-to-head clinical
trials are needed for a direct comparison of AE frequency, these preliminary data
from separate reports suggest the possibility that AEs may be less likely with
doxycycline than minocycline.

[How I prevent ... minor acne] [Article in French] Piérard GE, Piérard-Franchimont C. Rev Med Liege. 2005 Sep;60(9):741-3.

Acne is a disorder affecting the majority of subjects during adolescence that may
persist at various grades of severity during adulthood. This disorder may
manifest itself at different levels of severity ranging from discrete to severe.
The lesions may be sporadic or follow a wild course. The therapeutic strategy
depends on these progression characteristics and must fit to each individual
patient. This review focuses on the minor but the most frequent types of acne
that may benefit from dermocosmetic treatments.

Transfollicular drug delivery--is it a reality? Meidan VM, Bonner MC, Michniak BB. Int J Pharm. 2005 Dec 8;306(1-2):1-14. Epub 2005 Nov 2.

Once regarded as merely evolutionary remnants, the hair follicles and sebaceous
glands are increasingly recognised as potentially significant elements in the
percutaneous drug delivery paradigm. Interest in pilosebaceous units has been
directed towards their use as depots for localised therapy, particularly for the
treatment of follicle-related disorders such as acne or the alopecias.
Furthermore, considerable attention has also been focused on exploiting the
follicles as transport shunts for systemic drug delivery. This paper reviews
various key facets of this field including; relevant aspects of pilosebaceous
anatomy and physiology, the design and efficacy of follicle-targeting
formulations and the emergence of quantitative modeling systems. Several novel
developments in this area promise to greatly expand our understanding of this
field in the near future.

Novel drug delivery systems: potential in improving topical delivery of antiacne agents. Date AA, Naik B, Nagarsenker MS. Skin Pharmacol Physiol. 2006;19(1):2-16.

Acne is the most common cutaneous disorder of multifactorial origin with a
prevalence of 70-85% in adolescents. The majority of the acne sufferers exhibit
mild to moderate acne initially, which progresses to the severe form in certain
cases. Topical therapy is employed as first-line treatment in mild acne, whereas
for moderate and severe acne, systemic therapy is required in addition to topical
therapy. Currently, several topical agents are available that affect at least one
of the main pathogenetic factors responsible for the development of acne.
Although topical therapy has an important position in acne treatment, side
effects associated with various topical antiacne agents and the undesirable
physicochemical characteristics of certain important agents like tretinoin and
benzoyl peroxide affect their utility and patient compliance. Novel drug delivery
strategies can play a pivotal role in improving the topical delivery of antiacne
agents by enhancing their dermal localization with a concomitant reduction in
their side effects. The current review emphasizes the potential of various novel
drug delivery strategies like liposomes, niosomes, aspasomes, microsponges,
microemulsions, hydrogels and solid lipid nanoparticles in optimizing and
enhancing the topical delivery of antiacne agents. (c) 2006 S. Karger AG, Basel

Optical treatments for acne. Ross EV. Dermatol Ther. 2005 May-Jun;18(3):253-66.

Light-based treatments for acne are becoming increasingly commonplace in
dermatology. This article reviews various light approaches in acne therapy.
Methods are discussed from an anatomical and a functional perspective. The
emphasis is on the practicality of treatment as well as the pros and cons of
various devices. Also, a review of the recent literature is presented. The
article is intended to give the reader a panoramic view of this still-young and
developing area. Most likely, light-based acne treatment will receive more
popularity as dermatologists learn how to integrate this type of therapy within
the context of more established drug agents.

Photodynamic therapy for cosmetic applications. Uebelhoer NS, Dover JS. Dermatol Ther. 2005 May-Jun;18(3):242-52.

With the advent of short contact and pulsed light techniques, topical
5-aminolevulinic acid photodynamic therapy (5-ALA PDT) has become a viable
clinical modality. Intense pulsed light, the pulsed dye laser, and blue
light-emitting lamps have become the most commonly used devices in inducing a
cosmetic PDT effect. More recently, by combining the photothermal effects of
pulsed light with the photochemical effects of PDT, an enhanced cosmetic effect
has been demonstrated in a variety of dermatologic conditions. In addition, the
use of shorter 5-ALA incubation times allows for improved patient tolerance
during treatment and subsequently fewer adverse effects in the postoperative
period. A review of the current literature on cosmetic uses of PDT as well as our
personal techniques are discussed in detail.

Photodynamic therapy in dermatology: current concepts in the treatment of skin cancer. Garcia-Zuazaga J, Cooper KD, Baron ED. Expert Rev Anticancer Ther. 2005 Oct;5(5):791-800.

Photodynamic therapy is a treatment modality that is developing rapidly and
increasing in utilization within various medical specialties, including
dermatology. This technique requires the presence of a photosensitizer, light
energy and molecular oxygen to selectively destroy pathologic cells. A thorough
understanding of photobiology and tissue optics is necessary to correctly and
effectively utilize photodynamic therapy in dermatology. Photodynamic therapy has
been approved by the US Food and Drug Administration to treat actinic keratoses.
In Europe, photodynamic therapy is currently being used in the treatment of
actinic keratoses and basal cell carcinoma. Other off-label uses of photodynamic
therapy have included cutaneous lesions of Bowen's disease, psoriasis, cutaneous
T-cell lymphoma and acne. Most recently, photodynamic therapy has been employed
in photorejuvenation. The advantages of photodynamic therapy include the capacity
for noninvasive targeted therapy via topical application of the drug and local
irradiation of involved areas, as well as the ability to generate excellent
cosmetic results with minimal discomfort. This review summarizes the fundamentals
of photodynamic therapy and its role in the treatment of cutaneous disorders,
particularly skin malignancies.

[Systemic acne therapy] [Article in German] Thielitz A, Gollnick H. Hautarzt. 2005 Nov;56(11):1040-7.

The development of scarring in inflammatory acne may induce permanent
disfigurement and considerable psychosocial impact on the lives of affected
individuals. The early use of systemic acne therapy can help to prevent these
unfortunate consequences. Antiinflammatory antibiotics such as tetracyclines are
required in moderate to severe papulopustular acne. The recommended treatment
duration is 3 months; combination with topical retinoids and benzoyl peroxide
increases the speed and efficacy of lesion reduction and helps to prevent
bacterial resistance. Oral isotretinoin is the treatment of choice in severe acne
resistant to adequate conventional therapy. Hormonal treatment represents an
alternative regimen for women with acne and is the first choice in late-onset
acne and in those with clinical signs of hyperandrogenism.

Review of the innate immune response in acne vulgaris: activation of Toll-like receptor 2 in acne triggers inflammatory cytokine responses. Kim J. Dermatology. 2005;211(3):193-8.

Acne vulgaris is a common disorder that affects 40-50 million people in the USA
alone. The pathogenesis of acne is multifactorial, including hormonal,
microbiological and immunological mechanisms. One of the factors that contributes
to the pathogenesis of acne is Propionibacterium acnes; yet, the molecular
mechanism by which P. acnes induces inflammation is not known. Recent studies
have demonstrated that microbial agents trigger cytokine responses via Toll-like
receptors (TLRs). TLRs are pattern recognition receptors that recognize
pathogen-associated molecular patterns conserved among microorganisms and elicit
immune responses. We investigated whether TLR2 mediates P. acnes-induced cytokine
production in acne. Using transfectant cells we found that TLR2 was sufficient
for NF-kappaB activation in response to P. acnes. In addition, peritoneal
macrophages from wild-type, TLR6 knockout and TLR1 knockout mice, but not TLR2
knockout mice, produced IL-6 in response to P. acnes.P. acnes induced activation
of IL-12 and IL-8 production by primary human monocytes, and this cytokine
production was inhibited by anti-TLR2-blocking antibody. Finally, in acne
lesions, TLR2 was expressed on the cell surface of macrophages surrounding
pilosebaceous follicles. These data suggest that P. acnes triggers inflammatory
cytokine responses in acne by activation of TLR2. As such, TLR2 may provide a
novel target for the treatment of this common skin disease. Copyright 2005 S.
Karger AG, Basel.

[Light, laser and PDT therapy for acne] [Article in German] Borelli C, Merk K, Plewig G, Degitz K. Hautarzt. 2005 Nov;56(11):1027-32.

In recent years, a number of studies have evaluated the treatment of acne using
electromagnetic waves, such as lasers, photodynamic therapy, visible light or
radio waves. While the efficacy of laser treatment is still uncertain,
photodynamic therapy shows promising results, but with marked side-effects, as
destruction of sebaceous glands. Treatment with blue light (405-420 nm
wavelength) also appears effective and can be regarded as an treatment option for
inflammatory acne.

Nonablative laser surgery for pigmented skin. Goldberg DJ. Dermatol Surg. 2005 Oct;31(10):1263-7.

BACKGROUND: Nonablative laser surgery has been proven to improve early
photodamaged skin and acne scars. These techniques include treatments with
lasers, light sources, and/or radiofrequency devices. OBJECTIVES: To review the
history of nonablative technology and its applicability to darker skin types and
to provide an objective look at the various published studies documenting the
efficacy of nonablative technology. CONCLUSION: Nonablative laser surgery can
improve skin quality and acne scars in all skin types. Complications are rare but
can occur. Future studies are required to compare the efficacy of the various
nonablative technologies.

Common dermatoses in moderately pigmented skin: uncommon presentations. Abdel-Naser MB, Verma SB, Abdallah MA. Clin Dermatol. 2005 Sep-Oct;23(5):446-56.

Several common dermatoses appear different in people of color. Most international
literature, especially the reputed textbooks, are replete with photographs of
skin diseases in fair-skinned patients. The orientation of Western dermatologists
to common diseases in pigmented skin therefore is needed. The reverse is also
true. Dermatologists who work in pigmented skin communities are known to have
initial problems with fair skin. It is therefore important to have a judicious
balance of entities seen in both of these skin types in major international
literature, especially in textbooks. In addition, common dermatoses may appear
strange and confusing particularly when they are in their advanced form. People
with pigmented skin living in developing countries often present with diseases
that appear greatly altered, because of various reasons. Main ones are treatment
taken at home with household remedies, especially topical therapy, inappropriate
treatment given by general practitioners with sparse knowledge of dermatology,
and injudicious steroid use. All these factors lead to exacerbation of the
disease or superimposed irritation or infection, which all contribute to a
different appearance. Equally important is the delay in seeking treatment because
of financial constraints.

Combined nonablative rejuvenation techniques. Shah GM, Kilmer SL. Dermatol Surg. 2005 Sep;31(9 Pt 2):1206-10; discussion 1210.

BACKGROUND: Nonablative technologies have been used for fine lines and
improvement of skin texture without significant downtime. Nonablative
technologies may also be used in combination. OBJECTIVE: To present a brief
review on nonablative technologies and discuss using nonablative procedures in
combination and with other adjunctive therapies. MATERIALS AND METHODS: A review
of the literature was done to identify combination nonablative studies. We also
discuss our own experience in combining these procedures. RESULTS: Various
nonablative technologies can be used together, often with better outcomes and
fewer treatments. CONCLUSION: Nonablative and adjunctive treatments should be
performed in combination to optimize the results. Much of the information in this
publication is from personal experience and expresses the opinions of these
authors while citing relevant literature and studies.

Effective and safe use of lasers, light sources, and radiofrequency devices in the clinical management of Asian patients with selected dermatoses. Chan HH. Lasers Surg Med. 2005 Sep;37(3):179-85.

BACKGROUND AND OBJECTIVES: The use of lasers, light sources, and radiofrequency
devices in Asian patients differs from their use in Caucasians in several
respects. STUDY DESIGN/MATERIALS AND METHODS: The disease spectrum is very
different with pigmentary disorders being more commonly encountered in Asian
populations. Asian skin, with its higher epidermal melanin content, is more
likely to develop adverse reactions, especially post-inflammatory
hyperpigmentation (PIH), following treatment. RESULTS AND CONCLUSIONS: The
purpose of this article is to discuss the effective and safe use of lasers, light
sources, and radiofrequency devices in the clinical management of Asian patients
with selected dermatoses. Copyright 2005 Wiley-Liss, Inc.

[Surgical management of acne inversa] [Article in German] Weyandt G. Hautarzt. 2005 Nov;56(11):1033-9.

The pathogenesis of acne inversa is follicular hyperkeratosis with occlusion and
rupture. The subsequent acute inflammatory response leads to erythema, abscesses,
fistulas, sinus tracts and scarring. Sites of predilection are the intertriginous
regions. Many conservative therapies have only a supportive character. Therapy of
choice is the early surgical intervention with complete excision of the involved
areas, as conservative therapy is at best supportive. Although healing by second
intention is preferred, all variations of flaps and grafts have been used.
Usually the course of acne inversa lasts years until patients elect surgery after
a physical and psychological odyssey.

Considerations for treating acne in ethnic skin. Callender VD. Cutis. 2005 Aug;76(2 Suppl):19-23.

Patients with ethnic skin are at an increased risk for developing
postinflammatory hyperpigmentation (PIH) and keloid scarring subsequent to acne
lesions. Treatment approaches for acne in darker skinned patients must balance
early aggressive intervention with the selection of efficacious and nonirritating
agents. Most patients with prominent or long-lasting PIH will require treatment
with a topical retinoid and hydroquinone, the gold standard in the treatment of
PIH. Keloids may be treated with surgical excision, but the rate of recurrence
can be as high as 50%. Successful management of ethnic skin with acne can be
achieved with the appropriate combination drug regimen and good patient
compliance. For best results, clinicians should manage the entire grooming
regimen of the skin and hair of their ethnic patients.

The role of the vehicle in combination acne therapy. Del Rosso JQ. Cutis. 2005 Aug;76(2 Suppl):15-8.

The choice of vehicle is an important consideration in acne therapy. Because the
epidermal barrier may be impaired by both the underlying disorder and the use of
some topical treatments for acne, vehicle formulations that minimize barrier
impairment, help to restore barrier function, and limit signs and symptoms of
skin irritation are valuable components of acne therapy, especially early in the
course of treatment or with combination regimens. Formulations with ingredients
that provide moisturization, such as humectants and emollients, are ideal in the
management of acne. Tretinoin microsphere and tretinoin polyolprepolymer-2 are
vehicle modifications designed to release tretinoin in a slow controlled manner,
thus minimizing the potential for irritation associated with standard tretinoin
formulations. A combination of clindamycin and benzoyl peroxide in a water-based
gel formulated with the humectant glycerin and the emollient dimethicone has been
shown to improve skin tolerability and overall patient preference compared with
the same active ingredients formulated without the special additives that provide
moisturization.

Combination therapy is the standard of care. Tanghetti EA. Cutis. 2005 Aug;76(2 Suppl):8-14.

Acne is a multifactorial disease characterized by abnormalities in sebum
production, follicular epithelial desquamation, bacterial proliferation, and
inflammation. Despite these multiple pathogenic factors, most current therapies
for acne do not target all 4 areas of acne pathophysiology. Combination therapies
using agents with complementary mechanisms of action increasingly are recognized
as an effective strategy for treating acne. Several common regimens have shown
this multiple-target efficacy, including the combination of a topical antibiotic
with benzoyl peroxide. In combination, these agents produce greater and faster
results than when each is used as monotherapy. For both initial treatment and
maintenance therapy, the ideal combination regimen is often a topical antibiotic
and benzoyl peroxide product plus a retinoid that is appropriate for the
patient's skin type. Combination regimens should be tailored to the individual
patient, bearing in mind the number and types of prevailing lesions and the skin
type. Because the vehicle for each agent may have an impact on tolerability, one
should pay attention to the combination of vehicles and patient care practices to
maximize tolerability.

Photodynamic therapy--mechanism and employment. Szpringer E, Lutnicki K, Marciniak A. Ann Univ Mariae Curie Sklodowska Med. 2004;59(2):498-502.

Photodynamic terapy (PDT) is a new treatment for a wide variety of malignancies
and premalignant dysplasias, as well as some non-cancer indications. Therapeutic
response to PTD is achieved through the activation of non-toxic photosensitiser
located within neoplastic tissue, using visible light tuned to the appropriate
absorption band of the photosensitiser molecule. This produces cytotoxic free
radical such as singlet oxigen, which result in local photo-oxidation, cell
damage and destruction of the tumour cells. Systemic administration of
photosensitisers has been used with endoscopic light exposure to treat a variety
of internal malignances. A topical drug delivery is used in the skin deseases
treatment. The selective distribution of photosensitiser in the target tissue is
the fundamental to the process of PDT. This tissue specific photosensitation and
normal tissue sparing results in good healing and often very good cosmetic
results. Peterson PTD can be used for the treatment of cutaneous lesions (e.g.,
SCC, BCC, Bowen's disease, mycosis fungoides, erythroplasia of Queyrat, Gorlin's
Syndrome, actinic keratoses), lower genital tract neoplasia (VIN and CIN),
gastrointestinal tumours, etc., as well as nononcological indications (e.g.,
acne, condyloma acuminatum, lichen planus, psoriasis, vitiligo, vulval lichen
sclerosus, warts and verrucae).

The role of testosterone therapy in postmenopausal women: position statement of The North American Menopause Society. North American Menopause Society. Menopause. 2005 Sep-Oct;12(5):496-511; quiz 649. Epub 2005 Sep 1.

OBJECTIVE: To create an evidence-based position statement regarding the role of
exogenous testosterone in postmenopausal women. DESIGN: The North American
Menopause Society (NAMS) enlisted a panel of clinicians and researchers
acknowledged to be experts in the field of testosterone therapy to review the
evidence obtained from the medical literature, compile supporting statements and
conclusions, and reach consensus on recommendations. The document was reviewed
and approved by the NAMS Board of Trustees. RESULTS: Endogenous testosterone
levels have not been clearly linked to sexual function in postmenopausal women.
Published evidence from randomized controlled trials, although limited, indicates
that exogenous testosterone, both oral and nonoral formulations, has a positive
effect on sexual function, primarily desire, arousal, and orgasmic response, in
women after spontaneous or surgically induced menopause. Data are inadequate to
support recommending testosterone use for any other indication, including
preserving or increasing bone mineral density, reducing hot flashes, increasing
lean body mass, or improving well-being. Hirsutism and acne have been associated
with testosterone therapy, but the actual risks are not well defined. It is not
known whether testosterone therapy increases the risk of breast cancer,
cardiovascular disease, or thromboembolic events. There are few data regarding
the safety and efficacy of testosterone therapy in women not using concomitant
estrogen therapy or for the use of testosterone therapy for longer than 6 months.
Clinically available laboratory assays do not accurately detect testosterone
concentrations at the values typically found in women, and no testosterone level
has been clearly linked to a clinical syndrome of hypoandrogenism or testosterone
insufficiency. CONCLUSIONS: Postmenopausal women with decreased sexual desire
associated with personal distress and with no other identifiable cause may be
candidates for testosterone therapy. Testosterone treatment without concomitant
estrogen therapy cannot be recommended because of a lack of evidence. When
evaluating a woman for testosterone therapy, recommendations are to rule out
causes not related to testosterone levels (eg, physical and psychosocial factors,
medications) and to ensure that there is a physiologic cause for reduced
testosterone levels (eg, bilateral oophorectomy). Laboratory testing of
testosterone levels should be used only to monitor for supraphysiologic levels
before and during therapy, not to diagnose testosterone insufficiency. Monitoring
should also include subjective assessments of sexual response, desire, and
satisfaction as well as evaluation for potential adverse effects. Transdermal
patches and topical gels or creams are preferred over oral products because of
first-pass hepatic effects documented with oral formulations. Custom-compounded
products should be used with caution because the dosing may be more inconsistent
than it is with government-approved products. Testosterone products formulated
specifically for men have a risk of excessive dosing, although some clinicians
use lower doses of these products in women. Testosterone therapy is
contraindicated in women with breast or uterine cancer or in those with
cardiovascular or liver disease. It should be administered at the lowest dose for
the shortest time that meets treatment goals. Counseling regarding the potential
risks and benefits should be provided before initiating therapy.

Acne vulgaris. Purdy S. Clin Evid. 2005 Jun;(13):2038-59.

Acne, depression, and suicide. Hull PR, D'Arcy C. Dermatol Clin. 2005 Oct;23(4):665-74.

Acne is a common disorder that may have a considerable psychologic impact
including anxiety and depression. Depression and suicide occur frequently in
adolescents and young adults. Although case reports suggest an association
between isotretinoin and depression and suicide, more rigorous observational
studies and epidemiologic studies, using different designs, have not shown any
effect of isotretinoin use in increasing the occurrence of depression and
suicide. It is prudent for the practitioner to continue to use isotretinoin to
treat severe acne, while at the same time informing patients and their relatives
that depressive symptoms should be actively assessed at each visit and, if
necessary, referral to a psychiatrist and a discontinuation of isotretinoin
should be considered.

The emotional impact of chronic and disabling skin disease: a psychoanalytic perspective. Koblenzer CS. Dermatol Clin. 2005 Oct;23(4):619-27.

This article discusses some major early factors that influence the evolving
psychologic development, which in turn helps determine the emotional impact that
chronic or disabling skin disease may have on patients' lives. If the emotional
environment, encompassed by the infant-caretaker relationship, is less than
optimal, the stability of the body image may be compromised, self-esteem
diminished, and affect less well handled and the somatic expression of emotional
content may ensue. Each of these is important in dermatology, as is the nature of
the disease and the capacity of families and of society to adapt. Psoriasis,
atopic dermatitis, and acne are used as examples.

Estrogens and the skin. Brincat MP, Baron YM, Galea R. Climacteric. 2005 Jun;8(2):110-23.

OBJECTIVE: A review of the medical literature concerning the effect of the
menopause and its hormonal treatment on the skin. METHODS: An extensive Medline
and Pubmed internet search utilizing the key words: collagen, elastin, estrogen,
hormone replacement therapy, skin and aging. RESULTS: The literature review
demonstrated a wide array of research ranging from basic science work to clinical
implications of the effects of the menopause and its treatment on the skin.
CONCLUSION: Estrogen loss at menopause has a profound influence on skin. Estrogen
treatment in postmenopausal women has been repeatedly shown to increase collagen
content, dermal thickness and elasticity, and data on the effect of estrogen on
skin water content are also promising. Further, physiologic studies on estrogen
and wound healing suggest that hormone replacement therapy (HRT) may play a
beneficial role in cutaneous injury repair. Results on the effect of HRT on other
physiologic characteristics of skin, such as elastin content, sebaceous
secretions, wrinkling and blood flow, are discordant. Given the responsiveness of
skin to estrogen, the effects of HRT on aging skin require further examination,
and careful molecular studies will likely clarify estrogen's effects at the
cellular level.

Caspase recruitment domain 15 mutations and rheumatic diseases. Rose CD, Martin TM. Curr Opin Rheumatol. 2005 Sep;17(5):579-85.

PURPOSE OF REVIEW: The purpose of this article is to review the foundational work
and current developments on a group of rheumatic disorders associated with
mutations in the caspase recruitment domain 15/nucleotide oligomerization domain
2 gene. RECENT FINDINGS: To date, there are at least 10 arthritic conditions for
which specific genetic mutations have been demonstrated. They include familial
Mediterranean fever; tumor necrosis factor receptor associated periodic syndrome;
hyper immunoglobulin D syndrome; neonatal onset multisystemic inflammatory
disease; pyogenic arthritis pyoderma gangrenosum and acne; Muckle-Wells syndrome;
familial cold autoinflammatory syndrome; immunodysregulation, polyendocrinopathy,
enteropathy, X-linked syndrome; Crohn's disease; and familial and sporadic
sarcoid granulomatous arthritis. This review focuses on recent progress in the
last two diseases and the caspase recruitment domain 15 genetic defects with
which they are associated. Up to 50% of patients with familial granulomatous
arthritis (Blau's syndrome), 90% of those with sporadic granulomatous arthritis
(early-onset sarcoidosis), and 40% of individuals with Crohn's disease have
documented mutations in the caspase recruitment domain 15 gene. SUMMARY: Although
histologically, Crohn's disease and familial and sporadic sarcoid granulomatous
arthritis are distinct from rheumatoid arthritis because of the defining presence
(albeit in not all cases) of non-caseating granulomata in the synovial and
intestinal tissues, respectively, they still represent a promising model of both
chronic synovitis and uveitis. In addition, once the actual mechanism is
discovered by which defects of the caspase recruitment domain 15 gene product
lead to chronic arthritis, it may uncover unsuspected biologic targets for
therapeutics.

Lasers and light therapy for acne vulgaris. Bhardwaj SS, Rohrer TE, Arndt K. Semin Cutan Med Surg. 2005 Jun;24(2):107-12.

Acne vulgaris remains an emotionally and debilitating dermatologic disease, and
is conventionally treated with a variety of oral and topical therapies with a
number of significant side effects. An evolving understanding of laser-tissue
interactions involving Propionibacterium acnes-produced porphyrins, and the
development of infrared nonablative lasers to target sebaceous glands, has lead
to the development of an escalating number of laser, light and radiofrequency
devices for acne. Used as monotherapy or in combination, these devices are
showing promise as a method to clear acne in a convenient, non-invasive manner,
though there remains a clear need for long-term data and randomized, blinded
studies.

Hormonal therapy for acne using oral contraceptive pills. Harper JC. Semin Cutan Med Surg. 2005 Jun;24(2):103-6.

The etiology of acne vulgaris is multifactorial and complex. The four key factors
involved in the development of acne include follicular plugging, inflammation,
the presence and activity of Propionibacterium acnes, and sebum. Androgen
hormones stimulate the sebaceous gland and promote sebum excretion. Therefore,
therapies that have an overall antiandrogen effect, like combination oral
contraceptive pills, may be useful in the management of acne vulgaris. Numerous
combination oral contraceptive pills have been evaluated in the treatment of acne
vulgaris and have been found to be effective. With a thorough understanding of
their proper use and potential associated risks, these hormonal treatments may be
prescribed safely and effectively to women with acne.

Depression and suicidal behavior in acne patients treated with isotretinoin: a systematic review. Marqueling AL, Zane LT. Semin Cutan Med Surg. 2005 Jun;24(2):92-102.

Isotretinoin (13-cis retinoic acid) is an effective treatment for severe cystic
or recalcitrant acne vulgaris; however, concerns have been raised regarding its
potential association with depression and suicidal behavior. We sought to explore
the proposed relationship between isotretinoin use and the risk of depression and
attempted and completed suicide in patients with acne vulgaris by performing a
systematic literature search for studies reporting primary data on depression and
suicidal behavior in patients treated with isotretinoin for acne vulgaris. Nine
studies met the qualifying criteria for our analysis. Rates of depression among
isotretinoin users ranged from 1% to 11% across studies, with similar rates in
oral antibiotic control groups. Overall, studies comparing depression before and
after treatment did not show a statistically significant increase in depression
diagnoses or depressive symptoms. Some, in fact, demonstrated a trend toward
fewer or less severe depressive symptoms after isotretinoin therapy. This
decrease was particularly evident in patients with pretreatment scores in the
moderate or clinical depression range. No correlation between isotretinoin use
and suicidal behavior was reported, although only one retrospective study
presented data on this topic. Although the current literature does not support a
causative association between isotretinoin use and depression, there are
important limitations to many of the studies. The available data on suicidal
behavior during isotretinoin treatment are insufficient to establish a meaningful
causative association.

Treatment of acne with topical antibiotics: lessons from clinical studies. Simonart T, Dramaix M. Br J Dermatol. 2005 Aug;153(2):395-403.

BACKGROUND: Over the past 20 years, major concerns have been repeatedly expressed
over antibiotic-resistant acne in Europe and in the U.S.A. However, the clinical
significance of these resistance patterns is poorly defined so that topical
antibiotics remain one of the cornerstones of acne management. OBJECTIVES: To
determine whether we are facing decreased efficacy of topical formulations of
erythromycin and clindamycin in clinical trials of therapeutic interventions for
acne. METHODS: To review systematically the results of the clinical trials
investigating topical formulations of erythromycin and clindamycin for the
treatment of inflammatory acne and to establish whether or not there is a
decrease in the efficacy of these topical antibiotic formulations since their
widespread introduction in the mid 1970s. RESULTS: Of the 50 eligible controlled
trials identified using a systematic electronic database search strategy, 45
(90%) incorporated a lesion count, making comparison across trials possible.
Analysis of clinical studies investigating the effect of topical erythromycin in
acne patients indicates a significant decrease in the effect of this antibiotic
on inflammatory and noninflammatory lesion count over time (r = -2.140, P = 0.001
and r = -2.032, P = 0.001, respectively). Efficacy of topical clindamycin
remained stable during the study period. CONCLUSIONS: There is a gradual decrease
in the efficacy of topical erythromycin in clinical trials of therapeutic
intervention for acne, which is probably related to the development of
antibiotic-resistant propionibacteria.

Polycystic ovary syndrome in adolescence. Buggs C, Rosenfield RL. Endocrinol Metab Clin North Am. 2005 Sep;34(3):677-705, x.

Polycystic ovary syndrome (PCOS) is a syndrome of variable combinations of
menstrual irregularity, hirsutism or acne, and obesity. It can be diagnosed in
adolescence and has early childhood antecedents. PCOS is the single most common
endocrine cause of an ovulatory infertility and a major risk factor for the
metabolic syndrome and, in turn, development of type 2 diabetes mellitus in
women. Thus, it appears that PCOS increases a woman's risk of developing
cardiovascular disease. Therefore, identifying girls at risk for PCOS and
implementing treatment early in the development of PCOS may be an effective means
of preventing some of the long-term complications associated with this syndrome.
This article reviews the definition, clinical features, diagnosis, and treatment
of PCOS.

Applications of aminolevulinic Acid-based photodynamic therapy in cosmetic facial plastic practices. Zakhary K, Ellis DA. Facial Plast Surg. 2005 May;21(2):110-6.

Photodynamic therapy (PDT) using aminolevulinic acid (ALA) is a promising new
technique that is being studied extensively and used in a variety of cosmetic
facial plastic arenas. These applications include U.S. Food and Drug
Administration-approved treatment of premalignant and malignant skin conditions,
as well as off-label uses for photorejuvenation, and the treatment of acne
vulgaris, sebaceous gland hyperplasia, rosacea, and hirsutism. This article
reviews the interplay of factors that contribute to the appearance of actinically
damaged or photoaged skin, also known as dermatoheliosis. This is followed by a
brief review of the mechanisms of action of ALA-based PDT and some of its
cosmetic facial plastic uses.

The radiofrequency frontier: a review of radiofrequency and combined radiofrequency pulsed-light technology in aesthetic medicine. Sadick N, Sorhaindo L. Facial Plast Surg. 2005 May;21(2):131-8.

Radiofrequency (RF) and combined RF light source technologies have established
themselves as safe and effective treatment modalities for several dermatologic
procedures, including skin tightening, hair and leg vein removal, acne scarring,
skin rejuvenation, and wrinkle reduction. This article reviews the technology,
clinical applications, and recent advances of RF and combined RF light/laser
source technologies in aesthetic medicine.

Cosmetics in the treatment of acne vulgaris. Toombs EL. Dermatol Clin. 2005 Jul;23(3):575-81, viii.

This article describes scenarios of patients who have acne vulgaris have tried
over-the-counter products and cosmetics and are disheartened by the persistence
of their disease and the resulting scars. They may have seen an aesthetician,
plastic surgeon, or even a general practitioner before seeing a well-informed
skin specialist. Patients perceive the dermatologist to be the skin care expert
and seek guidance to obtain otherwise unobtainable results. Therefore, practicing
dermatologists should take advantage of the available tools to treat patients
aggressively and completely. Appropriately applied cosmetics can play a role in
achieving this goal. This article describes scenarios that integrate cosmetics
into an anti-acne treatment regimen that is effective and safe for all ethnic
groups and is well tolerated by both male and female patients.

The management of skin reactions in cancer patients receiving epidermal growth factor receptor targeted therapies. Segaert S, Tabernero J, Chosidow O, Dirschka T, Elsner J, Mancini L, Maughan T, Morere JF, Santoro A, Sobrero A, Van Cutsem E, Layton A. J Dtsch Dermatol Ges. 2005 Aug;3(8):599-606.

The use of epidermal growth factor receptor (EGFR) inhibitors for the treatment
of solid tumours is increasing. However, the tolerability profile for
EGFR-inhibitors, such as the monoclonal antibody cetuximab and the tyrosine
kinase inhibitor erlotinib, is characterised by a unique group of skin reactions
dominated by an acneiform eruption, xerosis, eczema and changes in the hair and
nails. The possibility that this skin toxicity correlates with anti-tumour
activity offers the potential to titrate dosing on a case-by-case basis. These
skin effects may constitute a significant obstacle to treatment compliance.
Accordingly, there is a need for consistent, multi-disciplinary management
strategies that will allow patients to receive the recommended dosages of such
targeted therapies. The eruption responds well to some acne therapies and xerosis
can be controlled by standard emollients. Here we present an overview of the
treatment options for skin reactions that are available today, and evaluate some
of the ways in which the treatment of such EGFR-inhibitor-related skin reactions
may be improved in the future. Evidence-based studies are needed to determine the
best way to manage these effects.

The new age of acne therapy: light, lasers, and radiofrequency. Rotunda AM, Bhupathy AR, Rohrer TE. J Cosmet Laser Ther. 2004 Dec;6(4):191-200.

BACKGROUND: Current treatments for acne vulgaris include topical and oral
medications that counteract microcomedone formation, sebum production,
Propionibacterium acnes, and inflammation. Concerns about the short- and
long-term consequences of these medications, along with technological
advancements, have to significant progress in the management of acne. These
developments include light, laser, and radio frequency, which may offer faster
onset of action, equal or greater efficacy, and greater convenience than
traditional approaches. CONCLUSION: Research emphasizing long-term follow-up and
comparative, randomized trials is necessary to determine whether these emerging
technologies will become a viable alternative to standard therapies such as
antibiotics.

The development of BRL 7660 as an anti-acne agent. Bowring N. Skinmed. 2005 Jul-Aug;4(4):211-3.

BRL 7660, a 16,16 di-substituted androstene steroid, was initially developed by
Beecham Pharmaceuticals as a potential anti-fertility agent for males. It proved
inactive in this area, but subsequent studies showed it to be a potent
testosterone 5-alpha-reductase inhibitor. It showed little classical steroidal
activity but reduced sebum secretion in the rat. In the hamster flank organ, it
reduced the stimulant effect of testosterone but not 5-alpha-dihydrotestosterone
after topical administration, but had little oral activity. Human studies showed
that topical administration significantly reduced sebum secretion. Acne symptoms
were reduced in many patients who showed enthusiasm for the treatment. Placebo
effects were variable and reduced significance, which suggested that further
formulation studies were required. Commercial pressures from other drugs in
development prevented our researchers from pursuing this approach, and the
project was terminated.

Noncontraceptive health benefits of combined oral contraception. ESHRE Capri Workshop Group. Hum Reprod Update. 2005 Sep-Oct;11(5):513-25. Epub 2005 Jul 8.

Contraception is one of the keystones of reproductive health. The availability of
effective contraception has helped to change dramatically the structure of the
world's population during the last 50 years, through a demographic transition
involving lower fertility rates and longer survival. As the transition evolves
more slowly in developing countries, different effects on population structures
contribute to civil strains. Oral contraception (OC) is an extremely effective
method of contraception that also confers health benefits beyond pregnancy
prevention. Notable effects on the reproductive system include relief from
troublesome symptoms associated with menstruation such as heavy periods, painful
periods and irregular bleeding. Many women also have improvement in acne and
hirsutism. Moreover, OCs may be used to treat menorrhagia or symptomatic
endometriosis. Use of OCs is associated with a long lasting reduction in the risk
of developing cancer of the ovary and the endometrium. The effects on benign
breast disease (BBD), bone health and colon cancer are less clear and merit
further investigation.

Training room management of medical conditions: sports dermatology. Cordoro KM, Ganz JE. Clin Sports Med. 2005 Jul;24(3):565-98, viii-ix.

Athletes' skin is subject to a distinct array of physical and environmental
stressors. Trauma, the elements, and pathogenic organisms constantly challenge
the skin's integrity. This article intends to arm the clinician with a
fundamental knowledge of infections, mechanical injuries, and environmental
insults common to the skin of athletes. Photographs corresponding to the
described entities are included as figures. Because rapid return to play is the
ultimate goal after injury or illness, there is a section dedicated to play
restrictions as set forth by the National Collegiate Athletic Association.
Although the evaluation and management of cutaneous disease is a challenging
endeavor, a consistent and systematic approach to this most accessible organ can
result in early diagnosis, appropriate treatment, and ultimate performance.

Managing adolescent acne: a guide for pediatricians. Krowchuk DP. Pediatr Rev. 2005 Jul;26(7):250-61.

Clindamycin/tretinoin: clindamycin phosphate/tretinoin gel. [No authors listed] Drugs R D. 2005;6(4):231-4.

Connetics Corporation (USA) has licensed a first-in-class, dual-action 1%
clindamycin/0.025% tretinoin aqueous gel [Clindamycin phosphate/tretinoin gel,
Velac, Velac Gel] from Yamanouchi Europe BV. The product combines the
anti-inflammatory and antibacterial properties of clindamycin with the beneficial
effects of tretinoin [all-trans-retinoic acid], and is in phase III trials for
the treatment of acne. On 1 April 2005, Yamanouchi merged with Fujisawa to form
Astellas Pharma. Connetics has exclusive development and commercialisation rights
for clindamycin/tretinoin gel in the US and Canada, and has non-exclusive rights
to the product in Mexico. Under the licensing agreement terms, Connetics
initially paid Yamanouchi a dollar US 2 million licensing fee, as well as
milestone payments and royalties on future products. In the fourth quarter of
2002, a dollar US 2 million milestone payment was made to Yamanouchi following
the initiation of pivotal phase III trials in the US and Canada, and in the third
quarter of 2004 a dollar US 3 million milestone payment was made to Yamanouchi
following the filing of an NDA to the US FDA. In March 2004, Connectics reported
that clindamycin/tretinoin is approved in Europe. It appears that this approval
was specifically for France. In October 2004, Connetics announced that the US FDA
has accepted its NDA filing for clindamycin/tretinoin. Two pivotal phase III
trials of clindamycin/tretinoin have been conducted in the US and Canada. These
trials included 2219 patients with acne who received 12 weeks' treatment in the
double-blind, placebo- and active-controlled trials. Results of these trials were
reported in March 2004. Connetics anticipates launch of the product during
mid-2005. An action date of 25 June 2005 has been given by the FDA for it to
respond to the NDA submission. Phase III trials in patients with acne in Europe
have shown clindamycin/tretinoin gel to be as effective and safe as other leading
topical therapies. Data from a combined analysis of six controlled efficacy and
safety trials of clindamycin/tretinoin have been reported.The patent for
clindamycin/tretinoin gel is held by Yamanouchi in the US and
internationally.Other analysts, at CIBC World Markets, were quoted saying that
Evoclin represents Connetics' 'first foray' into the acne market (followed by
others, such as Velac), a market that has been valued at dollar US 1.7 billion,
of which that for topical antibiotics is worth approximately dollar US 500
million.

Epidermal stem cells. Barthel R, Aberdam D. J Eur Acad Dermatol Venereol. 2005 Jul;19(4):405-13.

The identification of adult epidermal stem cells that are capable of self-renewal
and can reconstitute not only the epidermis but also the cutaneous appendages
opens new perspectives for the treatment of a variety of human skin disorders
including severe burns, cutaneous cancers, alopecia and acne. However, the
implementation and improvement of these novel treatment strategies require a
better understanding of the biology of stem cells, in particular regarding their
isolation and the maintenance of their unique characteristics in culture. In this
review, we summarize the main features of epidermal stem cells and we present the
most recent advances in our understanding of the development and maintenance of
these cells. In addition, we discuss some of the challenges and the potential
clinical applications of epidermal stem cell technology.

The role of toll-like receptors in the pathogenesis and treatment of dermatological disease. McInturff JE, Modlin RL, Kim J. J Invest Dermatol. 2005 Jul;125(1):1-8.

Toll-like receptors (TLR) are crucial players in the innate immune response to
microbial invaders. These receptors are expressed on immune cells, such as
monocytes, macrophages, dendritic cells, and granulocytes. Importantly, TLR are
not only expressed by peripheral blood cells, but their expression has been
demonstrated in airway epithelium and skin, important sites of host-pathogen
interaction. Host cells expressing TLR are capable of recognizing conserved
pathogen-associated molecular patterns, such as lipopolysaccharide and CpG DNA,
and their activation triggers signaling pathways that result in the expression of
immune response genes and cytokine production. As TLR are instrumental in both
launching innate immune responses and influencing adaptive immunity, regulation
of TLR expression at sites of disease such as in leprosy, acne, and psoriasis may
be important in the pathophysiology of these diseases. Furthermore, since TLR are
vital players in infectious and inflammatory diseases, they have been identified
as potential therapeutic targets. Indeed, synthetic TLR agonists such as
imiquimod have already established utility in treating viral pathogens and skin
cancers. In the future, it seems possible there may also be drugs capable of
blocking TLR activation and thus TLR-dependent inflammatory responses, providing
new treatment options for inflammatory diseases.

Polycystic ovary syndrome in adolescents: pathophysiology and treatment implications. Pelusi C, Pasquali R. Treat Endocrinol. 2003;2(4):215-30.

Polycystic ovary syndrome is a heterogeneous clinical syndrome, which has been
defined as the association of hyperandrogenism with chronic anovulation in women
without specific adrenal and pituitary gland disease. A family history of
polycystic ovary syndrome may be present in a subset of patients; however, the
genetic basis of the syndrome remains unclear. Most often, the age of onset is
perimenarchal and it is characterized by the appearance of menstrual
disturbances, hirsutism, acne, and more rarely, a male pattern of alopecia. In
some cases, premature adrenarche may present as a precursor to the development of
the syndrome. Polycystic ovary syndrome is also associated with metabolic
disturbances, such as obesity and insulin resistance with hyperinsulinemia, for
which the pathophysiological role in the development of the syndrome has been
recognized. The therapeutic approaches to polycystic ovary syndrome include
lifestyle modifications, dietary-induced weight loss, insulin-sensitizing agents,
antiandrogens, and oral contraceptives. These treatments may improve the clinical
manifestations of excess androgen production and normalize menses in many
adolescents and young women with polycystic ovary syndrome. Early recognition of
the syndrome and thus, early treatment, may prevent and possibly ameliorate all
the symptoms and the potential later development of metabolic and cardiovascular
complications.

Body dysmorphic disorder. Mackley CL. Dermatol Surg. 2005 May;31(5):553-8.

BACKGROUND: Body dysmorphic disorder (BDD) is a syndrome characterized by
distress secondary to imagined or minor defects in one's appearance. Although it
is a psychiatric disorder, most affected patients present to the dermatologist or
plastic surgeon to improve their perceived defect. OBJECTIVE: The objective was
to review the literature on BDD, examining the epidemiology, etiology, clinical
features, diagnostic criteria, and treatment of the disorder. METHODS: Three
representative cases of BDD are presented; in addition, a search of MEDLINE was
completed and a review of all published data on BDD was performed. RESULTS: BDD
has an estimated prevalence of 1 to 2% in the general population; this prevalence
is increased in patient populations. There is significant comorbidity associated
with BDD. CONCLUSIONS: BDD is a relatively common psychiatric disorder in which
patients typically present to cosmetic surgeons for treatment of their perceived
or imagined defect. Surgical treatments usually prove unsatisfactory to the
patient and to the practitioner. Psychiatric treatment is extremely challenging.

Non-acne dermatologic indications for systemic isotretinoin. Akyol M, Ozçelik S. Am J Clin Dermatol. 2005;6(3):175-84.

Systemic isotretinoin has been used to treat severe acne vulgaris for 20 years.
However, isotretinoin also represents a potentially useful choice of drugs in
many dermatologic diseases other than acne vulgaris. Diseases such as psoriasis,
pityriasis rubra pilaris, condylomata acuminata, skin cancers, rosacea,
hidradenitis suppurativa, granuloma annulare, lupus erythematosus and lichen
planus have been shown to respond to the immunomodulatory, anti-inflammatory and
antitumor activities of the drug. Isotretinoin also helps prevent skin cancers
such as basal cell carcinoma or squamous cell carcinoma. A combination of
systemic isotretinoin and interferon-alpha-2a may provide a more potent effect
than isotretinoin alone in the prevention and treatment of skin cancers.Systemic
isotretinoin may be considered as an alternative drug in some dermatologic
diseases unresponsive to conventional treatment modalities. However, randomized
clinical trials aimed at determining the role of systemic isotretinoin therapy in
dermatologic diseases other than acne vulgaris are required.

Dermatologic signs in patients with eating disorders. Strumia R. Am J Clin Dermatol. 2005;6(3):165-73.

Eating disorders are significant causes of morbidity and mortality in adolescent
females and young women. They are associated with severe medical and
psychological consequences, including death, osteoporosis, growth delay and
developmental delay. Dermatologic symptoms are almost always detectable in
patients with severe anorexia nervosa (AN) and bulimia nervosa (BN), and
awareness of these may help in the early diagnosis of hidden AN or BN. Cutaneous
manifestations are the expression of the medical consequences of starvation,
vomiting, abuse of drugs (such as laxatives and diuretics), and of psychiatric
morbidity. These manifestations include xerosis, lanugo-like body hair, telogen
effluvium, carotenoderma, acne, hyperpigmentation, seborrheic dermatitis,
acrocyanosis, perniosis, petechiae, livedo reticularis, interdigital intertrigo,
paronychia, generalized pruritus, acquired striae distensae, slower wound
healing, prurigo pigmentosa, edema, linear erythema craquele, acral coldness,
pellagra, scurvy, and acrodermatitis enteropathica. The most characteristic
cutaneous sign of vomiting is Russell's sign (knuckle calluses). Symptoms arising
from laxative or diuretic abuse include adverse reactions to drugs. Symptoms
arising from psychiatric morbidity (artefacta) include the consequences of
self-induced trauma.The role of the dermatologist in the management of eating
disorders is to make an early diagnosis of the 'hidden' signs of these disorders
in patients who tend to minimize or deny their disorder, and to avoid
over-treatment of conditions which are overemphasized by patients' distorted
perception of skin appearance. Even though skin signs of eating disorders improve
with weight gain, the dermatologist will be asked to treat the dermatological
conditions mentioned above. Xerosis improves with moisturizing ointments and
humidification of the environment. Acne may be treated with topical benzoyl
peroxide, antibacterials or azaleic acid; these agents may be administered as
monotherapy or in combinations. Combination antibacterials, such as erythromycin
with zinc, are also recommended because of the possibility of zinc deficiency in
patients with eating disorders. The antiandrogen cyproterone acetate combined
with 35 microg ethinyl estradiol may improve acne in women with AN and should be
given for 2-4 months. Cheilitis, angular stomatitis, and nail fragility appear to
respond to topical tocopherol (vitamin E). Russell's sign may decrease in size
following applications of ointments that contain urea. Regular dental treatment
is required to avoid tooth loss.

Case report and review of minocycline-induced cutaneous polyarteritis nodosa. Culver B, Itkin A, Pischel K. Arthritis Rheum. 2005 Jun 15;53(3):468-70.

Acne keloidalis in females: case report and review of literature. Ogunbiyi A, George A. J Natl Med Assoc. 2005 May;97(5):736-8.

Acne keloidalis, also known as folliculitis nuchae, is a form of chronic scarring
folliculitis characterized by fibrotic papules and nodules of the nape of the
neck and the occiput. It particularly affects men of African descent and is
rarely ever seen in women. We here report the clinical findings of two Nigerian
women who developed acne keloidalis. This report also reviews the pathogenesis of
this disease.

The anti-inflammatory effects of tetracyclines. Weinberg JM. Cutis. 2005 Apr;75(4 Suppl):6-11.

Tetracyclines commonly are used in medicine and dentistry because of their
efficacy and safety as bacteriostatic antimicrobial agents. As such,
tetracyclines function by inhibiting bacterial multiplication and growth. In
addition to these effects, tetracyclines have anti-inflammatory properties and
have been shown to exhibit several intracellular and extracellular biologic
effects that are not related to antibiotic activity. These activities correlate
with anti-inflammatory and anticollagenolytic properties. This article will
review the anti-inflammatory properties of the tetracyclines and the various
clinical applications related to these actions. In addition, the use of
subantimicrobial dose doxycycline 20 mg twice a day (SDD) will be discussed
because of its anti-inflammatory effects.

[The treatment of acne] [Article in French] Dréno B. Presse Med. 2005 Apr 9;34(7):540-3.

The treatment of acne is based on local and systemic treatments. It must be
adapted to the type of acne and take some prognostic factors into account.
Because of the possibility of drug resistance, systemic and local antibiotics
should be used for only limited periods and preferably as part of combined
treatments. Prescription of isotretinoin to women must follow strict rules. Some
new-generation contraceptive pills are an interesting alternative for acne
treatment in women. Zinc, which basically targets inflammatory acne, is a
possible option for pregnant women and during the summer. Cosmetic care is also a
fundamental part of acne treatment.

Mechanism-based treatment of acne vulgaris: the value of combination therapy. Webster G. J Drugs Dermatol. 2005 May-Jun;4(3):281-8.

Acne vulgaris has multiple pathogenic mechanisms that act in concert to produce
disease. Effective therapy addresses more than one pathogenic factor to speed
resolution of disease. Typically, retinoids are used to inhibit comedo formation
and an antibacterial is used to suppress Propionibacterium acnes (P. acnes).
Using combinations of agents can enhance efficacy, but increase side effects.
Therefore, the tolerability of a topical retinoid is important. Strategies to
enhance retinoid tolerability include the use of new retinoids such as adapalene,
new delivery systems such as the tretinoin microsphere delivery system, or
alternative dosing schedules such as short contact or every other day (QOD).

Photodynamic therapy in dermatology--an update. Babilas P, Karrer S, Sidoroff A, Landthaler M, Szeimies RM. Photodermatol Photoimmunol Photomed. 2005 Jun;21(3):142-9.

Topical photodynamic therapy (PDT) is a well-established treatment modality which
has mainly shown to be effective for dermatooncologic conditions like actinic
keratoses (AK), Bowen's disease, in situ squamous cell carcinoma and superficial
basal cell carcinoma (BCC). However, a therapeutical benefit of PDT is also
evident for inflammatory dermatoses like localized scleroderma, acne vulgaris and
granuloma annulare. Recent work has been focused on the development and
evaluation of topical photosensitizers like the heme precursor 5-aminolevulinic
acid (5-ALA) or its methyl ester (methyl aminolevulinate) inducing
photosensitizing porphyrins. These drugs do not induce strong generalized
cutaneous photosensitization like the systemically applied porphyrins or their
derivatives. For dermatological purposes, incoherent lamps or light-emitting
diode arrays can be used for light activation. Depending on the applied light
dose and the concentration of the photosensitizer either cytotoxic effects
resulting in tumor destruction or immunomodulatory effects improving the
inflammatory conditions occur. Treating superficial oncologic lesions (tumor
thickness <2-3 mm) cure rates achieved by PDT are equal to the cure rates of the
respective standard therapeutic procedure. The benefits of PDT are the low level
of invasiveness and the excellent cosmetic results after treatment.

Ethinylestradiol/drospirenone: a review of its use as an oral contraceptive. Keam SJ, Wagstaff AJ. Treat Endocrinol. 2003;2(1):49-70.

Ethinylestradiol 30microg/drospirenone 3mg (Yasmin, petibelle) [EE/DRSP] is a
combined contraceptive pill (CC) for the prevention of pregnancy in women of
reproductive age. Drospirenone is a novel progestogen with antimineralocorticoid,
progestogenic and antiandrogenic activity. The theoretical (0-0.07) and corrected
(0.41-0.71) Pearl indices and pregnancy ratios (0.3-0.84) in young, healthy women
aged 18-35 years (or 18-30 years if smokers) given 13-26 cycles of EE/DRSP in
large multi-center trials indicate that this CC is highly effective in preventing
pregnancy. EE/DRSP is equally as effective as ethinylestradiol
30microg/desogestrel 150microg (EE/DSG; corrected Pearl index 0.28-0.41) in
preventing pregnancy. EE/DRSP is generally well tolerated. The frequency and type
of adverse event reported in clinical trials are typical of those observed with
other CCs, and comparable to those in women receiving EE/DSG. The incidence of
intermenstrual bleeding (spotting, breakthrough bleeding or both) during
treatment with EE/DRSP in young, healthy women decreased rapidly after the first
cycle to 9 to 18% in the second cycle and 6% after 26 cycles, indicating good
cycle control. The incidence of intermenstrual bleeding was similar in recipients
of EE/DSG (9 and 14% in cycle 2 and 10% in cycle 26). Bodyweight was maintained
+/- 2kg in most young women who received EE/DRSP for up to 26 cycles. Neither
EE/DRSP nor EE/DSG showed clinically significant effects on blood pressure.
EE/DRSP improved premenstrual and menstrual symptoms (negative affect, water
retention, increased appetite) compared with baseline in a noncomparative trial.
A similar improvement in skin condition (acne, seborrhea) was observed in women
receiving EE/DRSP or ethinylestradiol 35microg/cyproterone acetate 2mg in a
randomized, double-blind trial. CONCLUSIONS: Data from several 1- to 2-year
studies show that EE/DRSP is an effective oral contraceptive, with Pearl index
values similar to those of established low-dose CCs. This combination is well
tolerated, demonstrating good cycle control and a beneficial effect on skin
condition and well-being (including some premenstrual and menstrual symptoms).
EE/DRSP has demonstrated similar efficacy and tolerability to EE/DSG, but
long-term clinical experience is required to establish the position of EE/DRSP
among other available CCs and to clarify any potential tolerability advantages.
Nevertheless, because the management of tolerability is complicated by the
idiosyncratic nature of the response of women to CCs containing different
progestogens, EE/DRSP appears to be a useful treatment option for women desiring
oral contraception.

New modalities of transdermal testosterone replacement. Basaria S, Dobs AS. Treat Endocrinol. 2003;2(1):1-9.

Hypogonadism, irrespective of its etiology, has a negative impact on various
physiologic parameters. These parameters may improve with testosterone
replacement therapy. Before 1990, intramuscular testosterone esters were the
principal modality of testosterone replacement in men with hypogonadism. Although
effective, they have a non-physiologic pharmacokinetic profile. Recently,
transdermal preparations of testosterone have become widely available. These
include a scrotal patch, non-scrotal patches and, the most recent development, a
gel. Several studies have shown that transdermal testosterone replacement is
physiologic, efficacious and has a good safety profile. Transdermal testosterone
replacement improves bone mass and lean body mass, decreases fat mass, and
improves mood and sexual function. There are no harmful effects on the prostate
and lipids. Acne, polycythemia, and gynecomastia are less common with this form
of therapy than with the intramuscular esters.

Acneiform facial eruptions: a problem for young women. Cheung MJ, Taher M, Lauzon GJ. Can Fam Physician. 2005 Apr;51:527-33.

OBJECTIVE: To summarize clinical recognition and current management strategies
for four types of acneiform facial eruptions common in young women: acne
vulgaris, rosacea, folliculitis, and perioral dermatitis. QUALITY OF EVIDENCE:
Many randomized controlled trials (level I evidence) have studied treatments for
acne vulgaris over the years. Treatment recommendations for rosacea,
folliculitis, and perioral dermatitis are based predominantly on comparison and
open-label studies (level II evidence) as well as expert opinion and consensus
statements (level III evidence). MAIN MESSAGE: Young women with acneiform facial
eruptions often present in primary care. Differentiating between morphologically
similar conditions is often difficult. Accurate diagnosis is important because
treatment approaches are different for each disease. CONCLUSION: Careful visual
assessment with an appreciation for subtle morphologic differences and associated
clinical factors will help with diagnosis of these common acneiform facial
eruptions and lead to appropriate management.

HER1/EGFR inhibitor-associated rash: future directions for management and investigation outcomes from the HER1/EGFR inhibitor rash management forum. Pérez-Soler R, Delord JP, Halpern A, Kelly K, Krueger J, Sureda BM, von Pawel J, Temel J, Siena S, Soulières D, Saltz L, Leyden J. Oncologist. 2005 May;10(5):345-56.

Skin rash associated with HER1/epidermal growth factor receptor (EGFR) inhibitors
is common. The lack of clinical and patient guidance for this often chronic and
sometimes distressing side effect makes rash management and etiology
investigation high priorities. To address this, oncologists and dermatologists
with experience with HER1/EGFR inhibitors attended the HER1/EGFR Inhibitor Rash
Management Forum. Recommendations include continued analysis of the correlation
between rash and clinical outcome and improving the accuracy and reproducibility
of terminology and grading systems. Because acne vulgaris has a unique pathology,
and the pathology and etiology of rash are unclear yet distinct from acne
vulgaris, using such terms as acne, acne-like, or acneiform should be avoided.
Until there is a specific dermatological definition, rash is best described using
phenotypic terms for its appearance and location. It is currently unknown which
agents are best for treating rash. Clinical trials of rash treatments are
urgently required, and suggestions for agents to consider are made based on
current knowledge. The effect of dose reduction or interruption on rash should
also be investigated. Secondarily infected rash may be more frequent than has
been previously recognized, and some investigators favor empiric use of an oral
antibiotic if this appears to be the case. Suggestions for patients include
makeup to camouflage the rash and an emollient to prevent and alleviate skin
dryness. The increasing use of HER1/EGFR-targeted agents makes managing rash
important. We hope the outcomes from this Forum provide background for future
studies.

[Acne vulgaris] [Article in German] Jessberger B, Worret WI. Med Monatsschr Pharm. 2005 Apr;28(4):117-22.

Polycystic ovary syndrome in adolescent girls. Pfeifer SM. Semin Pediatr Surg. 2005 May;14(2):111-7.

Polycystic ovary syndrome (PCOS) has traditionally been thought of as a triad of
oligomenorrhea, hirsutism, and obesity. PCOS is now recognized as a heterogeneous
disorder that results in overproduction of androgens primarily from the ovary
leading to anovulation and hirsutism and is associated with insulin resistance.
Symptoms in the adolescent include oligomenorrhea, hirsutism, acne, and weight
gain. These symptoms are often attributed to normal pubertal events, which can
lead to a delay in diagnosis. Insulin resistance, impaired glucose tolerance and
diabetes have been shown to occur in adolescents with PCOS. Treatment should be
instituted early to decrease symptoms and long-term sequellae of PCOS. Weight
loss, oral contraceptives and antiandrogens are very effective in treating the
symptoms of this disorder. Insulin-sensitizing medications show promise, but
should be used with caution until larger randomized trials have shown short- and
long-term benefit and efficacy over traditional therapies in the adolescent
population.

Managing cutaneous manifestations of hyperandrogenic disorders: the role of oral contraceptives. Wiegratz I, Kuhl H. Treat Endocrinol. 2002;1(6):372-86.

Cutaneous manifestations of hyperandrogenic disorders (acne, seborrhea, hirsutism
and androgenetic alopecia) can be caused by elevated levels of free testosterone
or androgen precursors. In women with normal serum levels of testosterone or
androgen precursors, enhanced local conversion to testosterone, or to the more
potent androgen dihydrotestosterone, may lead to increased androgen activity in
the pilosebaceous unit. Large individual variations in the response to normal or
elevated androgens suggests considerable differences in local androgen metabolism
and androgen receptor-mediated activities, which may partly be related to genetic
disposition. Androgens cause opposite effects on hair follicles in the scalp
compared with the face and body, and there are large differences in the length of
anagen phase. Androgens enhance sebum production and keratinization, prolong the
growth phase of face and body hair, stimulate the transformation of vellus to
terminal hair, and shorten the anagen phase of scalp hair. Estrogens may
antagonize the androgen-induced actions on sebaceous glands and hair follicles.
Treatment with oral contraceptives (OCs) reduces the production of androgens and
androgen precursors and increases sex hormone-binding globulin, resulting in a
decrease of free testosterone levels. According to type and dose, the estrogen
and progestogen components of OCs may directly reduce the effect of androgens
within sebaceous glands and hair follicles. Therefore, OCs with a predominant
estrogen effect may improve mild to moderate forms of acne and seborrhea,
hirsutism and androgenetic alopecia, in a time-dependent manner. In women who do
not respond satisfactorily, treatment with OCs containing a progestogen with
antiandrogenic activity is recommended. In many women with severe acne or
hirsutism, a considerable increase in the local concentration of the
antiandrogenic progestogen is required to reduce the androgenic interaction with
the androgen receptor. For this therapy, an OC containing cyproterone acetate can
be used. If necessary, the dose of cyproterone acetate can be increased in a
stepwise manner. While androgenetic alopecia is best treated with a low-dose OC
containing cyproterone acetate (optimal effect occurs after at least 12 months of
therapy), severe acne and hirsutism are significantly improved after 6-12 months
of regimens containing high doses of cyproterone acetate (25-100 mg/day). After
termination of treatment the disorders may reappear, therefore treatment with
suitable low-dose formulations is recommended to maintain the therapeutic effect.

The use of topical retinoids for inflammatory acne: a review of the pharmacoeconomic considerations. Harper J. Manag Care Interface. 2005 Mar;18(3):51-5.

Few pharmacoeconomic studies exist regarding the use of topical retinoids for
inflammatory acne vulgaris. Those pharmacoeconomic studies that do exist
predictably involve new entrants (topical tazarotene in various formulations).
The use of topical retinoids in combination with antimicrobial agents constitutes
cost-effective therapy for inflammatory acne. The growing U.S. trend toward use
of isotretinoin for less-severe forms of acne instead of topical retinoid-based
combination therapy is problematic from clinical and cost perspectives. More
pharmacoeconomic studies that consider the importance of compliance are necessary
for clinicians and managed care professionals to make informed choices about the
treatment of inflammatory acne.

Clinical practice. Acne. James WD. N Engl J Med. 2005 Apr 7;352(14):1463-72.

Microdermabrasion. Spencer JM. Am J Clin Dermatol. 2005;6(2):89-92.

Microdermabrasion is a simple, safe, office cosmetic procedure in which aluminum
oxide crystals or other abrasive substances are blown onto the face, then
vacuumed off, using a single handpiece. This procedure has rapidly become widely
utilized for a variety of cosmetic objectives, including the improvement of
photoaging, hyperpigmentation, acne, scars and stretch marks. Despite its
widespread use, little is known about its actual mechanism of action. The few
published studies suggest that patients and physicians alike report a mild
benefit when microdermabrasion is utilized for photoaging. Histologic evaluation
reveals little actual abrasion of the skin with the procedure, yet changes are
seen in the dermis. Given the safety, simplicity and patient satisfaction
associated with microdermabrasion, it is likely to remain a popular treatment.

Acne vulgaris: a review of antibiotic therapy. Tan AW, Tan HH. Expert Opin Pharmacother. 2005 Mar;6(3):409-18.

Antibiotic therapy has been integral to the management of inflammatory acne
vulgaris for many years. Systemic antibiotics work via antibacterial,
anti-inflammatory and immunomodulatory modes of action, and have been found to be
useful in managing moderate-to-severe acne. Commonly prescribed antibiotics
include tetracyclines, erythromycin and trimethoprim, with or without
sulfamethoxazole. In selecting the appropriate antibiotic for patients needing to
receive topical or systemic antibiotic therapy, the clinician should take into
account the severity of the acne, cost-effectiveness, the safety profile of the
drug and the potential for development of resistance. The widespread and
long-term use of antibiotics over the years has unfortunately led to the
emergence of resistant bacteria. The global increase in the antibiotic resistance
of Propionibacterium acnes may be a significant contributing factor in treatment
failures. It is therefore essential that clinicians prescribing antibiotics for
the treatment of acne adopt strategies to minimise further development of
bacterial resistance. This includes addressing compliance issues, using
combination therapies, avoiding prolonged antibiotic treatment, and avoiding
concomitant topical and oral antibiotics with chemically dissimilar antibiotics.

Polycystic ovary syndrome. Ehrmann DA. N Engl J Med. 2005 Mar 24;352(12):1223-36.

Acne vulgaris. Kerkemeyer K. Plast Surg Nurs. 2005 Jan-Mar;25(1):31-5.

Vitex agnus castus: a systematic review of adverse events. Daniele C, Thompson Coon J, Pittler MH, Ernst E. Drug Saf. 2005;28(4):319-32.

Vitex agnus castus L. (VAC) [Verbenaceae] is a deciduous shrub that is native to
Mediterranean Europe and Central Asia. Traditionally, VAC fruit extract has been
used in the treatment of many female conditions, including menstrual disorders
(amenorrhoea, dysmenorrhoea), premenstrual syndrome (PMS), corpus luteum
insufficiency, hyperprolactinaemia, infertility, acne, menopause and disrupted
lactation. The German Commission E has approved the use of VAC for irregularities
of the menstrual cycle, premenstrual disturbances and mastodynia. Clinical
reviews are available for the efficacy of VAC in PMS, cycle disorders,
hyperprolactinaemia and mastalgia, but so far no systematic review has been
published on adverse events or drug interactions associated with VAC. Therefore,
this review was conducted to evaluate all the available human safety data of VAC
monopreparations. Literature searches were conducted in six electronic databases,
in references lists of all identified papers and in departmental files. Data from
spontaneous reporting schemes of the WHO and national drug safety bodies were
also included. Twelve manufacturers of VAC-containing preparations and five
herbalist organisations were contacted for additional information. No language
restrictions were imposed. Combination preparations including VAC or homeopathic
preparations of VAC were excluded. Data extraction of key data from all articles
reporting adverse events or interactions was performed independently by at least
two reviewers, regardless of study design. Data from clinical trials,
postmarketing surveillance studies, surveys, spontaneous reporting schemes,
manufacturers and herbalist organisations indicate that the adverse events
following VAC treatment are mild and reversible. The most frequent adverse events
are nausea, headache, gastrointestinal disturbances, menstrual disorders, acne,
pruritus and erythematous rash. No drug interactions were reported. Use of VAC
should be avoided during pregnancy or lactation. Theoretically, VAC might also
interfere with dopaminergic antagonists. Although further rigorous studies are
needed to assess the safety of VAC, the data available seem to indicate that VAC
is a safe herbal medicine.

Psychosocial effects of acne. Thomas DR. J Cutan Med Surg. 2004;8 Suppl 4:3-5.

This article discusses the psychological effect of acne vulgaris. It is shown
that acne has significant effect on self-image and impacts quality of life. The
impact of acne may be equivalent to that of asthma or epilepsy. Anxiety and
depression and a reduction in social functioning are a consequence of this
condition. Effective treatment results in improvement of quality-of-life
measurement. Most of the data is gathered from case control studies. Further
work, particularly prospective longitudinal cohort studies, needs to be performed
to validate the impact of acne on quality of life. Acne severity grading should
incorporate life quality scores to better establish the true impact of this
condition on our patients in order to optimize therapy.

Hormonal therapy of acne. Haroun M. J Cutan Med Surg. 2004;8 Suppl 4:6-10.

Hormonal treatment of acne: review of current best evidence. Tan J. J Cutan Med Surg. 2004;8 Suppl 4:11-5.

BACKGROUND: Recent controlled clinical trials have demonstrated the efficacy of
various hormonal preparations, including oral contraceptives, in treatment of
acne. OBJECTIVE: The goal of this article is to evaluate the best current
evidence on the efficacy of hormonal treatment of acne. METHODS: English-language
controlled clinical trials of systemic hormonal treatment of acne were sought by
search of references of general dermatology texts, reviews on acne, drug product
monographs, and computer-assisted search of MEDLINE, CINAHL, and COCHRANE
databases between 1970 and 2003 using the key words hormonal, oral contraceptive,
acne, spironolactone, cyproterone, flutamide, and therapy. For each agent,
studies fulfilling the highest level of evidence were selected for further
evaluation. RESULTS: The literature search recovered two placebo-controlled
random controlled trials (RCTs) each of ethinyl estradiol 0.035 mg and
norgestimate and ethinyl estradiol 20 microg and leonorgestrel 100 microg, three
active-comparator RCTs of ethinyl estradiol 0.035 mg and cyproterone acetate 2
mg, one active comparator RCT of ethinyl estradiol 30 mug and drosperinone 3 mg,
three small placebo-controlled RCTs of spironolactone, and one active-comparator
RCT of flutamide. CONCLUSIONS: The efficacy of Tri-Cyclen and Alesse in acne is
supported by high-quality RCTs (level A evidence). Evidence for the efficacy of
Diane-35, spironolactone, and flutamide is derived from lower-quality RCTs (level
B evidence). Results from a population-based epidemiological study suggests that
Diane-35 is the most effective of these oral contraceptives in the treatment of
acne (level B evidence; epidemiological study).

Practical approach to the hormonal treatment of acne. Poulin Y. J Cutan Med Surg. 2004;8 Suppl 4:16-21.

Acne is a disease of the pilosebaceous units and these are mainly under hormonal
control. In female patients, hormonal therapy is a unique opportunity for the
treatment of acne. Several combined oral contraceptives (COCs), cyproterone
acetate, spironolactone, flutamide, and others, have been tried for the control
of acne. An overview on the use of the most useful drugs in clinical practice was
conducted. COCs are thoroughly discussed, also taking into consideration their
potential side effects. A practical approach with guidelines on the use of COC in
acne is proposed.

A review of clinical experience and recommendations for improving patient care. Weiss J. Cutis. 2005 Feb;75(2 Suppl):32-8; discussion 39.

This article reviews the history of retinoids from the 1960s to the present,
clinical experiences, and recommendations for improving care for patients with
acne. How a retinoid is chosen by the clinician based on irritation potential,
treatment outcome, patient profile, type of acne, and the patient's clinical
experience is discussed, as well as the use of retinoids in the treatment of
photoaging and other approved and off-label uses.

An update on the safety and efficacy of topical retinoids. Phillips TJ. Cutis. 2005 Feb;75(2 Suppl):14-22, 24; discussion 22-3.

Adapalene, tazarotene, and tretinoin are topical retinoids that are approved by
the US Food and Drug Administration (FDA) and have overall favorable safety
profiles. These agents are effective in a variety of skin disorders. Local
adverse events, seen especially during the early course of treatment, include
peeling, erythema, dryness, burning, and itching. The degree of local skin
intolerance varies among patients and may relate to the vehicle formulation used.
These local effects can be minimized by decreasing exposure to sunlight, avoiding
extreme temperatures, and using moisturizers. Use of these agents has been found
to be advantageous over current systemic retinoids from a toxicologic
perspective. This article reviews the safety, efficacy, and photostability of the
available topical retinoids.

The mechanism of action of topical retinoids. Kang S. Cutis. 2005 Feb;75(2 Suppl):10-3; discussion 13.

UV irradiation of human skin sets in motion a complex sequence of events that
causes damage to the dermal matrix. When topical tretinoin is applied to human
skin, any collagen deficiency existing in photoaged skin is remedied at least
partially, and the skin is primed to prevent further matrix degradation induced
by solar UV. Retinoids, therefore, have become essential in the treatment and
prevention of photoaging. This article describes the mechanism of action of
retinoids, including how they are mediated through retinoic acid receptors (RARs)
and retinoid X receptors (RXRs), how they block inflammation mediators, and how
production of procollagen is increased to augment the formation of types I and
III collagen. Three naturally occurring retinoids are reviewed.

Topical tretinoin or adapalene in acne vulgaris: an overview. Jain S. J Dermatolog Treat. 2004 Jul;15(4):200-7.

Retinoids target several pathoetiologic events of acne vulgaris. The undisputed
efficacy of tretinoin, and yet its underutilization, due to apprehension of
retinoid dermatitis, triggered a search for newer, well-tolerated retinoids. The
discovery of nuclear retinoic acid receptors has provided clues to a rational
design of synthetic, receptor-selective retinoic acid agonists. Adapalene is an
addition to the arsenal of topical retinoids. It possesses the biological
properties of tretinoin, but has a distinct physiochemical profile, including
high lipophilicity and increased chemical and photostability. It exhibits
selective affinity for nuclear retinoic acid receptors and does not bind to
cytosolic retinoic acid binding proteins. It exemplifies the formulation of a
novel retinoid with specific pharmacologic profile and clinical objectives.
Accordingly, numerous clinical trials have compared adapalene and tretinoin in
the management of acne vulgaris and concluded that tretinoin 0.05% gel exhibits a
greater anti-acne efficacy than adapalene 0.1% gel, but has higher skin
irritation potential. This article reviews the pharmacology of adapalene,
including its retinoid receptor binding profile, antiproliferative effects, cell
differentiation modulation, comedolytic and anti-inflammatory activity, and
specifically focuses on the comparison of the efficacy and irritation profile of
adapalene and tretinoin.

The potential immunomodulatory effects of topical retinoids. Jones DA. Dermatol Online J. 2005 Mar 1;11(1):3.

New research has refined our understanding of the immunopathophysiology of acne.
Various immune factors, including both innate and adaptive immune responses, have
been implicated in the pathophysiology of inflammatory acne. Topical retinoids
such as tretinoin, adapalene, and tazarotene, exhibit immunomodulatory effects
that may help to explain their efficacy in the resolution of inflammatory
lesions.

Transcriptional activities of retinoic acid receptors. Lefebvre P, Martin PJ, Flajollet S, Dedieu S, Billaut X, Lefebvre B. Vitam Horm. 2005;70:199-264.

Vitamin A derivatives plays a crucial role in embryonic development, as
demonstrated by the teratogenic effect of either an excess or a deficiency in
vitamin A. Retinoid effects extend however beyond embryonic development, and
tissue homeostasis, lipid metabolism, cellular differentiation and proliferation
are in part controlled through the retinoid signaling pathway. Retinoids are also
therapeutically effective in the treatment of skin diseases (acne, psoriasis and
photoaging) and of some cancers. Most of these effects are the consequences of
retinoic acid receptors activation, which triggers transcriptional events leading
either to transcriptional activation or repression of retinoid-controlled genes.
Synthetic molecules are able to mimic part of the biological effects of the
natural retinoic acid receptors, all-trans retinoic acid. Therefore, retinoic
acid receptors are considered as highly valuable therapeutic targets and limiting
unwanted secondary effects due to retinoid treatment requires a molecular
knowledge of retinoic acid receptors biology. In this review, we will examine
experimental evidence which provide a molecular basis for the pleiotropic effects
of retinoids, and emphasize the crucial roles of coregulators of retinoic acid
receptors, providing a conceptual framework to identify novel therapeutic
targets.

RALGA (Diacneal), a retinaldehyde and glycolic acid association and postinflammatory hyperpigmentation in acne--a review. Katsambas AD. Dermatology. 2005;210 Suppl 1:39-45.

Acne vulgaris affects 3 out of 4 adolescents and usually vanishes at the end of
puberty with either no sequelae or mild to moderate sequelae, such as
postinflammatory hyperpigmenation (PIH), which may result in psychological and
emotional damages. The poor tolerability of the actual treatments (secondary
inflammation) is a hindrance to therapy. Retinaldehyde (RAL), a precursor of
retinoic acid, has shown depigmenting activity. Glycolic acid (GA) decreases the
excess of pigment by a wounding and re-epithelization process. Thus, a
synergistic effect was expected from the combination of RAL 0.1% and GA 6% RALGA
(Diacneal) in the treatment of acne vulgaris and PIH. Efficacy results of
preclinical and clinical trials tend to confirm the expectations for both acne
and PIH treatment. A good tolerability was observed. In conclusion, the cosmetic
cream Diacneal is a well-tolerated treatment for the prevention and healing of
PIH in acne patients.

Polycystic ovary syndrome in adolescence. New insights in pathophysiology and treatment. Homburg R. Endocr Dev. 2005;8:137-49.

Polycystic ovary syndrome (PCOS) is a prevalent cause of menstrual disorders,
acne and hirsutism presenting during adolescence. In the majority of cases, a
familial trait is obvious but the offending genes have yet to be identified.
However, much of the pathophysiology of the syndrome causing the overproduction
of ovarian androgens is now becoming clearer. The early diagnostic signs are
often mistakenly dismissed as normal changes of adolescence but it is important
to make an early diagnosis in order to save the adolescent from the early and
late stigmata of the syndrome. The avoidance of overweight, frank obesity and the
consequential exaggeration of symptoms by the associated insulin resistance is of
prime importance as hyperinsulinemia plays a key role in the pathogenesis.
Anti-androgens are the most widely used medication and, in combination with
estrogen, are capable of restoring menstrual regularity and reducing the symptoms
of acne and hirsutism, so important for the improvement of the disturbing
psychosocial effect that they may play at this age. The use of metformin, an
insulin sensitizer, for affected adolescents is the topic of a presently heated
debate.

Isotretinoin, depression and suicide: a review of the evidence. Magin P, Pond D, Smith W. Br J Gen Pract. 2005 Feb;55(511):134-8.

There is currently considerable controversy regarding a proposed causal
relationship between the use of isotretinoin and depression and suicide. A search
was made of the MEDLINE, EMBASE and PsychINFO databases using the search terms
'isotretinoin', 'depression' and 'suicide'. Despite numerous case reports linking
isotretinoin to depression, suicidal ideation and suicide, there is, as yet, no
clear proof of an association. While isotretinoin, used to treat acne vulgaris,
has not been demonstrated to be associated with depression or suicide, the
possibility of a relatively rare idiosyncratic adverse effect remains. GPs have a
role in the clinical application of these findings.

[The wider application of photodynamic therapy in dermatology] [Article in Dutch] Thissen MR, Kuijpers DI, Neumann HA. Ned Tijdschr Geneeskd. 2005 Jan 29;149(5):232-7.

Photodynamic treatment is increasingly employed in the detection and treatment of
malignant and non-malignant skin disease. --Indications for photodynamic therapy
so far are actinic keratosis, Bowen's disease and superficially growing basal
cell carcinomas, and probably verrucae and acne vulgaris. --This technology is
also currently under investigation for fluorescence diagnostics oftumour margins.
--The exact position of photodynamic therapy has not yet been established because
there are too less long-term comparative studies demonstrating its effectiveness.
--Based on the short-term results, photodynamic therapy deserves a place within
the total therapeutic arsenal of the dermatologist of today for the indications
mentioned above.

Mechanisms of the comedolytic and anti-inflammatory properties of topical retinoids. Bikowski JB. J Drugs Dermatol. 2005 Jan-Feb;4(1):41-7.

Retinoids comprise a family of compounds with structures and mechanisms of action
that resemble those of vitamin A (retinol), an essential nutrient which plays a
role in cell growth and differentiation. The retinoids, which interact with
nuclear receptors and affect gene transcription, have enormous therapeutic
potential, particularly if they are receptor- and function-selective. Tretinoin
was the first topical retinoid employed for the treatment of acne. In recent
years, other topical retinoids for the treatment of acne have been designed from
a disease-specific approach, with enhanced receptor and function selectivity,
which translates to improved therapeutic effects and more favorable tolerability.
The properties that differentiate the topical retinoids tretinoin, adapalene, and
tazarotene have permitted clinicians to tailor acne treatment regimens for
maximum therapeutic outcomes. Tretinoin (all-trans-retinoic acid), considered a
first-generation retinoid, acts by altering the milieu of the microcomedo and
influences desquamation of abnormal epithelium. Two receptor-selective synthetic
retinoids, adapalene and tazarotene, may be classified as third-generation
retinoids. Adapalene, a derivative of naphthoic acid, has comedolytic,
antiproliferative, and anti-inflammatory properties. Tazarotene is a prodrug
metabolized to tazarotenic acid that modulates cellular differentiation,
desquamation, and inflammation.

Diagnosis and treatment of polycystic ovarian syndrome. Jones AE. Nurs Times. 2005 Jan 18-24;101(3):40-3.

Polycystic ovarian syndrome is a hormonal disturbance that results in a
collection of symptoms and has wide-ranging health implications. There is
evidence that it may run in families, and it is associated with the development
of type 2 diabetes and recurrent miscarriage. Diagnosis involves eliminating
other potential conditions, while treatment aims to manage individual symptoms
rather than provide a cure.

A review of the use of infliximab to manage cutaneous dermatoses. Gupta AK, Skinner AR. J Cutan Med Surg. 2004 Mar-Apr;8(2):77-89. Epub 2004 May 4.

BACKGROUND: Infliximab is a chimeric monoclonal antibody that binds specifically
to human tumor necrosis factor-alpha (TNF-alpha), decreasing the effect of the
cytokine in inflammatory diseases. OBJECTIVE: The aim of this study was to review
the efficacy and safety of infliximab in the treatment of dermatological
diseases. METHODS: A MEDLINE search (1966-January 2003), using the keyword
"infliximab" was performed to find relevant articles pertaining to the use of
infliximab in dermatology. RESULTS: Infliximab has been used in the following
dermatological diseases: psoriasis, Behcet's disease, graft versus host disease,
hidradenitis suppurativa, panniculitis, pyoderma gangrenosum, SAPHO (synovitis,
acne, pustulosis, hyperostosis and osteitis) syndrome, sarcoidosis, subcorneal
pustular dermatosis, Sweet's syndrome, toxic epidermal necrolysis, and Wegener's
granulomatosis. There is a generally good safety profile for infliximab, which is
similar to that when it is used to treat Crohn's disease and rheumatoid
arthritis. CONCLUSION: Although not approved for use in dermatological diseases,
there have been numerous reports of the efficacy of infliximab in cutaneous
inflammatory diseases. The most promise lies in those diseases that have
increased amounts of TNF-alpha in the cutaneous lesions, such as psoriasis.

[Human beta defensins: a new perspective in acne treatment?] [Article in German] Körber A, Lehnen M, Grabbe S, Dissemond J. Dtsch Med Wochenschr. 2005 Feb 4;130(5):210-2.

Medication-induced intracranial hypertension in dermatology. Friedman DI. Am J Clin Dermatol. 2005;6(1):29-37.

Pseudotumor cerebri (PTC) is a syndrome of intracranial hypertension that is
idiopathic or from an identified secondary cause. It is characterized by
headaches and visual manifestations. The hallmark of PTC is papilledema and the
feared consequence is visual loss that may be severe and permanent. The
idiopathic form generally occurs in obese women of childbearing age.Various
medications may produce PTC in patients at any age, including children. Several
medications used in dermatology, particularly those used in the treatment of acne
vulgaris, are associated with PTC. There is a strong association with
tetracycline usage. Minocycline and doxycycline have also been linked to PTC,
although there are relatively few reported cases. PTC has also been described
with retinoids, including vitamin A (retinol) and isotretinoin. Although
corticosteroids are often used to lower intracranial pressure acutely,
corticosteroid withdrawal after long-term administration may induce increased
intracranial pressure. A high index of suspicion, early diagnosis and treatment
generally yield a good prognosis.

Retinoid therapy for acne. A comparative review. Chivot M. Am J Clin Dermatol. 2005;6(1):13-9.

Retinoids play a vital role in the treatment of acne because they act on the
primary lesion, the microcomedo. They are synthetic derivatives of vitamin A
(retinol), and are selected for their effectiveness. Several compounds are used
for acne, either in topical or systemic form.We describe and compare the
different topical retinoids, tretinoin (all-trans-retinoic acid), isotretinoin
(13-cis-retinoic acid), adapalene (derived from naphthoic acid), and tazarotene
(acetylenic retinoid). They act mainly as comedolytics, but anti-inflammatory
actions have also been discovered recently. The retinoids have great beneficial
effects, but also some adverse effects, the main one being teratogenicity. It is
preferable not to use them in topical form for pregnant women, although a
pregnancy test is only compulsory for tazarotene.Only isotretinoin is used in
systemic form. It acts on all the factors of acne and offers long remissions, and
sometimes complete cures. Precautions must be taken for women of childbearing age
due to its teratogenicity. It is also important to be aware of its other adverse
effects, explain them to the patient and, if possible, deal with them in advance.

Acne and its management beyond the age of 35 years. Marks R. Am J Clin Dermatol. 2004;5(6):459-62.

Although acne is not usually considered to be a disorder that affects the
elderly, the disorder occurs sufficiently often in mature individuals to be
noteworthy. The variety known as 'persisting acne' is, as its name suggests,
ordinary acne that continues into adult life. 'Chin acne' is a curious type that
occurs premenstrually in mature women, while 'sporadic acne' describes the sudden
development of significant acne in later life for no apparent reason. When acne
develops in an individual outside the usual susceptible age group precipitating
causes such as exposure to comedogenic substances or drugs must be excluded.
Similarly, endocrine causes such as androgen-secreting tumors and the
administration of anabolic steroids need to be considered. All inflammatory
processes are decreased in the elderly and this may be one reason for the
persistence and intransigence of acne lesions in older age groups. The principles
of treatment of acne in the elderly do not differ from those in other age groups,
although the emphasis during counseling needs to focus on explanation and
reassurance rather than prognosis. Topical retinoids and benzoyl peroxide easily
irritate elderly skin, so azelaic acid and even sulfur preparations are
preferable. Low-dose systemic isotretinoin is reported to be helpful to patients
in this age group and is certainly worth a trial.

Selecting an oral contraceptive agent for the treatment of acne in women. van Vloten WA, Sigurdsson V. Am J Clin Dermatol. 2004;5(6):435-41.

In women, acne can be successfully treated with oral contraceptives. This article
focuses on the results of clinical studies on the treatment of acne with oral
contraceptives. From the literature, 12 such studies could be traced over the
last 10 years. Most of the studies were multicenter, randomized, and double
blind. Five studies were placebo controlled. All of these studies were analyzed
and compared with each other. Statistically, all placebo-controlled studies
showed a better result with the active treatment, than with the placebo. However,
the placebo groups also showed an improvement in the acne lesions. In seven
studies, two oral contraceptives were compared for their effect on acne vulgaris.
All oral contraceptives studied showed a beneficial effect on the severity of
acne.It can be concluded, based on these studies, that all oral contraceptives
have a more or less beneficial effect on mild to moderate acne in women.
Comparing the various clinical trials, ethinylestradiol/drospirenone is as good
as ethinylestradiol/cyproterone, which is slightly better than
ethinylestradiol/desogestrel and ethinylestradiol/gestodene.
Ethinylestradiol/chlormadinone is slightly better than
ethinylestradiol/levonorgestrel, which is as effective as
ethinylestradiol/norethindrone, which is far better than the placebo.
Ethinylestradiol/norgestimate is better than placebo.

Light-emitting diode-based therapy. Abramovits W, Arrazola P, Gupta AK. Skinmed. 2005 Jan-Feb;4(1):38-41.

[How I treat... Belgian consensus document on the treatment of acne] [Article in French] de la Brassinne M, De Weert J, Lambert J. Rev Med Liege. 2004 Nov;59(11):626-9.

This article describes the consensus on the treatment of acne, reached by a
Belgian working group. An effective treatment has to rely as much as possible on
the pathophysiologic factors: the increased production of sebum, the abnormal
desquamation (retention hyperkeratosis) of the epithelium of he sebaceous gland,
the proliferation of Propionibacterium acnes and inflammation. The therapeutic
arsenal contains topical as well as systemic drugs. This consensus gives an
overview of both modalities and an algorithm is presented describing the
practical approach to acne treatment.

A systematic review of the evidence for 'myths and misconceptions' in acne management: diet, face-washing and sunlight. Magin P, Pond D, Smith W, Watson A. Fam Pract. 2005 Feb;22(1):62-70. Epub 2005 Jan 11.

BACKGROUND: Lay perceptions that diet, hygiene and sunlight exposure are strongly
associated with acne causation and exacerbation are common but at variance with
the consensus of current dermatological opinion. OBJECTIVES: The objective of
this study was to carry out a review of the literature to assess the evidence for
diet, face-washing and sunlight exposure in acne management. METHODS: Original
studies were identified by searches of the Medline, EMBASE, AMED (Allied and
Complementary Medicine), CINAHL, Cochrane, and DARE databases. Methodological
information was extracted from identified articles but, given the paucity of high
quality studies found, no studies were excluded from the review on methodological
grounds. RESULTS: Given the prevalence of lay perceptions, and the confidence of
dermatological opinion in rebutting these perceptions as myths and
misconceptions, surprisingly little evidence exists for the efficacy or lack of
efficacy of dietary factors, face-washing and sunlight exposure in the management
of acne. Much of the available evidence has methodological limitations.
CONCLUSIONS: Based on the present state of evidence, clinicians cannot be
didactic in their recommendations regarding diet, hygiene and face-washing, and
sunlight to patients with acne. Advice should be individualized, and both
clinician and patient cognizant of its limitations.

Understanding symptoms and management of skin disorders. Freak J. Nurs Times. 2004 Dec 7-13;100(49):34-7.

It is estimated that at any one time about 25 per cent of the population has a
skin problem that could benefit from medical care. Skin diseases can be
physically disabling, disfiguring, painful, intensely irritating and distracting.
Relatively few skin diseases are life-threatening, but they can all have severe
psychological, physical and social effects.

Index of suspicion. Duong M, Dinoulos JG, Gupta A, Bryk T, Saps M, Di Lorenzo C, Sveen A, Waseem M, Kin LL. Pediatr Rev. 2005 Jan;26(1):23-33.

Use of macrolides and tetracyclines for chronic inflammatory diseases. Voils SA, Evans ME, Lane MT, Schosser RH, Rapp RP. Ann Pharmacother. 2005 Jan;39(1):86-94. Epub 2004 Nov 23.

OBJECTIVE: To review the efficacy of macrolides and tetracyclines in several
chronic inflammatory conditions. DATA SOURCES: Searches of MEDLINE (1966-March
2004) and an extensive bibliography search were undertaken. Key terms included
acne, blepharitis, cardiovascular disease, cystic fibrosis, periodontitis,
rosacea, and rheumatoid arthritis. STUDY SELECTION AND DATA EXTRACTION: Data were
obtained primarily from randomized placebo-controlled trials upon which key
recommendations are based. DATA SYNTHESIS: Antibiotics are often prescribed for
months or even years for treatment of chronic inflammatory conditions such as
acne, blepharitis, cardiovascular disease, cystic fibrosis, periodontitis,
rosacea, and rheumatoid arthritis. Randomized controlled trials have shown that
azithromycin is useful in the management of cystic fibrosis and the tetracyclines
are beneficial in the management of rheumatoid arthritis, acne, blepharitis, and
periodontitis. Several large, randomized controlled trials have failed to show
any benefit of macrolides in the secondary prevention of cardiovascular disease.
No randomized placebo-controlled clinical trials have been performed to assess
the efficacy of macrolides or tetracyclines in patients with rosacea.
CONCLUSIONS: The use of tetracyclines and macrolides for rosacea is based
primarily on anecdotal reports or open-label trials. Limited clinical trials
support the use of tetracyclines or macrolides in acne, blepharitis,
periodontitis, rheumatoid arthritis, and cystic fibrosis. Trials to date do not
support the use of antibiotics for secondary prevention of cardiovascular
disease.

[S.A.PH.O. syndrome: a still little known clinical syndrome] [Article in Italian] Colina M, Lo Monaco A, Trotta F. Recenti Prog Med. 2004 Oct;95(10):491-6.

S.A.P.H.O. syndrome is characterized by the association, even not simultaneous,
of osteoarticular and cutaneous manifestations. This review has the purpose to
clear up some features of clinical manifestations and the osteo-articular
involvement. Articular mainly feature is the involvement of anterior chest wall,
that begins with slow evolving pain. Skin involvement is characterized by acne
conglobata and pustolosis palmaris-plantaris. Instrumental investigations that
fit better for studying the anterior chest wall, complex region, are bone
scintigraphy, computed tomography and nuclear magnetic resonance, with their
domain pattern. Symptomatic therapy are mostly represented by NSAIDs, but still
opiate drugs can be prescribed; corticosteroids have variable and unforeseeable
efficacy. Bisphosfonates are usually utilized due to their anti-osteoclastic
effects. Finally, because of documented incremented production of TNFalpha,
TNFalpha blocking agents should be effectively utilized.

Guidelines for treating acne. Katsambas AD, Stefanaki C, Cunliffe WJ. Clin Dermatol. 2004 Sep-Oct;22(5):439-44.

Acne, a chronic inflammatory disease of the pilosebaceous units of the face,
neck, chest, and back, is the most common skin disorder occurring universally,
with an estimated prevalence of 70-87%.(1) It is a pleomorphic disorder
characterized by both inflammatory (papules, pustules, nodules) and
noninflammatory (comedones, open and closed) lesions. Grading of acne is
mandatory to determine the appropriate therapeutic strategy. Mild acne can be
purely comedonal or mild papulopustular, with a few papulopustules present as
well.(2) Moderate acne is characterized by numerous comedones, few to many
pustules, and few small nodules, with no residual scarring.(2) In severe acne
papulopustules are numerous, many nodules can be detected, inflammation is
marked, and scarring is present.(2) Very severe acne can be recognized by sinus
tracts, grouped comedones, many deeply located nodules, and severe inflammation
and scarring.(2) Although acne does not affect health overall, its impact on
emotional well-being and function can be critical and is often associated with
depression, anxiety, and higher-than-average unemployment rates.(3) Effective
treatment can dramatically improve a person's quality of life.

Acne: treatment of scars. Jemec GB, Jemec B. Clin Dermatol. 2004 Sep-Oct;22(5):434-8.

Acne is a common disease affecting a significant proportion of the
population.(1-3) It causes considerable morbidity through soreness,
disfigurement, and social handicap due to inflammatory lesions.(4,5) Modern
therapy ensures that a considerable proportion of all patients can be offered
effective treatment of their disease, but the morbidity is not restricted solely
to the inflammatory lesions of acne.(6,7) Despite appropriate and effective
primary prevention of scarring, scarring occurs in some degree in 95% of all
patients irrespective of the severity of inflammatory acne (although severe acne
causes more scarring than the milder forms). The scarring causes long-term
morbidity that requires specific therapy.(7)

Acne: physical treatment. Dreno B. Clin Dermatol. 2004 Sep-Oct;22(5):429-33.

Different physical treatments may be used in acne therapy. The main indications
are for treating retentional lesions (open and comedones), inflamed lesions, and
scars.

Acne: hormonal concepts and therapy. Thiboutot D. Clin Dermatol. 2004 Sep-Oct;22(5):419-28.

Acne vulgaris is the most common skin condition observed in the medical
community. Although we know that hormones are important in the development of
acne, many questions remain unanswered regarding the mechanisms by which hormones
exert their effects. Androgens such as dihydrotestosterone (DHT) and
testosterone, the adrenal precursor dehydroepiandrosterone sulfate (DHEAS),
estrogens such as estradiol, and other hormones, including growth hormone and
insulin-like growth factors (IGFs), may be important in acne. It is not known
whether these hormones are taken up from the serum by the sebaceous gland,
whether they are produced locally within the gland, or whether a combination of
these processes is involved. Finally, the cellular and molecular mechanisms by
which these hormones exert their influence on the sebaceous gland have not been
fully elucidated. Hormonal therapy is an option in women with acne not responding
to conventional treatment or with signs of endocrine abnormalities.

Acne: systemic treatment. Katsambas A, Papakonstantinou A. Clin Dermatol. 2004 Sep-Oct;22(5):412-8.

Acne vulgaris is a disease affecting mostly adolescents and young adults that,
when severe, has the potential to result in scarring and permanent disfigurement.
Systemic treatment is necessary to prevent significant psychological and social
impairment in these patients.(1) Significant inflammatory and nodulocystic acne
is usually recalcitrant to topical treatment, whereas uncommon acne variants,
such as acne fulminans, pyoderma faciale, and acne conglobata, need to be
promptly and effectively controlled. In all of these circumstances, systemic
agents are indispensable. The choices include oral antibiotics, isotretinoin, and
hormonal treatment (Table 1).

Comparison of topical retinoids in the treatment of acne. Rigopoulos D, Ioannides D, Kalogeromitros D, Katsambas AD. Clin Dermatol. 2004 Sep-Oct;22(5):408-11.

Topical retinoids are been used to successfully treat acne for almost 3 decades.
At the beginning, a retinoid was a compound of similar structure and action to
retinol (vitamin A).(1) Changes at the carboxylic end group, the polyene chain,
and the aromatic ring can result in the modification of the original molecule. To
date, three generations of retinoids have been developed: the nonaromatics
(retinol, tretinoin, and isotretinoin), the monoaromatics (etretinate and
acitretin), and the polyaromatics (arotinoid, adapalene, and tazarotene). The new
synthetic retinoid molecules have little resemblance with retinol but nonetheless
are included in this family because they have the ability to bind with or
activate retinoid receptors. Therefore, retinoids are vitamins and also
hormones.(3)

Acne: topical treatment. Krautheim A, Gollnick HP. Clin Dermatol. 2004 Sep-Oct;22(5):398-407.

Acne vulgaris is a common skin disease, affecting about 70-80% of adolescents and
young adults. It is a multifactorial disease of the pilosebaceous unit.(1) The
influence of androgens at the onset of adolescence leads to an enlargement of the
sebaceous gland and a rise in sebum production. Additional increased
proliferation and altered differentiation of the follicular epithelium eventually
blocks the pilosebaceous duct, leading to development of the microcomedo as the
primary acne lesion. Concomitantly and subsequently, colonization with
Propionibacterium acnes increases, followed by induction of inflammatory
reactions from bacteria, ductal corneocytes, and sebaceous proinflammatory agents
(Fig 1).(2-5)

The assessment of acne: an evaluation of grading and lesion counting in the measurement of acne. Witkowski JA, Parish LC. Clin Dermatol. 2004 Sep-Oct;22(5):394-7.

The basic morphology of acne--comedones, papules, pustules, and nodules--and the
extent of involvement do not permit simple evaluation due to the number of
variables involved. Because these acne lesions may vary in number during the
natural course of the disease, various measurements have been developed, based on
clinical examination and photographic documentation. These range from global
assessments to lesion counting, with the latter providing more objective data.

Acne and Propionibacterium acnes. Bojar RA, Holland KT. Clin Dermatol. 2004 Sep-Oct;22(5):375-9.

The involvement of microorganisms in the development of acne has a long and
checkered history. Just over 100 years ago, Propionibacterium acnes (then known
as Bacillus acnes) was isolated from acne lesions, and it was suggested that P.
acnes was involved in the pathology of the disease. The 1960s saw the use of
antibiotics to treat acne, and the consequent clinical success combined with
reductions in P. acnes gave new impetus to the debate. Over the past two decades,
the inevitable emergence of antibiotic-resistant strains of P. acnes as a
consequence of acne therapy not only has reopened the debate as to the role of P.
acnes in acne, but also has created some serious health care implications.

Comedone formation: etiology, clinical presentation, and treatment. Cunliffe WJ, Holland DB, Jeremy A. Clin Dermatol. 2004 Sep-Oct;22(5):367-74.

An important feature in the etiology of acne is the presence of pilosebaceous
ductal hypercornification, which can be seen histologically as microcomedones
(Fig 1) and clinically as blackheads, whiteheads, and other forms of comedones,
such as macrocomedones. There is a significant correlation between the severity
of acne and the number and size of microcomedones (follicular casts), the
presence of which is a measure of comedogenesis. This correlation can be
demonstrated by skin surface biopsy using cyanoacrylate gel. In this procedure,
microcomedones are sampled by applying cyanoacrylate gel to the skin surface. A
glass microscopic slide is then applied on top of the gel and pressed firmly onto
the skin for 1 minute(1-3). The glass slide is gently removed, taking with it the
upper part of the stratum corneum and microcomedones, which are then analyzed by
low-power microscopy or digital image analysis.(1-3)

Acne and sebaceous gland function. Zouboulis CC. Clin Dermatol. 2004 Sep-Oct;22(5):360-6.

The embryologic development of the human sebaceous gland is closely related to
the differentiation of the hair follicle and the epidermis. The number of
sebaceous glands remains approximately the same throughout life, whereas their
size tends to increase with age. The development and function of the sebaceous
gland in the fetal and neonatal periods appear to be regulated by maternal
androgens and by endogenous steroid synthesis, as well as by other morphogens.
The most apparent function of the glands is to excrete sebum. A strong increase
in sebum excretion occurs a few hours after birth; this peaks during the first
week and slowly subsides thereafter. A new rise takes place at about age 9 years
with adrenarche and continues up to age 17 years, when the adult level is
reached. The sebaceous gland is an important formation site of active androgens.
Androgens are well known for their effects on sebum excretion, whereas terminal
sebocyte differentiation is assisted by peroxisome proliferator-activated
receptor ligands. Estrogens, glucocorticoids, and prolactin also influence
sebaceous gland function. In addition, stress-sensing cutaneous signals lead to
the production and release of corticotrophin-releasing hormone from dermal nerves
and sebocytes with subsequent dose-dependent regulation of sebaceous nonpolar
lipids. Among other lipid fractions, sebaceous glands have been shown to
synthesize considerable amounts of free fatty acids without exogenous influence.
Sebaceous lipids are responsible for the three-dimensional skin surface lipid
organization. Contributing to the integrity of the skin barrier. They also
exhibit strong innate antimicrobial activity, transport antioxidants to the skin
surface, and express proinflammatory and anti-inflammatory properties. Acne in
childhood has been suggested to be strongly associated with the development of
severe acne during adolescence. Increased sebum excretion is a major factor in
the pathophysiology of acne vulgaris. Other sebaceous gland functions are also
associated with the development of acne, including sebaceous proinflammatory
lipids; different cytokines produced locally; periglandular peptides and
neuropeptides, such as corticotrophin-releasing hormone, which is produced by
sebocytes; and substance P, which is expressed in the nerve endings at the
vicinity of healthy-looking glands of acne patients. Current data indicate that
acne vulgaris may be a primary inflammatory disease. Future drugs developed to
treat acne not only should reduce sebum production and Propionibacterium acnes
populations, but also should be targeted to reduce proinflammatory lipids in
sebum, down-regulate proinflammatory signals in the pilosebaceous unit, and
inhibit leukotriene B(4)-induced accumulation of inflammatory cells. They should
also influence peroxisome proliferator-activated receptor regulation.
Isotretinoin is still the most active available drug for the treatment of severe
acne.

Overview of the tolerability of gefitinib (IRESSA) monotherapy : clinical experience in non-small-cell lung cancer. Forsythe B, Faulkner K. Drug Saf. 2004;27(14):1081-92.

Cytotoxic chemotherapy treatment options for patients with non-small-cell lung
cancer (NSCLC) have limited efficacy and are often associated with significant
toxicity. Therefore, there is an unmet need for novel drugs that are not only
effective in treating this disease but are also well tolerated. Gefitinib is an
orally active epidermal growth factor receptor tyrosine kinase inhibitor that
blocks the signal transduction pathways implicated in cancer cell growth and
survival. It has recently been approved for the treatment of advanced/refractory
NSCLC. This review presents the tolerability data from phase I and II gefitinib
monotherapy trials, along with data from the worldwide 'Expanded Access
Programme' and post-marketing use of gefitinib.Gefitinib was found to be
generally well tolerated at the approved dosage of 250 mg/day; the most commonly
reported adverse drug reactions (ADRs) were mild to moderate skin rash and
diarrhoea, which were manageable and non-cumulative. Other ADRs observed with the
use of gefitinib included: dry skin, pruritus, acne, nausea, vomiting, anorexia,
asthenia and asymptomatic elevations in liver transaminase levels. Well
recognised adverse effects seen with cytotoxic chemotherapy (such as bone marrow
depression, neurotoxicity and nephrotoxicity) were not observed. Although the
frequency and severity of ADRs increased with the dosage across the range studied
(50-1000 mg/day), few patients required dosage reductions or the withdrawal of
treatment, and those who did usually received gefitinib >or=600 mg/day.Thus, the
available data indicate that gefitinib is well tolerated in patients with a range
of solid tumours, including locally advanced or metastatic NSCLC.

Spotlight on adapalene in acne vulgaris. Waugh J, Noble S, Scott LJ. Am J Clin Dermatol. 2004;5(5):369-71.

Adapalene (Differin) is a retinoid agent indicated for the topical treatment of
acne vulgaris. In clinical trials, 0.1% adapalene gel has proved to be effective
in this indication and was as effective as 0.025% tretinoin gel, 0.1% tretinoin
microsphere gel, 0.05% tretinoin cream and 0.1% tazarotene gel once every two
days; however, the drug was less effective than once-daily 0.1% tazarotene gel.
It can be used alone in mild acne or in combination with antimicrobials in
inflammatory acne and has proved efficacious as maintenance treatment. Adapalene
has a rapid onset of action and a particularly favorable tolerability profile
compared with other retinoids. These attributes can potentially promote patient
compliance, an important factor in treatment success. Adapalene is, therefore,
assured of a role in the first-line treatment of acne vulgaris.

Advances in the topical treatment of acne and rosacea. Ceilley RI. J Drugs Dermatol. 2004 Sep-Oct;3(5 Suppl):S12-22.

Acne and rosacea are common skin diseases which may present similarly and both
involve inflammation. Both can result in significant cosmetic impairment and lead
to quality of life decrements if not optimally treated. The conventional approach
for both diseases involves the use of topical therapy to treat inflammatory
lesions in combination, when needed, with a systemic or topical antibiotic. An
important issue in the management of both diseases at present is the need to
reduce antibiotic usage due to the increasing problem of bacterial resistance.
One of the emerging treatment paradigms that is becoming increasingly useful as
an antibiotic-sparing strategy is the use of procedural therapies in combination
with medical management. Such procedural modalities include lasers, intense
pulsed light (IPL), and photodynamic therapies (PDT). Topical regimens are used
pre-treatment and following physical modalities for maintenance of remission.

Combination therapy in clinical and cosmetic dermatology: the marriage of device and drug. Nestor MS. J Drugs Dermatol. 2004 Sep-Oct;3(5 Suppl):S4-11.

The first generations of lasers used in clinical and cosmetic dermatology
achieved their effects by means of epidermal and dermal ablation. While effective
in removing some of the stigmata of photodamage including pigmentary changes and
rhytides, vascular abnormalities associated with such conditions as melasma and
rosacea, were not sufficiently effective. The new generation of laser and
non-laser light devices (eg, intense pulsed light or IPL) offer excellent results
in the management of clinical and cosmetic conditions, including significant
changes in improvement in vascular conditions such as rosacea and actinic damage
and stimulating dermal collagen production, without significant injury to the
epidermis. The combination of light therapies and topical agents adds to the
efficacy of these procedures, particularly in post-procedural maintenance.
Light-based therapies have been an important addition to the anti-acne
armamentarium as they are effective and do not add to the increasing bacterial
resistance problem.

Topical retinoids in the management of acne: the best path to clear results. Del Rosso JQ. Cutis. 2004 Oct;74(4 Suppl):2-3.

[Adverse reactions to minocycline treatment of acne vulgaris] [Article in Hebrew] Somech R, Asia A. Harefuah. 1999 Apr 2;136(7):578-81.

Ocular rosacea: an update on pathogenesis and therapy. Stone DU, Chodosh J. Curr Opin Ophthalmol. 2004 Dec;15(6):499-502.

PURPOSE OF REVIEW: Ocular rosacea is a common and potentially blinding eye
disorder with an uncertain etiology. Therapies currently in vogue for ocular
rosacea have not been rigorously studied with regards to specific indications,
optimal dosing regimens, or treatment efficacy. This review will summarize the
recent literature with regards to etiology and therapy of ocular rosacea, and
will also examine current thinking about the parent disorder, acne rosacea.
RECENT FINDINGS: Comparatively few papers on ocular rosacea were published in the
past year. Recent articles on the prevalence of ocular rosacea in patients with
acne rosacea suggested that between 6 and 18% of acne rosacea patients have signs
or symptoms of ocular rosacea, but few cases were confirmed by an
ophthalmologist. Recent articles on the pathogenesis of ocular rosacea have
focused on the role of bacterial lipases, and interleukin-1alpha and matrix
metalloproteinases in the blepharitis and corneal epitheliopathy, respectively.
Other reports highlighted the presence of the disorder in children, and the lack
of masked, placebo-controlled studies for those therapies currently in common
use. SUMMARY: The epidemiology, etiology, and optimal therapy of ocular rosacea
remain to be determined, and will require a more concerted effort to delineate.

[Hormonal factors in etiology of common acne] [Article in Polish] Bergler-Czop B, Brzezińska-Wcisło L. Pol Merkur Lekarski. 2004 May;16(95):490-2.

Common acne is steatorrhoeic chronic disease, to which specific is, among others,
the presence of blackheads, papulopustular eruptions, purulent cysts and
cicatrices. Such hormonal factors belong to elements inherent in etiology of the
affection. Sebaceous glands have cell receptors on their surface for androgens.
In etiopathogenesis of common/simple acne, a decisive role is played by a
derivative of testosterone, i.e. 5-alpha-dihydrotestosterone (DHT). However, some
experts are of opinion that there is no correlation between the increased
intensity of common acne and other symptoms of hyperandrogenism. Numerous authors
assume, however, that common acne-affected patients may be sometimes subjected to
intense reactions caused by sebaceous glands against physiological androgens
concentrations. Naturally, estrogens can inhibit release of such androgens. Under
physiological conditions, natural progesterone does not conduct to
intensification of the seborrhea, but the activity of sebum secretion may be
triggered off by its synthetic counterparts. Hormonal etiology can be very
distinctly visible in the steroid, androgenic, premenstrual, menopausal acne, as
well as in juvenile acne and acne neonatorum. In case of females affected by
acne, hormonal therapy should be persistently supported and consulted with
dermatologists, endocrinologists and gynecologists. Antiandrogenic preparations
are applied, such as: cyproterone acetate concurrently administered with
estrogens and, as well as not so frequently with chlormadinone acetate
(independently or during estrogenic therapy).

Androgen action on human skin — from basic research to clinical significance. Zouboulis CC, Degitz K. Exp Dermatol. 2004;13 Suppl 4:5-10.

Androgens affect several functions of the human skin, such as sebaceous gland
growth and differentiation, hair growth, epidermal barrier homeostasis and wound
healing. Their effects are mediated by binding to nuclear androgen receptors.
Androgen activation and deactivation are mainly intracellular events. They differ
from cell type to cell type and between cells at different locations. The major
circulating androgens, dehydroepiandrosterone sulfate and androstenedione, are
predominantly produced in the adrenal glands, and testosterone and
5alpha-dihydrotestosterone are mainly synthesized in the gonads. Testosterone in
women and 5alpha-dihydrotestosterone in both genders are also synthesized in the
skin. Skin cells express all androgen metabolizing enzymes required for the
independent cutaneous synthesis of androgens and the development of
hyperandrogenism-associated conditions and diseases, such as seborrhea, acne,
hirsutism and androgenetic alopecia. The major thrust of drug design for the
treatment of androgen-associated disorders has been directed against several
levels of androgen function and metabolism. Partial effectiveness has only been
achieved either by androgen depletion, inhibition of androgen metabolism or
blockade of the androgen receptor.

Tetracycline and other tetracycline -derivative staining of the teeth and oral cavity. Sánchez AR, Rogers RS 3rd, Sheridan PJ. Int J Dermatol. 2004 Oct;43(10):709-15.

Tetracyclines (TCN) were introduced in 1948 as broad-spectrum antibiotics that
may be used in the treatment of many common infections in children and adults.
One of the side-effects of tetracyclines is incorporation into tissues that are
calcifying at the time of their administration. They have the ability to chelate
calcium ions and to be incorporated into teeth, cartilage and bone, resulting in
discoloration of both the primary and permanent dentitions. This permanent
discoloration varies from yellow or gray to brown depending on the dose or the
type of the drug received in relation to body weight. Minocycline hydrochloride,
a semisynthetic derivative of tetracycline often used for the treatment of acne,
has been shown to cause pigmentation of a variety of tissues including skin,
thyroid, nails, sclera, teeth, conjunctiva and bone. Adult-onset tooth
discoloration following long-term ingestion of tetracycline and minocycline has
also been reported. The remarkable side-effect of minocycline on the oral cavity
is the singular occurrence of “black bones”, “black or green roots” and blue-gray
to gray hue darkening of the crowns of permanent teeth. The prevalence of
tetracycline and minocycline staining is 3-6%. The mechanism of minocycline
staining is still unknown. Most of the reviewed literature consisted of case
reports; longitudinal clinical trials are necessary to provide more information
on the prevalence, severity, etiology and clinical presentation of tetracycline
and TCN-derivative staining in the adult population.

Topical antibacterial therapy for acne vulgaris. Dreno B. Drugs. 2004;64(21):2389-97.

Topical antibiotics and benzoyl peroxide, are the two main topical antibacterial
treatments indicated for mild-to-moderate acne vulgaris. Topical antibiotics act
both as antibacterial agents suppressing Propionibacterium acnes in the sebaceous
follicle and as anti-inflammatory agents. Benzoyl peroxide is a powerful
antimicrobial agent that rapidly destroys both bacterial organisms and yeasts.
Topical clindamycin and erythromycin have been proven to be effective against
inflammatory acne vulgaris in concentrations of 1-4% with or without the addition
of zinc. However, none of the antibacterials tested was more effective than
benzoyl peroxide, which also has the advantage of not being associated with
antimicrobial resistance.Topical antibacterial therapy should be discontinued
once improvement is observed. If no improvement is observed within 6-8 weeks, the
agent should be discontinued and a therapeutic switch considered. The primary
limitation of benzoyl peroxide for some acne vulgaris patients is cutaneous
irritation or dryness.Antibacterial therapy can be used in combination with other
agents. Combining topical antibiotics and topical retinoids may enhance the
efficacy, since the retinoid will improve the penetration of the antibiotic.
Combining a topical antibiotic with benzoyl peroxide may increase the
bactericidal effect of the antibiotic and reduce the potential for bacterial
resistance. Topical and oral antibacterials should not be used in combination for
the treatment of acne vulgaris, since this association may increase the risk of
bacterial resistance.

Antibacterial photodynamic therapy in dermatology. Maisch T, Szeimies RM, Jori G, Abels C. Photochem Photobiol Sci. 2004 Oct;3(10):907-17. Epub 2004 Sep 16.

Photodynamic therapy (PDT) appears to be endowed with several favourable features
for the treatment of localized microbial infections, especially after the advent
of cationic photosensitising agents (phenothiazines, meso-substituted porphyrins,
polylysine-bound chlorins) which properly interact with the outer wall at the
surface of several types of bacterial and yeast cells, increase their
permeability, and allow significant amounts of photosensitizer to be accumulated
at the level of the cytoplasmic membrane. These photosensitisers are
characterized by a broad spectrum of activity, being effective toward both wild
strain and antibiotic-resistant gram-positive and gram-negative bacteria and
yeasts. In general, extensive eradication of pathogens can be achieved under mild
irradiation conditions, such as short incubation times and low fluence-rates,
which guarantees a high degree of selectivity in comparison with the main
constituents of host tissues, such as keratinocytes and fibroblasts. Moreover,
the photosensitised inactivation of microorganisms is typically a multi-target
process; as a consequence, the selection of photoresistant microbial strains is
very unlikely and has not been experimentally observed so far. Possible initial
targets of antimicrobial PDT applications include periodontal diseases, impetigo,
atopic dermatitis, acne vulgaris, infected wounds, and superinfected posriatic
plaques.

The role of combined oral contraceptives in the management of acne and seborrhea. del Marmol V, Teichmann A, Gertsen K. Eur J Contracept Reprod Health Care. 2004 Jun;9(2):107-24.

Acne and seborrhea (or facial oiliness) are related androgenic skin disorders
which affect a high proportion of women after menarche. They can have a negative
effect on psychological well-being and social life. Androgens play an important
role in the pathogenesis of acne through the stimulation of sebum secretion,
increasing sebaceous gland size and possibly through follicular
hyperkeratinization. Conversely, estrogens decrease sebum production by
suppressing gonadotropin release and androgen production and increasing sex
hormone binding globulin production. One of the treatment options for these
conditions is hormonal therapy, especially for women who require contraception.
The effect of combined oral contraceptives in androgenic skin disorders depends
on their estrogen:progestogen balance and on the antiestrogenic activity of the
progestogen component. Improved understanding of what women value about oral
contraceptives suggests that the choice of product should be tailored as much as
possible to the individual. Several combined oral contraceptives containing
new-generation progestogens (e.g. desogestrel, gestodene) or progestational
antiandrogens (e.g. cyproterone acetate, chlormadinone acetate) have demonstrated
efficacy in the treatment of women with acne, although comparisons between trials
are difficult because of differing endpoints. Seborrhea has been less well
studied, but the few studies that are available show an improvement in women with
this condition using combined oral contraceptives.

Current recommendations for the diagnostic evaluation and follow-up of patients presenting with symptomatic polycystic ovary syndrome. Fraser IS, Kovacs G. Best Pract Res Clin Obstet Gynaecol. 2004 Oct;18(5):813-23.

Recent international agreement on the definitions of polycystic ovary syndrome
(PCOS) has helped to clarify the clinical approach to diagnosis of PCOS. However,
in the precise assessment of an individual patient it is still necessary for a
detailed history of menstrual disorder (especially oligo- and amenorrhoea and
anovulatory dysfunctional uterine bleeding), infertility or miscarriage,
hyperandrogenism (mainly acne, hirsutism and scalp hair loss, distinguished from
virilization) and obesity supplemented by the demonstration of polycystic ovaries
on transvaginal ultrasound scanning. Assessment of endocrine changes in serum
levels of luteinizing hormone, follicle stimulating hormone, oestradiol and
prolactin, plus appropriate measures of circulating androgens (especially total
and free testosterone, sex hormone binding globulin, 17 hydroxy-progesterone,
dehydro-epiandrosterone sulphate and sometimes a 24-hour urinary free control)
might help in further defining the abnormalities. Assessment of ovulatory status,
obesity (body mass index and waist-hip ratio) and insulin resistance (oral
glucose tolerance test with serum insulin levels) are also important in most
cases. PCOS is a highly variable condition and investigation and management needs
to be individualized. Long-term follow-up is also to a great extent dictated by
the constellation of symptoms and clinical features of individual patients, but
potential long-term hazards should be defined and patients warned of these.

Hirsutism and acne in polycystic ovary syndrome. Archer JS, Chang RJ. Best Pract Res Clin Obstet Gynaecol. 2004 Oct;18(5):737-54.

Polycystic ovary syndrome (PCOS) is the most common endocrine abnormality
affecting reproductive age women. Population-based studies estimate a prevalence
of 5-10% [Obstet Gynecol 101 (2003) 995; Aust N Z J Obstet Gynaecol 41 (2001)
202]. The clinical characteristics of PCOS include hyperandrogenism, chronic
anovulation, insulin resistance and infertility. Hyperandrogenism is generally
manifested as hirsutism and acne. Both these clinical symptoms are treated with
similar drug therapies, including oral contraceptive pills (OCPs), topical
medications or antiandrogens such as spironolactone, flutamide and finasteride,
as well as topical medications. Recent studies have shown that lower doses of
these medications are as efficacious as high doses and have the advantage of
decreased cost and an improved side-effect profile. Although hirsutism and acne
can be considered cosmetic in nature, they cause significant social embarrassment
and emotional distress. Physicians should be sensitive to these issues and
approach patients in a caring and sympathetic manner.

A status report on the use of subantimicrobial-dose doxycycline: a review of the biologic and antimicrobial effects of the tetracyclines. Del Rosso JQ. Cutis. 2004 Aug;74(2):118-22.

The pathophysiology of acne vulgaris in children and adolescents, Part 1. Bergfeld WF. Cutis. 2004 Aug;74(2):92-7.

Microcomedones, the earliest lesions of acne, appear at adrenarche, which
typically occurs at about 8 years of age when androgens of adrenal origin begin
to stimulate follicular hyperkeratosis and sebaceous hyperplasia in pilosebaceous
units on the face. Comedones appear about 2 years later, when androgens of
gonadal origin are produced and colonization of follicles by Propionibacterium
acnes increases. Inflammatory lesions, such as pustules, papules, and nodules,
are the result of the host’s immune responses to P acnes; the proinflammatory
cytokines are released by immunocompetent leukocytes that are recruited in
response to this bacterium and its metabolic by-products. Androgens also affect
the barrier function of the skin, and disturbances of barrier function may
stimulate epidermal DNA synthesis. This leads to epidermal hyperplasia, which may
also contribute to follicular hyperkeratosis in acne. Optimal treatment for this
disorder will address these various pathophysiologic factors.

Tacrolimus ointment: utilization patterns in children under age 2 years. Housman TS, Norton AB, Feldman SR, Fleischer AB Jr, Simpson EL, Hanifin JM, Antaya RJ. Dermatol Online J. 2004 Jul 15;10(1):2.

Atopic dermatitis (AD) is a common eczematous skin condition; as many as 10-17
percent of all children are affected, and 35-60 percent of affected patients
manifest symptoms manifest during the first year of life. Treatment principles
for AD in young children involve conservative measures such as avoidance of hot
water and environmental irritants, combined with liberal use of emollients after
bathing. Low potency topical corticosteroids (TCS) are the current standard of
therapy for AD in young children, reserving mid- and high-potency TCS for severe
disease. However, complications of long-term use of TCS include skin atrophy,
stria formation, telangiectasia, hypopigmentation, secondary infections, steroid
acne, allergic contact dermatitis, and miliaria. The pediatric population is also
at increased risk for systemic absorption because of their high ratio of skin
surface to body mass. Systemic absorption may result in
hypothalamic-pituitary-adrenal axis suppression and ultimately growth
retardation. Although most topical and systemic corticosteroids are not approved
by the Food and Drug Administration for use in children less than 2 years of age,
conservative treatment often fails in this age group and frequently patients are
treated with TCS, antibiotics, and antihistamines.

Spontaneous clinical improvement in HIV-associated follicular syndrome. Blasdale C, Turner RJ, Leonard N, Ong EL, Lawrence CM. Clin Exp Dermatol. 2004 Sep;29(5):480-2.

Since 1991 infrequent reports have described a distinctive triad of nodulocystic
acne, striking follicular spines and an eruption resembling pityriasis rubra
pilaris (PRP) in HIV-positive patients. It has been suggested that this may
represent a subtype of PRP, or alternatively that it should be viewed as a unique
HIV-associated follicular occlusion triad. Clinical manifestations may be severe,
and in several cases have been ultimately fatal, with death occurring due to
complications of cutaneous sepsis. We describe a case demonstrating severe
conglobate acne, follicular keratotic spines and histologically confirmed PRP in
association with HIV infection. Clinical features and treatment modalities of
previously reported cases are reviewed. Despite refusing all topical and systemic
treatment our patient showed spontaneous remission of skin signs after 2 years.

Psychosocial impact of acne vulgaris: evaluating the evidence. Tan JK. Skin Therapy Lett. 2004 Aug-Sep;9(7):1-3, 9.

This paper reviews current evidence presented by recent studies on the impact of
acne on psychosocial health. Study methodologies, including case-control and
cross-sectional surveys, have demonstrated psychological abnormalities including
depression, suicidal ideation, anxiety, psychosomatic symptoms, including pain
and discomfort, embarrassment and social inhibition. Effective treatment of acne
was accompanied by improvement in self-esteem, affect, obsessive-compulsiveness,
shame, embarrassment, body image, social assertiveness and self-confidence. Acne
is associated with a greater psychological burden than a variety of other
disparate chronic disorders. Future studies with a longitudinal cohort design may
provide further validation of the causal inference between acne and psychosocial
disability provided by the current literature.

Polycystic ovary (Stein-Leventhal) syndrome: etiology, complications, and treatment. Hoyt KL, Schmidt MC. Clin Lab Sci. 2004 Summer;17(3):155-63.

Polycystic ovary syndrome (PCOS) occurs in approximately 3% to 5% of the female
population and may be the leading cause of infertility in those of reproductive
age. PCOS presents clinically with a variety of signs and symptoms; the most
common being menstrual irregularities, hyperandrogenism, infertility, and
obesity. The true pathophysiology has not been clearly elucidated; however, there
is growing agreement that gonadotropin dynamic dysfunction, hyperandrogenism, and
insulin resistance are key features. The diagnosing of PCOS involves radiologic
and laboratory studies. Radiologic studies typically include pelvic ultrasound;
laboratory data should be obtained regarding pertinent gonadotropins and other
hormone levels. PCOS is not a benign condition. It may lead to complications
involving glucose metabolism, dyslipidemias, cardiovascular disease, and cancer.
The goals of treatment should focus on restoring menstrual regularity, decreasing
androgen excesses, and decreasing insulin resistance.

Current concepts in the management of acne. [No authors listed] J Drugs Dermatol. 2004 Jul-Aug;3(4 Suppl):S3-20.

Treatment of acne vulgaris. Haider A, Shaw JC. JAMA. 2004 Aug 11;292(6):726-35.

CONTEXT: Management of acne vulgaris by nondermatologists is increasing. Current
understanding of the different presentations of acne allows for individualized
treatments and improved outcomes. OBJECTIVE: To review the best evidence
available for individualized treatment of acne. DATA SOURCES: Search of MEDLINE,
EMBASE, and the Cochrane database to search for all English-language articles on
acne treatment from 1966 to 2004. STUDY SELECTION: Well-designed randomized
controlled trials, meta-analyses, and other systematic reviews are the focus of
this article. DATA EXTRACTION: Acne literature is characterized by a lack of
standardization with respect to outcome measures and methods used to grade
disease severity. DATA SYNTHESIS: Main outcome measures of 29 randomized
double-blind trials that were evaluated included reductions in inflammatory,
noninflammatory, and total acne lesion counts. Topical retinoids reduce the
number of comedones and inflammatory lesions in the range of 40% to 70%. These
agents are the mainstay of therapy in patients with comedones only. Other agents,
including topical antimicrobials, oral antibiotics, hormonal therapy (in women),
and isotretinoin all yield high response rates. Patients with mild to moderate
severity inflammatory acne with papules and pustules should be treated with
topical antibiotics combined with retinoids. Oral antibiotics are first-line
therapy in patients with moderate to severe inflammatory acne while oral
isotretinoin is indicated for severe nodular acne, treatment failures, scarring,
frequent relapses, or in cases of severe psychological distress. Long-term
topical or oral antibiotic therapy should be avoided when feasible to minimize
occurrence of bacterial resistance. Isotretinoin is a powerful teratogen
mandating strict precautions for use among women of childbearing age.
CONCLUSIONS: Acne responses to treatment vary considerably. Frequently more than
1 treatment modality is used concomitantly. Best results are seen when treatments
are individualized on the basis of clinical presentation.

The use of sulfur in dermatology. Gupta AK, Nicol K. J Drugs Dermatol. 2004 Jul-Aug;3(4):427-31.

Sulfur has antifungal, antibacterial, and keratolytic activity. In the past, its
use was widespread in dermatological disorders such as acne vulgaris, rosacea,
seborrheic dermatitis, dandruff, pityriasis versicolor, scabies, and warts.
Adverse events associated with topically applied sulfur are rare and mainly
involve mild application site reactions. Sulfur, used alone or in combination
with agents such as sodium sulfacetamide or salicylic acid, has demonstrated
efficacy in the treatment of many dermatological conditions.

5 alpha-reductase and finasteride in pattern alopecia and acne. Burkhart CG, Burkhart CN. J Drugs Dermatol. 2004 Jul-Aug;3(4):363-4.

Androgen replacement therapy in women. Cameron DR, Braunstein GD. Fertil Steril. 2004 Aug;82(2):273-89.

OBJECTIVE: Review of literature with regard to androgen replacement therapy in
women. DESIGN: Review of the MEDLINE database and references from articles.
CONCLUSIONS: Androgens affect sexual function, bone health, muscle mass, body
composition, mood, energy, and the sense of well-being. Androgen insufficiency
clearly has been demonstrated in patients with hypopituitarism, adrenalectomy,
oophorectomy, and in some women placed on oral estrogen therapy which increases
sex hormone-binding globulin (SHBG) levels and lowers the free and bioavailable
forms of T. Symptoms of androgen insufficiency in women may include a diminished
sense of well-being, low mood, fatigue, and hypoactive sexual desire disorder
with decreased libido, or decreased sexual receptivity and pleasure that causes a
great deal of personal distress. The preponderance of evidence from clinical
trials supports the correlation of decreased endogenous androgen levels with
these symptoms and alleviation of many of the symptoms with the administration of
T or, in some cases, DHEA. There are no Food and Drug Administration-approved
androgen preparations on the market for treating androgen insufficiency in women.
The safety profile of androgens in doses used for the treatment of hypoactive
sexual desire disorder has been excellent with only mild acne and hirsutism being
noted in a minority of patients.

Benzoyl peroxide-based combination therapies for acne vulgaris: a comparative review. Taylor GA, Shalita AR. Am J Clin Dermatol. 2004;5(4):261-5.

Benzoyl peroxide, with its broad-spectrum antimicrobial activity, is among the
most widely used topical agents in the treatment of inflammatory acne vulgaris.
Benzoyl peroxide is marketed either alone or in combination with other topical
antibiotics; namely, erythromycin and clindamycin. The combination products
confer specific advantages over benzoyl peroxide alone, particularly in
decreasing the in vivo follicular counts of Propionibacterium acnes, the
anaerobic bacterium implicated in the pathogenesis of acne. In addition, the
topical treatment of inflammatory acne has been complicated by the development of
P acnes resistance to topical erythromycin and clindamycin. Combination products
containing benzoyl peroxide and the topical antibiotics have been shown to both:
(i) prevent the development of antibiotic resistance in acne patients; and (ii)
confer significant clinical improvement to patients who have already developed
antibiotic resistance.

Phototherapy in the treatment of acne vulgaris: what is its role? Charakida A, Seaton ED, Charakida M, Mouser P, Avgerinos A, Chu AC. Am J Clin Dermatol. 2004;5(4):211-6.

Acne vulgaris is a common dermatosis affecting 80% of the population. To date,
different treatments have been used to manage this condition. Antibacterials and
retinoids are currently the mainstay of treatment for acne, but their success
rate varies. Phototherapy is emerging as an alternative option to treat acne
vulgaris.Studies examining the role of different wavelengths and methods of light
treatment have shown that phototherapy with visible light, specifically blue
light, has a marked effect on inflammatory acne lesions and seems sufficient for
the treatment of acne. In addition, the combination of blue-red light radiation
seems to be superior to blue light alone, with minimal adverse effects.
Photodynamic therapy has also been used, even in nodular and cystic acne, and had
excellent therapeutic outcomes, although with significant adverse effects.
Recently, low energy pulsed dye laser therapy has been used, and seems to be a
promising alternative that would allow the simultaneous treatment of active acne
and acne scarring.Further studies are needed to clarify the role of phototherapy
as a monotherapy or an adjuvant treatment in the current management of acne
vulgaris.

5-aminolevulinic acid photodynamic therapy: where we have been and where we are going. Gold MH, Goldman MP. Dermatol Surg. 2004 Aug;30(8):1077-83; discussion 1083-4.

BACKGROUND: Photodynamic therapy, utilizing the topical administration of 20%
5-aminolevulinic acid, has generated a great deal of interest in the dermatology
community over the past several years. OBJECTIVE: The purpose of this article is
to review the history of photodynamic therapy in dermatology and to review recent
new advances with this technology that will increase its appeal to all
dermatologists. METHODS: A literature review and results of new clinical trials
with regards to photorejuvenation and acne vulgaris treatments with
5-aminolevulinic acid photodynamic therapy are presented. RESULTS: Short-contact,
full-face 5-aminolevulinic acid photodynamic therapy treatments with a variety of
lasers and light sources have shown to be successful in treating all facets of
photorejuvenation and the associated actinic keratoses as well as disorders of
sebaceous glands, including acne vulgaris. The treatments are relatively
pain-free, efficacious, and safe. They are also making already available
laser/light source therapies work better for acne vulgaris and photorejuvenation.
CONCLUSIONS: The use of 5-aminolevulinic acid photodynamic therapy with
short-contact, full-face broad-application therapy is now able to bridge the
world of medical and cosmetic dermatologic surgery. This therapy is available for
all dermatologists to utilize in the care of their patients.

Acne update: 2004. Smolinski KN, Yan AC. Curr Opin Pediatr. 2004 Aug;16(4):385-91.

PURPOSE OF REVIEW: Acne vulgaris is a common skin disorder among children and
young adults that carries enormous financial and psychosocial impact.
Contemporary therapies attempt to address factors underlying acne as a disorder
of the pilosebaceous unit. These longstanding paradigms regarding pathogenesis
and treatment continue to evolve in light of recent work on this ubiquitous
disease. RECENT FINDINGS: This review focuses on new literature that has emerged
regarding the biology of the folliculosebaceous unit, the identification of
particular mediators responsible for inflammatory acne, the use of topical and
systemic retinoids in acne therapy, and approaches to address the emergence of
antibiotic-resistant Propionibacterium acnes strains. In addition, the use of
several novel therapeutic avenues is discussed, including combination therapies,
lipoxygenase inhibitors, and lasers. SUMMARY: As the understanding of the factors
that initiate and exacerbate acne vulgaris continues to increase, so does the
diversity of therapeutic options. Rational use of available treatment options
based on the type and severity of acne lesions is a key component of successful
acne therapy and allows the physician who treats adolescents with acne to provide
optimum care.

Combined oral contraceptive pills for treatment of acne. Arowojolu AO, Gallo MF, Grimes DA, Garner SE. Cochrane Database Syst Rev. 2004;(3):CD004425.

BACKGROUND: Acne is a common skin disorder among women. Although no uniform
approach to the management of acne exists, combination oral contraceptives
(COCs), which contain an estrogen and a progestin, often are prescribed for
women. OBJECTIVES: To determine the effectiveness of COCs for the treatment of
facial acne compared to placebo or other active therapies. SEARCH STRATEGY: We
searched the computerized databases Cochrane Skin Group trial register, Cochrane
Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, POPLINE,
Biological Abstracts and LILACS for randomized controlled trials of COCs and
acne. We wrote to authors of identified trials to seek any unpublished or
published trials that we might have missed. SELECTION CRITERIA: All randomized
controlled trials reported in any language that compare the effectiveness of a
COC containing an estrogen and a progestin to placebo or another active therapy
for acne in women were eligible. DATA COLLECTION AND ANALYSIS: We extracted data
on total and specific (i.e. open or closed comedones, papules, pustules and
nodules) facial lesion counts; acne severity grades; global assessments by the
clinician or the participant and discontinuation due to adverse events. Data were
entered and analyzed in RevMan 4.2. MAIN RESULTS: The search yielded five
placebo-controlled trials that made three different comparisons and 14 trials
that made nine comparisons between two COC regimens. An additional trial compared
a COC to an antibiotic. COCs reduced acne lesion counts, severity grades and
self-assessed acne compared to placebo. Differences in the comparative
effectiveness of COCs containing varying progestin types and dosages, though,
were less clear. COCs that contained chlormadinone acetate or cyproterone acetate
improved acne better than levonorgestrel although this apparent advantage was
based on limited data. A COC with cyproterone acetate might result in better acne
outcomes than one with desogrestrel; however, the three studies comparing these
COCs produced conflicting results. Likewise, levonorgestrel showed a slight
improvement over desogestrel in acne outcomes in one trial, but a second trial
found no difference between the COCs. REVIEWERS’ CONCLUSIONS: The three COCs
evaluated in placebo-controlled trials are effective in reducing inflammatory and
non-inflammatory facial acne lesions. Few differences were found in acne
effectiveness between COC types. How COCs compare to alternative acne treatments
is unknown since limited data were available regarding this question.

Risks and side effects of islet transplantation. Ryan EA, Paty BW, Senior PA, Shapiro AM. Curr Diab Rep. 2004 Aug;4(4):304-9.

Islet transplantation can deliver stable glycemic control, relief from recurrent
severe hypoglycemia, and insulin independence. Accessing the portal vein via the
percutaneous hepatic approach carries the risk of bleeding, and the infusion of
islets a risk of portal vein thrombosis. In the long term, common minor problems
with immunosuppression are mouth ulcers, diarrhea, and acne. Longer-term risks
include malignancy and serious infection, both rare to date in clinical islet
transplantation. Sensitization to donor antigens may also occur. The long-term
diabetes complications may stabilize, but of this aspect little is known to date.
In the short term, there may be some elevation of serum cholesterol and blood
pressure, in some patients there has been a decline in renal function, and in a
few, acute retinal bleeds. For most, improvement in glucose control with
resolution of glycemic lability and hypoglycemia has been a net benefit.

Medical treatment of hidradenitis suppurativa. Jemec GB. Expert Opin Pharmacother. 2004 Aug;5(8):1767-70.

Hidradenitis suppurativa (HS) is a common skin disease affecting an estimated 2%
of the population. It causes significant symptoms and is notoriously difficult to
treat. In this article, the current medical therapy is reviewed. At the present
time, therapy appears to be based on an interpretation of the disease as either
infectious or a form of acne. The understanding of the pathogenesis of HS
suggests that these are not adequate models in order to understand the disease
and this may explain the insufficiency of currently available medical treatment.
The literature is sparse and there is a shortage of randomised, controlled
trials. Three small, randomised, controlled trials have suggested that
clindamycin, tetracycline and oestrogens and cyproteroneacetate may have an
effect in some patients. Preceiving HS as an inflammatory skin disease suggests
the use of general immunosuppressive drugs in the treatment of this condition.
This approach, using both traditional immunosupressants and monoclonal
antibodies, has been assessed in a small number of patients and appears to have
some potential. However, the main source of evidence for this are case series and
there is a strong need for more formal studies in this potentially debilitating
disease.

Acne vulgaris. Robertson KM. Facial Plast Surg Clin North Am. 2004 Aug;12(3):347-55, vi.

Acne vulgaris is a common inflammatory skin condition that presents management
difficulties to cosmetic surgeons. Acute management and treatment focuses on
early diagnosis as well as treatment with topical agents, oral antibiotics,
hormonal therapy,and nonablative chemical peel and laser applications. The
treatment of postinflammatory scarring must be individualized to address
potential macular dyschromia, cystic lesions,epithelial bridges, or deep pitted
scars. A review of interventional options is presented to apply to the spectrum
of acne scarring as well as a review of the literature to address objectively
published reports on efficacy.

An update on the pathogenesis and management of acne vulgaris. Harper JC. J Am Acad Dermatol. 2004 Jul;51(1 Suppl):S36-8.

[Zinc salts in dermatology] [Article in French] Stéphan F, Revuz J. Ann Dermatol Venereol. 2004 May;131(5):455-60.

Zinc is an essential trace element for the human organism. It acts like cofactor
for the metalloenzymes involved in many cellular processes. Its anti-inflammatory
activity, which is the basis of therapeutic use, other than acrodermatitis
enteropathica, is not well known: production of cytokines, antioxidant activity.
Its toxicity is very low, but marked at high doses during chronic administration
by the risk of hypocupremia. It is not teratogenic and can be given during
pregnancy. Its absorption, through the duodenum, is inhibited by excessive
phytate intake. Maximum concentration is reached after 2 to 3 hours. It is widely
distributed in the organism, mainly in muscles and bone. Excretion is
predominantly digestive. Its spectacular effect in acrodermatitis enteropathica,
through compensation of genetically determined malabsorption was discovered in
1973. Its usefulness in acne is based on the anti-inflammatory action and was
first described with zinc sulfate, then with better tolerated gluconate. Many
controlled studies have shown an efficacy on inflammatory lesions. Doses varied
from 30 to 150 mg of elemental zinc and studies against cyclines have shown that
minocycline has a superior effect; but zinc might be an alternative treatment
when cyclines are contraindicated. To date we don’t have convincing data for its
use in other indications (leishmaniosis, warts, cutaneous ulcers). Tolerance at
usual doses (200 mg of zinc gluconate or 30 mg of elemental zinc) is good. Major
side effects are abdominal with nausea, vomiting, but are fleeting and dose
dependent.

Antibiotic resistance in the topical treatment of acne vulgaris. Leyden JJ. Cutis. 2004 Jun;73(6 Suppl):6-10.

Topical antimicrobial agents are the first line of treatment in mild to moderate
acne vulgaris. The primary pathogenic agent implicated in the development of
inflammatory acne is Propionibacterium acnes. P acnes also may play a secondary
role in noninflammatory acne or comedogenesis. Over the past 20 years, concern
has grown about the gradual worldwide increase in the prevalence of
antibiotic-resistant P acnes strains. Factors associated with the development of
resistant P acnes following treatment with topical antibiotics, clinical
relevance of antibiotic resistance, and strategies to reduce the incidence of P
acnes resistance are discussed in this review.

Adapalene: a review of its use in the treatment of acne vulgaris. Waugh J, Noble S, Scott LJ. Drugs. 2004;64(13):1465-78.

Adapalene (Differin) is a retinoid agent indicated for the topical treatment of
acne vulgaris. In clinical trials, 0.1% adapalene gel has proved to be effective
in this indication and was as effective as 0.025% tretinoin gel, 0.1% tretinoin
microsphere gel, 0.05% tretinoin cream and 0.1% tazarotene gel once every two
days; however, the drug was less effective than once-daily 0.1% tazarotene gel.
It can be used alone in mild acne or in combination with antimicrobials in
inflammatory acne and has proved efficacious as maintenance treatment. Adapalene
has a rapid onset of action and a particularly favourable tolerability profile
compared with other retinoids. These attributes can potentially promote patient
compliance, an important factor in treatment success. Adapalene is, therefore,
assured of a role in the first-line treatment of acne vulgaris.

Cutis verticis gyrata secondary to acne scleroticans capitis. Ulrich J, Franke I, Gollnick H. J Eur Acad Dermatol Venereol. 2004 Jul;18(4):499-502.

We report the case of a 35-year-old patient with secondary cutis verticis gyrata
(CVG) that histologically presented as acne scleroticans capitis. Clinically, the
diagnosis of acne conglobata was made. The CVG developed under systemic
corticosteroid treatment of an ulcerative colitis. Corticosteroids were
discontinued and a therapeutic attempt was made with isotretinoin. Although under
this treatment the conglobate acne healed, the CVG remained unaltered.
Dermatosurgical intervention by a scalp reduction plasty finally resulted in a
marked improvement of symptoms and acceptable cosmetic outcome.

Oral mucosal pigmentation secondary to minocycline therapy: report of two cases and a review of the literature. Treister NS, Magalnick D, Woo SB. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004 Jun;97(6):718-25.

Minocycline is a semisynthetic broad-spectrum antimicrobial agent that was first
introduced into clinical practice in 1967. The most common use of minocycline is
for the long-term treatment of acne vulgaris. A well-recognized side effect of
minocycline treatment is pigmentation, which has been reported in multiple
tissues and fluids including thyroid, skin, nail beds, sclera, bone, and teeth.
While there have been several reports of oral pigmentation following minocycline
therapy, these have been, for the most part, pigmentation of the underlying bone
with the overlying oral mucosa only appearing pigmented. We report two cases of
actual pigmented oral mucosal lesions on the hard palate secondary to minocycline
therapy with the accompanying histopathology, followed by a discussion of
minocycline-induced oral pigmentation and a differential diagnosis of these
lesions. Copyright 2004 Elsevier Inc.

[The use of retinoids in dermatology] [Article in Polish] Brzezińska-Wcisło L, Pierzchała E, Kamińska-Budzińska G, Bergler-Czop B, Trzmiel D. Wiad Lek. 2004;57(1-2):63-9.

Retinoids–new agents derived from vitamin A have initiated a new era in therapy
of many skin diseases. They are highly effective medicines used in the treatment
of severe forms of psoriasis. Also they are administered in many forms of acne,
as alternative drugs do not exist. Moreover, retinoids show antineoplastic
activity. They are also effective in the symptomatic treatment of the congenital
keratinization disorder syndromes. The recent development of retinoids combined
with the growth of expertise with regard to the biological function and
mechanisms of retinoid receptors, are likely to improve the present therapeutic
methods and to reveal new potentials regarding the use of retinoids in the
therapy of many skin disorders.

Patented antiinflammatory plant drug development from traditional medicine. Darshan S, Doreswamy R. Phytother Res. 2004 May;18(5):343-57.

Patents secured on antiinflammatory plant drugs derived from 38 plants are
reviewed. An attempt has been made to compare the modern and traditional use of
plant drugs and to establish the relevance of folk claims in developing modern
drugs. The role of plant botanicals such as polysaccharides, terpenes,
curcuminoids, alkaloids, etc. in alleviating inflammatory diseases including
arthritis, rheumatism, acne skin allergy and ulcers is highlighted. Chemicals
that alleviate swelling are derived from plants including grape, boswellia,
turmeric, devil’s claw and some essential oils such as clove, eucalyptus,
rosemary, lavender, mint, myrrh, millefolia and pine have been patented and used
as mixed formulations. Plants containing polysaccharides are the most potent in
curing inflammatory diseases. Copyright 2004 John Wiley & Sons, Ltd.

Steroid sulfatase inhibitors. Nussbaumer P, Billich A. Med Res Rev. 2004 Jul;24(4):529-76.

Steroid sulfatase (STS) regulates the local production of estrogens and androgens
from systemic precursors in several tissues. The enzyme catalyzes the hydrolysis
of the sulfate esters of 3-hydroxy steroids, which are inactive transport or
precursor forms of the active 3-hydroxy steroids. STS inhibitors are expected to
block the local production and, consequently, to reduce the local levels of the
hormones. Therefore, they are considered as potential new therapeutic agents for
the treatment of estrogen- and androgen-dependent disorders. Indications range
from cancers of the breast, endometrium and prostate to androgenetic alopecia and
acne. In this review, we give a comprehensive summary of the current knowledge
and problems in the field of medicinal chemistry of STS inhibitors. The various
types of inhibitors are presented and their structure-activity relationships are
discussed. In addition to potent arylsulfamate-based, irreversible inhibitors,
novel types of reversible inhibitors were recently discovered. The recent
publication of the X-ray structure of STS will further boost research activities
on this attractive target. Copyright 2004 Wiley Periodicals, Inc. Med Res Rev,
24, No. 4, 529-576, 2004

American Academy of Dermatology Consensus Conference on the safe and optimal use of isotretinoin: summary and recommendations. Goldsmith LA, Bolognia JL, Callen JP, Chen SC, Feldman SR, Lim HW, Lucky AW, Reed BR, Siegfried EC, Thiboutot DM, Wheeland RG; American Academy of Dermatology. J Am Acad Dermatol. 2004 Jun;50(6):900-6.

Diagnosis and treatment of acne. Feldman S, Careccia RE, Barham KL, Hancox J. Am Fam Physician. 2004 May 1;69(9):2123-30.

Acne can cause significant embarrassment and anxiety in affected patients. It is
important for family physicians to educate patients about available treatment
options and their expected outcomes. Topical retinoids, benzoyl peroxide,
sulfacetamide, and azelaic acid are effective in patients with mild or moderate
comedones. Topical erythromycin or clindamycin can be added in patients with mild
to moderate inflammatory acne or mixed acne. A six-month course of oral
erythromycin, doxycycline, tetracycline, or minocycline can be used in patients
with moderate to severe inflammatory acne. A low-androgen oral contraceptive pill
is effective in women with moderate to severe acne. Isotretinoin is reserved for
use in the treatment of the most severe or refractory cases of inflammatory acne.
Because of its poor side effect profile and teratogenicity, isotretinoin
(Accutane) must by prescribed by a physician who is a registered member of the
manufacturer’s System to Manage Accutane-Related Teratogenicity program.

Retinoid chemoprevention in high-risk skin cancer patients. Reilly P, DiGiovanna JJ. Dermatol Nurs. 2004 Apr;16(2):117-20, 123-6; quiz 127.

More commonly known for their dramatic effects on acne and psoriasis for the past
20 years, systemic retinoids can be a valuable chemopreventive treatment option
for those individuals in a wide variety of high-risk populations who are actively
developing large numbers of sun-induced skin cancers.

Drospirenone, a progestogen with antimineralocorticoid properties: a short review. Oelkers W. Mol Cell Endocrinol. 2004 Mar 31;217(1-2):255-61.

Progesterone (P) has high affinity to the mineralocorticoid receptor (MCR), and
it is an MCR antagonist. Almost all synthetic progestogens are devoid of this
antimineralocorticoid (anti-MC) effect. They are unable to antagonize the salt
retaining effect of estrogens. This could be one cause of weight gain and an
increase in blood pressure with the use of combined oral contraceptives (OC) and,
in some susceptible women, with postmenopausal estrogen/(progestogen) treatment.
The purpose of this presentation is to review results of clinical studies with
drospirenone (DRSP), a new progestogen developed by Schering A.G., with anti-MCR
activity. DRSP is a derivative of 17-alpha-spirolactone. In rats, rabbits and in
man, it is a PR-agonist and an MCR- and androgen-R antagonist with no effect on
the glucocorticoid-R and the estrogen-R. In normally menstruating women, 2-3mg
DRSP per day, taken from day 5 to 25 of the cycle, inhibit ovulation, lead to a
mild natriuresis, and a slight compensatory activation of the renin-aldosterone
system. Compared with an OC containing 30 microg ethinylestradiol (EE) and 150
microg levonorgestrel, a combination of 3mg DRSP with 30 microg EE given over 6
months led to a slight decrease in body weight and blood pressure. The reduction
in mean body weight by a combination of DRSP with EE compared with a conventional
OC could be confirmed in a study over 26 months in 900 young women. The OC
containing DRSP has favorable effects in patients suffering from the premenstrual
syndrome (PMS), and, partly due to the antiandrogenic effect of DRSP, in those
with acne vulgaris. For postmenopausal women, a combination of DRSP with
estradiol has been developed with the expectation that the slight blood pressure
lowering and weight reducing effects will minimize cardiovascular morbidity in
patients needing hormone treatment because of hot flushes and other climacteric
symptoms. CONCLUSIONS: DRSP, by its anti-MCR effect and its potential to slightly
decrease body weight and blood pressure, shares many pharmacodynamic properties
with progesterone, and it is a candidate for reducing cardiovascular morbidity in
women using OCs or postmenopausal hormone treatment.

Synthetic retinoids and their nuclear receptors. Dawson MI. Curr Med Chem Anticancer Agents. 2004 May;4(3):199-230.

In addition to all-trans-retinoic acid and its 9 and 13-cis isomers, four
synthetic retinoids are currently available to treat diseases of
hyperproliferation, such as acne, psoriasis, and actinic keratosis, or cancers
such as acute promelocytic leukemia, cutaneous T-cell lymphoma, and squamous or
basal cell carcinoma. The retinoids extert their antiproliferative effects by
interacting with their retinoic acid and retinoid X receptors that act as
ligand-inducible transcription factors. These homologous receptors function
either directly on retinoid response elements or indirectly by modifying the
responses of other transcription factors. Their major domains for binding DNA and
their ligands have been characterized by either nuclear magnetic resonance
spectroscopy or X-ray crystallography. The identification and design of synthetic
retinoids are overviewed, as are their selective interactions with specific
retinoid receptor subtypes and their clinical effects against cancer. Emphasis is
placed on the retinoid X receptors and their ligands.

Chemical peeling in ethnic/dark skin. Roberts WE. Dermatol Ther. 2004;17(2):196-205.

Chemical peeling for skin of color arose in ancient Egypt, Mesopotamia, and other
ancient cultures in and around Africa. Our current fund of medical knowledge
regarding chemical peeling is a result of centuries of experience and research.
The list of agents for chemical peeling is extensive. In ethnic skin, our efforts
are focused on superficial and medium-depth peeling agents and techniques.
Indications for chemical peeling in darker skin include acne vulgaris,
postinflammatory hyperpigmentation, melasma, scarring, photodamage, and
pseudofolliculitis barbae. Careful selection of patients for chemical peeling
should involve not only identification of Fitzpatrick skin type, but also
determining ethnicity. Different ethnicities may respond unpredictably to
chemical peeling regardless of skin phenotype. Familiarity with the properties
each peeling agent used is critical. New techniques discussed for chemical
peeling include spot peeling for postinflammatory hyperpigmentation and
combination peels for acne and photodamage. Single- or combination-agent chemical
peels are shown to be efficacious and safe. In conclusion, chemical peeling is a
treatment of choice for numerous pigmentary and scarring disorders arising in
dark skin tones. Familiarity with new peeling agents and techniques will lead to
successful outcomes.

Acne in ethnic skin: special considerations for therapy. Callender VD. Dermatol Ther. 2004;17(2):184-95.

Acne vulgaris occurs in people of all ethnicities and races. Although the
pathophysiology and treatment options are similar in all skin phototypes,
darker-skinned patients have higher incidence rates of two sequelae of acne:
postinflammatory hyperpigmentation and keloidal scarring. Postinflammatory
hyperpigmentation may also be triggered by skin irritation. In choosing therapies
for patients of color, therefore, clinicians must find a balance between
aggressive early intervention to target inflammatory acne lesions, and gentle
treatments to increase tolerability and avoid skin irritation. For most patients,
a combination of topical retinoids, and topical or oral antibiotics with
hydroquinone (as needed) to control hyperpigmentation will be successful. For
patients with sensitive skin, topical agents in lower concentrations and cream
vehicles are preferred. If tolerated, the retinoid strength can be titrated
upward after four to six weeks. Ethnic patients also need to be counseled on use
of noncomedogenic and nonirritating skin and hair-care products. Individualized
care and close monitoring is required.

Topical antibacterial treatments for acne vulgaris : comparative review and guide to selection. Tan HH. Am J Clin Dermatol. 2004;5(2):79-84.

Topical antibacterial agents are an essential part of the armamentarium for
treating acne vulgaris. They are indicated for mild-to-moderate acne, and are a
useful alternative for patients who cannot take systemic antibacterials. Topical
antibacterials such as clindamycin, erythromycin, and tetracycline are
bacteriostatic for Propionibacterium acnes, and have also been demonstrated to
have anti-inflammatory activities through inhibition of lipase production by P.
acnes, as well as inhibition of leukocyte chemotaxis. Benzoyl peroxide is a
non-antibiotic antibacterial agent that is bactericidal against P. acnes and has
the distinct advantage that thus far, no resistance has been detected against it.
Combined agents such as erythromycin/zinc, erythromycin/tretinoin,
erythromycin/isotretinoin, erythromycin/benzoyl peroxide, and clindamycin/benzoyl
peroxide are increasingly being used and have been proven to be effective. They
generally demonstrate good overall tolerability and are useful in reducing the
development of antibacterial resistance in P. acnes. The selection of a topical
antibacterial agent should be tailored for specific patients by choosing an agent
that matches the patient’s skin characteristics and acne type. Topical
antibacterial agents should generally not be used for extended periods beyond 3
months, and topical antibacterials should ideally not be combined with systemic
antibacterial therapy for acne; in particular, the use of topical and systemic
antibacterials is to be avoided as far as possible.

Topical retinoid and antibiotic combination therapy for acne management. Weiss JS, Shavin JS. J Drugs Dermatol. 2004 Mar-Apr;3(2):146-54.

The agents most commonly used in combination for the management of acne include
topical retinoids and antibiotics. Topical retinoids normalize desquamation of
the follicular epithelium, whereas antibiotics inhibit the growth of P. acnes and
the production of free fatty acids. This therapeutic combination decreases
comedogenesis, bacterial growth, and inflammation, thus targeting three of the
four pathogenic factors associated with acne. Efficacy and tolerance are
maximized with combination therapy, and the degree of skin irritation is
minimized. Furthermore, adjunctive therapy with topical retinoids and antibiotics
tends to produce results more quickly than single-agent therapy. This article
will examine the individual agents used in combination for acne management, and
discuss the mechanisms by which they achieve efficacy. The rationale of utilizing
topical retinoids with antibiotics will be highlighted, particularly in relation
to improved tolerance and reduced irritation.

Tazarotene: therapeutic strategies in the treatment of psoriasis, acne and photoaging. Roeder A, Schaller M, Schäfer-Korting M, Korting HC. Skin Pharmacol Physiol. 2004 May-Jun;17(3):111-8.

Tazarotene is a member of the new generation of receptor-selective, synthetic
retinoids for the topical treatment of mild to moderate plaque psoriasis, acne
vulgaris and photoaging. Though they are effective in monotherapy, clinical
studies with a focus on novel combination treatments and a comparison of
different agents for these skin disorders are accumulating. The concomitant use
of tazarotene with a mid-potency or high-potency corticosteroid enhances the
efficacy in psoriatic plaques and reduces the risk of steroid-induced skin
atrophy. Combining phototherapy with adjunctive tazarotene accelerates the
clinical response and reduces the cumulative UVB or PUVA exposure load.
Tazarotene applied once daily is superior to adapalene monotherapy in acne
vulgaris and is efficacious in the treatment of photodamage. Novel therapeutic
regimens such as short-contact therapy have been developed for both acne and
psoriasis in order to diminish the major adverse events like pruritus, burning,
local skin irritation and erythema. Copyright 2004 S. Karger AG, Basel

Dermatologists and office-based care of dermatologic disease in the 21st century. Stern RS. J Investig Dermatol Symp Proc. 2004 Mar;9(2):126-30.

Most professional care of skin diseases is provided in physicians’ offices. In
the past 25 y, medical practice has changed substantially. Since 1973, the
National Ambulatory Medical Care Survey has provided data about patients seen in
physicians’ offices. Using 1974, 1980, and 1989 data, we have previously analyzed
these data as they pertain to skin diseases. To provide a more current assessment
of dermatologists’ practices and the care of skin diseases in office-based
practice, we analyzed National Ambulatory Medical Care Survey data for 1999 to
2000. We used statistical methods for survey data to estimate the number and
characteristics of visits to dermatologists and others for skin diseases. We
compared the characteristics of dermatologists’ office-based practices with those
of other physicians. In 1999 to 2000, there were approximately 35 million visits
annually to office-based dermatologists, double the number for 1974. Eight
diagnostic groups account for 65% of all visits to dermatologists. Acne is still
the most frequent primary diagnosis at visits to dermatologists, but since 1974
the proportion of all visits that were for acne has decreased by half. Compared
to other office-based physicians, dermatologists are significantly more likely to
own their practices (OR, 2.78; 95% CI, 1.52-5.02) and much less likely to see
capitated patients (OR, 0.30; 95% CI, 0.17-0.53). Over 26 y, utilization of
dermatologists’ services has grown in proportion to the increase in the number of
office-based dermatologists. The organization of their practices has changed
little. Dermatologists dominate the care of many of the same diagnoses as they
did 20 y ago.

Clinical inquiries. Does treatment of acne with Retin A and tetracycline cause adverse effects? Kelly BF, Burroughs M, Mertens M. J Fam Pract. 2004 Apr;53(4):316-8.

Safety and adverse effects of androgens: how to counsel patients. Basaria S, Dobs AS. Mayo Clin Proc. 2004 Apr;79(4 Suppl):S25-32.

Recently, interest has grown in the use of androgen replacement therapy for
postmenopausal women. Androgen replacement in women improves libido, bone
density, and body composition. The adverse effects, like hirsutism, are generally
mild, and the safety profile of transdermal testosterone replacement is more
favorable than that of other modes of androgen therapy. Further studies may help
to determine the effect of lipid changes on cardiac outcomes. We believe that
long-term studies are necessary to observe the potential effect of androgen
replacement on cardiovascular mortality, breast and endometrial tissues, and mood
and anger before this therapy can be used routinely in women.

The role of androgens in female sexual dysfunction. Shifren JL. Mayo Clin Proc. 2004 Apr;79(4 Suppl):S19-24.

There are many treatment options for female sexual dysfunction (FSD), with the
optimal therapy depending on the etiology of the problem. The cause of sexual
dysfunction is multifactorial and may include psychological problems such as
depression or anxiety disorders, conflict within the relationship, partner
performance and technique, issues relating to prior abuse, medical illness,
medications, fatigue, stress, or gynecological problems that make sexual activity
uncomfortable. The role of low androgen concentrations in FSD is gaining
increasing attention. Available therapeutic options include adjusting
medications, counseling, treating depression or anxiety, reducing stress and
fatigue, sex therapy, devices, estrogen therapy for genitourinary atrophy, and
possibly vasoactive substances. Although no androgen therapies are currently
approved by the Food and Drug Administration for FSD, they are being used in
clinical practice, and early clinical trial results suggest that they may be both
effective and safe in the treatment of FSD, specifically low libido. Androgen
therapy should be considered primarily in women who have a physiological reason
for reduced androgen concentrations, including aging, hypopituitarism,
oophorectomy, or adrenal insufficiency. Products in use include oral
methyltestosterone and dehydroepiandrosterone, topical testosterone ointment, and
testosterone implants and injections. Products available for men, including skin
patches and gels, are currently being studied at doses appropriate for women.
Possible risks include hirsutism, acne, liver dysfunction, lowering of the voice,
adverse lipid changes, virilization of a female fetus, and, as androgens are
aromatized to estrogens, potentially the risks of estrogen therapy.

Nonablative resurfacing. Hirsch RJ, Dayan SH. Facial Plast Surg. 2004 Feb;20(1):57-61.

In expert hands, ablative laser resurfacing has a long history of excellent
results in the treatment of photodamage-induced rhytids, depressed acne scars,
and other signs of cutaneous aging. Over the last decade there have been a
growing number of reports in the emerging area of nonablative resurfacing.
Nonablative modalities provide less impressive clinical results for rhytid
reduction but have shown particular promise for the treatment of scars and
superficial dyschromias. It is also ideally suited for those patients seeking a
minimally invasive, greatly reduced downtime procedure.

Selective non-steroidal inhibitors of 5 alpha-reductase type 1. Occhiato EG, Guarna A, Danza G, Serio M. J Steroid Biochem Mol Biol. 2004 Jan;88(1):1-16.

The enzyme 5 alpha-reductase (5 alpha R) catalyses the reduction of testosterone
(T) into the more potent androgen dihydrotestosterone (DHT). The abnormal
production of DHT is associated to pathologies of the main target organs of this
hormone: the prostate and the skin. Benign prostatic hyperplasia (BPH), prostate
cancer, acne, androgenetic alopecia in men, and hirsutism in women appear related
to the DHT production. Two isozymes of 5 alpha-reductase have been cloned,
expressed and characterized (5 alpha R-1 and 5 alpha R-2). They share a poor
homology, have different chromosomal localization, enzyme kinetic parameters, and
tissue expression patterns. Since 5 alpha R-1 and 5 alpha R-2 are differently
distributed in the androgen target organs, a different involvement of the two
isozymes in the pathogenesis of prostate and skin disorders can be hypothesized.
High interest has been paid to the synthesis of inhibitors of 5 alpha-reductase
for the treatment of DHT related pathologies, and the selective inhibition of any
single isozyme represents a great challenge for medical and pharmaceutical
research in order to have more specific drugs. At present, no 5 alpha R-1
inhibitor is marketed for the treatment of 5 alpha R-1 related pathologies but
pharmaceutical research is very active in this field. This paper will review the
major classes of 5 alpha R inhibitors focusing in particular on non-steroidal
inhibitors and on structural features that enhance the selectivity versus the
type 1 isozyme. Biological tests to assess the inhibitory activity towards the
two 5 alpha R isozymes will be also discussed.

Polycystic ovary syndrome: a review for primary providers. Buccola JM, Reynolds EE. Prim Care. 2003 Dec;30(4):697-710.

PCOS is a metabolic syndrome that exists throughout the world with much clinical
heterogeneity. PCOS is now appreciated as encompassing two interrelated metabolic
phenomena–insulin resistance and hyperandrogenism. Patients present with
oligo-amenorrhea and clinical hyperandrogenism, and the diagnosis is based on
clinical grounds with few laboratory tests necessary. Because patients are at
higher than normal risk for diabetes, glucose intolerance, and hyperlipidemia,
and perhaps at higher risk for coronary heart disease, newly diagnosed patients
with PCOS should be evaluated for glucose intolerance and hyperlipidemia. The
cornerstone of therapy today includes weight management, and further therapeutic
intervention is focused on reproductive and cardiovascular health and treatment
of insulin resistance. Clinical case continued The 17-year-old mentioned in the
beginning of this article probably does have PCOS. She fits the clinical
criteria: oligo-ovulation and hyper-androgenism (the acne and hirsutism). In
addition, she is obese, which is also associated with PCOS. Her TSH and prolactin
were normal, and as her presentation was not suggestive of an adrenal tumor or
congenital adrenal hyperplasia (she had mild hirsutism, and those diagnoses are
associated with more severe hyperandrogenism), no further laboratory evaluation
was deemed necessary. Once the diagnosis was made, she was screened for lipid
abnormalities and for glucose intolerance. Her LDL was 150, HDL 35; oral glucose
tolerance test (OGTT) was normal. A pregnancy test was negative, and she was
started on OCPs. Devoting herself to exercise and dietary change, she lost 10
pounds in her first 3 months after diagnosis. Her hirsutism and acne have
improved with the OCPs and weight loss, and her menses are regular. She has
elected to defer oral insulin sensitizers until her weight loss has stabilized.
Findings PCOS is common in reproductive-aged women. Diagnosis is clinical and is
supported by lab findings; there is significant clinical heterogeneity. Insulin
resistance is likely central to the pathophysiology along with androgen excess.
Health implications include infertility, diabetes, endometrial cancer,
hyperlipidemia, and possibly coronary heart disease. Treatment is evolving and
includes weight loss, OCPs, and insulin sensitizers.

Polycystic ovary syndrome in adolescence–a therapeutic conundrum. Homburg R, Lambalk CB. Hum Reprod. 2004 May;19(5):1039-42. Epub 2004 Mar 11.

The polycystic ovary syndrome (PCOS) often presents in adolescence with menstrual
disorders, acne and hirsutism. The early diagnostic signs are sometimes dismissed
as ‘normal’ changes of adolescence, and the opportunity to save the teenager from
the stigmata of the syndrome is missed. The finding that the metabolic syndrome
is a possible long-term sequela of PCOS now presents a challenge to make an early
diagnosis, educate patients regarding the importance of weight control and
exercise, and treat accordingly both symptomatically and prophylactically. The
use of long-term insulin sensitizers, particularly metformin, for these purposes
in adolescents is now the subject of an inter-disciplinary debate. Good, hard
supportive data are not yet forthcoming but, as in the adult, the establishment
of metformin treatment for the hyperinsulinaemic adolescent with PCOS may precede
the evidence.

Er:YAG laser treatment of verrucous epidermal nevi. Park JH, Hwang ES, Kim SN, Kye YC. Dermatol Surg. 2004 Mar;30(3):378-81.

BACKGROUND: The term verrucous epidermal nevi refers to benign hyperplasia of the
epidermis. Numerous treatment modalities have been tried, but no ideal treatment
is yet available. We would like to present our experience with Er:YAG laser
ablation in the treatment of verrucous epidermal nevi. OBJECTIVE: The purpose of
this study is to assess the long-term results of Er:YAG laser treatment of
verrucous epidermal nevi. METHODS: Twenty patients with verrucous epidermal nevi
were treated with Er:YAG laser. Twelve patients were treated with the
variable-pulsed Er:YAG laser, a 5-mm handpiece at the setting of 7.0 to 7.5
J/cm2, at a 500-micros pulse duration. The dual-mode Er:YAG laser, with a 2-mm
handpiece at the setting of 6.3 J/cm2, at a 350-micros pulse duration (25 microns
ablation), was used in eight patients. The laser was fired at 5 Hz until all
epidermal nevi were removed. The results of treatment were evaluated for the
changes of skin lesions, texture, and color by physicians over a 24-month period.
RESULTS: After a single laser treatment, successful elimination of the verrucous
epidermal nevi was observed in 15 patients. Five patients (25%) showed a relapse
within 1 year after the treatment. Postoperative healing time was 7 to 10 days.
Erythema occurred in all patients after the laser treatment and subsided in 2
months. Postinflammatory hyperpigmentation occurred in two patients (10%). One
patient (5%) experienced transient hypopigmentation. Mild to moderate
postoperative acne flare-up occurred in one patient (5%) with facial lesions. No
other adverse effects, including scarring, were observed. CONCLUSION: The Er:YAG
laser ablation is an effective, safe, and nonscarring method for the treatment of
verrucous epidermal nevi.

Safety and side effects of the acne drug, oral isotretinoin. Charakida A, Mouser PE, Chu AC. Expert Opin Drug Saf. 2004 Mar;3(2):119-29.

Isotretinoin is a very effective medication for the treatment of severe
recalcitrant acne. However, its use is associated with many side effects, some of
which can be very serious. The most important issue is its teratogenicity, which
has resulted in new pregnancy prevention policies and programmes implemented by
the manufacturer. Recently, the association of isotretinoin with depression has
been recognised and new guidelines have been adopted for this possible side
effect. The most common adverse events, observed during treatment, are
mucocutaneous and ophthalmological. In addition, laboratory abnormalities and
effects in the nervous, musculoskeletal, gastrointestinal, pulmonary and other
systems have been described.

An aberrant ACTH-producing ectopic pituitary adenoma in the sphenoid sinus. Suzuki J, Otsuka F, Ogura T, Kishida M, Takeda M, Tamiya T, Nishioka T, Tanaka Y, Hashimoto K, Makino H. Endocr J. 2004 Feb;51(1):97-103.

A 32-year-old woman with an ectopic adrenocorticotropic hormone (ACTH)-secreting
pituitary adenoma (EAPA) is presented. She had rapidly gained weight and suffered
recurrent facial acne for a few years but lacked the typical Cushingoid features.
Endocrine examinations revealed that her plasma ACTH was markedly high (196 to
280 pg/ml) without showing normal circadian rhythm and failed to respond to
corticotropin-releasing hormone stimulation. Her cortisol levels ranged from 22
to 30 microg/dl throughout observation but low doses (1 and 2 mg) of
dexamethasone failed to suppress either ACTH or cortisol level. Magnetic
resonance imaging study revealed a 3-cm mass occupying the sphenoidal sinus with
partial enhancement by gadolinium, which was separated from the normal pituitary
in the sella region. The tumor resected by transsphenoidal surgery was
histologically diagnosed as an ACTH-producing pituitary adenoma. After surgery
her weight gain and acne remitted in accordance with decreases in plasma ACTH.
Analysis of patient plasma by gel filtration method revealed the existence of big
ACTH molecules eluted with a peak of authentic 1-39 ACTH, suggesting that this
biologically less-active ACTH might be the reason why overt features of Cushing’s
syndrome failed to develop in this case. Although EAPA is clinically rare in
parasellar disorders, the presence of ectopic pituitary adenoma should be
considered in such cases showing ACTH hypersecretion without typical Cushingoid
features.

The use of polyhydroxy acids (PHAs) in photoaged skin. Grimes PE, Green BA, Wildnauer RH, Edison BL. Cutis. 2004 Feb;73(2 Suppl):3-13.

The beneficial effects of alpha-hydroxyacids (AHAs) on skin were discovered by
Drs. Van Scott and Yu in the early 1970s, including exfoliation, skin smoothing,
and antiaging effects. A new generation of AHAs, called polyhydroxy acids (PHAs),
was discovered that provide similar effects as AHAs but do not cause the sensory
irritation responses that can limit the use of classical AHAs. PHAs have been
found to be compatible with clinically sensitive skin, including rosacea and
atopic dermatitis, and can be used after cosmetic procedures. PHAs provide
additional humectant and moisturization properties compared with AHAs and can
enhance stratum corneum barrier function, therefore increasing the skin’s
resistance to chemical challenge. Most PHAs also possess antioxidant properties.
PHAs such as gluconolactone or lactobionic acid may be used in combination with
other products, ingredients, or procedures such as laser and microdermabrasion to
provide additional benefits to therapy or to enhance the therapeutic effect.
Several studies were conducted in support of this, and methods and results are
discussed. In summary, PHA-containing products were used in combination with
retinoic acid in treating adult facial acne and were found to be well tolerated.
PHAs plus retinyl acetate (pro-vitamin A) in a cream base exhibited significant
antiaging skin benefits such as skin smoothing and plumping. PHAs plus
hydroquinone showed excellent improvement in antiaging and skin lightening
parameters. Finally, PHA-containing products were shown to be compatible with
African American, Caucasian, and Hispanic/Asian skin and provided significant
improvements in photoaging in these populations.

Systemic therapy for acne vulgaris. Layton AM. Hosp Med. 2004 Feb;65(2):80-5.

There are three main groups of systemic therapies available for the treatment of
acne vulgaris: systemic antibiotics, hormonal therapy (for females) and oral
isotretinoin. This article outlines when these treatments should be prescribed
for the treatment of acne, considers the impact of therapy on aetiology, and
advises on dosage regimens, potential adverse effects and expected efficacy.

Cationic antimicrobial peptides – an update. Zhang L, Falla TJ. Expert Opin Investig Drugs. 2004 Feb;13(2):97-106.

Cationic antimicrobial peptides play a very important role in nature as a first
line of defence against attack and damage. However, their application to the
clinic has not been very encouraging to date. There are indications that the
barriers to their success may now be eroding with companies developing peptides
to be more stable, cost effective and targeted to specific indications. These
include systemic infectious disease, acne, vaginitis, wound infection and
inflammation. In addition, the use of such peptides as modulators of innate
immunity in the treatment of infectious disease and inflammation has added a
further dimension to the field.

Cutaneous adverse effects of lithium: epidemiology and management. Yeung CK, Chan HH. Am J Clin Dermatol. 2004;5(1):3-8.

Acneiform eruption, psoriasis, folliculitis, and maculopapular eruption have been
described as adverse reactions to lithium therapy. In controlled studies,
patients treated with lithium developed more cutaneous reactions, particularly
acne and psoriasis, than patients receiving other psychotropics, with a
prevalence in lithium-treated patients as high as 45%. Male patients taking
lithium are more susceptible to developing cutaneous reactions than their female
counterparts. Lithium tends to worsen or precipitate cutaneous conditions that
are characterized by the pathological findings of neutrophilic infiltration. As
lithium-related cutaneous adverse effects can be distressing to patients and may
affect medication compliance, attention should be paid to skin problems in
patients receiving lithium therapy. Management without cessation of lithium
therapy is usually feasible except in some patients with psoriasis that is
resistant to treatment. Paradoxically, therapeutic effects of topically applied
lithium have been noted in seborrheic dermatitis and recurrent herpes infections.

[Treating acne: avoid the development of antibiotic resistance by applying topical and combined therapy] [Article in German] Abeck D. MMW Fortschr Med. 2003 Dec 18;145(51-52):29.