Palmoplantar psoriasis: a phenotypical and clinical review with introduction of a new quality-of-life assessment tool. Farley E, Masrour S, McKey J, Menter A. J Am Acad Dermatol. 2009 Jun;60(6):1024-31.

BACKGROUND: Palmoplantar psoriasis is associated with significant quality-of-life
issues. Its epidemiology and phenotypical expression remain ill defined.
OBJECTIVE: We reviewed the literature and our clinical experience and developed a
new quality-of-life assessment tool. METHODS: We conducted a retrospective review
of 150 patients with palmoplantar psoriasis. RESULTS: In all, 78 (52%) patients
displayed predominantly hyperkeratotic palmoplantar lesions, 24 (16%) pustular,
18 (12%) combination, and 30 (20%) had an indeterminate phenotype. In 27 (18%)
patients, lesions were confined to the palms and soles. A new quality-of-life
index was constructed to characterize disease severity. In all, 27 (18%) had
mild, 72 (48%) moderate, and 51 (34%) severe disease involvement. Palmoplantar
disease severity appeared independent from the degree of body surface area
involvement. LIMITATIONS: This was a retrospective review. The quality-of-life
index remains to be statistically verified in prospective clinical studies.
CONCLUSION: Defining morphologic subtypes together with the use of a specific
quality-of-life assessment tool in patients with palmoplantar psoriasis will
improve our understanding and treatment of this recalcitrant form of psoriasis.

Methotrexate and psoriasis: 2009 National Psoriasis Foundation Consensus Conference. Kalb RE, Strober B, Weinstein G, Lebwohl M. J Am Acad Dermatol. 2009 May;60(5):824-37.

BACKGROUND: Methotrexate remains a valuable option for the treatment of
psoriasis. This report will summarize studies regarding the use of methotrexate
since the last guidelines were published in 1998. OBJECTIVE: A task force of the
National Psoriasis Foundation Medical Board was convened to evaluate treatment
options. Our aim was to achieve a consensus on new updated guidelines for the use
of methotrexate in the treatment of psoriasis. METHODS: Reports in the literature
were reviewed regarding methotrexate therapy. RESULTS: A consensus was achieved
on use of methotrexate in psoriasis including specific recommendations on dosing
and monitoring. The consensus received unanimous approval from members of the
Medical Board of the National Psoriasis Foundation. LIMITATIONS: There are few
evidence-based studies on the treatment of psoriasis with methotrexate. Many of
the reviewed reports are for the treatment of rheumatoid arthritis. CONCLUSIONS:
Methotrexate is a safe and effective drug for the treatment of psoriasis.
Appropriate patient selection and monitoring will significantly decrease the
risks of side effects. In patients without risk factors for hepatic fibrosis,
liver biopsies may not be indicated or the frequency of liver biopsies may be
markedly reduced.

Treatment of severe scalp psoriasis: from the Medical Board of the National Psoriasis Foundation. Chan CS, Van Voorhees AS, Lebwohl MG, Korman NJ, Young M, Bebo BF Jr, Kalb RE,Hsu S. J Am Acad Dermatol. 2009 Jun;60(6):962-71. Epub 2009 Apr 17.

BACKGROUND: The scalp is the most commonly affected part of the body in patients
with psoriasis. Signs and symptoms of scalp psoriasis vary significantly for
individual patients. OBJECTIVE: A task force of the National Psoriasis Foundation
was convened to evaluate treatment options. Our aim was to achieve a consensus
for scalp psoriasis therapy. METHODS: Reports in the medical literature were
reviewed regarding scalp psoriasis therapy. LIMITATIONS: There is a paucity of
evidence-based and double-blind studies in the treatment of scalp psoriasis
particularly for long-term therapy. Many of the studies in scalp psoriasis were
designed to attain Food and Drug Administration approval for a medication and not
to provide treatment guidance. CONCLUSIONS: The recommended short-term or
intermittent therapy for scalp psoriasis is topical corticosteroids. The primary
alternatives are topical retinoids, vitamin D analogues, and salicylic acid.
Combination therapy has many advantages. The choice of an appropriate vehicle is
crucial to increase patient compliance. While scalp psoriasis can often be
adequately treated with topical therapy, recalcitrant disease may require more
aggressive approaches, including systemic agents.

[Biologics--the new horizon for medical therapy] [Article in German] Ziegenhagen DJ. Versicherungsmedizin. 2009 Mar 1;61(1):4-9.

Biologics include a wide range of medications that are produced by means of
biological processes involving recombinant DNA technology. Approximately one in
four of the recently approved new therapeuticals belongs to this group. Biologics
have added major therapeutic options for the treatment of many diseases with an
especially profound impact on rheumatoid arthritis, chronic inflammatory bowel
disease, psoriasis, multiple sclerosis and a great array of malignancies. Many
more targets are already screened in clinical research. Despite their clinical
promises, monoclonal antibodies are raising concern about the potential adverse
effects of long-term use. Costs are dramatically higher than for conventional
medications, raising severe pharmacoeconomic concerns.

Topical treatments for chronic plaque psoriasis. Mason AR, Mason J, Cork M, Dooley G, Edwards G. Cochrane Database Syst Rev. 2009 Apr 15;(2):CD005028.

BACKGROUND: Chronic plaque psoriasis is the most common type of psoriasis and is
characterised by redness, thickness and scaling. First line management of chronic
plaque psoriasis is with topical treatments, including vitamin D analogues,
topical corticosteroids, tar-based preparations, dithranol, salicylic acid and
topical retinoids. OBJECTIVES: To compare the effectiveness, tolerability and
safety of topical treatments for chronic plaque psoriasis with placebo; to
compare vitamin D analogues with other topical treatments. SEARCH STRATEGY: The
Cochrane Skin Group’s Trials Register was searched (2004/12). To update an
unpublished 2002 review we also searched CENTRAL in The Cochrane Library (Issue
1,2005); MEDLINE (to 2005/02); EMBASE (to 2005/08); Science Citation Index (to
2005); Biosis (to 2005); Dissertation Abstracts (all publication years); Inside
Conferences (all publication years); SIGLE (to 2005); National Research Register
(all projects with a start date of 2001 to 2005); metaRegister of Current
Controlled Trials. SELECTION CRITERIA: Randomised trials comparing treatments
against placebo or against vitamin D analogues in people with chronic plaque
psoriasis. DATA COLLECTION AND ANALYSIS: One author extracted study data and
assessed study quality. A second author checked these data. We routinely
contacted triallists and companies for missing data. We extracted data on
withdrawals and adverse events. MAIN RESULTS: The review included 131 RCTs with
21,448 participants. Vitamin D was significantly more effective than placebo,
although there was a wide variation in effect size with the standardised mean
difference (SMD) ranging from -0.82 (95% CI -1.34 to -0.29) to -1.90 (95% CI
-2.09 to -1.71). With one exception, all corticosteroids performed better than
placebo, with potent corticosteroids (SMD: -0.95 (95% CI: -1.11 to -0.80; I(2):
61.1%; 17 studies; 2386 participants)) having smaller benefits than very potent
corticosteroids (SMD: -1.29 (95% CI: -1.45 to -1.13; I(2): 53.2%; 11 studies;
1571 participants)). Dithranol and tazarotene performed better than placebo.
Head-to-head comparisons of vitamin D against potent or very potent
corticosteroids found no significant differences. However, combined treatment
with vitamin D /corticosteroid performed significantly better than either vitamin
D alone or corticosteroid alone. Vitamin D performed better than coal tar, but
findings relative to dithranol were mixed. Potent corticosteroids were less
likely than vitamin D to cause local adverse events. No comparison of topical
agents found a significant difference in systemic adverse effects. AUTHORS’
CONCLUSIONS: Corticosteroids perform as well as vitamin D analogues and are
associated with a lower incidence of local adverse events. Further research is
required to inform long-term maintenance treatment.

The genetics of psoriasis. Zippin JH. J Drugs Dermatol. 2009 Apr;8(4):414-7.

Biologic survival. Noiles K, Vender R. J Drugs Dermatol. 2009 Apr;8(4):329-33.

BACKGROUND: The results of long-term studies on the efficacy and safety profiles
of the biologics for patients with psoriasis are starting to appear in the
literature. Not only are the results promising for the biologics as a whole, but
the high number of patients remaining in these clinical trials after extended
periods of time, or retention, may also reflect additional benefits of these
biologics. The aim of this review was to manuscript aims to compare rates of
attrition for the various biologic therapies in pivotal clinical trials in order
to assess and compare adherence of patients to long-term use of the different
biologic agents, also known as biologic survival. METHODS: An in-depth literature
review was conducted using PubMed and MEDLINE. Randomized, controlled trials
utilizing biologic agents as monotherapy for the treatment of psoriasis were
analyzed for patient numbers over time. Studies which provided data on patient
retention for at least 24 weeks were selected, graphed, and compared. Reasons for
discontinuation were noted. RESULTS: Nineteen trials were selected, graphed and
charted to compare attrition rates of the various biologic therapies. Due to
differences in sample size, study design, dosing regimens, study duration and
limited data with regards to patient numbers, it is difficult to reach a
definitive conclusion as to which biologic agent is associated with the lowest
rate of discontinuation. However, given the data available, etanercept appears to
be the most successful therapy in terms of patient retention in studies both
greater than and less than 30 weeks. For the studies using various dosing
regimens, intrastudy attrition rates are also compared. CONCLUSION: While the
data available thus far on patient retention for the biologic therapies are very
limited, preliminary conclusions can be drawn. Among the available biologic
agents, etanercept appears to be associated with the lowest rate of
discontinuation. This may be due to greater superior effiacy and to a decreased
likelihood of experiencing adverse events.

Treatments for psoriasis and the risk of malignancy. Patel RV, Clark LN, Lebwohl M, Weinberg JM. J Am Acad Dermatol. 2009 Jun;60(6):1001-17. Epub 2009 Apr 2.

BACKGROUND: There are multiple therapeutic options for the treatment of moderate
to severe psoriasis. The process of choosing among potential treatment options
requires both the physician and the patient to weigh the benefits of individual
modalities against their potential risks. Traditional systemic therapies for
psoriasis, including methotrexate (MTX) and cyclosporine (CsA), have a
well-documented array of toxicities, particularly end-organ toxicities. Over the
past several years, the use of biologic therapies for the treatment of moderate
to severe psoriasis has been a major clinical and research focus. With the advent
of these novel immunosuppressive therapies, one of the central safety issues
surrounding these agents is their potential to increase the risk of malignancy.
OBJECTIVE: Our objective was to review the risk of malignancy associated with
therapies for moderate to severe psoriasis, including phototherapy, traditional
systemic therapies, and biologic therapies. We reviewed the existing body of
literature in order to define the known incidence of malignancy associated with
psoralen and ultraviolet A (PUVA), narrowband and broadband ultraviolet B (UVB),
MTX, CsA, mycophenolate mofetil (MMF), and biologic therapies, including
alefacept, efalizumab, infliximab, etanercept, adalimumab, and ustekinumab.
RESULTS: PUVA, when given long term, is associated with increased risks of
cutaneous squamous cell carcinoma and malignant melanoma. Reviews of studies on
UVB, both narrowband and broadband, do not indicate any increased risk of
nonmelanoma skin cancer or melanoma. The traditional systemic psoriasis
therapies-MTX, CsA, and MMF-may be associated with an increased risk of
lymphoproliferative disorders during treatment, demonstrated in clinical trials
in patients with rheumatoid arthritis and documented in case reports concerning
psoriasis patients. The risk of malignancy with biologic therapy is still
unclear. However, the majority of studies examining this carcinogenic risk
suggest that tumor necrosis factor-alpha inhibitors may cause a slightly
increased risk of cancer, including nonmelanoma skin cancer and hematologic
malignancies. LIMITATIONS: The majority of studies cited in this review lack the
power and randomization of large clinical trials, as well as the long-term
follow-up periods which would further substantiate the hypothetical link between
these antipsoriatic treatment regimens and the potential for malignancy. Because
of the substantial lack of clinical data, the majority of studies evaluated focus
on the treatment of patients with rheumatoid arthritis, which is a systemic
inflammatory disorder comparable to psoriasis. Additionally, the increased risk
of malignancy associated with psoriasis itself is a confounding factor.
CONCLUSION: Many of the therapies for moderate to severe psoriasis, including
PUVA, traditional systemic therapies, and some biologic therapies, may increase
the risk of malignancy. Appropriate patient counseling and selection, as well as
clinical follow-up, are necessary to maximize safety with these agents. Further
long-term study is necessary to more precisely quantify the risks associated with
biologic therapies.

Ustekinumab. Weber J, Keam SJ. BioDrugs. 2009;23(1):53-61. doi: 10.2165/00063030-200923010-00006.

Ustekinumab is a fully human monoclonal antibody that binds with high specificity
and affinity to the cytokines interleukin (IL)-12 and IL-23, thereby suppressing
IL-12- and IL-23-mediated inflammation associated with psoriasis. In two large,
phase III trials in patients with moderate to severe plaque psoriasis,
significantly more subcutaneous ustekinumab 45 or 90 mg recipients (administered
as two injections 4 weeks apart) than placebo recipients achieved a 75%
improvement on the Psoriasis Area and Severity Index (PASI 75) score at 12 weeks.
Other efficacy measures, including the physician’s global assessment of clinical
response at week 12, also favored ustekinumab over placebo. Psoriatic symptom
control was maintained during ustekinumab maintenance therapy (administered once
every 12 weeks) for up to 76 weeks. In a phase II trial in patients with active
plaque psoriasis and psoriatic arthritis, signs and symptoms of arthritis and
psoriatic symptom control were improved to a greater extent with ustekinumab than
with placebo at 12 weeks, based on the proportion of patients achieving a 20%
improvement in American College of Rheumatology response criteria (arthritis) or
PASI 75 (skin symptoms). Health-related quality of life, assessed using the
Dermatology Life Quality Index and the Health Assessment Questionnaire disability
index, was improved to a significantly greater extent with ustekinumab than with
placebo at week 12. Subcutaneous ustekinumab was generally well tolerated in
clinical trials, with most treatment-emergent adverse events being of mild
severity.

Inflammatory arthritis: an overview for primary care physicians. Brent LH. Postgrad Med. 2009 Mar;121(2):148-62.

Continuing advances in the treatment of inflammatory arthritides such as
rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis
(PsA) have made remission a realistic goal for patients. Despite these advances,
early diagnosis of inflammatory arthritis by primary care physicians (PCPs) and
subsequent referral to a rheumatologist remain a challenge. Delayed diagnosis and
referral, which may extend to several years in some cases, may lead to
irreversible joint destruction and compromised function. The aim of this review
is to aid PCPs in preventing the potential delay in disease recognition and
patient referral by highlighting the currently accepted criteria for disease
activity, clinical response, and remission of RA, AS, and PsA. In addition, a
discussion of the benefits and risks of the currently approved traditional
disease-modifying antirheumatic drugs and biologic treatments, and the importance
of comanagement of these conditions across specialties, will be addressed.
Because PCPs are often the first point of contact for disease recognition, they
can play a critical role in the management of these patients.

Pruritus measurement and treatment. Langner MD, Maibach HI. Clin Exp Dermatol. 2009 Apr;34(3):285-8.

Pruritus measurement is problematic, because of its subjective nature and poor
localization. Ratio scales enhance the usefulness of the visual analogue scale
(VAS) by reducing variation; other scales such as the generalized labelled
magnitude scale may also be useful. Pruritus neuroanatomy includes peripheral
receptors, peripheral and central nerves, ascending and descending spinal
pathways, and several brain regions. Pruritus receptors include Merkel discs and
free nerve endings, and itch receptors have fast or slow adaptation. In this
review, we discuss the pathophysiology of pruritus in atopic dermatitis,
psoriasis and scabies. Pruritus treatment is reviewed for topical agents and
antihistamines. Future research directions are suggested.

Nail psoriasis and biologics. Noiles K, Vender R. J Cutan Med Surg. 2009 Jan-Feb;13(1):1-5.

BACKGROUND: Since the advent of biologic therapies for psoriasis, reports of
efficacy in nail psoriasis have appeared in the literature and at international
conferences with increasing frequency. OBJECTIVE: This article aims to review the
existing literature on the use of biologics in the treatment of nail psoriasis.
METHODS: An extensive literature review was conducted using OVID Medline. Studies
examining the efficacy of biologics in the treatment of nail psoriasis were
documented. RESULTS: A literature review revealed few clinical trials
specifically concentrating on nail psoriasis; however, nails have been assessed
in larger clinical trials for cutaneous psoriasis. A large, multicenter, phase
III, double-blind, placebo-controlled study of infliximab administered as a brief
induction regimen at weeks 0, 2, and 6 followed by a single infusion every 8
weeks revealed statistically significant mean percent improvement in the Nail
Psoriasis Severity Index (NAPSI) score over placebo at both week 10 (26.8% vs
-7.7%, respectively; p < .001) and week 24 (57.2% vs -4.1%, respectively; p <
.001). For other biologics, evidence has thus far been largely anecdotal,
appearing as either case studies or extracted secondarily from open-label
prospective trials in plaque psoriasis or psoriatic arthritis. CONCLUSION:
Infliximab appears to be the most effective treatment for nail psoriasis to date.

[The use of statins, a new approach to the treatment of autoimmune diseases] [Article in Russian] Shirinskiĭ IV, Kozlov VA, Shirinskiĭ VS. Vestn Ross Akad Med Nauk. 2009;(2):26-32.

HMG-CoA inhibitors (statins) are widely used for the prevention of cardiovascular
events and the management of hypercholesterolemia. Recently, multiple
cholesterol-independent properties of statins have been discovered. The present
review focuses on immunomodulatory and anti-inflammatory effects of statins and
their implications for the treatment of autoimmune diseases, such as rheumatoid
arthritis, multiple sclerosis, and psoriasis.

Significance of heat shock proteins in the skin upon UV exposure. Jonak C, Klosner G, Trautinger F. Front Biosci. 2009 Jan 1;14:4758-68.

The expression of heat shock proteins (Hsp) expression is induced in all cells by
exposure to heat and other environmental stress and Hsp can protect cells from
damage through further exposure. Hsp are highly conserved and it is likely that
they are essential for survival in a potentially harmful environment. Most Hsp
are molecular chaperones sensing unfolded proteins and mediating their
re-folding, transport, and interaction. In human epidermis Hsp are associated
with differentiation, photoprotection, and skin disease. Recent research has
mainly focused on the 27kD and 72kD Hsp that are constitutively expressed in
keratinocytes. Cell death induced by ultraviolet radiation (UV) can be inhibited
by previous heat shock and UV itself can induce Hsp experimentally. Regulation of
Hsp can be pharmacologically modified and topical and systemic inducers and
inhibitors of Hsp expression are under development. Whether phototherapy exerts
its clinical efficacy by modulation of Hsp has not been sufficiently studied. The
UV-wavelength ranges, -intensities and -doses that are required to interfere with
the heat shock response in the skin still remain to be elucidated.

Regulation of cellular immunity by Photo(chemo)therapy. Grundmann SA, Beissert S. Front Biosci. 2009 Jan 1;14:4326-36.

Phototherapy and photochemotherapy are important treatment regimens for
inflammatory as well as malignant diseases in dermatology. Both treatment
modalities have been developed already three decades ago and therefore profound
knowledge exists on the use, efficacy, and long-term side effects. Since the
development of new mmunosuppressive medications, biologics, and changes in
medical reimbursement policies, phototherapy is currently less frequently used
compared to previous years to treat psoriasis or atopic dermatitis. However,
cost-effectiveness analysis demonstrated that phototherapy can significantly
induce therapeutic beneficial effects on a large number of inflammatory and
malignant skin disorders at a low cost of treatment rate. Since many chronic skin
disorders require rotational treatment regimens to decrease the development of
(long-term) adverse events, phototherapy will play an important role in
dermatology in future years. In the following the molecular as well as cellular
mechanisms of phototherapy are described and discussed in light of the fact that
photobiology is a very active field in biomedical research.

Glomangioma: a case report and review of the literature. Schopp JG, Sra KK, Wilkerson MG. Cutis. 2009 Jan;83(1):24-7.

Glomus tumors are benign localized tumors of the skin accounting for 1% to 2% of
all soft tissue tumors. They may present as a solitary tumor or multiple tumors,
termed glomangioma. We describe a 69-year-old man with a medical history of
psoriasis and hypertension who presented with an incidental finding of multiple
asymptomatic, noncompressible, blue lesions over his arms, chest, and back. The
lesions, present since childhood, had never been subject to a workup. The patient
had no history of gastrointestinal bleeding and no known family history of
similar lesions. Physical examination revealed multiple nontender, blue,
subcutaneous nodules that were 1 to 2 cm in diameter and located on the bilateral
arms, chest, and back. The diagnosis of glomangioma was made and no further
treatment was indicated.

Management of moderate to severe plaque psoriasis (part 2): clinical update on T-cell modulators and investigational agents. Sobell JM, Kalb RE, Weinberg JM. J Drugs Dermatol. 2009 Mar;8(3):230-8.

This second part of a 2-part review on the use of biologics for treatment of
patients with psoriasis is focused on currently approved therapies that work
through modulation of T cells: alefacept, a leukocyte function-associated antigen
3-immunoglobulin G fusion molecule; and efalizumab, an anti-CD11 humanized
antibody. Efficacy and safety data from pivotal clinical trials are summarized
and new data are presented for these biological agents, and considerations for
optimal therapeutic selection are discussed. Clinical data from investigational
agents currently in development are also reviewed. One of these new agents is
ustekinumab, a humanized antibody that targets interleukins 12 and 23 and
inhibits the differentiation of Th17 cells, a recently identified subset of CD4+
T-helper cells.

Association of psoriasis and alcoholism: psychodermatological issue. Dediol I, Buljan M, Buljan D, Bulat V, Zivković MV, Situm M. Psychiatr Danub. 2009 Mar;21(1):9-13.

Psoriasis is a chronic, hereditary disease generally characterized by eruption of
erythematous, silvery-scaled plaques, predominantly on the elbows, knees, scalp
and trunk, affecting between 1-2% of the population worldwide. Psoriasis is a
multifactorial disease of unknown etiology. It has been shown that in some
patients alcohol abuse has been associated with psoriasis. Chronic alcohol abuse
results in the impairment of health-related, social and occupational functioning.
Therefore the association of psoriasis and alcoholism represents one of the major
psychodermatological issues where a multidisciplinary approach (including
dermatologist, psychiatrist, psychologist and others) is crucial for optimal
outcome.

The impact of biologic agents to treat plaque psoriasis. Phung OJ, Coleman CI, Kugelman L, White CM. Conn Med. 2009 Feb;73(2):79-83.

Emerging drugs for psoriasis. Naldi L, Raho G. Expert Opin Emerg Drugs. 2009 Mar;14(1):145-63.

BACKGROUND: Psoriasis is a relatively common, chronic and disabling skin disease,
due to a disturbed proliferation and differentiation of keratinocytes,
accompanied by vascular alterations and infiltration of inflammatory cells with a
local T(H)1-type cytokine immune response. There is no cure, but several
treatment options are available. Objective: The treatment of psoriasis is far
from being satisfactory, due to the impractical modalities of topical treatment
and the suboptimal safety profile of the systemic treatments available. In the
last few years, parallel to an improved understanding of the disease
pathogenesis, there has been a boosting of research in new agents for the
treatment of psoriasis. These new agents are the focus of this paper. METHODS:
After a short review of the treatment options already available (mainly based on
the available systematic reviews), we focused on agents that are still in
clinical development (Phase I - III) and have not yet entered the market. For the
purpose of this study, we systematically searched the main registries of ongoing
trials up to August 2008. RESULTS/CONCLUSION: The field is very dynamic, with
both immunopharmacology of recombinant DNA techniques and more traditional
small-molecule pharmacology actively delivering new agents. With the increasing
number of new options, there is a need for research systems that enable to
effectively collect long-term safety data on treated patients.

Key role of macrophages in the pathogenesis of CD18 hypomorphic murine model of psoriasis. Wang H, Peters T, Sindrilaru A, Scharffetter-Kochanek K. J Invest Dermatol. 2009 May;129(5):1100-14. Epub 2009 Feb 26.

Psoriasis is a chronic skin disorder of unsolved pathogenesis affecting skin in
2-3% of the general population. Research into the pathogenesis of psoriasis has
profited from suitable animal models. Previously, we reported on the CD18
hypomorphic (CD18(hypo)) PL/J mouse model clinically resembling human psoriasis,
which is characterized by reduced expression of the common chain of
beta(2)-integrins (CD11/CD18) to only 2-16% of wild-type levels. Aside from
common clinical and pathophysiological features shared with human psoriasis, the
psoriasiform skin disease in CD18(hypo) PL/J mice also depends on the presence of
CD4(+) T-cells. This review focuses on the role of activated macrophages in the
pathogenesis of CD18(hypo) T-cell-mediated mouse model of psoriasis, and extends
our understanding in unrestrained pathogenic T-cells whose activation may be
crucial for the recruitment and activation of macrophages within skin. The
findings in the CD18(hypo) PL/J model are discussed in the context of current
literatures of human and other autoimmune disorders.

Treatment strategies for early psoriatic arthritis. Olivieri I, D'Angelo S, Palazzi C, Padula A. Expert Opin Pharmacother. 2009 Feb;10(2):271-82.

BACKGROUND: Until a few years ago, the early diagnosis of psoriatic arthritis
(PsA) did not receive much attention, especially in view of the lack of drugs
capable of altering the disease course. This changed with the introduction of the
TNF-alpha-blocking agents, as a result of which the early diagnosis of PsA is now
a topic of great interest. OBJECTIVE: The aim of the study was to review the
treatment for PsA in order to determine the optimal approach to managing early
disease. METHODS: The systematic review performed by members of GRAPPA (Group of
Research and Assessment of Psoriasis and Psoriatic Arthritis) was integrated with
data from more recent studies. RESULTS/CONCLUSION: After making the diagnosis of
PsA, the next step is to stage of the disease with the aim of establishing the
prevalent manifestation (peripheral arthritis, peripheral enthesitis, axial
involvement and dactylitis) and degree of severity (mild, moderate or severe) of
the disease. Each patient should be treated according to the defined disease
status following the suggested treatment algorithms.

Effects of tumor necrosis factor-alpha blockade on metabolic syndrome components in psoriasis and psoriatic arthritis and additional lessons learned from rheumatoid arthritis. Channual J, Wu JJ, Dann FJ. Dermatol Ther. 2009 Jan-Feb;22(1):61-73.

Psoriasis (PsO) and psoriatic arthritis (PsA) are chronic T cell-mediated
inflammatory diseases that manifest not only in the skin and joints but also in
the form of cardiometabolic disturbances, which include insulin resistance,
dyslipidemia, and obesity. Thus, PsO and PsA patients are predisposed to
metabolic syndrome (MetS), diabetes, and cardiovascular disease. In recent years,
the introduction of targeted therapy in the form of tumor necrosis factor-alpha
(TNF-alpha) antagonists, such as infliximab, etanercept, and adalimumab has been
an important and effective addition to the treatment armamentarium for PsO and
PsA. Although TNF-alpha antagonists have produced promising results clinically in
reducing cutaneous and joint manifestations of PsO and PsA, their effects on MetS
components in these patients are presently unclear. This review summarizes the
current limited evidence on the effects of TNF-alpha antagonists on MetS
components in PsO and PsA patients and extrapolates from related literature in
rheumatoid arthritis, which is also a T cell-mediated inflammatory disease, for
additional information.

New biologics for psoriasis and psoriatic arthritis. Rozenblit M, Lebwohl M. Dermatol Ther. 2009 Jan-Feb;22(1):56-60.

The prevalence of psoriasis is estimated to be 2.2% in the United States, and
6-39% of patients with psoriasis also develop psoriatic arthritis. New advances
have been made in developing treatment options. A new human tumor necrosis factor
(TNF)-alpha antibody, golimumab, has been shown to significantly improve symptoms
of psoriatic arthritis. In addition, clinical trials of certolizumab pegol, a
PEGylated Fab' fragment of an anti-TNF-alpha monoclonal antibody, show promising
results for treating rheumatoid arthritis and suggest that it may be applicable
for treating psoriasis and psoriatic arthritis in the future. New biologic
therapies also include antibodies to interleukin-12 and interleukin-23. Phase II
studies suggest that ustekinumab is effective in alleviating symptoms of
psoriasis and psoriatic arthritis. However, longer studies with radiographic
evaluation will be required before their impact on joint destruction can be
assessed.

Psoriatic arthritis. Gladman DD. Dermatol Ther. 2009 Jan-Feb;22(1):40-55.

Although there is still some controversy about the existence of psoriatic
arthritis (PsA) as a specific form of inflammatory arthritis associated with
psoriasis, epidemiological and clinical studies support the unique features of
PsA. Because of lack of diagnostic or classification criteria, the disease has
been thought of as uncommon. New classification criteria should facilitate case
definition of PsA. Over the past several decades, it has become clear that the
disease leads to serious disability and even increased mortality. Traditional
medications have not been effective in preventing the progression of joint
damage. New medications, including biologics, have emerged with potential to
controlling the inflammation and arresting the progression of joint damage.

Pediatric psoriasis: updates in biologic therapies. Sukhatme SV, Gottlieb AB. Dermatol Ther. 2009 Jan-Feb;22(1):34-9.

Psoriasis is not a rare disease in the pediatric population. Early recognition
and treatment is necessary to improve the physical and psychological symptoms of
psoriasis and minimize its adverse effects on future health. In
moderate-to-severe cases, treatment is challenging. There is no Food and Drug
Administration (FDA)-approved systemic treatment for children and adolescents
with moderate-to-severe plaque-type psoriasis other than topical corticosteroids,
and current treatment is limited to the ones that are used in adults, which may
have more severe side effects in children. Recently, there have been advances in
the use of biologic therapies, specifically tumor necrosis factor (TNF)-alpha
blockers, for pediatric autoimmune diseases and pediatric psoriasis. The present
review will summarize the data on TNF inhibitors for pediatric psoriasis, as well
as detail studies that led to the approval of biologics in other pediatric
autoimmune diseases.

Long-term efficacy of biologics in dermatology. Castelo-Soccio L, Van Voorhees AS. Dermatol Ther. 2009 Jan-Feb;22(1):22-33.

Chronic dermatologic diseases affect millions of people. The long-term nature of
these diseases creates psychological and financial burden as well as
substantially impacts patients' quality of life. Biologics, including adalimumab,
etanercept, alefacept, efalizumab, and infliximab, are the newest therapeutic
agents in the treatment of moderate-to-severe psoriasis and psoriatic arthritis
and have been used in a variety of other dermatologic diseases. These agents act
relatively quickly and effectively in 12-week clinical trials. Because these
agents are used to treat patients for longer than 12 weeks, there is a need to
review the safety and efficacy of these agents over longer periods of time. Many
levels of evidence are available for biologics including high level of evidence
from large, randomized, double-blind, placebo-controlled clinical studies. This
review focuses on the available data for efficacy and safety for greater than 24
weeks of therapy. The studies supporting the use of rituximab and intravenous
immunoglobulin in autoimmune blistering diseases are also presented in this
review.

Targeting protein kinases for the development of anti-inflammatory drugs. Cohen P. Curr Opin Cell Biol. 2009 Apr;21(2):317-24. Epub 2009 Feb 13.

In recent years, protein kinases have become the pharmaceutical industry's most
studied class of drug target, and some 10 protein kinase inhibitors have so far
been approved for the treatment of cancer. However, whether safe drugs that
modulate protein kinase activities can also be developed for the treatment of
chronic diseases, where they may need to be taken for decades, is an issue that
is still unresolved. A number of compounds that inhibit the p38alpha MAPK have
entered clinical trials for the treatment of rheumatoid arthritis and psoriasis,
but side effects have prevented their progression to Phase III clinical trials.
Here I briefly review the potential problems in targeting p38 MAPK and discuss
other protein kinases that regulate the innate immune system, such as Tpl2,
MAPKAP-K2/3, MSK1/2 and IRAK4, which may be better targets for the treatment of
chronic inflammatory diseases, and NIK, which is an attractive target for the
treatment of multiple myeloma, a late stage B-cell malignancy.

[Update in treatment of psoriatic arthritis] [Article in French] Abdelmoula LC, Ben M'Barek R, Yahia CB, Tekaya R, Testouri N, Chaabouni L, Zouari R. Tunis Med. 2008 Dec;86(12):1036-41.

Psoriatic arthritis is a chronic rheumatic disease making part of
spondylarthropathies. It is the most frequent chronic inflammatory rheumatism
after rheumatoid arthritis. Eventhough, it is usually a benign affection, it may
be destructive leading to handicap. Several new medications have been introduced,
including anti-tumor necrosis factor (TNF alpha blockers) and leflunomide for
treatment of psoriatic arthritis. Many studies show the efficacy of these
medications in this disease.

Management of moderate to severe plaque psoriasis (part I): clinical update on antitumor necrosis factor agents. Sobell JM, Kalb RE, Weinberg JM. J Drugs Dermatol. 2009 Feb;8(2):147-54.

Psoriasis is an immunologic disorder mediated by T cells and proinflammatory
cytokines. Novel biologic therapies, targeted at key pathogenic steps, have been
developed and provide efficacy without the potential end-organ toxicity induced
by traditional therapies. The biologic therapies currently approved for treatment
of psoriasis are classified into 2 categories, as defined by their mechanism of
action: inhibition of tumor necrosis factor (TNF) (etanercept, infliximab,
adalimumab) and modulation of pathogenic activated T cells (alefacept,
efalizumab). This review has been prepared in 2 parts: Part 1 focuses on anti-TNF
agents and includes new data that have become available through increased
clinical experience and use in eligible patients. Part 2 will present new data on
T-cell modulators, new molecules in development, and considerations for optimal
therapeutic selection for treatment of patients with psoriasis (Journal of Drugs
in Dermatology, March 2009).

[Psoriasis in childhood and adolescence: clinical features and therapy] [Article in German] Benoit S, Hamm H. Hautarzt. 2009 Feb;60(2):100-8.

Psoriasis starts in the first two decades of life in about one-third of patients.
Initially the diagnosis may be difficult because of atypical or mild involvement.
Plaque psoriasis is the most frequent type in children, just as in adults.
However, lesions are often smaller, thinner and less scaly. Treatment of
childhood psoriasis represents a special challenge to dermatologists since many
therapeutic agents are not approved and guidelines are generally lacking for this
age group. Apart from clinical type, severity of the disease and patient's age,
the choice of treatment must be based on safety concerns and accessibility of
treatment. We herein focus on the peculiarities of clinical presentations and on
the management of psoriasis in children and adolescents.

[Therapeutic strategies for psoriasis and psoriatic arthritis] [Article in German] Wozel G. Hautarzt. 2009 Feb;60(2):91-9.

Psoriasis is a chronic, immune-mediated inflammatory disorder with a genetic
background, whose treatment is currently undergoing a paradigm shift. For many
patients clinical signs and symptoms of psoriatic skin and joint disease are most
important. From the public health perspective, however, recent findings that
suggest a high degree of co-morbidity is becoming increasingly relevant. Because
it is also highly significant from the patients' perspective, the improvement of
health-related quality of life should be considered as the third treatment goal.
Modern therapeutic concepts interact with specific pathogenetically relevant
molecular targets. The development of such"targeted therapies" reflects our
increasing understanding of the pathogenetic principles of psoriasis. Provided
that the whole spectrum of approved remedies is employed as indicated, psoriasis
has become a condition that is amenable to early intervention and can be treated
effectively in the long run.

New insights into the pathogenesis and genetics of psoriatic arthritis. Nograles KE, Brasington RD, Bowcock AM. Nat Clin Pract Rheumatol. 2009 Feb;5(2):83-91.

Psoriasis vulgaris and psoriatic arthritis (PsA) are inter-related heritable
diseases. Psoriatic skin is characterized by hyperproliferative, poorly
differentiated keratinocytes and severe inflammation. Psoriatic joints are
characterized by highly inflamed synovia and entheses with focal erosions of
cartilage and bone. Genetic analyses have uncovered risk factors shared by both
psoriasis and PsA. Predisposition to psoriasis and PsA arising from common
variation is most strongly conferred by the HLA class I region. Other genetic
risk factors implicate the interleukin (IL)-23 pathway and the induction and
regulation of type 17 T-helper cells in the pathogenesis of both diseases.
Secretion of cytokines, such as IL-22 and IL-17, could result in the
hyperproliferative phenotype of keratinocytes and potentially synoviocytes,
leading to a vicious cycle of cellular proliferation and inflammation in both the
skin and joints. In synovial tissue, disease-related cytokines could also promote
osteoclast formation, resulting in bone erosion. The next step will be to
identify genetic risk factors specifically associated with PsA. Although
therapies that target tumor necrosis factor are often highly successful in the
treatment of both diseases, genetic findings are likely to lead to the
development of treatments tailored to an individual's genetic profile.

Efalizumab: a review of its use in the management of chronic moderate-to-severe plaque psoriasis. Frampton JE, Plosker GL. Am J Clin Dermatol. 2009;10(1):51-72. doi: 10.2165/0128071-200910010-00009.

Efalizumab (Raptiva) is a recombinant, humanized, monoclonal antibody that
targets CD11a, the alpha-subunit of the heterodimeric lymphocyte surface protein
lymphocyte function-associated antigen-1 (LFA-1). It is approved for the
treatment of adult patients (aged > or = 18 years) with chronic
moderate-to-severe plaque psoriasis who are candidates for systemic therapy or
phototherapy (in the US), or who have failed to respond to, have a
contraindication to, or are intolerant of, other systemic therapies, including
cyclosporine (ciclosporin), methotrexate, and psoralen plus UVA photochemotherapy
(in the EU). Weekly subcutaneous injections of efalizumab are effective and
generally well tolerated in the treatment of adults with chronic
moderate-to-severe plaque psoriasis, including high-need individuals (i.e. those
for whom at least two currently available systemic therapies are unsuitable due
to lack of efficacy, intolerance, or contraindication), and patients with
difficult-to-treat forms of the disease affecting the scalp, hands/feet, or
nails. Clinical improvements are maintained, with no evidence of cumulative or
end-organ toxicity, during continuous administration of efalizumab for up to 3
years; 4-, 5-, and 7-year safety data are being collected. The therapeutic
profile of efalizumab cannot be directly compared with that of other
antipsoriasis agents because of a lack of head-to-head comparative studies.
Nonetheless, a considerable body of data indicates that efalizumab is an
appropriate alternative to other biologic or nonbiologic therapies for the
treatment of chronic moderate-to-severe plaque psoriasis that, additionally,
offers the potential convenience of self-injection at home.

Adalimumab: in plaque psoriasis. Croom KF, McCormack PL. Am J Clin Dermatol. 2009;10(1):43-50. doi: 10.2165/0128071-200910010-00008.

Adalimumab is a recombinant, human, IgG1 monoclonal antibody specific for tumor
necrosis factor. The clinical efficacy and safety of adalimumab (40 mg
administered subcutaneously every other week) in patients with moderate-to-severe
chronic plaque psoriasis have been demonstrated in several randomized,
double-blind clinical trials, including the pivotal trials REVEAL (n = 1212) and
CHAMPION (n = 271). Based on these trials, adalimumab was significantly more
effective than placebo and methotrexate at relieving the signs and symptoms of
psoriasis after 16 weeks of treatment, as assessed by the percentage of patients
achieving a 75% improvement from baseline in Psoriasis Area and Severity Index.
Based on open-label extension studies of up to 2 years’ duration, the efficacy of
adalimumab was sustained over the long term. Of patients who had responded to 33
weeks of treatment with adalimumab in REVEAL, patients randomized to remain on
adalimumab for an additional 19 weeks of treatment were significantly less likely
to experience loss of an adequate response than patients who were transferred to
placebo. Compared with placebo or methotrexate, adalimumab was associated with
significantly greater improvements in dermatology-specific and general measures
of health-related quality of life in patients with plaque psoriasis. Adalimumab
was generally well tolerated in trials in patients with plaque psoriasis, and the
adverse-event profile was similar to that associated with its use in rheumatoid
arthritis.

Psoriasis disappearance after the first phase of an oncologic treatment: a serendipity case report. Cagiano R, Bera I, Vermesan D, Flace P, Sabatini R, Bottalico L, Auteri P, Santacroce L. Clin Ter. 2008 Nov-Dec;159(6):421-5.

Psoriasis is a multifaceted disorder with psychosocial and physical aspects that
negatively impact the quality of life. Strategies of treatment must address both
rapid control of the disease and maintenance of benefits. For short and long-term
control of localized psoriasis, recent data support the combined use of topical
corticosteroids and either calcipotriene or tazarotene which seem to be the most
effective approach. For generalized disease, UVB treatment provides the safest
means of achieving long-term control of the disease. Acitretin is a very helpful
adjunct for improving the efficacy of phototherapy. For patients with severe,
refractory disease, methotrexate may be most effective while cyclosporine may be
most valuable for patients needing rapid, short-term improvement. Other
molecules, with different pharmacological properties, are actually under
consideration. Herein it is reported a case of a 55 year old male, who refers, 2
weeks after the fi rst cycle of oncologic therapy with gemcitabine and cisplatin
for a lung neoplasm, about the complete remission of the psoriasis on both
fingernails and scalp, suffered since almost ten years. Three months after the
fortuitous detection of the psoriasis disappearance, there is no further evidence
of psoriatic lesions.

Immunopathogenesis of mycosis fungoides/Sézary syndrome (cutaneous T-cell lymphoma). Wong HK. G Ital Dermatol Venereol. 2008 Dec;143(6):375-83.

T cells are critical effectors of the adaptive immune response and play an
important role in cutaneous immunity. In the skin, various cell types cooperate
together, from components of both the innate immunity and adaptive immunity,
provide sentinel function to mediate the immune response. However, when T cell
function becomes abnormal, there is a loss of normal effector immune function,
and the abnormal T cells become a cause of disease as well. Mycosis fungoides
(MF) is a cutaneous T cell lymphoma (CTCL) that preferentially travels to the
epidermis. When skin homing T cells become malignant, the clinical consequences
reflect not only the presence of the malignant cells, but likely from a complex
reaction of the immune response to the malignant cell. The clinical presentation
is the evolving manifestation of the steps in cancer immunosurveillance. Analysis
of gene expression in MF/CTCL patients has provided support for the role of the
immune response in the early phase of the disease and a loss of immune response
in advance stages of MF/CTCL. This review will focus on cytokine gene expression
abnormalities in the clinical stages of the disease and discuss the relationship
between the clinical and immunologic abnormalities to gain a better understanding
of mechanisms important in the evolution of this disease. A better understanding
of the immunopathogenesis of MF/CTCL would support innovative strategies for the
development of novel therapies to treat this T cell malignancy.

From interleukin-23 to T-helper 17 cells: human T-helper cell differentiation revisited. Boniface K, Blom B, Liu YJ, de Waal Malefyt R. Immunol Rev. 2008 Dec;226:132-46.

Protracted inflammation leading to dysregulation of effector T-cell responses
represents a common feature of a wide range of autoimmune diseases. The
interleukin-12 (IL-12)/T-helper 1 (Th1) pathway was thought to be responsible for
the pathogenesis of multiple chronic inflammatory diseases, including psoriasis,
inflammatory bowel disease, arthritis, or multiple sclerosis, mainly through
their production of interferon-gamma and its effects on macrophage activation and
chemokine production. However, this initial concept of T-cell-mediated chronic
inflammation required an adjustment with the discovery of an IL-12-related
cytokine, designated IL-23. IL-23 was rapidly recognized for its involvement in
the establishment of chronic inflammation and in the development of a Th cell
subset producing IL-17, designated Th17, which is distinct from the previously
reported Th1 and Th2 populations. This review aims to describe the
characterization of IL-23 and its receptor, its biological activities, as well as
its involvement in the development of human Th17 cells and autoimmunity.

[The role of streptococci in psoriasis] [Article in German] Prinz JC. Hautarzt. 2009 Feb;60(2):109-15.

Infections with Streptococcus pyogenes are highly relevant among the
environmental factors that contribute to first onset or relapses of psoriasis in
predisposed individuals. Streptococcal angina or pharyngitis, but also perianal
streptococcal dermatitis, vulvovaginitis or balanoposthitis are potential causes.
Several mechanisms such as molecular mimicry or superantigens may be involved.
Many patients develop a chronic streptococcal infection or colonization that may
result from the ability of streptococci for intracellular uptake and persistence
in epithelial cells. Whether and under what conditions a curative treatment of
streptococcal infection by tonsillectomy or antibiotic treatment may affect the
course of psoriasis, as proposed by several observations, needs to be determined
in more detail by clinical trials.

[Co-morbidities in psoriasis vulgaris] [Article in German] Boehncke WH, Buerger C, Boehncke S. Hautarzt. 2009 Feb;60(2):116-21.

Epidemiologic data document not only a higher prevalence of joint involvement
among psoriasis patients than previously thought, but also an association with
numerous other diseases, including depression, smoking, alcoholism, Crohn’s
disease, and metabolic syndrome. The resulting increased cardiovascular mortality
is of particular clinical importance, and its pathogenetic link as a complication
of the psoriatic inflammation is well recognized. Thus, we need to re-invent the
management of psoriasis: Dermatologists are not only the sentinel regarding the
early diagnosis of psoriatic arthritis, but also of metabolic complications such
as dyslipidemia or diabetes. Moreover, they need to keep in mind interactions
between (systemic) anti-psoriatic drugs and the co-medication of their patients
as well as possible consequences of these co-medications on the course of
psoriasis. To successfully accomplish this mission, a comprehensive management
concept and ground-breaking research are urgently needed.

Mycophenolate mofetil in dermatology. Orvis AK, Wesson SK, Breza TS Jr, Church AA, Mitchell CL, Watkins SW. J Am Acad Dermatol. 2009 Feb;60(2):183-99; quiz 200-2.

Mycophenolate mofetil (MMF) is the prodrug of mycophenolic acid (MPA), a
medication used to treat psoriasis in the 1970s until side effects and the
concern of carcinogenesis led to its discontinuation. The prodrug, MMF, emerged
decades later in the transplant field. Dermatologists have since used MMF
off-label to treat various inflammatory skin conditions, with most research
concentrating on its use in psoriasis, autoimmune blistering disorders,
dermatitides, and connective tissue disorders. The appeal of MMF is predicated
upon its lymphocyte specificity and consequent decreased toxicity profile. These
attributes may make it a preferable treatment option. Its use in the field of
dermatology is currently limited by a lack of randomized controlled trials,
potential unknown side effects, and cost of treatment. In reviewing both current
literature and our own clinic records, MMF appears to be a promising therapeutic
option for the treatment of cutaneous inflammatory diseases. LEARNING OBJECTIVE:
After completing this learning activity, participants should be able to summarize
the history and pharmacology of mycophenolate mofetil as an immunosuppressant;
recognize its potential role in the treatment of dermatologic conditions,
including general dosing guidelines, use in pregnancy and pediatrics, and
potential adverse effects; and identify future considerations and developing
areas of research regarding the use of mycophenolate mofetil in dermatology.

NF-kappaB links keratinocytes and lymphocytes in the pathogenesis of psoriasis. Tsuruta D. Recent Pat Inflamm Allergy Drug Discov. 2009;3(1):40-8.

Psoriasis is a common, chronic and relapsing autoimmune skin disease. Clinical
characteristics of this disease are sharply-demarcated erythematous plaques
covered with silver scales. Histologically, it is characterized by increased
epidermal thickness, elongated papillae, and a moderate inflammatory infiltrate
composed of lymphocytes, macrophages and neutrophils. The histological hallmark
of psoriasis is Munro’s microabscess, which is an accumulation of
polymorphonuclear leukocytes in the keratinous layer. The mechanism of this
disease is still an enigma, but genetic susceptibility, abnormal function of
keratinocytes, or immunological disturbance, especially in T cells, are
postulated. Over the past decades, there have been arguments about
“keratinocyte-dependent” pathology as opposed to “immunocyte-dependent”
pathology. Thus far, there have been some rodent models for psoriasis. Among
them, the recent article from Rebholz et al. is quite intriguing because they
explain the crosstalk between keratinocytes and lymphocytes: now evidence has
been presented that while the aberrant NF-kappaB activation in either
keratinocytes or lymphocytes could not reproduce psoriasis-like histology, such
activation in both reproduced all of the aforementioned “hallmarks” of psoriasis
pathology. Therefore, NF-kappaB may well act as a link between the T
cell-mediated and keratinocyte-mediated arguments concerning the pathogenesis of
psoriasis. This article also discusses some recent patent related to the field.

Targeting hypoxia-inducible factor-1 (HIF-1) signaling in therapeutics: implications for the treatment of inflammatory bowel disease. Hirota SA, Beck PL, MacDonald JA. Recent Pat Inflamm Allergy Drug Discov. 2009;3(1):1-16.

In response to hypoxia, adaptive hypoxia-inducible factor-1 (HIF-1) signaling
events are activated to increase oxygen transport, anaerobic energy production
and protective pathways to minimize ischemic tissue damage. Although the
activation and subsequent induction of gene transcription by HIF-1 is normally
associated with hypoxia, it is now established that HIF-1 signaling can be
triggered under inflammatory conditions. HIF-1 has been implicated in a number of
inflammatory diseases including rheumatoid arthritis, allergic asthma, psoriasis
and inflammatory bowel disease (IBD). In the gastrointestinal tract,
HIF-1-regulated gene products, such as vascular endothelial growth factor,
intestinal trefoil factor and CD73, have been shown to provide protection in
animal models of intestinal inflammation. Given the importance of HIF-1 signaling
in the aforementioned diseases, there exists considerable interest in the
development of methods to modulate HIF-1 expression as well as down-stream
signaling events. This review examines HIF-1 signaling with a special focus on
the gastrointestinal tract. The patents pertaining to the modulation of HIF-1
signaling are summarized, and their relevance to the treatment of inflammatory
bowel disease is discussed.

B-cell-directed therapy for inflammatory skin diseases. Nagel A, Hertl M, Eming R. J Invest Dermatol. 2009 Feb;129(2):289-301.

The basic understanding of inflammatory dermatoses and autoimmune-mediated skin
disorders has greatly advanced and broadened our understanding of underlying
immune mechanisms that shape the complex network of chronic inflammation and
autoimmunity. The new treatment options for psoriasis exemplify how new insights
into (auto)immune responses, especially the role and function of various immune
cells and proinflammatory cytokines, may lead to new therapeutic strategies. The
concept of targeting B cells in autoimmune-mediated disorders is closely related
to the discovery of autoantibodies and their cellular origin. However, the
appreciation of B cells in autoimmunity has significantly changed and is not
limited to their role as progenitors of autoantibody secreting plasma cells.
Recent investigations of various inflammatory skin diseases, that is, autoimmune
blistering disorders, collagen vascular diseases, and atopic dermatitis, actually
support the concept that B cells might be as important as T cells in the
etiopathogenesis of these disorders. The striking clinical improvement seen in
patients with rheumatoid arthritis following B-cell depletion with the anti-CD20
mAb rituximab has tremendously catalyzed the interest in B-cell-targeted
therapies in different autoimmune diseases. Future translational and clinical
investigations are mandatory to precisely define the role and the contribution of
impaired B-cell function in (auto)immune-mediated skin diseases.

Role of the vitamin D3 pathway in healthy and diseased skin–facts, contradictions and hypotheses. Lehmann B. Exp Dermatol. 2009 Feb;18(2):97-108.

Irradiation of human keratinocytes with UVB (280-320 nm) in vitro and in vivo
activates the metabolism of 7-dehydrocholesterol to hormonally active calcitriol.
The production of calcitriol in the skin strongly depends on the photosynthesis
of vitamin D(3) which is biologically inactive in the first instance. Vitamin
D(3) serves as the starting substrate for two subsequent enzymatic hydroxylation
steps in epidermal keratinocytes. Both the amount of vitamin D(3) and the
activity of anabolic and catabolic vitamin D hydroxylases determine the cutaneous
level of calcitriol. The hormonally active metabolite of vitamin D(3) regulates a
huge number of genes in keratinocytes, and thus acts in an autocrine and/or
paracrine manner. This local pathway of vitamin D(3) is unique, but its relevance
for healthy and diseased skin is widely unknown, yet. Experimental findings
implicate several questions: (1) Is UVB-induced formation of calcitriol involved
in regulation of growth and differentaition of epidermal cells as well as
immunological and skin protective processes? (2) What endogenous and exogenous
factors including drugs affect the cutaneous vitamin D(3) pathway? From a
therapeutical point of view, it has been known for a long time that topical
application of calcitriol and its analogs can improve hyperproliferative skin
diseases like psoriasis. In spite of many encouraging studies in recent years,
the fields of the routinely therapeutical application of calcitriol or vitamin D
analogs in dermatology (e.g. treatment of immunological, inflammatory,
malignancies and infectious skin diseases) have not been intensified. Why is
that?

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

[Targeting therapy for inflammatory diseases by anti-TNFalpha biologics] [Article in Japanese] Sugita T. Yakugaku Zasshi. 2009 Jan;129(1):19-24.

TNFalpha (tumor necrosis factor-alpha) plays a critical role in the pathogenesis
of inflammatory diseases including rheumatoid arthritis and Crohn’s disease.
Infliximab is a monoclonal antibody that recognizes human TNFalpha. Clinical
trials have been persuasive that infliximab is effective and far superior to the
conventional drug therapy in various inflammatory diseases. Combination of
infliximab plus methotrexate is effective in patients with active rheumatoid
arthritis who have not responded adequately to traditional disease-modifying
anti-rheumatic drugs, and has produced significant improvement in clinical,
radiographic, and functional outcomes. Infliximab is also an important treatment
option in patients with active Crohn’s disease who have not responded to
conventional therapy and in those with this disease who have fistulae. Moreover,
infliximab treatment has resulted in effective suppression of ankylosing
spondylitis, psoriasis and ocular inflammation in patients with refractory
uveoretinitis due to Behçet’s disease. Thus, biologics targeting TNFalpha have
revolutionized the therapy of inflammatory diseases. Here, the current status of
clinical application of anti-TNFalpha biologics is reviewed by describing the
clinical outcome of infliximab and future prospects of biologics are discussed.

Small RNAs in development and disease. Sun BK, Tsao H. J Am Acad Dermatol. 2008 Nov;59(5):725-37; quiz 738-40.

MicroRNAs (miRNAs) and short interfering RNAs (siRNAs) are classes of regulatory
small RNA molecules, ranging from 18 to 24 nucleotides in length, whose roles in
development and disease are becoming increasingly recognized. They function by
altering the stability or translational efficiency of messenger RNAs (mRNAs) with
which they share sequence complementarity, and are predicted to affect up to
one-third of all human genes. Computer algorithms and microarray data estimate
the presence of nearly 1000 human miRNAs, and direct examination of candidate
miRNAs has validated their involvement in various cancers, disorders of neuronal
development, cardiac hypertrophy, and skin diseases such as psoriasis. This
article reviews the history of miRNA and siRNA discovery, key aspects of their
biogenesis and mechanism of action, and known connections to human health, with
an emphasis on their roles in skin development and disease.

Prolactin and the skin: a dermatological perspective on an ancient pleiotropic peptide hormone. Foitzik K, Langan EA, Paus R. J Invest Dermatol. 2009 May;129(5):1071-87. Epub 2008 Dec 25.

The polypeptide hormone prolactin (PRL) is best known as the pituitary modulator
of lactation and reproduction. However, based on the almost ubiquitous
distribution of PRL receptors (PRLR) and an ever-growing list of extrapituitary
PRL-expressing tissues, a vast range of PRL actions “beyond the mammary horizon”
has now been documented or claimed. For example, PRL modulates hair growth in
domestic animals with seasonal hair growth changes (”PRL-pelage axis”). Given
that the mammary gland is an epidermal derivative, it is not surprising that the
pilosebaceous unit, another epidermal derivative, has also surfaced as a
prominent, PRLR-expressing, nonclassical PRL target organ. Moreover, the fact
that murine and human hair follicles even synthesize PRL strongly invites one to
explore fully the dermatological dimensions of this multifunctional,
cytokine-like neuroendocrine bioregulator, which remain insufficiently charted.
After describing the relevant essentials of general PRL/PRLR biology, we
summarize clinical observations that provide insights into how PRL may impact on
the skin, and define important research frontiers and controversies in the quest
to better characterize the complex role of PRL in human skin biology and
pathology. Focusing on psoriasis, alopecia, and stress-related dermatoses, we
then discuss the possible role of PRL/PRLR in cutaneous pathology, and identify
potential therapeutic targets for the management of these skin disorders. We
close by delineating major open questions at this emerging frontier of basic and
clinical cutaneous neuroendocrinology, and argue that systematic exploration of
the “PRL-skin connection” will fertilize the development of previously unreported
neuroendocrinological strategies for managing selected skin disorders.

[Current approaches to diagnosis and treatment of psoriatic arthritis (review)] [Article in Russian] Shostak NA, Klimenko AA. Ter Arkh. 2008;80(10):82-7.

Treatment of intertriginous psoriasis: from the Medical Board of the National Psoriasis Foundation. Kalb RE, Bagel J, Korman NJ, Lebwohl MG, Young M, Horn EJ, Van Voorhees AS; National Psoriasis Foundation. J Am Acad Dermatol. 2009 Jan;60(1):120-4.

BACKGROUND: Involvement of areas of the skin fold is common in patients with
psoriasis although the exact incidence is unknown. This report summarizes studies
regarding the therapy of intertriginous psoriasis. OBJECTIVE: A task force of the
National Psoriasis Foundation Medical Board was convened to evaluate treatment
options. Our aim was to arrive at a consensus on therapy for intertriginous or
inverse psoriasis. METHODS: Reports in the literature were reviewed regarding
psoriasis affecting the skin-fold areas and its therapy. LIMITATIONS: There are
few evidence-based studies on the treatment of intertriginous psoriasis. RESULTS:
The recommended short-term (2-4 weeks) therapy for inverse psoriasis is low- to
mid-potency topical steroids. For long-term therapy, topical calcipotriene
(calcipotriol) or one of the immunomodulating agents, pimecrolimus or tacrolimus,
is favored. CONCLUSIONS: Low- to mid-potency topical steroids are recommended as
first-line, short-term treatment. It is recommended that their use should either
be of limited duration (less than 2-4 weeks) or that the lowest effective
strength be used intermittently for long-term care to minimize the potential for
risks. Calcipotriene (calcipotriol), pimecrolimus, and tacrolimus, while not as
highly efficacious as topical steroids, are associated with fewer long-term risks
and are therefore recommended for long-term therapy when feasible.

[Psoriasis and HIV infection] [Article in Spanish] Leal L, Ribera M, Daudén E. Actas Dermosifiliogr. 2008 Dec;99(10):753-63.

Dermatologists face diagnostic and therapeutic difficulties when psoriasis
coexists with human immunodeficiency virus (HIV) infection. This article will
review some of the aspects of this coexistence from the epidemiologic,
pathogenic, histopathologic, clinical, and prognostic point of view. The main
skin diseases that should be included in the differential diagnosis are
described. Also analyzed are the different therapeutic options in these patients
according to the degree of immunodeficiency. Possibilities include antiretroviral
treatment, topical treatment, retinoids, and classic immunosuppressants. The
review will also cover current literature on the use of new biologic therapies in
patients with HIV infection. Finally, we will discuss the risk of drug
interactions during psoriasis treatment in these patients, who receive multiple
pharmacologic therapies.

[Cathelicidins: multifunctional defense molecules of the skin] [Article in German] Peric M, Koglin S, Ruzicka T, Schauber J. Dtsch Med Wochenschr. 2009 Jan;134(1-2):35-8. Epub 2008 Dec 17.

The human skin is constantly exposed to microbial pathogens but infections only
rarely occur. Innate cutaneous immunity is a primary system for protection
against infection, and antimicrobial peptides (AMPs) expressed in skin are
essential defence molecules. The AMPs include molecules such as the defensins
that were first characterized for their antimicrobial properties as well as other
peptides and proteins first known for their activity as chemokines, enzymes,
enzyme inhibitors and neuropeptides. Cathelicidins are unique AMPs that act as
defensive and signalling molecules. Two different pathways are involved in this
function: cathelicidins have direct antimicrobial activity and they also initiate
a host of cellular responses in cytokine release, inflammation and angiogenesis.
Several skin diseases are associated with cathelicidin dysfunction. In atopic
eczema, for example, cathelicidin expression is suppressed, whereas in rosacea
cathelicidin peptides are abnormally processed to forms that induce cutaneous
inflammation and a vascular response. In psoriasis cathelicidin peptide converts
self-DNA to a potent stimulus in an autoinflammatory cascade. Current studies
have unexpectedly identified vitamin D3 as a major factor for the regulation of
cathelicidin expression. This finding may provide new strategies in the
management of infectious and inflammatory diseases of the skin by targeting
control of the expression and function of cathelicidin and other AMPs.

The role of nuclear factor-kappaB in the development of autoimmune diseases: a link between genes and environment. Kuryłowicz A, Nauman J. Acta Biochim Pol. 2008;55(4):629-47. Epub 2008 Dec 16.

Although autoimmune diseases are relatively common, mechanisms that lead to their
development remain largely unknown. Nuclear factor-kappaB (NF-kappaB), as a key
transcription factor involved in the regulation of immune responses and
apoptosis, appears to be a good candidate for studies on the pathogenesis of
autoimmunity. This review presents how perturbations of the NF-kappaB signaling
pathway may contribute to self-tolerance failure, initiation of autoimmune
inflammatory response as well as its persistent maintenance and therefore to the
development of common autoimmune diseases including rheumatoid arthritis,
multiple sclerosis, type 1 diabetes mellitus, thyroid autoimmune diseases,
systemic lupus erythematosus as well as inflammatory bowel diseases and
psoriasis. A special emphasis is put on the genetic variations in the NF-kappaB
related genes and their possible association with susceptibility to autoimmune
diseases, as well as on the therapeutic potential of the NF-kappaB targeted
strategies in the treatment of autoimmunity.

[Infliximab] [Article in Spanish] Herrera E, Habicheyn S. Actas Dermosifiliogr. 2008 Jul;99 Suppl 4:7-13.

Infliximab is a chimeric monoclonal antibody, which specifically binds to tumor
necrosis factor (TNF-alpha) and blocks its activity. Based on previous evidence
that TNF-alpha has been involved in the pathogenesis of psoriasis, multiple
controlled trials have shown that infliximab has provided a high degree of
clinical benefit in the treatment of psoriasis and psoriatic arthritis allowing a
major and rapid improvement in these patients. We review several clinical trials,
which have firmly established both efficacy and safety of Infliximab in the
treatment of moderate to severe psoriasis and psoriatic arthritis.

[Introduction to biological drugs] [Article in Spanish] Fernández-Cruz E, Alecsandru D, Rodríguez-Sainz C. Actas Dermosifiliogr. 2008 Jul;99 Suppl 4:2-6.

Biological therapies have revolutionized the treatment of chronic systemic
diseases in which the immune system disorders form a part of the disease
mechanism. In these diseases, the patients follow different drug treatments for
long periods of time that causes serious adverse reactions and often obtain
unsatisfactory efficacy results. Due to the research conducted in the last 10
years, biological drugs have been introduced into the treatment that are aimed
against specific targets, such as inflammatory and immunopathological responses
that give rise to tissue injury. The new biological therapies have improved the
currently available treatments due to greater efficacy, fast action and greater
tolerability. The present work aims to provide a global and up-dated view on the
biological agents used most in the usual clinical practice and their importance
in the management of the chronic immunologically based inflammatory diseases.

Epigenetics and dermatological disease. Millington GW. Pharmacogenomics. 2008 Dec;9(12):1835-50.

Epigenetics is the study of differences in phenotype, in the absence of variation
in the genetic code. Epigenetics is relevant in the pathogenesis of many skin
diseases. In the case of the common skin cancers, aberrant methylation of tumor
suppressor gene promoters is associated with their transcriptional inactivation.
Environmental carcinogens such as ultraviolet radiation and arsenic may act
through epigenetic mechanisms. Hypomethylation is associated with activation of
systemic autoimmune diseases, such as systemic lupus erythematosus, subacute
cutaneous lupus erythematosus and scleroderma. This may be through a mechanism of
immunological cross-reactivity with hypomethylated DNA from pathogenic bacteria.
Epigenetic factors may also be relevant in the pathogenesis of psoriasis and
other inflammatory skin diseases, as well as in the pathogenesis of the disorders
of genomic imprinting with cutaneous features.

Mortality in psoriatic arthritis. Gladman DD. Clin Exp Rheumatol. 2008 Sep-Oct;26(5 Suppl 51):S62-5.

Psoriatic arthritis has been demonstrated to be a severe form of arthritis in a
proportion of patients. Progression of joint damage has been noted even within
the first 2 years of disease in almost half the patients. Polyarticular
presentation, disease activity, and damage predict progression of joint damage.
An increased mortality was reported from large studies of 428 and 680 patients
with psoriatic arthritis. Cardiovascular-related disease is the most common cause
of death, followed by respiratory diseases, cancer, and injuries and poisoning.
Deaths from respiratory disease, cardiovascular disease, and injuries and
poisoning were found to be higher than those in the general population.
Predictors for mortality include a high sedimentation rate and radiological
damage at presentation. Since disease activity is associated with progression of
damage, and damage predicts mortality, it is important to treat patients
aggressively to prevent these outcomes.

Etanercept provides a more physiological approach in the treatment of psoriasis. Altomare G, Ayala F, Berardesca E, Chimenti S, Giannetti A, Girolomoni G, Lotti T, Martini P, Peserico A, Guerra AP, Vena GA. Dermatol Ther. 2008 Oct;21 Suppl 2:S1-14.

Psoriasis is a common chronic inflammatory disease affecting the skin and joints.
Moderate to severe psoriasis is traditionally treated with systemic treatments,
which can be effective but are often associated with relevant adverse effects,
even when administered intermittently or rotationally. Biologic therapies may
provide high and consistent efficacy over time, long-term safety, and simple
administration schedules compared with nonbiologic therapies, and can be used in
patients intolerant and/or resistant to these therapies. TNF-antagonists have a
definite advantage over other biologic agents (e.g., T-cell targeting drugs) in
the early and late manifestations of joint involvement. TNF-antagonists are a
class of drugs with distinct pharmacokinetic and pharmacodynamic properties, and
different safety profiles. Etanercept provides a more “physiological” mechanism
of action compared to anti-TNF antibodies. Etanercept has less dramatic effects
on TNF homeostasis although it has been proved to be highly effective in blocking
psoriatic joint erosions. It maintains stable efficacy over time on skin
psoriasis, also when used intermittently. Moreover, etanercept has been shown to
be not immunogenic, and it only slightly increases the risk of granulomatous
infections compared to anti-TNF antibodies. According to the “physiologic”
paradigm of selection among TNF-antagonists linked to more or less physiologic
mechanism of action, etanercept appears to be the anti-TNF of choice for treating
most patients with moderate to severe plaque psoriasis and psoriatic arthritis,
possibly even at an early stage.

AJC editor’s consensus: psoriasis and coronary artery disease. Friedewald VE, Cather JC, Gelfand JM, Gordon KB, Gibbons GH, Grundy SM, Jarratt MT, Krueger JG, Ridker PM, Stone N, Roberts WC. Am J Cardiol. 2008 Dec 15;102(12):1631-43.

MicroRNAs and the skin: tiny players in the body’s largest organ. Sand M, Gambichler T, Sand D, Skrygan M, Altmeyer P, Bechara FG. J Dermatol Sci. 2009 Mar;53(3):169-75. Epub 2008 Dec 5.

MicroRNAs (miRNAs) are very small endogenous RNA molecules about 22-25
nucleotides in length, capable of post-transcriptional gene regulation. miRNAs
bind to their target messenger RNAs (mRNAs), leading to cleavage or suppression
of target mRNA translation based on the degree of complementarity. miRNAs have
recently been shown to play pivotal roles in diverse developmental and cellular
processes and linked to a variety of skin diseases and cancers. Disruption of
miRNA metabolism is also involved in wound healing and inflammatory skin
conditions. Here, we review the role of miRNAs in cutaneous biology.

The skin: an indispensable barrier. Proksch E, Brandner JM, Jensen JM. Exp Dermatol. 2008 Dec;17(12):1063-72.

The skin forms an effective barrier between the organism and the environment
preventing invasion of pathogens and fending off chemical and physical assaults,
as well as the unregulated loss of water and solutes. In this review we provide
an overview of several components of the physical barrier, explaining how barrier
function is regulated and altered in dermatoses. The physical barrier is mainly
localized in the stratum corneum (SC) and consists of protein-enriched cells
(corneocytes with cornified envelope and cytoskeletal elements, as well as
corneodesmosomes) and lipid-enriched intercellular domains. The nucleated
epidermis also contributes to the barrier through tight, gap and adherens
junctions, as well as through desmosomes and cytoskeletal elements. During
epidermal differentiation lipids are synthesized in the keratinocytes and
extruded into the extracellular domains, where they form extracellular
lipid-enriched layers. The cornified cell envelope, a tough protein/lipid polymer
structure, resides below the cytoplasmic membrane on the exterior of the
corneocytes. Ceramides A and B are covalently bound to cornified envelope
proteins and form the backbone for the subsequent addition of free ceramides,
free fatty acids and cholesterol in the SC. Filaggrin is cross-linked to the
cornified envelope and aggregates keratin filaments into macrofibrils. Formation
and maintenance of barrier function is influenced by cytokines, 3′,5′-cyclic
adenosine monophosphate and calcium. Changes in epidermal differentiation and
lipid composition lead to a disturbed skin barrier, which allows the entry of
environmental allergens, immunological reaction and inflammation in atopic
dermatitis. A disturbed skin barrier is important for the pathogenesis of contact
dermatitis, ichthyosis, psoriasis and atopic dermatitis.

Postmenopausal vulval disease. Olsson A, Selva-Nayagam P, Oehler MK. Menopause Int. 2008 Dec;14(4):169-72.

Vulval disease in the postmenopausal age group is relatively common. Some vulval
conditions such as lichen sclerosus are more prevalent in the postmenopausal
years. Often more than one condition is present at the same time. Accurate
diagnosis is essential for effective treatment. The risk of progression to
malignancy associated with some of these diseases dictates long-term
surveillance.

Induction of tolerogenic dendritic cells by vitamin D receptor agonists. Adorini L, Penna G. Handb Exp Pharmacol. 2009;(188):251-73.

Dendritic cells induce and regulate T cell responses, and tolerogenic dendritic
cells (DCs) can promote the development of regulatory T cells with suppressive
activity. Thus, the possibility to manipulate DCs using different pharmacological
or biological agents enables them to exert tolerogenic activities, could be
exploited to better control a variety of chronic inflammatory conditions, from
autoimmune diseases to allograft rejection. A variety of both biological and
pharmacological agents can induce tolerogenic DCs, and several in vitro studies
have demonstrated that human regulatory T cells can be induced by DCs manipulated
to acquire and/or enhance tolerogenic properties, with in vivo data also
accumulating. Within this context, we have explored the immunoregulatory
activities of vitamin D receptor (VDR) agonists, secosteroid hormones able to
induce tolerogenic DCs and regulatory T cells. Tolerogenic DCs induced by a short
treatment with VDR agonists promote CD4(+) CD25(+) Foxp3(+) suppressor T cells
that are able to mediate transplantation tolerance and to arrest the development
of autoimmune diseases. VDR agonists not only favour the induction of CD4(+)
CD25(+) regulatory T cells, but can also enhance their recruitment to
inflammatory sites. VDR agonists have been proven effective and safe drugs in a
variety of autoimmune disease and graft rejection models, highlighting their
potential applicability to chronic inflammatory conditions sustained by
autoreactive or alloreactive immune responses. In addition to the topical
treatment of psoriasis, a Th1-mediated autoimmune disease of the skin where VDR
agonists are the most used topical drugs; these agents might eventually find a
broader application in the treatment of inflammatory conditions, where their
modulatory effects on DCs enhancing T cells with regulatory functions could turn
out to be quite beneficial.

Psoriasis: an opportunity to identify cardiovascular risk. Federman DG, Shelling M, Prodanovich S, Gunderson CG, Kirsner RS. Br J Dermatol. 2009 Jan;160(1):1-7. Epub 2008 Oct 25.

Psoriasis is highly prevalent and is associated with skin-associated complaints
as well as arthritis, depression and a lower quality of life. Recently, it has
been demonstrated that not only do patients with psoriasis have an increased
prevalence of cardiovascular risk factors, but an increased risk of myocardial
infarction, and for those with severe disease, increased mortality.
Dermatologists and other health professionals need to be cognizant of this
association and ensure that cardiovascular risk factors are evaluated and treated
appropriately in those patients with psoriasis. We review the association between
psoriasis, atherosclerosis and inflammation, as well as some treatable
cardiovascular risk factors that may prove beneficial in reducing a patient’s
cardiovascular risk.

Tuberculosis and tumour necrosis factor-alpha inhibitor therapy: a report of three cases in patients with psoriasis. Comprehensive screening and therapeutic guidelines for clinicians. Perlmutter A, Mittal A, Menter A. Br J Dermatol. 2009 Jan;160(1):8-15. Epub 2008 Oct 22.

Tumour necrosis factor (TNF)-alpha inhibitors, long used in rheumatology and
gastroenterology, have made a significant impact on the therapy of psoriasis and
psoriatic arthritis. TNF-alpha is an important cytokine in normal physiological
processes such as the immune response to granulomatous infection. Inhibition of
this process by TNF-alpha inhibitors has been reported to increase the
susceptibility of patients to granulomatous infections such as Mycobacterium
tuberculosis. Despite the numerous reported cases in the literature and
appropriate warnings on the labels for the three currently approved TNF-alpha
inhibitors, current guidelines do not address case-specific issues across the
full spectrum of tuberculosis. The probability of developing active tuberculosis
has been reported to be as much as seven times higher when recommendations are
not followed. We report three cases of tuberculosis induced by TNF-alpha
inhibitors despite a rigorous screening policy in our tertiary care psoriasis
centre, and suggest tuberculosis-specific guidelines for clinicians using these
agents based on a review of the literature.

Transcriptional regulation of peptidylarginine deiminase expression in human keratinocytes. Ying S, Dong S, Kawada A, Kojima T, Chavanas S, Méchin MC, Adoue V, Serre G, Simon M, Takahara H. J Dermatol Sci. 2009 Jan;53(1):2-9. Epub 2008 Nov 11.

Peptidylarginine deiminase (PAD, EC 3.5.3.15) enzyme catalyzes the conversion of
arginine residues to citrulline residues in the presence of calcium ion, which is
an elaborate post-translational modification on the target protein. Recently,
five isoforms have been identified in mammals. Among them, three isoforms (type
I, II, III) are expressed in the human epidermis, and involved in several skin
physiological and pathological processes. In the past few years, several
researches concerning the transcriptional regulation of three human PADI type
genes (PADI1, PADI2 and PADI3) in the epidermis have been carried out. In this
review, we describe an overview of the current outcomes about these studies with
their significance. It is anticipated that these investigations will provide
novel therapeutic and prophylactic targets for future approaches to the treatment
or prevention of severe psoriasis and bullous congenital ichthyosiform
erythroderma.

Inflammasomes and inflammatory caspases in skin inflammation. Iversen L, Johansen C. Expert Rev Mol Diagn. 2008 Nov;8(6):697-705.

The inflammatory caspases comprise a subclass of caspases associated with immune
responses. Caspase-1 was the first identified member of this class, which also
includes caspase-4, -5, -11 and -12. Caspase-1 was identified as the
IL-1beta-converting enzyme and, more recently, it has also been shown to activate
IL-18 and IL-33. Activation of the inflammatory caspases occurs upon assembly of
multiprotein complexes, termed inflammasomes. The inflammasomes and inflammatory
caspases are part of the innate immune system, which constitutes the first line
of defense that detects pathogens, such as nonself antigens, bacterial and viral
components, and other danger signals, and orchestrates the immune response.
Inflammasomes and inflammatory caspases have also been suggested to bridge the
innate immune responses to the adaptive immune system. More recently, the
expression and role of inflammasomes and inflammatory caspases have been studied
in both human and rodent skin, and findings have indicated a possible key role of
these regulators of the immune system in the pathogenesis of inflammatory skin
diseases. This article will review some of the most recent findings, identifying
inflammasomes and inflammatory caspases as potential inducers and regulators of
skin inflammation in contact hypersensitivity and psoriasis.

Small molecule p38 MAP kinase inhibitors for the treatment of inflammatory diseases: novel structures and developments during 2006-2008. Pettus LH, Wurz RP. Curr Top Med Chem. 2008;8(16):1452-67.

The p38 mitogen-activated protein (MAP) kinase plays a central role in
inflammation. It has been the subject of extensive efforts in both basic research
and drug discovery for the treatment of inflammatory diseases such as rheumatoid
arthritis, inflammatory bowel disease, and psoriasis, where aberrant cytokine
signaling is the driver of the disease. This article reviews the patent and
journal publication activities during 2006-2008 describing novel small molecule
p38alpha inhibitors.

[Rheumatic diseases in pregnancy] [Article in German] Märker-Hermann E, Bauer H, Gromnica-Ihle E. Dtsch Med Wochenschr. 2008 Nov;133(46):2410-4. Epub 2008 Nov 4.

Rheumatic diseases can influence the reproduction, the course of pregnancy and
the development of the fetus. The inflammatory rheumatic disease itself can be
modulated in its activity in terms of amelioration or exacerbation of the
rheumatic symptoms. The associations between rheumatic diseases and pregnancy
will be illustrated with rheumatoid arthritis, ankylosing spondylitis, psoriatic
arthritis, and systemic lupus erythematosus as examples. Antirheumatic drug
therapy during pregnancy and the breast feeding period has to be adapted
critically.

Fumarates for the treatment of multiple sclerosis: potential mechanisms of action and clinical studies. Linker RA, Lee DH, Stangel M, Gold R. Expert Rev Neurother. 2008 Nov;8(11):1683-90.

All licensed disease-modifying drugs for the treatment of relapsing-remitting
multiple sclerosis (MS) only display partial efficacy and hitherto require
parenteral administration. Thus, there is a high demand for innovative and at the
same time orally available MS therapeutics. Fumaric acids and their esters (FAE)
may represent such a new class of compounds. FAE display immunomodulatory
properties and may also exert neuroprotective effects, as shown in vitro as well
as in experimental models of MS. A first Phase II study with the new, modified
FAE BG00012/FAG-201 (BG-12) in relapsing-remitting MS revealed significant
effects on MRI parameters such as gadolinium-enhancing lesions, T1 hypointense
lesions and T2 lesion load after 24 weeks of treatment. The trial also underlined
the safety and good tolerability of FAE that are already in clinical use for the
systemic treatment of severe psoriasis. Presently, two Phase III studies are
ongoing to investigate the clinical long-term efficacy of BG-12. In summary, FAE
are potential candidates that may open a new therapeutic option for
relapsing-remitting MS in the near future.

Enhancing the nail permeability of topically applied drugs. Murdan S. Expert Opin Drug Deliv. 2008 Nov;5(11):1267-82.

The topical therapy of nail diseases, especially of onychomycosis, and to a
smaller extent, of nail psoriasis, is desirable to avoid the side effects
associated with their systemic therapy, to increase patient compliance and reduce
the cost of treatment. Systemic therapy is however the mainstay of treatment due
to the poor permeability of the nail plate to topically applied drugs. For
effective topical therapy, ungual drug permeation must be enhanced. This can be
achieved by disrupting the nail plate using physical techniques or chemical
agents. Alternatively, drug permeation into the intact nail plate may be
encouraged, for example, by iontophoresis or by formulating the drug within a
vehicle which enables high drug partition out of the vehicle and into the nail
plate. The physical techniques (manual and electrical nail abrasion, acid
etching, ablation by lasers, microporation, application of low-frequency
ultrasound and electric currents) and chemicals (thiols, sulphites, hydrogen
peroxide, urea, water, enzymes) that have shown ungual enhancer activity are
discussed in this review. Optimal drug formulation, while crucial to ungual drug
delivery, is only briefly reviewed due to the limited literature.

The treatment of psoriatic arthritis and inflammatory spondylitis. Castro-Rueda H, Kavanaugh A. Curr Pain Headache Rep. 2008 Dec;12(6):412-7.

NSAIDs still remain the initial therapeutic modality for psoriatic arthritis and
inflammatory spondylitis. Disease-modifying antirheumatic drugs have only been
proven to be useful in peripheral arthritis, without efficacy in axial
inflammatory spondylitis. In recent years, the introduction of tumor necrosis
alpha inhibitors into clinical practice has produced a substantial impact in both
peripheral and axial disease, with improvement in pain, function, and quality of
life. Factors such as cost-effectiveness and safety will need to be better
characterized over time.

Topical treatments for scalp psoriasis. Warren RB, Brown BC, Griffiths CE. Drugs. 2008;68(16):2293-302. doi: 10.2165/0003495-200868160-00003.

Psoriasis is a common, chronic inflammatory skin disease that affects the scalp
more commonly than any other site. Scalp psoriasis causes significant
psychosocial disability as it is highly visible and can, on occasion, extend onto
the face. Furthermore, current treatment regimens are messy, time consuming and,
in some instances, ineffective, leading to a high level of non-compliance. The
majority of current evidence for topical treatments for this condition comes from
open-label, uncontrolled studies. From such studies, there are data to support
the use of topical corticosteroids in a number of different formulations and
topical vitamin D analogues. However, these studies have not addressed issues
such as the need for keratolytics, which may be required to remove adherent scale
before a topical corticosteroid or vitamin D analogue may prove efficacious.
There is an urgent need for well designed, controlled trials to assess the
efficacy of existing and new treatment regimens for scalp psoriasis. The aim of
this review is to critically assess the relative effectiveness and tolerability
of available topical therapies for this problematic condition and provide
recommendations for selection of treatment.

EBV-associated diffuse large B-cell lymphoma in a psoriatic treated with methotrexate. Hsiao SC, Ichinohasama R, Lin SH, Liao YL, Chang ST, Cho CY, Chuang SS. Pathol Res Pract. 2009;205(1):43-9. Epub 2008 Oct 31.

Methotrexate-associated lymphoproliferative disorder (MTX-LPD) is a lymphoid
proliferation or lymphoma in a patient immunosuppressed with MTX, which is
usually administered for treating autoimmune diseases. The majority of MTX-LPD
cases develop in patients with rheumatoid arthritis and occasionally with
psoriasis who had been treated with MTX. Here, we report on a 50-year-old
Taiwanese male with severe psoriasis, who received high doses of MTX. The patient
developed EBV-positive MTX-LPD at nodal and extranodal sites. The diffuse and
polymorphic lymphoid infiltrate consisted predominantly of immunoblasts and
plasmablasts expressing B-cell markers, CD138, Epstein-Barr virus (EBV)-LMP1, and
EBNA2, and these were monotypic for kappa light chain. The tumor cells were also
positive for EBV by in situ hybridization. These findings indicated a type III
latency infection of EBV. The patient died of progressive disease after 19
months. A review of the previously reported cases shows that MTX-LPD, in
association with psoriasis, occurs in middle-aged males. The tumors are diffuse
large B-cell lymphomas with immunoblastic morphology, and frequently show
plasmacytic differentiation.

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.

The impact of treatment with tumour necrosis factor-alpha antagonists on the course of chronic viral infections: a review of the literature. Domm S, Cinatl J, Mrowietz U. Br J Dermatol. 2008 Dec;159(6):1217-28. Epub 2008 Sep 25.

Biologics that antagonize the biological activity of tumour necrosis factor
(TNF)-alpha, namely infliximab, etanercept and adalimumab, are increasingly used
for treatment of immune-mediated inflammatory diseases, including psoriasis,
worldwide. TNF-alpha antagonists are known to increase the risk of reactivation
and infection, particularly of infections with intracellular bacteria such as
Mycobacterium tuberculosis. More frequently these agents are given to patients
with viral infections. Viral hepatitis and human immunodeficiency virus
infections are often present in these patients, with a considerable geographical
variation. Other concomitant viral infections such as herpes, cytomegalovirus and
varicella zoster virus may occur much more frequently than tuberculosis or
leprosy. General recommendations about the management related to possible
problems associated with anti-TNF-alpha treatment and these viral infections are
lacking. This short review will give an overview of the most recent data
available on the effects of anti-TNF-alpha therapy on viral infections with a
particular focus on patient management and screening recommendations.

Effect of folic or folinic acid supplementation on methotrexate-associated safety and efficacy in inflammatory disease: a systematic review. Prey S, Paul C Br J Dermatol. 2009 Mar;160(3):622-8. Epub 2008 Oct 20.

BACKGROUND: Methotrexate is a folic acid antagonist widely used for the treatment
of inflammatory disorders for more than 50 years. Methotrexate is a standard
systemic therapy for severe psoriasis and rheumatoid arthritis. Folic acid
supplementation has been advocated to limit the toxicity of methotrexate on blood
cells, gastrointestinal tract and liver. However, there is still controversy
regarding the usefulness of folic acid supplementation. OBJECTIVES: We sought to
assess the evidence for the efficacy of folic acid supplementation in patients
treated with methotrexate for inflammatory diseases. We also investigated whether
folic acid supplementation may decrease the efficacy of methotrexate. METHODS:
Cochrane and MEDLINE databases were systematically searched. Randomized
controlled trials in patients treated with methotrexate for rheumatoid arthritis
or psoriasis with or without arthritis were included. Study selection, assessment
of methodological quality, data extraction and analysis were carried out by two
independent researchers. We selected double-blind randomized placebo-controlled
trials. Analysis was performed for each subgroup of side-effects:
gastrointestinal, mucocutaneous, haematological and hepatic. RESULTS: Six
randomized controlled trials met the inclusion criteria, with a total sample of
648 patients. There were 257 patients in the placebo group, 198 patients treated
with folic acid, and 193 patients treated with folinic acid. The statistical
analysis showed a significant reduction of 35.8% of hepatic side-effects induced
by methotrexate for patients with supplementation with folic or folinic acid (95%
confidence interval -0.467 to -0.248). There was no statistical difference for
mucocutaneous and gastrointestinal side-effects although there was a trend in
favour of supplementation. The effect of supplementation on haematological
side-effects could not be assessed accurately due to a low incidence of these
events in the population studied. We were unable to analyse the effect of
supplementation on the effectiveness of methotrexate, as markers of activity used
in each study were not comparable. CONCLUSIONS: Supplementation with folic acid
is an effective measure to reduce hepatic adverse effects associated with
methotrexate treatment. There is no difference between folinic acid and folic
acid, but the lower cost of the latter promotes its use.

Alexithymia and dermatology: the state of the art. Willemsen R, Roseeuw D, Vanderlinden J. Int J Dermatol. 2008 Sep;47(9):903-10.

BACKGROUND: Alexithymia is a personality trait characterized by difficulties in
differentiating and describing feelings. Research indicates that alexithymia acts
as a triggering factor for many medical and psychiatric disorders. The interest
in alexithymia has increased considerably over the past decade. A state of the
art review of recent research on alexithymia in medical and dermatological
research is presented. METHODS: We reviewed most relevant publications on
alexithymia from the field of clinical research, psychology, psychosomatics, and
psycho-neuro-endocrinology. Systematic searches on alexithymia in dermatology
were undertaken using the Cochrane Library and PUBMed. RESULTS: Interdisciplinary
research, investigating alexithymia, is advancing rapidly into different fields
of medicine. Alexithymia has been found to be associated with changes in
sympathetic activity, immunity and brain activity. Some researchers link
alexithymia with insecure parental attachment and adverse childhood experiences.
Although research of alexithymia in dermatology is still scarce and reveals
conflicting results, preliminary data show that alexithymia seems to be
associated with alopecia areata, psoriasis, atopic dermatitis, vitiligo or
chronic urticaria. CONCLUSION: Present research findings on alexithymia in the
field of dermatology suggest important implications for the treatment of some
specific dermatological disorders. Besides treating comorbid psychological
problems such as anxiety and depression, dermatologists should also be aware of
alexithymia and its possible association with an underlying dermatologic disease.

Spondyloarthritis update: new insights regarding classifcation, pathophysiology, and management. Mease PJ. Bull NYU Hosp Jt Dis. 2008;66(3):203-9.

There has been a burgeoning interest in the spondyloarthritides (SpAs) due to a
confluence of elements. Basic science research has provided new insight into the
unique pathophysiology of synovium, enthesium, and bone, highlighting the
important differences from rheumatoid arthritis (RA). Through collaborative
research of international working groups, classification criteria for psoriatic
arthritis (PsA) and ankylosing spondylitis (AS) have been developed or are being
refined to aid characterization and diagnosis of SpAs and aid in research. These
same working groups, under the umbrella of Outcome Measures in Rheumatology
Clinical Trials (OMERACT), have developed domain core sets to be measured in
clinical trials and registries, and which allow validation of reliable outcome
measures. Both through clinical trials and observational data from national
clinical registries, the relative effectiveness and safety of old and new
therapies are being demonstrated. This has been particularly shown with long-term
data on anti-TNF therapy. Newer anti-TNF therapies are being developed, as are
treatments with different mechanisms of action in order to treat patients who do
not have long-term effectiveness or develop side effects to older disease
modifying therapy and anti-TNFs. International treatment recommendations have
been or are being developed based on the evidence base from clinical trials.

[Current state of anti-tumor necrosis factor therapy in autoimmune diseases] [Article in Spanish] Sánchez Cano D, Callejas Rubio JL, Ortego Centeno N. Med Clin (Barc). 2008 Oct 11;131(12):471-7.

Tumor necrosis factor (TNF) alpha plays a central role in both the inflammatory
response and that of the immune system. Thus, its blockade with the so-called
anti-TNF agents (infliximab, etanercept and adalimumab) represents an important
tool for the management of a variety of disorders, such as rheumatoid arthritis,
the spondyloarthropathies, inflammatory bowel disease and psoriasis. Nonetheless,
theoretically, some other autoimmune and inflammatory disorders may benefit from
these agents. We intend to update on these off-label uses of anti-TNF blockers in
this review.

Psoriasis in the patient with human immunodeficiency virus, Part 2: Review of treatment. Patel RV, Weinberg JM. Cutis. 2008 Sep;82(3):202-10.

Psoriasis is a chronic, immune-mediated skin disease affecting approximately 1%
to 3% of the human immunodeficiency virus (HIV)-infected population. Psoriasis
appears in patients with HIV either as the first clinical manifestation of the
disease or, less commonly, during the advanced stages of HIV when it has
progressed to AIDS. This 2-part series reviews the pathogenesis of HIV-associated
psoriasis as well as the various therapeutic regimens that have effectively
treated psoriasis in patients with HIV. These therapies address the profound
immune dysregulation that defines psoriasis. The second part of the series
focuses on the treatment of HIV-associated psoriasis.

Inhibitors of vascular endothelial growth factor in cancer. Pourgholami MH, Morris DL. Cardiovasc Hematol Agents Med Chem. 2008 Oct;6(4):343-7.

Angiogenesis is a complex process that is regulated by pro- and antiangiogenic
factors. These factors can emanate from diverse sources including cancer cells,
stromal cells, blood and extracellular matrix. Their relative contribution is
likely to change with tumor type and tumor site. Vascular endothelial growth
factor (VEGF) is now well confirmed as the primary and the most potent inducer of
angiogenesis. To activate cellular signaling pathways, VEGF binds to receptor
kinases VEGF-R1, R2 and R3. It then promotes several events required for the
formation of new blood vessels, such as endothelial cell survival, proliferation,
migration and vascular permeability. Activation of endothelial cells, leads to
the secretion of enzymes which degrade the extracellular matrix (ECM) and hence
promote metastasis. Similarly it promotes survival by inducing Bcl-2 expression
on VEGF receptor positive leukemia. Besides being a potent mitogen for
macrovascular cells derived from arteries, veins and lymphatics, it is also
highly involved in a number of angiogenic related disorders including
inflammatory diseases, rheumatoid arthritis, psoriasis, retinopathies and age
related macular degeneration. Neovascularization and increased vessel
permeability are being recognized as major causes of VEGF related pathogenesis.
Therefore, inhibition of VEGF pathway is a strategy being widely pursued to
provide new therapeutics for the treatment of VEGF related disorders. Over twenty
compounds with anti-angiogenic properties ranging from VEGF neutralizing
antibody, soluble receptors, receptor antagonists or tyrosine kinase inhibitors
(TKIs) are either approved or are currently under clinical (phase I – III) study.
This review aims to provide an updated account of how VEGF inhibitors are shaping
up to become an important class of drugs used in the treatment of cancer.

The use of galiximab in non-Hodgkin lymphoma. Vinjamaram S, Czuczman MS, Hernandez-Ilizaliturri FJ. Clin Lymphoma Myeloma. 2008 Oct;8(5):277-82.

Monoclonal antibodies are expanding the therapeutic options for patients with
B-cell lymphoma. Despite the antitumor activity of rituximab alone or in
combination with systemic chemotherapy against various subtypes of B-cell
lymphomas, a significant number of patients relapse or do not respond to initial
therapy, stressing the need to identify novel molecular targets. CD80 is a
surface glycoprotein and a member of the B7 family of costimulatory molecules.
CD80 antigen is expressed in antigen-presenting cells, normal B cells, and
various subtypes of B-cell lymphomas. Moreover, CD80 is an important regulator of
T-cell activation. In addition, in vitro binding of CD80 by specific monoclonal
antibodies (MoAbs) results in growth inhibition and apoptosis of normal and
malignant B cells. Galiximab is a primatized MoAb targeting CD80. Preclinical
studies had shown significant antitumor activity as a single agent or in
combination with rituximab against various B-cell lymphoma cell lines in vitro
and in vivo. An initial phase I/II study with galiximab as a single agent in
patients with relapsed B-cell lymphoma demonstrated its safety and antitumor
activity and had provided a framework for future studies. Interestingly, and in
contrast with what had been observed with other biologic agents, the time to best
response for the responding patients was delayed, suggesting an alternative
mechanism of action other than the traditional antibody-dependent cellular
cytotoxicity, apoptosis, and complement-mediated cytotoxicity. Ongoing and future
studies are warranted to further evaluate the therapeutic role of galiximab in
the treatment of patients with B-cell lymphomas in combination with rituximab or
systemic chemotherapy.

Importance of microRNAs in skin morphogenesis and diseases. Bostjancic E, Glavac D. Acta Dermatovenerol Alp Panonica Adriat. 2008 Sep;17(3):95-102.

MicroRNAs (miRNAs) are small (20-22 nt), non-coding RNAs involved in
post-transcriptional gene silencing. Their binding to the 3′ UTR of target mRNAs
influences the translation or stability of the transcripts. miRNAs have been
shown to regulate several developmental and physiological processes, including
stem cell differentiation and the immune response. Recent findings report their
involvement in hair follicle morphogenesis (ablation of miRNAs from keratinocytes
causes several defects, such as evagination instead of invagination), in
psoriasis (skin-specific expression of miR-203 and psoriasisspecific expression
of miR-146a, miR-21 and miR-125b in the skin), in autoimmune diseases affecting
the skin, such as SLE and ITP, in wound healing (changes in the expression of
specific miRNA at specific phases of the regeneration process), and in skin
carcinogenesis (a novel miRNA signature that includes induction of miR-21, a
candidate oncogenic miRNA). Researchers worldwide are interested in miRNAs as
potential therapeutic targets (such as in the case of psoriasis) and potential
diagnostic biomarkers (such as in case of SLE).

miRNAs, ’stemness’ and skin. Aberdam D, Candi E, Knight RA, Melino G. Trends Biochem Sci. 2008 Dec;33(12):583-91. Epub 2008 Oct 8.

The epidermis and its appendages provide organisms with protection from the
environment, keeping pathogens out and preventing the loss of essential body
fluids. To perform both functions, the skin has elaborated a complex
differentiation process known as cornification. The renewal capacity of the skin,
which is responsible for maintaining tissue homeostasis, regenerating hair and
repairing the epidermis after injury, resides in the basal proliferating
compartment in which epidermal stem cells are located. These cells possess the
remarkable capacity to both self-perpetuate and give rise to the differentiating
cells that form mature tissues. Recent findings indicate that microRNAs have an
essential role in orchestrating the formation of epidermis and skin appendages,
in particular, at the interface between stemness and differentiation.

Indications for psychological intervention in patients with psoriasis. Janowski K, Pietrzak A. Dermatol Ther. 2008 Sep-Oct;21(5):409-11.

Various forms of psychological interventions have since long been proposed as
potentially helpful adjuncts to standard pharmacological therapy of psoriasis.
All studies investigating the effectiveness of psychological intervention in
psoriasis reported its positive impact on the patients’ psychological well-being
and some studies also reported improvements in the skin condition as a result of
psychotherapy. When making a decision about the referral of a given patient to
the psychologist, both clinical (psoriasis-specific) and general
(psychotherapy-specific) indications should be taken into consideration. This can
allow a better identification of those psoriasis patients who are in real need
for psychological intervention and who are most likely to benefit from it.

Indications and results of videocapillaroscopy in clinical practice. Gallucci F, Russo R, Buono R, Acampora R, Madrid E, Uomo G. Adv Med Sci. 2008;53(2):149-57.

Nailfold videocapillaroscopy (NVC) is one of the best diagnostic non-invasive
imaging techniques to evaluate microcirculation in vivo and is increasingly
employed in the field of rheumatology. Indeed, at present, the most important
utility of NVC is in the identification of microvascular involvement in many
rheumatic diseases, particularly in systemic sclerosis. More recently, this
technique has been shown to be applicable to the study of many other
extra-rheumatic diseases, such as arterial hypertension, diabetes mellitus,
acromegaly, hyperthyroidism, cardiac syndrome X, primary biliary cirrhosis,
Crohn’s disease, psoriasis, familial Mediterranean fever. This article sets down
the methodology of examination and normal pattern of capillary vessels and
reviews the applications of NVC in clinical practice and its results in rheumatic
and non-rheumatic diseases.

[Biological agents in treatment of psoriatic arthritis] [Article in Polish] Lewicki M, Dutkiewicz B, Widuchowska M, Kucharz EJ. Pol Merkur Lekarski. 2008 Jul;25(145):97-100.

Psoriatic arthritis was reported in approximately 6-39% of patients with
psoriasis. It is a chronic disease that commonly leads to disability. The paper
reviews TNF-alpha inhibitors, the drugs which resulted in a substantial progress
in management of psoriatic arthritis. Numerous studies have shown efficacy of
these medical agents including inhibition of the disease progress, improvement of
skin changes, inhibition of bone destruction, and improvement in quality of life.
Other agents which can be used in psoriatic arthritis treatment are being tested
in clinical trials.

Psoriasis: improving adherence to topical therapy. Feldman SR, Horn EJ, Balkrishnan R, Basra MK, Finlay AY, McCoy D, Menter A, van de Kerkhof PC; International Psoriasis Council. J Am Acad Dermatol. 2008 Dec;59(6):1009-16. Epub 2008 Oct 2.

Topical therapy has an important role in psoriasis treatment. It is efficacious
and has a favorable safety profile as demonstrated in clinical trials. However,
poor treatment outcomes from topical therapy regimens likely result from poor
adherence and ineffective use of the medication. The International Psoriasis
Council Topical Therapy Working Group has developed a new model to describe the
complex interactions among patient, disease, and treatment characteristics,
adherence behavior, and treatment outcomes. Recommendations are provided that may
assist the health care provider in encouraging adherent behavior in their
patients. By understanding and manipulating the factors that affect treatment
adherence, improvement in adherence is possible and hence better control and
outcomes in the topical treatment of psoriasis are likely.

308 nm monochromatic excimer light in dermatology: personal experience and review of the literature. Mavilia L, Mori M, Rossi R, Campolmi P, Puglisi Guerra A, Lotti T. G Ital Dermatol Venereol. 2008 Oct;143(5):329-37.

For over five years, we have been using a new ultraviolet B ray source, a
Xenon-Chloride lamp emitting non-coherent, monochromatic 308-nm light that
represents the natural evolution of the excimer laser. A source of monochromatic
excimer light (MEL) produces 50 mW/cm(2) power density at a distance of 15 cm
from the source and has a maximum irradiating area of 504 cm(2), this feature
representing the greatest therapeutic advantage offered by 308 nm sources. On the
other hand, the benefits offered by the MEL compared to traditional
phototherapies are essentially correlated to the fact that there is no need to
administer oral psoralens (PUVA therapy) and that sessions need to be repeated
only every 7-15 days, an important condition for the improvement of the patient’s
quality of life (since at least 2-3 weekly sessions are required with the
traditional UVB therapy). Using MEL, UV B light can be applied on the entire
body, with partial subintrant skin irradiations, or on one or just a few
individual patches, taking care to accurately protect the healthy surrounding
skin and allowing for a phototherapy exclusively targeted onto the lesion to be
treated. Clinical indications and the reasons for choosing MEL for the treatment
of photosensitive skin disorders are virtually identical to those stated for PUVA
therapy or narrowband UV B light. Due to the absence of photosensitizing
substances and drug-induced toxicity, patients who work in the open air, pregnant
women and patients suffering from liver or kidney failure can also be treated.
Furthermore, the short time required for sessions, the duration of cycles and the
selective exposure of the skin areas to be treated undoubtedly represent
significant benefits for patients in terms of safety and efficacy. In addition to
psoriasis, the use of MEL can also be extended to other pathologies such as
vitiligo, alopecia areata, atopic dermatitis and patch-stage IA mycosis fungoides
with encouraging RESULTS:

Biological agents in the treatment of psoriasis. Tzu J, Krulig E, Cardenas V, Kerdel FA. G Ital Dermatol Venereol. 2008 Oct;143(5):315-27.

Psoriasis is a chronic immune-mediated inflammatory disease, with an estimated
prevalence of 1-3% worldwide. It is considered to be a multisystemic disorder,
primarily affecting the skin and joints (psoriatic arthritis), and associated
with other inflammatory conditions such as inflammatory bowel disease and
coronary heart disease among others. Today, thanks to recent scientific advances
that have allowed us to deepen our understanding of the pathogenesis of
psoriasis, we count with an expanded therapeutic armamentarium that includes
targeted therapy in the form of ”biologics”. These agents have gained
popularity as safe, effective, and convenient alternatives for the treatment of
chronic moderate to severe plaque psoriasis. This review will focus on the main
biologics used in the treatment of moderate to severe plaque psoriasis:
efalizumab, alefacept, etanercept, infliximab, adalimumab and the new Interleukin
(IL) 12/23 inhibitors.

Cardiovascular morbidity in psoriasis: epidemiology, pathomechanisms, and clinical consequences. Boehncke WH, Boehncke S. G Ital Dermatol Venereol. 2008 Oct;143(5):307-13.

Psoriasis is a common inflammatory skin condition. Around 25% of patients develop
joint involvement in the form of psoriatic arthritis as well. Recent
epidemiologic studies demonstrated an increased cardiovascular morbidity among
psoriasis patients. Although the association of psoriasis with cardiovascular
diseases such as hypertension, myocardial infarction, and heart failure, is now
widely accepted, the pathogenetic link remains yet unclear. High prevalence of
the metabolic syndrome as well as adverse effects of systemic anti-psoriatic
therapies may contribute to the observed association. Several pilot studies
suggest that insulin resistance may contribute to the development of
cardiovascular diseases in psoriasis patients who exhibit metabolic parameters
like patients developing diabetes. Retrospective data provide evidence that
continuous systemic therapy may reduce the risk of cardiovascular mortality in
psoriasis patients. The consequences for the management of psoriasis at this
point are two-fold: as co-morbidity goes along with co-medication, potential drug
interactions need to be kept in mind when choosing a systemic anti-psoriatic
therapy. Moreover, as psoriasis itself is a risk factor for cardiovascular
morbidity, patients must avoid other known risk factors such as obesity or
smoking. Dermatologists need to communicate this additional risk to their
patients and support them accordingly.

Genetic variation and psoriasis. Gudjonsson JE. G Ital Dermatol Venereol. 2008 Oct;143(5):299-305.

Psoriasis is a common chronic inflammatory skin disease with a strong genetic
basis, characterized by complex alteration in epidermal growth and
differentiation. The genetic basis of psoriasis has been appreciated for nearly
100 years, but only recently have several of the genetic variants involved in
psoriasis pathogenesis been identified. These genetic variants so far identified
are the HLA-Cw*0602 allele of the HLA-C gene on chromosome 6, the p40 subunit of
the IL-12 and IL-23 cytokines (IL12B), the IL-23 receptor and SNF313, a gene
implicated in protein ubiquitinylation. Psoriasis patients have also been shown
to have an increased number of copies of the beta-defensin gene cluster on
chromosome 8. Beta-defensin 2, which is located in this region, is amongst the
most highly up-regulated proteins in lesional skin and has cytokine-like
properties in addition to potent antimicrobial activity. Although several
additional genes remain to be identified, the variants that have so far been
described support the autoimmune basis of psoriasis indicating that the disease
may be mediated by T-cells reacting against (self)antigen(s) in the binding
pocket of HLA-C, with contribution from the recently described Th17 subset of
T-cells which are maintained by the IL-23 cytokine axis. These genetic variants
together with pro-inflammatory environment caused by exaggerated antimicrobial
response (beta-defensins) and dysregulation of signaling pathways (ubiquination),
suggest the type of mechanism by which psoriasis can arise. Elucidation of the
genetic basis of psoriasis and the underlying pathogenic mechanisms hold the
potential for eventual cure of this enigmatic disorder.

Vasoactive peptides in the pathogenesis of psoriasis. Reich A, Szepietowski JC. G Ital Dermatol Venereol. 2008 Oct;143(5):289-98.

Psoriasis, a chronic inflammatory skin disease, is believed to be exacerbated by
stress. The exact mechanism of this phenomenon is not fully understood, however,
it has been postulated that different substances released from dermal nerve
endings during stress may take part in initiation or modulation of psoriasis. One
of the most interesting group of mediators are polypeptides, also named as
neuropeptides, that possess vasoactive properties. It was documented that these
polypeptides could not only be released from nerve endings, but may also be
directly synthesised in the skin and liberated from numerous dermal cells.
Moreover, these substances are not only released by different cells, but may
activate various cell types showing a wide spectrum of biological actions. Thus,
this complex system of interactions seems to be important component of psoriatic
pathological reaction. The significant role of these neuromediators has also been
postulated in other chronic skin diseases, like palmoplantar pustulosis, atopic
and irritant eczema, rosacea, lichen sclerosus, vitiligo, pigmented urticaria or
prurigo nodularis. Among different neuropeptides, substance P, calcitonin
gene-related peptide, vasoactive intestinal peptide (VIP) and neuropeptide Y have
been mostly studied in psoriasis.

A possible role for vaccination in the treatment of psoriasis? Baker BS, Owles AV, Fry L. G Ital Dermatol Venereol. 2008 Apr;143(2):105-17.

Psoriasis is a multifactorial immune skin disease whose etiology involves a
strong genetic component, involving several genes encoding proteins involved in
epidermal differentiation and immune, inflammatory and pathogen responses, in
combination with microbial environmental factors. Although various microorganisms
appear to provoke or aggravate the disease, including Staphylococcus aureus,
Malassezia and Candida albicans, the association between S. pyogenes throat
infections and guttate psoriasis is supported by the strongest clinical evidence.
Furthermore, the identification of peptidoglycan-specific T cells in psoriatic
skin lesions has led to the proposal that cell wall peptidoglycan may mediate the
link between streptococcal infection in the tonsils and the subsequent induction
of skin lesions. These findings suggest that psoriasis may be a possible
candidate for therapeutic streptococcal vaccination. Current treatments for
psoriasis have several limitations including toxicity and an increased risk of
infection and malignancy. In contrast, vaccination could potentially induce
long-term tolerance without the side effects caused by global immunosuppression.
Future research will need to address the identity of the triggering microbial
antigen(s); such knowledge could open the way for vaccination as a therapeutic
tool for psoriasis.

Genetic variations in cytokines and cytokine receptors associated with psoriasis found by genome-wide association. Duffin KC, Krueger GG. J Invest Dermatol. 2009 Apr;129(4):827-33. Epub 2008 Oct 2.

Genetic variants have long been suspected to be important in psoriasis. Recent
work has suggested that HLA-Cw6 on chromosome 6 is the risk variant in the PSORS1
[MIM 177900] susceptibility locus that confers the greatest risk for early onset
of psoriasis. Although numerous minor susceptibility loci have been identified by
linkage analysis, few biologically relevant candidates have been discovered
within these intervals. Recent large-scale genome-wide association studies have
yielded new candidates in genes encoding cytokines with functional relevance to
psoriasis. Polymorphisms within the genes encoding the IL-12 p40 subunit, IL12B,
and one of the IL-23 receptor subunits, IL23R, have been replicated in US and
European populations and overlap with risk of Crohn’s disease. Polymorphisms
within the gene encoding IL-13, a Th2 cytokine, also confer risk for psoriasis.
Variants of the gene IL15 encoding IL-15 have been identified that associate with
psoriasis in a Chinese population. These discoveries pose the challenge of
elucidating the role of common genetic variants in susceptibility to and
manifestations of psoriasis.

Prediction and prevention of autoimmune skin disorders. Nancy AL, Yehuda S. Arch Dermatol Res. 2009 Jan;301(1):57-64. Epub 2008 Sep 24.

Autoimmune diseases can be preceded by a symptom-free phase which is defined by
the presence of autoantibodies, and may last for many years. These autoantibodies
may have a high positive predictive value for disease onset, severity and
organ-specific complications, especially in genetically prone individuals.
Characteristic autoantibodies and susceptible genes have been identified in many
autoimmune systemic and mucocutaneous diseases such as systemic lupus
erythematosus, pemphigus, vitiligo, dermatitis hepretiformis and even psoriasis.
Prevention of overt disease may be achieved once high-risk individuals are
identified and triggering factors are avoided. Numerous environmental factors,
such as vitamin D deficiency, ultraviolet light, smoking, drugs, etc., that may
trigger autoimmunity have been found. Alternatively, even if the autoimmune
disease cannot be prevented, it may be postponed or attenuated. Thus, although
large body of evidence has accumulated on characteristic autoantibodies,
susceptible genes and environmental factors, many more large scale studies are
needed to assess their predictive value, the preventive measurements and the
means to apply them to clinical management of healthy population and high-risk
individuals.

Principles of dermatologic ultrasound diagnostics. Zmudzinska M, Czarnecka-Operacz M, Silny W. Acta Dermatovenerol Croat. 2008;16(3):126-9.

Ultrasound is a valuable diagnostic tool widely used in medicine. Recently,
high-frequency ultrasonography has been introduced to dermatology owing to
technical advances. Currently, the most often used frequency for skin imaging is
between 20 and 25 MHz. Ultrasound images can be generated in different modes,
i.e. one-dimensional A mode, two-dimensional B mode and C mode. This type of skin
imaging is known as a noninvasive, reproducible and quantitative method, which
can be used to evaluate skin characteristics in a variety of dermatologic
diseases. It can found application in the assessment of skin tumors, morphea,
psoriasis, lipodermatosclerosis, skin aging and photodamage, hypertrophic scars,
wound healing processes and allergic reactions. Although skin ultrasonography and
its clinical applications are still being explored, most probably it will be
implemented in the routine dermatologic diagnosis in the forthcoming future.

Role of photodynamic therapy in psoriasis: a brief review. Tandon YK, Yang MF, Baron ED. Photodermatol Photoimmunol Photomed. 2008 Oct;24(5):222-30.

BACKGROUND AND PURPOSE: Photodynamic therapy (PDT) is a light treatment modality
which involves either systemic or local application of a photosensitizing
compound, which preferentially deposits in the target cells, and is then followed
by selective illumination of the lesion with visible light. The purpose of this
study was to review the literature to examine the success, side effects, and
different protocols used thus far to treat psoriasis using PDT. METHODS: A
thorough review of the literature was performed and analyzed. RESULTS AND
CONCLUSIONS: After a thorough review of the literature, PDT remains a potential
treatment for psoriasis. Clinical improvement has been observed in most studies.
The major limiting factor seen in many of the studies was the side effect of pain
and burning sensations associated with PDT. This highlights the need for other
photosensitizers with better tolerability profiles.

Therapeutic potential of inhaled p38 mitogen-activated protein kinase inhibitors for inflammatory pulmonary diseases. Chopra P, Kanoje V, Semwal A, Ray A. Expert Opin Investig Drugs. 2008 Oct;17(10):1411-25.

BACKGROUND: Over the past two decades, p38 MAPK (mitogen-activated protein
kinase) has been the subject of intense multidisciplinary research. p38 MAPK
inhibitors have been shown to be efficacious in several disease models, including
rheumatoid arthritis, psoriasis, Crohn’s disease, and stroke. Recent studies
support a role for p38 MAPK in the development, maintenance, and/or exacerbation
of a number of pulmonary diseases, such as asthma, cystic fibrosis, idiopathic
pulmonary fibrosis, and chronic obstructive pulmonary disease (COPD). OBJECTIVE:
Many previous attempts to develop p38 MAPK inhibitors have failed as a result of
unacceptable safety profiles. These toxicities have been varied and are believed
to derive from different off-target effects. METHOD: The above concerns can be
overcome by delivering the compound locally to minimize whole-body burden,
resulting in low exposure to the gastrointestinal, liver, and CNS. This review
discusses the role of p38 MAPK in various inflammatory diseases, followed by the
toxicity concerns associated with p38 MAPK inhibition. It also highlights the
possible beneficial effect of delivering drugs via the inhalation route.
CONCLUSION: We present proof-of-principle confirming the therapeutic potential of
inhaled p38 inhibitors for asthma and other inflammatory pulmonary diseases.

Clobetasol propionate–where, when, why? Pels R, Sterry W, Lademann J. Drugs Today (Barc). 2008 Jul;44(7):547-57.

Clobetasol propionate is the most potent of all topical steroids. It is
successfully applied in the treatment of various skin diseases such as atopic
dermatitis, psoriasis and vulvar lichen sclerosus. The therapy is, however,
mainly symptomatic. A preventive effect is only reported in the treatment of the
latter. Clobetasol propionate exerts antiinflammatory, immunosuppressive and
antimitotic effects influencing the growth, differentiation and function of
various cells and inhibiting cytokine production. Seven different dosage forms
are available to deliver the drug to the living cells of the skin. Their choice
might additionally affect patient compliance. The potency of clobetasol
propionate, however, is accompanied by local and systemic side effects, such as
skin atrophy and hypothalamic-pituitary-adrenal axis suppression. Patients
applying clobetasol propionate must be well instructed in how to use it.
Physicians prescribing clobetasol propionate should consider a diversity of
factors and be able to answer the questions where, when and why. Copyright 2008
Prous Science, S.A.U. or its licensors. All rights reserved.

Methotrexate for psoriasis in the era of biological therapy. Warren RB, Chalmers RJ, Griffiths CE, Menter A. Clin Exp Dermatol. 2008 Aug;33(5):551-4.

Methotrexate’s traditional role as a first line agent for moderate to severe
psoriasis is being challenged by the rapid and growing use of biological
therapies. A recent study comparing adalimumab with methotrexate showed
significantly superior efficacy of adalimumab over methotrexate over 16 weeks.
Although it is inexpensive, the future use of methotrexate may be compromised by
its unpredictable response and toxicity, and by the introduction of newer, more
effective biological therapies. However, recent advances in the screening of
liver fibrosis by monitoring serum levels of the aminoterminal peptide fragment
of type III procollagen have reduced the need for liver biopsy. Furthermore, the
potential for personalized methotrexate use by application of modern
pharmacogenetics and pharmacokinetics may ensure its place as a first-line agent
for the treatment of psoriasis for the foreseeable future.

Psoriasis in the patient with human immunodeficiency virus, part 1: review of pathogenesis. Patel RV, Weinberg JM. Cutis. 2008 Aug;82(2):117-22.

Psoriasis is a chronic, immune-mediated skin disease affecting approximately 1%
to 3% of the human immunodeficiency virus (HIV)-infected population. The
presentation of psoriasis in patients with HIV varies. It either presents as the
first clinical manifestation of HIV or, less commonly, appears in the advanced
stages of HIV when it has progressed to AIDS. This 2-part series reviews the
pathogenesis of HIV-associated psoriasis as well as the various therapeutic
regimens that have effectively treated psoriasis in patients with HIV These
therapies address the profound immune dysregulation that defines psoriasis. The
first part of the series focuses on the pathogenesis of HIV-associated psoriasis.

Platelet function in cutaneous diseases. Kasperska-Zajac A, Brzoza Z, Rogala B. Platelets. 2008 Aug;19(5):317-21.

Blood platelets participate actively in immune-inflammatory processes. Responding
to the variety of stimuli such as cell activation leads to the release of several
mediators, including RANTES, platelet factor 4, beta-thromboglobulin, thymus and
activation-regulated chemokine (TARC/CCL17), serotonin and arachidonic acid
metabolites. It also affects the expression of immunomodulatory and adhesive
molecules, including CD154 and P-selectin. Immune-inflammatory processes
associated with skin diseases could induce platelet activation, which, in turn,
would contribute to acceleration and modulation of these processes. Activated
platelets are capable of facilitating leukocyte rolling in the skin and the
release of skin inflammation mediators. Changes in platelet function and
behaviour may occur in certain types of skin inflammatory conditions and
platelets might then be an important effector cell of the skin immune system,
contributing to the pathogenesis of some skin inflammatory disorders. The changes
in platelet activity and reactivity have been demonstrated to show distinctly
different pathogenic mechanisms in cutaneous diseases, such as urticaria, atopic
eczema/dermatitis syndrome and psoriasis. Considering the risk of cardiovascular
events, some of them seem to be of clinical significance. This contribution is a
brief outline of the present knowledge of the platelet function in dermal
disorders.

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.

The relationship between quality of life and skin clearance in moderate-to-severe psoriasis: lessons learnt from clinical trials with infliximab. Reich K, Griffiths CE. Arch Dermatol Res. 2008 Nov;300(10):537-44. Epub 2008 Sep 11.

The physical presentation of psoriasis and its impact on health-related quality
of life (HRQoL) varies greatly between patients as well as over the course of the
disease. A number of instruments have been developed for evaluating disease
severity and its impact on HRQoL, the best known being the Psoriasis Area and
Severity Index (PASI). HRQoL is most commonly evaluated using the Dermatology
Life Quality Index (DLQI) and/or the Short-Form-36 Health Survey (SF-36). The
exact correlation between the reduction of skin symptoms upon therapy and changes
of HRQoL is not known. Since improvement of HRQoL is being established as an
independent goal of psoriasis therapy, a better understanding of the relationship
between skin symptoms and HRQoL during treatment will likely influence not only
disease concepts but also physicians treatment decisions. Based on a selective
review of the literature, this paper focuses on recent insight obtained from
clinical trials with infliximab on the correlation between skin clearance and
changes of HRQoL in psoriasis and compares these findings with results from
studies with other biologics. Together these data indicate that despite the lack
of a direct correlation between absolute PASI and DLQI values, significant
reductions of PASI are likely to correlate with significant improvements of
HRQoL. There is also evidence, that large improvements of HRQoL as currently
discussed as treatment goals in psoriasis are primarily achieved in patients with
an at least 75% reduction of their PASI.

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.

A PEGylated Fab’ fragment against tumor necrosis factor for the treatment of Crohn disease: exploring a new mechanism of action. Bourne T, Fossati G, Nesbitt A. BioDrugs. 2008;22(5):331-7.

Antibodies, having a high specificity for their particular target, are
increasingly being used as therapeutic agents with functions including agonist,
antagonist, and targeted drug delivery. The use of many biologic therapies,
including antibody fragments, is generally limited by their rapid clearance from
plasma. A commonly used approach to extend exposure to biologic therapies is the
attachment of polyethylene glycol.Tumor necrosis factor (TNF)-alpha is a
multifunctional cytokine involved in the regulation of immune responses. Elevated
levels of TNFalpha are found in a wide range of diseases, including the chronic
inflammatory conditions rheumatoid arthritis, psoriasis, and Crohn disease (CD).
Anti-TNFalpha antibodies have proved highly efficacious in the treatment of these
conditions. In addition, they have proved invaluable for investigating the role
of TNFalpha in disease etiology.Based on evidence showing that neutralizing
antibodies to TNFalpha were effective in animal models of CD, anti-TNFalpha
antibody treatments were assessed in clinical trials. Interestingly, the
anti-TNFalpha antibody etanercept proved ineffective at achieving remission in
active CD despite potently neutralizing soluble TNFalpha. This indicated that an
additional mode of action is also involved in the efficacy of the anti-TNFalpha
agents adalimumab, certolizumab pegol, and infliximab in CD; one suggestion was
apoptosis. However, etanercept, like adalimumab and infliximab, can induce
apoptosis. Furthermore, certolizumab pegol (which has demonstrated efficacy in
CD) does not cause complement-dependent cytotoxicity, antibody-dependent
cell-mediated cytotoxicity, apoptosis, or necrosis of neutrophils, all measured
in vitro. These functional differences observed with certolizumab pegol stem from
its unique structure that does not include the crystallizable fragment (Fc)
portion present in the other anti-TNFalpha agents, and the way in which it
signals through membrane TNF.It is well established that bacteria are a major
part of the inflammatory process in CD. The property identified that reflected
the efficacies of the anti-TNFalpha agents etanercept, adalimumab, certolizumab
pegol, and infliximab in CD was the ability to inhibit the cytokine production by
monocytes that is induced by bacterial lipopolysaccharide. It may therefore be
the case that this mode of action is important for efficacy in CD.

[Retinoids and their metabolism: new therapeutic approaches?] [Article in German] Baron JM, Skazik C, Merk HF. Hautarzt. 2008 Sep;59(9):745-6.

[Cutaneous reactions to molecular targeted therapies] [Article in German] Pföhler C, Ugurel S. Hautarzt. 2008 Oct;59(10):814-20.

The use of molecular targeted therapies currently is on the rise in the treatment
of severe diseases, particularly for malignant tumors. The targeted agents show a
high specificity against one or more molecular target structures, hereby
inhibiting or modifying signal transduction pathways connected to these targets,
and thus strongly altering proliferation, activation and interaction of the
targeted cells. These manipulations of highly specific signaling pathways are
associated with again highly specific side effects, which often affect the skin.
These cutaneous reactions present a new spectrum of adverse drug events to the
dermatologist. We reviews the cutaneous reactions of molecular targeted agents
used in the treatment of psoriasis (alefacept, efalizumab, etanercept, infliximab
and adalimumab), as well as agents used in cancer therapy (imatinib, sorafenib,
sunitinib, EGFR antagonists and CTLA-4-antagonists).

Pruritus ani. Siddiqi S, Vijay V, Ward M, Mahendran R, Warren S. Ann R Coll Surg Engl. 2008 Sep;90(6):457-63.

INTRODUCTION: Pruritus ani is a common condition with many causes, predominately
anorectal pathology. There are some new insights and therapies, but the most
recommendations are based on low-level evidence. PATIENTS AND METHODS: A
literature search was carried out using Medline and the internet with the
keywords ‘pruritus ani’ from 1950 to 2007. RESULTS: A review of the evidence is
presented and a management plan based on the elimination of irritants and
scratching, general control measures and active treatment measures is offered.
CONCLUSIONS: Treatment of primary and secondary pruritus ani has a good prospect
of regression of symptoms and skin changes.

Off-label use of biologicals in the management of inflammatory oral mucosal disease. O’Neill ID. J Oral Pathol Med. 2008 Nov;37(10):575-81. Epub 2008 Sep 1.

The recent development of novel biologic immunomodulators effective in the
treatment of immune-mediated inflammatory conditions has led to their widespread
use in rheumatology and dermatology. These include the tumour necrosis
factor-alpha antagonists, infliximab, etanercept and adalimumab and the T-cell
modulator modifiers efalizumab and alefacept. In dermatology, although these
agents are licensed only for psoriasis, increasingly off-label use has extended
to a number of conditions in which oral mucosal disease is a significant
component. These include Behçet’s disease, recurrent apthous stomatitis, benign
mucous membrane pemphigoid and lichen planus. This article provides a review of
the current literature on such off-label use in oral mucosal disease.

[Interleukin-20--a new target in psoriasis treatment] [Article in Danish] Stenderup K, Rosada C, Dam TN. Ugeskr Laeger. 2008 Sep 1;170(36):2777-81.

Interleukin-20 (IL-20) is suggested as a new target in psoriasis treatment. It
was first described in 2001, and the potential role of this cytokine in psoriasis
was suggested because mice which were over-expressing IL-20 developed a
psoriasis-like phenotype of the skin. Subsequently, IL-20 expression levels were
found to be increased in psoriasis skin, and it was observed that these levels
normalized upon psoriasis treatment. In the psoriasis xenograft transplantation
model, administration of IL-20 to non-lesional psoriasis skin transplanted onto
immune-deficient mice demonstrated that IL-20 was involved in the psoriasis
induction. More interestingly, improvement of psoriasis was induced by blocking
IL-20 signaling.

Future perspectives/quo vadis psoriasis treatment? Immunology, pharmacogenomics, and epidemiology. Kimball AB, Kupper TS. Clin Dermatol. 2008 Sep-Oct;26(5):554-61.

Advances in the understanding and treatment of psoriasis in the past several
years have been remarkable. New frontiers include better understanding the
immunologic pathways that underlie the disease and the development of
personalized strategies to maximize the benefit and minimize the risk for
patients. Although a cure may not be imminent, there are some strategies under
examination that may lead us closer to this goal.

Nonstandard and off-label therapies for psoriasis. Halverstam CP, Lebwohl M. Clin Dermatol. 2008 Sep-Oct;26(5):546-53.

Although most psoriasis patients respond to standard therapies, many
circumstances warrant the use of nonstandard or off-label treatments. For
instance, patients with treatment-resistant psoriasis or those who have had
multiple adverse effects to other therapies may be good candidates for off-label
treatments. Similarly, patients with unusual and hard-to-treat forms of psoriasis
such as pustular psoriasis and palmoplantar psoriasis or specific comorbidities
may benefit from certain nonstandard therapies. Drugs that may be used as
alternatives to standard therapies include mycophenolate mofetil, tacrolimus or
pimecrolimus, isotretinoin, colchicine, sulfasalazine, paclitaxel, dapsone,
azathioprine, and hydroxyurea. Other unconventional therapies include
climatotherapy at the Dead Sea and grenz ray therapy.

Chemokines and other mediators as therapeutic targets in psoriasis vulgaris. Homey B, Meller S. Clin Dermatol. 2008 Sep-Oct;26(5):539-45.

In recent years, our knowledge of the immunopathogenesis of chronic inflammatory
skin diseases has increased significantly. Accumulating evidence indicates that
the complex interaction of structural cells, in particular keratinocytes and
endothelial cells, with skin-infiltrating leukocytes is key to our understanding
of psoriasis. The recruitment of pathogenic leukocyte subsets into the skin
represents a prerequisite for the initiation and maintenance of psoriasis
vulgaris and is mediated by a complex chemokine and cytokine network. Results of
recent studies associating cytokines and chemokines with a psoriatic phenotype
are outlined herein, and their role as therapeutic targets in psoriasis is
discussed in detail.

Targeting leukocyte recruitment in the treatment of psoriasis. Li YY, Zollner TM, Schön MP. Clin Dermatol. 2008 Sep-Oct;26(5):527-38.

Tissue-selective recruitment of immunocytes to cutaneous tissues, a complex
multistep cascade mediated by a large variety of cytokines, chemokines, and
adhesion molecules, is thought to be a pivotal process in the pathogenesis of
psoriasis. Following this notion, specifically targeting leukocyte trafficking
remains an attractive approach for the treatment of psoriasis. It is increasingly
recognized that during the pathogenesis of psoriasis not only effector T cells
play important roles, but also multiple interactions between T cells, dendritic
cells, macrophages, mast cells, endothelial cells, and keratinocytes are crucial
for the full-fledged development of psoriasis. Meanwhile, the first biologics
specifically inhibiting key molecules involved in cutaneous leukocyte recruitment
have been approved for the treatment of psoriasis. It is, however, challenging to
predict that molecules in this complex process with many redundant and/or
functionally overlapping players will suffice as therapeutic targets. In this
review, we will discuss the molecules and mechanisms involved in trafficking of
different types of leukocytes and elucidate modes of action as well as
therapeutic strategies of existing drugs and drug candidates.

Fumaric acid esters. Yazdi MR, Mrowietz U. Clin Dermatol. 2008 Sep-Oct;26(5):522-6.

Several clinical studies have shown that systemic therapy with fumaric acid
esters (FAEs) in patients with moderate to severe psoriasis is effective and has
a good long-term safety profile. For therapeutic use, tablets with a defined
mixture of FAEs (dimethylfumarate [DMF] and three different salts of
monoethylfumarate) are registered in Germany. There is evidence that DMF is the
most essential component in this formulation with an antipsoriatic effect.
Currently, there are few data on the pharmacokinetics of fumarates in human
beings. DMF seems to act as a prodrug for its main metabolite:
monomethylfumarate. This hypothesis was supported by the observation that only
monomethylfumarate was detected in the plasma of human beings after the oral
administration of FAEs. FAEs have been tested in different biological assays, and
effects such as inhibition of the nuclear factor kappa B pathway or induction of
apoptosis by DMF have been described. For these data, the role of DMF as a
modulator of intracellular glutathione plays an important role.

Monitoring biologics for the treatment of psoriasis. Papp KA. Clin Dermatol. 2008 Sep-Oct;26(5):515-21.

Monitoring patients on therapy consists of 2 parts: evaluation of response and
mitigation of risk. Biologics for the treatment of psoriasis are no different.
Although laboratory assessments are sometimes necessary, the key elements to
appropriate monitoring are clinical assessments and vigilant reinforcement of
signs and symptoms, which may portend undesirable adverse effects to the patient.
Identifying expected response to therapy establishes one objective of monitoring.
There is no precise threshold for response, but given the array of therapies and
the relatively high response rates, a 75% improvement in clinical disease state
is reasonable. Less well established is a reasonable time over which the expected
improvement should occur. For alefacept, there are no data to support a plateau
in response. Efalizumab and etanercept show trends to optimal response between 24
and 36 weeks, suggesting at least 6 months of therapy is required to
categorically define a treatment failure. Infliximab is contrary to the other 3
biologics showing very thorough response in nearly all patients by week 14 but
progressive loss of response during a subsequent 34 weeks of therapy.
Categorizing adverse events into simple silos of probability and severity helps
identify appropriate monitoring strategies. A greater number of patients treated
with longer courses of therapy, coupled with careful observations and reporting,
will better define risks and benefits. The better risks and benefits are
understood, the more precise monitoring guidelines can be defined.

Efalizumab in the treatment of psoriasis: mode of action, clinical indications, efficacy, and safety. Schön MP. Clin Dermatol. 2008 Sep-Oct;26(5):509-14.

Efalizumab is a humanized monoclonal antibody directed against the CD11a subunit
of the lymphocyte function-associated antigen 1. It has been approved for the
treatment of moderate-to-severe plaque psoriasis. Efalizumab has been shown in
several clinical trials to be effective and well tolerated in the treatment of
patients with moderate-to-severe psoriasis. The safety profile of continuous
therapy with efalizumab–as far as it is currently available–is favorable. Mode
of action, pharmacological profile, clinical indications and efficacy, safety,
and tolerability as well as practical considerations of efalizumab are reviewed
in this article.

Alefacept in the treatment of psoriasis. Sugiyama H, McCormick TS, Cooper KD, Korman NJ. Clin Dermatol. 2008 Sep-Oct;26(5):503-8.

Alefacept is the first biologic agent approved by the US Food and Drug
Administration for the treatment of psoriasis. To date, more than 1000 patients
with moderate to severe psoriasis have been enrolled in phase III clinical trials
of alefacept. More than 30% of patients treated with 2 courses of alefacept
reached a Physician’s Global Assessment of clear to almost clear, and
approximately 40% and 70% of patients achieved a Psoriasis Area Severity Index
score of 75 and 50 after the same regimen. Alefacept is well tolerated, and there
have been no reports of significant systemic toxicity or serious
treatment-related adverse events.

Tumor necrosis factor antagonists in the therapy of psoriasis. Mössner R, Schön MP, Reich K. Clin Dermatol. 2008 Sep-Oct;26(5):486-502.

The identification of new pathophysiological mechanisms in chronic inflammatory
diseases and the development of techniques that allow production of antibodies
and fusion proteins that antagonize target molecules with high specificity has
not only revolutionized the treatment of rheumatoid arthritis and chronic
inflammatory bowel disease, but it also has revolutionized the treatment of
psoriasis in recent years. Two different classes of so-called biological
therapies (biologics) have become available to treat psoriasis: tumor necrosis
factor (TNF) antagonists and T-cell modulators. TNF antagonists that have been
studied with psoriasis include the antibodies infliximab and adalimumab and the
fusion protein etanercept. These treatments differ in their capacity to reduce
the skin symptoms of psoriasis and other important characteristics of the drug
profile. This article summarizes the important aspects of efficacy, safety, and
practicability of TNF antagonists in the treatment of psoriasis. This article may
be helpful for the daily routine when selecting the right therapy for a patient
and managing the TNF antagonist during maintenance therapy.

Climatotherapy of psoriasis. Kazandjieva J, Grozdev I, Darlenski R, Tsankov N. Clin Dermatol. 2008 Sep-Oct;26(5):477-85.

In the era when biological treatments for psoriasis are gaining more and more
popularity, climatotherapy represents a safe and efficient alternative to the
conventional therapeutic modalities. Climatotherapy comprises alternative
treatment methods, which are based on the healing capacities of natural
resources. This paper provides the reader with relevant information on the
different climatotherapeutic methods, the intimate mechanisms of their action,
and the cumulated clinical experience in the treatment of psoriasis. The positive
effect of thalassotherapy for psoriasis has been known since ancient times.
However, in the past decades a number of controlled studies revealed the efficacy
of thalassotherpay in the treatment of psoriasis. Herein, it is exemplified on
the experience in the centers at the Dead Sea and the Black Sea coast.
Originating from Europe, balneo- and spa therapy are becoming popular
alternatives for psoriasis treatment worldwide. A short review on the centers
profiled for psoriasis therapy is provided. The unique sites of Blue Lagoon in
Iceland and Kangal in Turkey are selected in this paper. Additionally,
alternative nature-based treatments for psoriasis such as high mountain
climatotherapy and naphtalotherapy are discussed.

Phototherapy and photochemotherapy. Schneider LA, Hinrichs R, Scharffetter-Kochanek K. Clin Dermatol. 2008 Sep-Oct;26(5):464-76.

Phototherapy, whose first application for psoriasis dates back to almost a
century now, is still an actual mainstay of treatment. We discuss in detail the
radiophysical aspects involved in the therapy, the different treatment
modalities, and all aspects related to clinical application of phototherapy. By
looking at new insights on the molecular mode of action, it becomes evident that
phototherapy is in fact the oldest “biological” therapeutic strategy, whose
target is directly the T-cell-mediated immunopathology of psoriasis. In an
outlook, we discuss finally the current cost effectiveness calculations,
important issues in times of increasingly tight public health budgets. In
summary, this review points out that phototherapy is clearly a first-line therapy
that is safe and effective. Guidelines in the patient management still have to be
harmonized, however, and further trials to improve the fine tuning of irradiation
protocols are still necessary.

Psoriatic arthritis: therapeutic principles. Feuchtenberger M, Kleinert S, Tony HP, Kneitz C. Clin Dermatol. 2008 Sep-Oct;26(5):460-3.

From the dermatologic point of view, psoriatic arthritis (PsA) was seen for a
long time as a rare complication of psoriasis. Recent studies, however, reveal a
high prevalence of PsA among patients with psoriasis, and the impact of PsA due
to chronic inflammation of peripheral joints, axial joints, and periarticular
structures leading to radiologic progression, functional impairment, and
reduction in quality of life is well recognized. Substantial improvement in
understanding immunopathology of PsA has led to a variety of new therapeutic
options. This article reviews the current therapeutic principles for PsA.

Psoriasis treatment in difficult locations: scalp, nails, and intertriginous areas. Wozel G. Clin Dermatol. 2008 Sep-Oct;26(5):448-59.

Psoriasis comprises a broad spectrum of different clinical courses among which
the chronic stable psoriasis by far occurs most frequently. The clinical
presentation ranges from mild disease to more serious forms involving large areas
of skin and/or joint disease. A number of modifying factors may impact on
treatment choice in individual cases (eg, location of the lesions, disease phase,
treatment history, response to previous treatments, comorbidity). Aside from this
consideration, there are special localizations that remain some of the most
difficult regions to control. Such entities are the scalp, nails, and
intertriginous areas. Topical treatment of such different-to-treat areas has to
be considered as a first-line intervention strategy, at least in those patients
who are presenting an exclusively isolated involvement. In some situations (eg,
in severe psoriasis or in patients who are refractory to topical treatment),
however, a systemic treatment is indicated. Most obvious difficulties in treating
these locations are due to unrealistic expectations from the patients’
perspectives, time-consuming applications, side effects, cosmetic injuries, and
restricted bioavailability of active compounds. Aside from hair care, initial use
of keratolytics for scalp psoriasis, corticosteroids, and vitamin D3 and
analogues are currently standard treatments. Recently developed new formulations
of both active ingredients such as foam or gel appear to be more acceptable to
patients than traditional creams or ointments. Current treatment options for nail
psoriasis are very often poorly efficacious, associated with undesirable effects,
or time consuming. Success has to be measured in terms of months. Topical
treatments (eg, corticosteroids, vitamin D analogues, tazarotene) are mainly
used, but impressive improvement rates mostly will be achieved by systemic
treatment of conventional and biologic agents. Finally, the usefulness of
corticosteroids, vitamin D and analogues, and calcineurin inhibitors in treating
intertriginous psoriasis clearly is demonstrated. Especially the use of
calcineurin inhibitors exhibits efficacy in intertriginous regions and therefore
may be seen as a promising treatment option in the future. Besides the important
innovations in the last years, there is a need for new effective and
well-tolerated treatment modalities, especially for long-term use in the 3
difficult-to-treat locations, which encompass cosmetic acceptability.

Systemic therapies for psoriasis: methotrexate, retinoids, and cyclosporine. Warren RB, Griffiths CE. Clin Dermatol. 2008 Sep-Oct;26(5):438-47.

Despite the current use and ongoing development of the biological therapies
‘traditional’ systemic agents will continue to form a key part of the therapeutic
armamentarium for patients with severe psoriasis. Long-term maintenance therapy
with retinoids and methotrexate is cost-effective and, for many patients with
psoriasis, life changing. Regular monitoring is required for both treatments,
particularly methotrexate to prevent significant bone marrow suppression and
hepatotoxicity. Ideally, cyclosporine should be used for short courses of 3 to 4
months duration, within which it provides excellent disease control. Close
assessment of renal function and blood pressure is essential.

Topical treatments in psoriasis: today and tomorrow. Bos JD, Spuls PI. Clin Dermatol. 2008 Sep-Oct;26(5):432-7.

Topical therapy in psoriasis is of use in mild cases. It is also applied as an
adjunct to phototherapy and systemic treatments in moderate to severe cases.
Long-established pharmaceuticals such as cignolin, tar preparations, and
glucocorticoids are still in use. Newer topical agents such as vitamin A and D
derivatives are gradually replacing them. Combining a vitamin D derivative and a
strong glucocorticoid now seems to be the most efficient way to treat psoriasis
when topical agents are indicated. There is a growing list of “alternative”
treatment options, where evidence is generally absent. Rewarding investments
should perhaps be directed at intervening with molecules of innate immunity.
Superfluous activation of natural immune system cascades is now in view as the
major culprit in psoriasis, replacing the T-cell hypothesis of the disease.
Agents directed at tumor necrosis factor alpha, Toll-like receptors, and
neutrophils may have great impact in future topical therapy of psoriasis.
Finally, innovations in the development of more targeted glucocorticoids and
vitamin A and D derivatives, where desired effects are better separated from
undesired side effects, may lead to an increased benefit/risk ratio of these
nuclear receptor-directed therapies.

Economic considerations in psoriasis management. Radtke MA, Augustin M. Clin Dermatol. 2008 Sep-Oct;26(5):424-31.

With a prevalence of 2% to 3%, psoriasis is a very common chronic disease
worldwide and generates therapy costs and continuing cost for health insurance
and patients and their families. Cost-political changes in health care and the
ever increasing health-economic demands in all areas of the health system make it
necessary to differentiate between the two when recording the expenses for a
disease. The main characteristics of the pharmacoeconomic evaluation are the
record of costs, the cost-benefit and cost-effectiveness ratio, and efficiency of
various treatment forms. Numerous publications discuss the cost of individual
forms of therapy in the treatment of psoriasis, but there are fewer studies on
the total cost of psoriasis therapy, especially studies that take both direct and
indirect costs into account. The scientific articles on pharmacoeconomy and
quality of life in psoriasis have proven (without a doubt) that, despite the lack
of a vital threat, psoriasis is highly important to the national economy and to
those who have the disease. This justifies appropriate monetary expenditure for
treatment. Studies that address the cost of therapies (especially for chronic
diseases) will be necessary in the future and will create the required
transparency to guarantee reasonable medical care that takes the cost-benefit
ratio and the best outcome for the patient’s quality of life into account.

Adalimumab in dermatology. Traczewski P, Rudnicka L. Br J Clin Pharmacol. 2008 Nov;66(5):618-25. Epub 2008 Jul 11.

Adalimumab is a biological agent, one of the tumour necrosis factor-alpha
inhibitors. Pivotal studies evaluating its efficacy in plaque psoriasis
(CHAMPION, REVEAL) and psoriatic arthritis (PsA) (ADEPT) were carried out in
recent years. Adalimumab proved highly effective in psoriasis patients and in PsA
patients previously unresponsive to nonsteroidal anti-inflammatory drugs. Results
of smaller studies suggest therapy with the drug may be successful in psoriasis
resistant to other biologics and PsA unresponsive to disease-modifying
antirheumatic drugs. Adalimumab has also been shown to improve patients’ quality
of life significantly. Although they should be further extended as far as
dermatological conditions are concerned, available data indicate adalimumab is
safe and well tolerated. Numerous case reports featuring its off-label use
suggest the drug could be helpful in treating hidradenitis suppurativa, pyoderma
gangrenosum, Sweet’s syndrome, cutaneous sarcoidosis, pemphigus, systemic
vasculitides, multicentric reticulohistiocytosis and stomatitis.

[Metabolic syndrome and skin diseases] [Article in Czech] Svacina S. Cas Lek Cesk. 2008;147(6):307-10.

Skin symptoms were originally described only in some components of the metabolic
syndrome (e.g. in obesity, diabetes and polycystic ovary syndrome). In the last
years several skin symptoms were described also in the metabolic syndrome. These
relations were mostly described between psoriasis and metabolic syndrome, where
perhaps common pathogenetic mechanisms are present. Even more important is the
fact that physical activity, weight loss and diet treatment can have a common
positive effect on both diseases. Also some drugs can influence both diseases
together.

Long-term safety of mycophenolate mofetil and cyclosporine: a review. Buell C, Koo J. J Drugs Dermatol. 2008 Aug;7(8):741-8.

The prevailing notion in dermatology is that mycophenolate mofetil (MMF) is safer
than cyclosporine (CsA), but that CsA has greater efficacy. This literature
review evaluates the available long-term safety data of MMF and CsA. Literature
in the fields of dermatology, autoimmune disease, and transplantation were
retrieved from PubMed. Data regarding immunosuppressive and non-immunosuppressive
side effects of MMF and CsA are presented along with available pregnancy safety
data. Surprisingly, there is a paucity of data on long-term MMF monotherapy.
Transplant data is presented separately due to the concomitant use of other
immunosuppressants along with MMF. Trends that can be identified include a less
discernable cancer or end-organ damage risk in MMF compared to CsA. However, MMF
appears to have a greater risk in pregnancy and increased reports of herpes
simplex and zoster infection compared to CsA.

Is there a role for mast cells in psoriasis? Harvima IT, Nilsson G, Suttle MM, Naukkarinen A. Arch Dermatol Res. 2008 Oct;300(9):461-78. Epub 2008 Aug 22.

Mast cells have traditionally been considered as effector cells in allergy but
during the last decade it has been realized that mast cells are essentially
involved in the mechanisms of innate and acquired immunity. Upon activation by
anaphylactic, piecemeal degranulation or degranulation-independent mechanisms
mast cells can secrete rapidly or slowly a number of soluble mediators, such as
serine proteinases, histamine, lipid-derived mediators, cytokines, chemokines and
growth factors. Mast cells can express cell surface co-stimulatory receptors and
ligands, and they can express MHC class II molecules and thereby present
antigens. These soluble factors and cell surface molecules can interact with
other cells, such as endothelial cells, keratinocytes, sensory nerves,
neutrophils, T cell subsets and antigen presenting cells which are essential
effectors in the development of skin inflammation. Besides promoting
inflammation, mast cells may attempt in some circumstances to suppress the
inflammation and epidermal growth but the regulation between suppressive and
proinflammatory mechanisms is unclear. Psoriasis is characterized by epidermal
hyperplasia and chronic inflammation where tryptase- and chymase-positive MC(TC)
mast cells are activated early in the developing lesion and later the cells
increase in number in the upper dermis with concomitant expression of cytokines
and TNF superfamily ligands as well as increased contacts with
neuropeptide-containing sensory nerves. Due to the intimate involvement of mast
cells in immunity and chronic inflammation the role of mast cells in psoriasis is
discussed in this review.

308-nm excimer laser in psoriasis vulgaris, scalp psoriasis, and palmoplantar psoriasis. Gattu S, Rashid RM, Wu JJ. J Eur Acad Dermatol Venereol. 2009 Jan;23(1):36-41. Epub 2008 Aug 19.

BACKGROUND: The 308-nm excimer laser is a recent development in the treatment of
psoriasis vulgaris, palmoplantar psoriasis, and psoriasis of the scalp. The XeCl
excimer emits a 308-nm wavelength beam of light that is monochromatic and
coherent. These properties allow selectivity when used as phototherapy against a
psoriatic lesion while sparing healthy surrounding tissue. OBJECTIVE: In this
manuscript, we review recent updates on the efficacy of excimer and its most
recent trials in psoriasis. METHODS: A review of the medical literature in Pubmed
database was performed using the terms ‘psoriasis’ and ‘308 nm excimer laser’.
All trials to date that studied the 308-nm excimer including those that compared
the excimer with other modalities were included. RESULTS: Eighteen trials show
positive results surrounding the efficacy of the excimer. Selectivity of the
308-nm excimer, when compared with non-selective narrowband UVB (NB-UVB)
phototherapy allows one to adjust the fluency to the lesion. The excimer may also
stand superior to NB-UVB in its efficacy of mechanism. CONCLUSION: Excimer is a
useful and effective treatment for psoriasis that may be used as a compliment to
topical medications as well as NB-UVB. However, large randomized trials with
long-term follow-up are needed to further support this.

Spotlight on fumarates. Lee DH, Linker RA, Gold R. Int MS J. 2008 Mar;15(1):12-8.

The recent years have witnessed great efforts in establishing new therapeutic
options for multiple sclerosis (MS). There is a clear need for more effective,
safe and at the same time orally available treatment options. Here we review the
potential of fumaric acid esters (FAE) as a new therapeutic option for MS. FAE
have been claimed to possess immunomodulatory properties and are already in
clinical use as second-line therapy for severe systemic psoriasis. They also
displayed beneficial effects in experimental autoimmune encephalomyelitis (EAE),
a model mimicking many aspects of MS. In addition, FAE may also act on the
blood-brain barrier and exert neuroprotective properties via activation of
anti-oxidative pathways. A first magnetic resonance imaging (MRI) based Phase II
study in relapsing-remitting MS (RRMS) revealed a dose-dependent, significant
reduction of brain lesion activity for BG-12, a dimethyl FAE compound. Currently,
two multicentre, Phase III studies for testing clinical efficacy in RRMS are
initiated. In view of their profile, FAE compounds may have the potential to add
to our therapeutic options in RRMS in the future.

Long-term data in the treatment of psoriasis. Thaçi D. Br J Dermatol. 2008 Aug;159 Suppl 2:18-24.

Moderate-to-severe plaque psoriasis is associated with a considerable disease
burden and treatment needs are often unmet. Several conventional systemic drugs
are available as treatments, including methotrexate, cyclosporin, retinoids and
psoralen ultraviolet A, which, although effective, are associated with
considerable toxicity that limits their long-term use. Recent developments in
more targeted therapies involving biological agents, such as anti-T-cell agents
and inhibitors of tumour necrosis factor-alpha, offer an alternative treatment
approach with the possibility of longer continuous therapy, which may translate
into disease control and improved quality of life. Although the majority of data
supporting the use of biological agents have been obtained in short-term studies
of 3-6 months’ duration, some agents have been evaluated for longer periods of
continuous administration. Comparison of efficacy among these agents may better
define their role as long-term therapy. This article discusses the data currently
available on both conventional and biological systemic therapies for psoriasis,
in terms of short-term and long-term use.

Inflammation in atherosclerosis and psoriasis: common pathogenic mechanisms and the potential for an integrated treatment approach. Späh F. Br J Dermatol. 2008 Aug;159 Suppl 2:10-7.

Inflammation plays a key role in the pathogenesis of a number of chronic
inflammatory systemic diseases (CISDs), including psoriasis, rheumatoid
arthritis, systemic lupus erythematosus and Crohn’s disease, and also in the
pathogenesis of atherosclerosis. CISDs and cardiovascular diseases, such as
atherosclerosis, share common pathogenic features, and cardiovascular disease is
an important cause of morbidity and mortality in patients with CISDs. Activated
inflammatory cells and pro-inflammatory cytokines contribute to the development
of psoriatic lesions and play an important role in the breakdown of
atherosclerotic plaques. Psoriasis and atherosclerosis also have similar
histological characteristics involving T cells, macrophages and monocytes. In
particular, the extravasation of T cells through the epithelium is characteristic
of both psoriatic and atherosclerotic plaques. Cardiovascular disease is an
important cause of morbidity and mortality in patients with psoriasis, which is
associated with an increased cardiovascular risk profile compared with the
general population. Patients with psoriasis are at increased risk of arterial
hypertension, coronary heart disease, hyperlipidaemia, obesity and type II
diabetes, which are more prevalent than in control patients. This increased risk
could be due to the effects of chronic inflammatory changes, particularly the
infiltration of T cells and subsequent secretion of pro-inflammatory cytokines.
Some drugs used in the treatment of cardiovascular disease, such as
3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) and
angiotensin-converting enzyme inhibitors have anti-inflammatory activity. In
addition, systemic treatments for psoriasis may, by decreasing inflammation,
reduce the risk of cardiovascular disease. It is suggested, therefore, that an
integrated approach to the treatment of the inflammatory processes underlying
both psoriasis and atherosclerosis may be beneficial in reducing cardiovascular
risk in patients with psoriasis. The newer targeted biological therapies, such as
efalizumab and infliximab, which offer the potential for long-term disease
control in psoriasis, may be of particular use in this setting.

Long-term prognosis in patients with psoriasis. Gulliver W. Br J Dermatol. 2008 Aug;159 Suppl 2:2-9.

Psoriasis is a chronic, inflammatory, immune-mediated skin disease associated
with substantial comorbidity. Traditional comorbid conditions include
psychological/psychiatric disorders, psoriatic arthritis and inflammatory bowel
disease. Increasingly, an association with metabolic dysfunction, including
obesity and the metabolic syndrome, and cardiovascular disease, with consequent
effects on morbidity and mortality, has been recognized in psoriasis. The
underlying inflammatory mechanisms of both psoriasis and psoriasis-associated
comorbidities involve mediation by proinflammatory T-helper type 1 cytokines. For
effective management of psoriasis and related comorbidities, an integrated
approach targeting both cutaneous and systemic inflammation may be beneficial,
and strategies to improve overall management of the patient should be encouraged
to reduce the disease burden. This paper discusses the emerging role of
biological agents in this approach, and offers an appreciation of the role of
existing anti-psoriasis and adjunctive therapies.

[Efficacy of adalimumab] [Article in Spanish] Casado M. Actas Dermosifiliogr. 2008 Feb;99 Suppl 3:10-4.

After a comment about new biologic treatments in psoriasis, we do a revision
about efficiency with adalimumab: mechanism form, therapeutic indications,
different guidelines and doses, and review of principals clinical trials about
adalimumab in psoriasis, particularly CHAMPION and REVEAL.

Origin of threshold behaviour in psoriatic skin. Lejeune O, Simonart T. Dermatology. 2008;217(4):295-8. Epub 2008 Aug 15.

The mechanisms that lead to the psoriatic morphology are not fully elucidated.
Several lines of evidence suggest that the positive feedback between
keratinocytes and immunocytes plays a key role in the development of the lesions.
On the other hand, little information is available on the negative regulatory
controls that maintain a new homoeostasis level in psoriatic skin. We suggest
here that the interplay of these two contrary feedbacks is likely to entail a
hysteresis effect and that psoriasis is likely to be interpreted as a critical
phenomenon characterized by a catastrophic shift of the skin from a normal to a
hyperplastic state. 2008 S. Karger AG, Basel.

Tuberculosis in the age of biologic therapy. Hernandez C, Cetner AS, Jordan JE, Puangsuvan SN, Robinson JK. J Am Acad Dermatol. 2008 Sep;59(3):363-80; quiz 382-4.

The introduction of biologic therapies for psoriasis has revolutionized the
treatment of plaque psoriasis. These changes in our drug armamentarium have
resulted in the need for dermatologists to have a through command of knowledge
regarding tuberculosis given the potential for reactivation with this class of
medications. The focus of this review is to update dermatologists on pertinent
information regarding the microbiology, immunology, screening, and recognition of
the clinical presentations of tuberculosis. The current literature regarding the
occurrence of tuberculosis with biologics, specifically antitumor necrosis factor
therapy, is reviewed. Special emphasis is placed on the different clinical
presentations between newly acquired tuberculosis versus reactivation of latent
disease while receiving these medications. Given the ever-widening use of
biologic therapy in our specialty, we must be capable of rapidly identifying
infected patients, including those with asymptomatic latent disease. The failure
to screen for tuberculosis before the initiation of biologic therapy may result
in adverse outcomes for both the patient and the overall health of our
communities.

Targeting tumor necrosis factor alpha in psoriasis and psoriatic arthritis. Fantuzzi F, Del Giglio M, Gisondi P, Girolomoni G. Expert Opin Ther Targets. 2008 Sep;12(9):1085-96.

BACKGROUND: Psoriasis is an immune-mediated chronic inflammatory disease
triggered and maintained by inflammatory mediators, including TNF-alpha.
OBJECTIVE/METHODS: To summarize the role of anti-TNF-alpha agents psoriasis
therapy, focusing on the mechanisms and biological pathways involved, by
reviewing relevant literature. RESULTS/CONCLUSIONS: The three TNF-alpha
antagonists currently available (etanercept, infliximab and adalimumab) are
effective in the therapy of psoriasis and psoriatic arthritis. Certolizumab pegol
and golimumab are TNF-alpha inhibitors not approved for therapy of psoriasis yet.
In addition to neutralizing soluble TNF-alpha, TNF-alpha blockers bind to
membrane TNF-alpha and change the behavior of TNF-alpha-expressing cells,
resulting in hastened cell cycle arrest and apoptosis, and suppression of
cytokine production. TNF-alpha blockers may also affect adaptive immune responses
by reducing T helper cell (Th)1 and Th17 responses, and favoring the development
of T-regulatory cells. TNF-alpha antagonists can regulate differentiation and
activation of osteoclasts, thus reducing bone destruction in psoriatic arthritis.
Anti-TNF-alpha agents differ in their pharmacokinetics and pharmacodinamic
properties, which is reflected in their therapeutic and safety profiles. The
safety of TNF-alpha antagonists has been established, and patient selection and
monitoring allow risk minimization.

Emollients, moisturizers, and keratolytic agents in psoriasis. Fluhr JW, Cavallotti C, Berardesca E. Clin Dermatol. 2008 Jul-Aug;26(4):380-6.

Emollients, moisturizers, and keratolytic agents are essential in the topical
treatment of psoriasis. They are adjuvants for classic treatments and help to
reduce the scale load of individual patients. The major role for emollients and
moisturizers is the supportive role in normalizing hyperproliferation,
differentiation, and apoptosis; furthermore, they exert anti-inflammatory
effects, for example, through physiologic lipids. Subsequently, an improved
barrier function and stratum corneum hydration makes the epidermis more resistant
to external stressors and reduces the induction of Koebner phenomena. Most of the
emollients are lipid-rich (sometimes oily). The keratolytic agents, especially
salicylic acid, and higher concentration of urea should be used in the initial
keratolytic phase, whereas moisturizing products and emollients are especially
suitable in the intermediate phase and the chronic/remission phase of psoriasis.
They should be combined with bath oils.

Anti-selectin therapy for the treatment of inflammatory diseases. Rossi B, Constantin G. Inflamm Allergy Drug Targets. 2008 Jun;7(2):85-93.

Leukocyte migration into the tissues represents a key process in the pathogenesis
of inflammatory diseases. Data obtained in clinical trials have convincingly
shown that inhibition of leukocyte migration into the target organs represents an
effective therapeutic approach for diseases in which inflammation has a noxious
effect. Leukocyte tethering and rolling are the earliest steps of leukocyte
adhesion cascade in inflamed vessels. Selectins are type I transmembrane
glycoproteins that bind sialylated carbohydrate structures in a calcium-dependent
manner and are involved in the tethering and rolling of leukocytes under
physiological and pathological conditions. Three selectins have been identified:
L-, P- and E-selectin. Current understanding of the glycosylation-dependent
selectin function reveals a complex role for selectins and their ligands during
inflammatory diseases. Among selectin ligands, mucin P-selectin glycoprotein
ligand-1 (PSGL-1) binds all three selectins and has a well-documented role in
organ targeting during inflammation in animal models. However, although
inhibition of selectins and their ligands in animal models of inflammatory
diseases has proven the validity of this approach in vivo, only a limited number
of anti-selectin drugs have been tested in humans. Recent results obtained in
clinical trials for asthma and psoriasis show that, although very challenging,
the development of selectin antagonists holds concrete promise for the therapy of
inflammatory diseases.

Role of IL-10 in the resolution of airway inflammation. Ogawa Y, Duru EA, Ameredes BT. Curr Mol Med. 2008 Aug;8(5):437-45.

IL-10 can be considered an important agent in the resolution of inflammation.
Originally named “cytokine synthesis inhibitory factor” for its ability to
inhibit IFN-gamma and IL-2 production in Th2 cells, it is secreted by monocytes,
macrophages, mast cells, T and B lymphocytes, and dendritic cells (DCs). IL-10
production and release by monocytic cells in response to allergic challenge is
upregulated by TNF-alpha, and by negative feedback regulation of itself. However,
it is also secreted by T regulatory cells (Tregs), under the control of IL-2.
Importantly in the context of asthma, IL-10 inhibits eosinophilia, by suppression
of IL-5 and GM-CSF, by direct effects on eosinophil apoptosis, and effects on
cell proliferation through down-regulation of IL-1. A number of its cytokine
suppressive characteristics are now thought to occur through its upregulation of
suppressor of cytokine signaling (SOCS)-3. IL-10 is also a suppressor of nitric
oxide (NO) production, which may have ramifications for its role in airway
inflammatory diseases. Initial clinical trials have demonstrated relative safety
and few clinically adverse events at doses of recombinant human IL-10 below 50
microg/kg, with mixed success in treatment of patients with inflammatory bowel
disease and psoriasis. However, both steroid therapy and allergen specific
immunotherapy are known to elevate endogenous IL-10 levels, which may account for
their efficacy, suggesting that further study of IL-10 as a target for treatment
of airway inflammatory diseases such as asthma and COPD is warranted.

The role of the New Zealand Intensive Medicines Monitoring Programme in identification of previously unrecognised signals of adverse drug reactions. Clark DW, Harrison-Woolrych M. Curr Drug Saf. 2006 May;1(2):169-78.

The New Zealand Intensive Medicines Monitoring Programme (IMMP) was established
in 1977 to enhance monitoring for previously unrecognised adverse drug reactions
associated with selected new medicines. This involved establishing cohorts from
prescription data and collection of event information: thus New Zealand was a
pioneer in the development of the methodology now known as Prescription Event
Monitoring (PEM). In the IMMP, PEM cohorts are established using information,
supplied by pharmacies, from prescriptions for medicines that have been selected
for monitoring. Events are identified subsequently from follow-up questionnaires
to prescribing physicians and from other sources, including spontaneous reporting
of events. The objective of this review is to illustrate how the IMMP methodology
enables identification of signals of previously unrecognised adverse reactions.
This is enhanced by high response rates from pharmacists and prescribers in
providing prescription and event data respectively. In addition, high quality
event reports are obtained from multiple sources including follow-up event
returns from prescribers, reports received through the national spontaneous
reporting programme, prescription returns and from record linkage to other
databases. Collaboration with other national centres and with the WHO
Collaborating centre for international drug monitoring in Uppsala, Sweden
(WHO-UMC) enables information on cases from their databases to be used in
validation of IMMP signals. The NZ IMMP methodology and signals of previously
unrecognised adverse drug reactions arising from the IMMP databases are reviewed.
Recent signals include amnesia and QTc prolongation with sibutramine; pain
activation with sumatriptan; epistaxis with risperidone; psychiatric and visual
disturbances with the COX-2 inhibitors celecoxib and rofecoxib and psoriasis with
rofecoxib. In addition, other types of investigation are discussed along with the
importance of rapid communication to prescribers of new information concerning
the risks of medications. The IMMP has features that differ from those of other
centres that incorporate PEM methodology. New Zealand is a small country
(approximately 4 million) and thus communication is relatively easy. This
facilitates good rapport with prescribing doctors. However, mainly because of the
small population, several years may be required to achieve a large cohort.
Although this has drawbacks in terms of rapid results, it enables a longitudinal
approach to prescription data analysis, including aspects of prescribing such as
reasons for cessation of therapy and changes in prescribing practise. Although
not specifically reviewed in this article, the programme has also made
significant contributions in determining the incidence of certain adverse drug
reactions and in carrying out in-depth epidemiological investigations relating to
the safe use of medicines. Through these activities, the New Zealand IMMP
provides an ongoing contribution to safety in the use of medicines.

[Vitamin D and the skin] [Article in German] Hösl M, Berneburg M. Hautarzt. 2008 Sep;59(9):737-42; quiz 743.

Along with other organs like prostate, bones and kidney, skin is capable of
vitamin D synthesis. Primarily keratinocytes but also macrophages and fibroblasts
synthesize active vitamin D from cholesterol precursors by photochemical
activation. The synthesized vitamin D functions by binding to nuclear vitamin D
receptors. Vitamin D deficiency usually manifests as rickets in childhood
although it is today only relevant in diseases characterized by malabsorption due
to today’s recommended vitamin D prophylaxis. Excessive doses of vitamin D are
the usual cause of increased levels. The most common therapeutic target of
Vitamin D is psoriasis. Here, topical preparations are usually employed; their
anti-proliferative and cell differentiation-promoting action is mediated via
binding to cutaneous vitamin D receptors.

Resident and “inflammatory” dendritic cells in human skin. Zaba LC, Krueger JG, Lowes MA. J Invest Dermatol. 2009 Feb;129(2):302-8. Epub 2008 Aug 14.

Dendritic cells (DCs) are a heterogeneous group of antigen-presenting leukocytes
that are important in activation of both the innate and adaptive arms of the
immune system. Although there are several different DC populations in the body,
DCs are globally defined by their capacity for potent antigen presentation and
naive T-cell activation. In noninflamed human skin during steady state, there are
three main cutaneous DC populations: epidermal Langerhans cells, dermal myeloid
DCs, and dermal plasmacytoid DCs. In psoriasis, a model for cutaneous
inflammation, there is an additional population of myeloid dermal
DCs–”inflammatory DCs”–which appears to be critical for disease pathogenesis.

Recommendations for the long-term treatment of psoriasis with infliximab: a dermatology expert group consensus. Reich K, Griffiths C, Barker J, Chimenti S, Daudén E, Giannetti A, Gniadecki R, Katsambas A, Langley R, Mrowietz U, Ogilvie A, Ortonne JP, Reider N, Saurat JH. Dermatology. 2008;217(3):268-75. Epub 2008 Aug 6.

BACKGROUND/AIMS: Infliximab has been approved for the treatment of chronic plaque
psoriasis for only a few years. As physicians gain confidence in initiating and
maintaining this therapy, guidance on the management of patients beyond several
months or years is needed. To date, there is little or no information about the
long-term management in clinical trials or guidelines. METHODS: Here we report on
the key aspects related to the use of infliximab for the treatment of psoriasis.
The data presented here were derived using a modified Delphi survey to obtain a
consensus opinion of 11 dermatologists from Europe and Canada experienced in
long-term therapy with infliximab. RESULTS/CONCLUSION: The Delphi participants
reviewed several important topics related to biological therapy and infliximab.
This paper is not intended to provide a recommendation on all practical aspects
related to biological therapy; it has rather been written to provide useful and
practical information on the ‘best practice’ use of infliximab. Copyright 2008 S.
Karger AG, Basel.

Tetrathiomolybdate, a copper chelator for the treatment of Wilson disease, pulmonary fibrosis and other indications. Medici V, Sturniolo GC. IDrugs. 2008 Aug;11(8):592-606.

Tetrathiomolybdate (TTM) is a copper chelator that has also demonstrated
antiangiogenic, antifibrogenic and anti-inflammatory actions in preclinical
studies. The drug, from the University of Michigan was licensed to Pipex
Pharmaceuticals Inc for development for several indications; development of the
drug for cancer was later licensed to Attenuon LLC. In a phase III clinical
trial, TTM stabilized neurological function in patients with Wilson disease,
causing significant recovery in 81% of patients at 3 years post initiation of
therapy; a second phase III trial was ongoing at the time of publication. A phase
I/II clinical trial demonstrated the efficacy of TTM in patients with idiopathic
pulmonary fibrosis, and led the FDA to grant TTM Orphan Drug status for this
disease. Several phase II clinical trials had also been completed in patients
with various cancers, and revealed mixed efficacy. TTM was also assessed in a
phase I clinical trial for age-related macular degeneration, but the results
reported from the trial were negative; no further development has occurred for
this indication. TTM was assessed for the treatment of psoriasis in a phase II
clinical trial, but no data have been reported. At the time of publication, phase
II and phase III clinical trials were ongoing in patients with Alzheimer’s
disease and primary biliary cirrhosis, respectively. The most common clinical
side effects observed for TTM over the range of indications have been anemia,
neutropenia, leukopenia and transaminase elevations. These side effects were
generally resolved with either a dose adjustment or temporary suspension of the
dosing regimen. TTM is predicted to most likely find a niche in the therapy of
Wilson disease, for which current treatment options are limited.

[Molecular genetic basis of predisposition to psoriasis] [Article in Russian] Galimova ES, Akhmetova VL, Khusnutdinova EK. Genetika. 2008 May;44(5):594-605.

Psoriasis is one of the most common chronic inflammatory dermatopathies, which is
observed in 0.3-7% of the world population. Numerous twin-, familial- and
population-based studies suggest the involvement of genetic factors in the
disease development. The present review summarizes the present state of knowledge
and analyzes of the most recent findings in the molecular genetics of psoriasis.

A review of common dermatologic disorders of the external ear. Garvey C, Garvey K, Hendi A. J Am Acad Audiol. 2008 Mar;19(3):226-32.

Skin disorders of the external ear are common. Although audiologists will not
necessarily treat these conditions, it is important for them to be aware of these
disorders and refer patients to a specialist in some instances. This report
summarizes eight of the most commonly encountered skin conditions with an
emphasis on recognition and appropriate referral. The cutaneous disorders of the
external ear discussed in the article are divided into benign, premalignant, and
malignant groups.

Altered bone remodeling in psoriatic arthritis. Mensah KA, Schwarz EM, Ritchlin CT. Curr Rheumatol Rep. 2008 Aug;10(4):311-7.

Bone is a highly dynamic organ that interacts with a wide array of cells and
tissues. Recent studies have unveiled unanticipated connections between the
immune and skeletal systems, and this relationship led to the development of a
new field called osteoimmunology. This field will enable investigators to
translate basic science findings in bone biology to clinical applications for
inflammatory joint diseases such as psoriatic arthritis (PsA). This review
examines the disruption of bone homeostasis in PsA and discusses the pivotal role
of osteoclasts, osteoblasts, and signaling pathways in the altered remodeling
observed in this inflammatory arthritis. It also discusses the effects of tumor
necrosis factor inhibition on bone resorption and new bone formation in PsA.

MRI in psoriatic arthritis: insights into pathogenesis and treatment response. McQueen FM, Dalbeth N, Doyle A. Curr Rheumatol Rep. 2008 Aug;10(4):303-10.

Psoriatic arthritis (PsA) is a clinically heterogeneous condition, and not
surprisingly, its MRI features are diverse. Synovitis and accompanying synovial
effusions are clearly depicted, and enthesitis is characterized by extracapsular
inflammation at the insertions of ligaments and tendons plus accompanying bone
edema at bony attachments. Other forms of MRI bone edema include subchondral and
diaphyseal involvement; the latter seeming relatively specific to PsA. The
pathology of dactylitis can also be elucidated by MRI, which frequently reveals
tenosynovitis and soft tissue edema in conjunction with various degrees of
synovitis, bone edema, and erosion. Bone erosions differ from those seen in
rheumatoid arthritis in their distribution and associated features such as bone
proliferation and sometimes periostitis. Finally, MRI can be used to score and
quantify these pathologic features, providing a sensitive tool with which to
evaluate disease progression.

Th17 cells: a new paradigm for cutaneous inflammation. Asarch A, Barak O, Loo DS, Gottlieb AB. J Dermatolog Treat. 2008;19(5):259-66.

Inflammatory processes of the skin have classically been segregated to either the
cell-mediated, T-helper type 1 (Th1) or the humoral (Th2) branch of the immune
system. The recent addition of Th17 cells, a novel T-helper cell named for its
secretion of interleukin (IL)-17, to current thinking in autoimmunity has
resulted in a significant paradigm shift in immunological thinking. Collectively,
Th17 cytokines have been found to stimulate cutaneous immune reactions through an
activation of a wide range of downstream inflammatory mediators and an induction
of immune cell and keratinocyte proliferation as well as angiogenesis. Newly
developed treatment modalities for neutralizing the Th17 branch of the immune
system are proving to be valuable additions to the current therapeutic
armamentarium. Here we describe a new schema for dermatologic T-cell-mediated
immunity. We elucidate experiments confirming the presence of Th17 cells,
followed by a discussion of their relevance to cutaneous inflammation and
psoriasis.

Asymptomatic palmar pits: clinical evaluation of six cases and review of the literature. De D, Narang T, Dogra S, Kanwar AJ. J Cutan Med Surg. 2008 Jul-Aug;12(4):198-202.

BACKGROUND: Palmar pits are intriguing and are found in association with diverse
dermatologic conditions. Some are innocuous, whereas others have sinister
implications. OBJECTIVE: Six cases of asymptomatic palmar pits are described, and
the literature is reviewed in brief. METHOD AND RESULTS: Of the six patients,
five were male and one was female, with a mean age of 63.5 years. In all six
patients, the palmar pits were noticed incidentally during a cutaneous
examination for some other unrelated dermatoses, except in one in whom the pits
were the reason for visiting a dermatologist. The number of pits varied from one
to nine. Dupuytren contracture was observed in five patients. Sole involvement
was seen in only one patient. None had overlying hyperkeratosis or associated
symptoms relating to palmar pits. CONCLUSIONS: Palmar pits may have sinister
implications in conditions such as nevoid basal cell carcinoma syndrome or Cowden
syndrome. The association of palmar pits and Dupuytren contracture seems to be
common but is underreported. Palmar pits may be the clinical cutaneous sign of
systemic diseases and may sometimes provide a diagnostic clue to other
dermatoses. This report emphasizes the significance of the art of clinical
observation in dermatology.

Review and expert opinion on prevention and treatment of infliximab-related infusion reactions. Lecluse LL, Piskin G, Mekkes JR, Bos JD, de Rie MA. Br J Dermatol. 2008 Sep;159(3):527-36. Epub 2008 Jul 9.

Infliximab (Remicade; Schering-Plough, Kenilworth, NJ, U.S.A.) is a chimeric
monoclonal antibody that acts as a tumour necrosis factor-alpha inhibitor.
Infliximab is registered for the treatment of rheumatoid arthritis, psoriatic
arthritis, Crohn disease, ulcerative colitis, ankylosing spondylitis and
plaque-type psoriasis. Like other foreign protein-derived agents, infliximab may
lead to infusion reactions during and after infusion. Infusion reactions occur in
3-22% of patients with psoriasis treated with infliximab. Most of these reactions
are mild or moderate and only few are severe. Nevertheless, they may lead to
discontinuation of treatment. As infliximab for psoriasis is prescribed as a last
resort and is in most cases very effective, discontinuation of treatment is
undesirable. With proper care and prevention of the infusion reactions the need
to discontinue treatment with infliximab can be diminished. The objective of this
article is to present a guideline for the management of infliximab-related
infusion reactions, based on the best available evidence. This guideline can be
used in patients with psoriasis as well as in dermatology patients receiving
infliximab for off-label indications such as hidradenitis suppurativa or pyoderma
gangrenosum.

Efficacy and tolerability of biologic and nonbiologic systemic treatments for moderate-to-severe psoriasis: meta-analysis of randomized controlled trials. Schmitt J, Zhang Z, Wozel G, Meurer M, Kirch W. Br J Dermatol. 2008 Sep;159(3):513-26. Epub 2008 Jul 9.

BACKGROUND: The comparative efficacy and tolerability of conventional and
biologic treatments for moderate-to-severe plaque psoriasis are unknown.
OBJECTIVES: To perform a systematic review and meta-analysis of randomized
controlled trials (RCTs) reporting efficacy of systemic treatments approved for
moderate-to-severe psoriasis by means of the Psoriasis Area and Severity Index
(PASI). METHODS: We identified relevant articles by systematic electronic
searches (Cochrane Library, Medline, Embase, Scopus). Efficacy was defined as
proportion of participants with >or= 75% decrease in PASI (PASI-75) at primary
efficacy measurement (week 8-16). PASI-75 response rates of double-blind
placebo-controlled trials were summarized as risk differences (RDs) and pooled
using random effects models. Tolerability was assessed from rates of withdrawals
and adverse events. RESULTS: Twenty-four RCTs totalling 9384 patients were
analysed qualitatively. Sixteen double-blind placebo-controlled trials were
eligible for meta-analysis. Infliximab was significantly superior to all other
interventions [RD 77%, 95% confidence interval (CI) 72-81%]. Adalimumab (RD 64%,
95% CI 61-68%) was superior to ciclosporin (RD 33%, 95% CI 13-52%), efalizumab
(RD 24%, 95% CI 19-30%), etanercept 50 mg twice weekly (RD 44%, 95% CI 40-48%)
and etanercept 25 mg twice weekly (RD 30%, 95% CI 25-35%). Efalizumab was
significantly less efficacious than fumaric acid esters (RD 48%, 95% CI 32-64%).
Rates of withdrawals due to adverse events were highest for methotrexate and
fumaric acid esters. CONCLUSIONS: The efficacy of systemic agents approved for
moderate-to-severe psoriasis differs considerably both within and between
biologics and nonbiologics. Infliximab is most efficacious, followed by
adalimumab. Patients receiving infliximab have an excess chance of 77% over
placebo to achieve PASI-75 response. Published evidence questions regulatory
guidelines that recommend biologics as second-line therapy for moderate-to-severe
plaque psoriasis.

Clobetasol propionate emollient formulation foam in the treatment of corticosteroid-responsive dermatoses. Frangos JE, Kimball AB. Expert Opin Pharmacother. 2008 Aug;9(11):2001-7.

BACKGROUND: Topical corticosteroids are the most common treatment modality for
patients with psoriasis and atopic dermatitis; however, the efficacy of topical
corticosteroids is often hampered by barriers to patient adherence, such as lack
of efficacy, side effects and inconvenience. Recently published studies have
investigated the safety and efficacy of a novel emollient foam (EF) formulation
of clobetasol propionate (CP), a class I topical corticosteroid in psoriasis and
atopic dermatitis. OBJECTIVES: To summarize recent literature on CP EF foam, and
to evaluate recent Phase II and III clinical trials of CP EF foam in psoriasis
and atopic dermatitis. METHODS: The MEDLINE (1950 – January 2008) database was
searched using the following terms: ‘clobetasol propionate foam’, ‘topical
corticosteroids’, ‘topical glucocorticoids’, ‘psoriasis’ and ‘atopic dermatitis’.
Results were evaluated for relevance and quality, and additional references were
obtained from bibliographies of selected articles. CONCLUSION: CP EF foam appears
to be safe and effective for corticosteroid-responsive dermatoses in adults and
children > or = 12 years of age. As compared to its hydroethanolic foam
predecessor, CP EF presents a potential advance for patients who are less likely
to tolerate alcohol-based foam. As alcohol-based foams can be irritating and
cause stinging in non-hair-bearing areas, this new emollient formulation has the
potential to widen the use of CP foam to more patients with atopic dermatitis and
to more non-scalp body sites in patients with psoriasis.

Th17 cells: a new therapeutic target in inflammatory dermatoses. Asarch A, Barak O, Loo DS, Gottlieb AB. J Dermatolog Treat. 2008;19(6):318-26.

Th17 cells, named for their secretion of interleukin-17 (IL-17), are a new class
of T-cells involved in a wide range of cutaneous autoimmune and inflammatory
conditions. An overactive Th17 cell response in the skin can produce damaging
results. There appears to be a partial role for the Th17 axis in the pathogenesis
of a range of dermatological diseases including allergic contact dermatitis,
atopic dermatitis, psoriasis, and scleroderma. Immunologists have also discovered
a unique association between Th17 cells and cutaneous T-cell lymphoma. The Th17
branch has been linked to a number of additional systemic inflammatory diseases
with significant cutaneous pathology such as systemic lupus erythematosus,
rheumatoid arthritis, inflammatory bowel disease, and Behcet’s disease. Newly
developed treatment modalities for neutralizing the Th17 branch of the immune
system are proving to be valuable additions to the current therapeutic
armamentarium.

An updated review of acitretin–a systemic retinoid for the treatment of psoriasis. Pang ML, Murase JE, Koo J. Expert Opin Drug Metab Toxicol. 2008 Jul;4(7):953-64.

BACKGROUND: Acitretin is a systemic retinoid used for psoriasis. It normalizes
cellular differentiation and maturation and is also used as a chemopreventive
agent against cutaneous malignancies. However, it is not used frequently because
of its side-effect profile. OBJECTIVE: Safety and efficacy of acitretin was
evaluated as monotherapy, as well as in combination with other systemic agents.
METHODS: Medical literature from 2005 to 2008 was reviewed. The most
scientifically rigorous clinical trials were selected for Psoriasis Area and
Severity Index. Articles were limited to case reports or clinical trials, human
subjects and English language journals. RESULTS/CONCLUSION: Acitretin is
effective as monotherapy for pustular and erythrodermic psoriasis and for plaque
psoriasis (with other systemic agents). Side effects of acitretin use occur more
commonly with high doses. Hence, acitretin is safe and effective for psoriasis.

[Immune activation and depression in the elderly] [Article in Dutch] Maas DW, Westendorp RG, van der Mast RC. Ned Tijdschr Geneeskd. 2008 Jun 21;152(25):1413-7.

Besides the monoamine hypothesis, the stress hypothesis and the vascular
hypothesis, the inflammatory hypothesis might be an etiological explanation for
late-life depression. There is a growing amount of evidence to support this
hypothesis. In animal studies, injection with cytokines was shown to cause
behavioural changes (’sickness behaviour’) similar to depressive symptoms in
humans. Cytokine treatment of certain tumours and chronic hepatitis can also
cause depressive symptoms. The prevalence of depression in patients with
autoimmune diseases is higher than in the general population. Etanercept had a
favourable effect on the depressive symptoms in patients with psoriasis,
independent of improvement of physical symptoms. Cytokines affect the
hypothalamus-pituitary-adrenal axis and cerebral neurotransmitter systems, both
of which are thought to be involved in depression. Immune activation has been
associated with depression, and several anti-depressive treatments affect immune
parameters, although inconsistently. Since the aging process is associated with a
dysregulation of the immune system, the inflammation hypothesis might be
particularly true in late-life depression.

New insights and therapies for teenage psoriasis. Belazarian L. Curr Opin Pediatr. 2008 Aug;20(4):419-24.

PURPOSE OF REVIEW: Psoriasis is an important disorder in the adolescent
population and has a tremendous physical and psychological impact on patients. It
is important to understand the genetics, various clinical presentations,
comorbidities, and treatment options associated with psoriasis. RECENT FINDINGS:
The human leukocyte antigen-C gene likely contains a susceptibility locus for
psoriasis. Cytokines interleukin-12 and interleukin-23 have been implicated in
the pathogenesis of psoriasis as well. Psoriasis is likely associated with an
increased risk of myocardial infarction, metabolic syndrome, Crohn’s disease, and
depression; it is difficult to assess the implications in the adolescent
population. SUMMARY: Psoriasis is not rare in the adolescent population. It is
important for physicians to be aware of the different clinical presentations as
well as the spectrum of treatment options that are available.

Development of TLR inhibitors for the treatment of autoimmune diseases. Barrat FJ, Coffman RL. Immunol Rev. 2008 Jun;223:271-83.

SUMMARY: The innate immune system is a critical element of protection from
invading pathogens. The specific receptors that recognize various components of
the pathogens trigger signals that result in the production of proinflammatory
cytokines as well as the activation of antigen-presenting cells, which activate
the adaptive immune system. The discovery of the Toll-like receptors (TLRs) as
important components of pathogen recognition has brought new understanding of the
key signaling molecules involves in innate immune activation. Interestingly, it
appears that most TLRs can recognize self-ligands as well and that mechanisms are
required to discriminate between self and non-self ligands. One of these
mechanisms is the expression of all the nucleic acid-specific TLR in endosomal
compartments and not on the cell surface. Inappropriate activation of TLRs by
self-components can result in sterile inflammation or autoimmunity. For example,
TLR7 and TLR9 activation by endogenous RNA and DNA, transported to the endosomes
in the form of immune complexes or non-covalently associated with cationic
peptides, could be an important mechanism involved in promoting diseases such as
systemic lupus erythematosus and psoriasis. In this review, we discuss the
rationale for self-recognition by TLR7 and TLR9 as an important part of the
development of lupus and other autoimmune diseases. We describe novel inhibitors
of these receptors and provide evidence to support their use as novel therapeutic
agents for autoimmunity.

Th17 cells in human disease. Tesmer LA, Lundy SK, Sarkar S, Fox DA. Immunol Rev. 2008 Jun;223:87-113.

SUMMARY: Our understanding of the role of T cells in human disease is undergoing
revision as a result of the discovery of T-helper 17 (Th17) cells, a unique
CD4(+) T-cell subset characterized by production of interleukin-17 (IL-17). IL-17
is a highly inflammatory cytokine with robust effects on stromal cells in many
tissues. Recent data in humans and mice suggest that Th17 cells play an important
role in the pathogenesis of a diverse group of immune-mediated diseases,
including psoriasis, rheumatoid arthritis, multiple sclerosis, inflammatory bowel
disease, and asthma. Initial reports also propose a role for Th17 cells in
tumorigenesis and transplant rejection. Important differences, as well as many
similarities, are emerging when the biology of Th17 cells in the mouse is
compared with corresponding phenomena in humans. As our understanding of human
Th17 biology grows, the mechanisms underlying many diseases are becoming more
apparent, resulting in a new appreciation for both previously known and more
recently discovered cytokines, chemokines, and feedback mechanisms. Given the
strong association between excessive Th17 activity and human disease, new
therapeutic approaches targeting Th17 cells are highly promising, but the
potential safety of such treatments may be limited by the role of these cells in
normal host defenses against infection.

Antimicrobial peptides and self-DNA in autoimmune skin inflammation. Gilliet M, Lande R. Curr Opin Immunol. 2008 Aug;20(4):401-7. Epub 2008 Jul 24.

Toll-like receptor (TLR)-mediated detection of viral nucleic acids and production
of type I interferons (IFNs) by plasmacytoid dendritic cells (pDCs) are key
elements of antiviral defense. By contrast, inappropriate recognition of
self-nucleic acids with induction of IFN responses in pDCs can lead to
autoimmunity. In this review we describe how pDC responses to self-DNA are
normally avoided and focus on our recent finding that in psoriasis, a common
autoimmune disease of the skin, these barriers can be breached by the cationic
antimicrobial peptide LL37. LL37 binds extracellular self-DNA fragments into
aggregated particles that enter pDCs and trigger robust IFN responses by
activating endosomal TLR9 as if they were viruses. We also describe the
mechanisms that normally control production and activity of LL37 in human skin
and propose that the persistent overexpression of LL37 in psoriasis leads to
uncontrolled IFN responses that drive autoimmune skin inflammation.

[The biological treatments for moderate to severe plaque psoriasis] [Article in French] Thielen AM, Marazza G. Rev Med Suisse. 2008 Apr 30;4(155):1089-90, 1092-4.

Psoriasis is a chronic inflammatory skin disorder that can cause substantial
disability. The recognition of psoriasis as an immunologically mediated disease
led to the development of agents that specifically target key steps in the
pathological process. In this review, we focus on the mechanism of action, the
efficacy and the safety data of the new biological treatments: alefacept,
efalizumab, etanercept, infliximab and adalimumab.

Genetics of psoriasis and psoriatic arthritis: update and future direction. Duffin KC, Chandran V, Gladman DD, Krueger GG, Elder JT, Rahman P. J Rheumatol. 2008 Jul;35(7):1449-53.

Psoriasis and psoriatic arthritis (PsA) both have substantive genetic
determinants. Numerous candidate regions and genes have now been replicated in
disease susceptibility, and to a lesser extent in disease expression, in both
disease entities. Intensive efforts are now under way or are being planned to
perform genome-wide association scans (GWAS) in psoriasis and PsA. A major
determinant of success for GWAS is likely to be accumulation of multiple large
well-phenotyped cohorts, sophisticated data management, and verification of the
findings. At the 2007 Annual Meeting of the Group for Research and Assessment of
Psoriasis and Psoriatic Arthritis (GRAPPA), members of the GRAPPA genetics
committee presented a discussion of the genetics of psoriasis and PsA, including
future trends. This article is a summary of that presentation and a review of the
literature.

Biological biomarkers in psoriatic disease. A review. de Vlam K, Gottlieb AB, Fitzgerald O. J Rheumatol. 2008 Jul;35(7):1443-8.

Biomarkers are important in clinical practice because they allow quantitative
assessment of diagnosis, disease processes, and treatment response. However,
because development of biomarkers lags significantly behind that of drug
development, absence of new and appropriate markers may slow the development of
patient-tailored targeted therapies. At the 2007 Annual Meeting of the Group for
Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), members of
the biomarker committee discussed the possible use of biomarkers in psoriasis and
psoriatic arthritis and reviewed the results of several studies of biomarkers in
the pathogenesis, diagnosis, and treatment of both the inflammatory and
dermatologic aspects of psoriatic disease. We review those discussions.

Clues to the pathogenesis of psoriasis and psoriatic arthritis from imaging: a literature review. Coates LC, Anderson RR, Fitzgerald O, Gottlieb AB, Kelly SG, Lubrano E, McGonagle DG, Olivieri I, Ritchlin CT, Tan AL, De Vlam K, Helliwell PS. J Rheumatol. 2008 Jul;35(7):1438-42.

This article summarizes a presentation on imaging of skin and joints in patients
with psoriasis and psoriatic arthritis (PsA) from the 2007 Annual Meeting of the
Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).
Plain radiography provides valuable insights into the pathogenesis of PsA but is
limited because only calcified tissue can be imaged. Newer techniques such as
magnetic resonance imaging (MRI) and ultrasound (US) provide additional clues to
the pathogenesis of this peripheral, axial, and dermatologic disease. MRI and to
a lesser extent US allow visualization of articular and periarticular structures,
showing widespread juxtaarticular inflammation in PsA. Bone edema, a surrogate
marker of inflammation, can occur throughout the digit in psoriatic dactylitis.
Localization of inflammatory change at the juxtaarticular entheses suggests this
as the primary site of inflammation. Recent imaging studies provide insights into
the relationship between nail and articular disease, demonstrating extension of
inflammation from entheseal structures at the distal interphalangeal joint to the
nail bed, but the temporal or anatomical progression of these changes remains
elusive. Imaging of the skin lags behind that of the articular structures, partly
because the skin is readily available for biopsy; however, newer techniques such
as laser Doppler imaging provide insights into angiogenesis at the advancing edge
of psoriatic plaques. Future work will explore the relationship between
immunohistology and imaging of skin and joints. Improvements in imaging articular
soft tissues with ultra-short echo time MRI and skin with multiphoton
fluorescence microscopy promise insights into anatomical and functional changes.

From skin to bone: translational perspectives on psoriatic disease. Ritchlin CT. J Rheumatol. 2008 Jul;35(7):1434-7.

In recent years, translational research has provided fresh insights into the
mechanisms that underlie both skin and joint inflammation in psoriatic arthritis
(PsA). Application of immunological and molecular techniques to the study of
involved tissues, combined with magnetic resonance imaging and relevant
preclinical models, has unveiled pivotal inflammatory cascades and cytokine
networks that lead to sustained inflammation and altered tissue architecture. In
this brief overview of a presentation from the 2007 Annual Meeting of the Group
for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) the key
pathophysiologic events associated with inflammation in psoriatic plaques,
synovial membranes, and soft tissues (entheses, tendons), and with abnormal bone
remodeling are discussed.

[Biological therapy for the treatment of rheumatic diseases] [Article in German] Pierer M, Baerwald C. Internist (Berl). 2008 Aug;49(8):938-46.

The analysis of cytokines (i.e. interleukins, interferons and colony-stimulating
factors) has only flourished in the last 25 years subsequently revealing new
insights into the pathogenesis of rheumatic diseases that revolutionised the
management of patients with chronic rheumatic disorders. Tumour necrosis
factor-alpha (TNF-alpha), interleukin-1 (IL-1) and interleukin-6 (IL-6) have been
found to play a pivotal role in rheumatic inflammation. As early as in 1992 the
first proof of concept study with a monoclonal antibody against TNF was able to
demonstrate positive effects in rheumatoid arthritis. Since the approval of the
first anti-TNF-alpha therapy, further agents against TNF and other
proinflammatory cytokines were approved and even more biological drugs are under
development aimed at modulating the disturbed immune system in patients with
rheumatic diseases. To date the following biologics are approved for therapy of
chronic rheumatic diseases: the TNF antagonists Etanercept, Infliximab and
Adalimumab; Anakinra as an IL-1 receptor antagonist; the anti-CD20 monoclonal
antibody Rituximab and the anti-CD80/86 fusion protein Abatacept. In the present
article, we report on biological therapy modalities in rheumatic diseases as well
as the recommendations for initiation of these agents.

Review paper: preclinical models of psoriasis. Danilenko DM. Vet Pathol. 2008 Jul;45(4):563-75.

Psoriasis is the most common autoimmune disease in man and is characterized by
focal to coalescing raised cutaneous plaques with consistent scaling and variable
erythema. The specific pathogenesis of psoriasis is not completely understood,
but the underlying mechanisms involve a complex interplay between epidermal
keratinocytes, T lymphocytes as well as other leukocytes (including dendritic
cells and other antigen presenting cells [APCs]), and vascular endothelium.
Mirroring the complexity of mechanisms that underlie psoriasis, there are a
relatively large number of models of psoriasis. Each model is based on a slightly
different pathogenic mechanism, and each has its similarities to psoriasis as
well as its limitations. In general, psoriasis models can be very broadly divided
on the basis of the pathogenic mechanisms that interplay to cause psoriasis, with
the addition of several relatively poorly defined spontaneous murine mutant
models. Other than the spontaneous mutant models, murine models of psoriasis can
be divided into those that are genetically engineered (transgenic and
knockout-with manipulation of either the epidermis, leukocytes, or the
endothelium), and those that are induced (either by immune transfer or by
xenotransplantation of skin from psoriatic patients). In addition to the murine
models, in vitro human epidermal models have recently become more widely
utilized. While no one single model of psoriasis is ideal, many have proven to be
extremely valuable in investigating and better understanding the molecular
mechanisms that underlie the complex interplay between epidermal keratinocytes,
the innate and adaptive immune system, and the vascular endothelium in psoriasis.

Congenital psoriasis: case report and literature review. Lehman JS, Rahil AK. Pediatr Dermatol. 2008 May-Jun;25(3):332-8.

While childhood psoriasis is fairly common, congenital psoriasis appears to be
rare and has not been well characterized. We present a patient with
histologically confirmed congenital psoriasis. By reviewing the literature, we
aim to both define this disease and compare it to infantile and childhood
psoriasis. Electronic searches found articles reporting patients with
biopsy-proven congenital psoriasis. We recorded clinical features, such as family
history, anatomic involvement, and disease severity. We compared these data with
previous descriptions of infantile and childhood psoriasis. We included nine
patients with congenital psoriasis in our analysis. No patient had a first-degree
family history of psoriasis. While the face, scalp, chest, and trunk were
frequently involved, the buttocks generally were spared. Several patients had
persistent disease despite therapy. In this series, congenital psoriasis differed
from infantile and childhood psoriasis in several respects. Specifically,
congenital psoriasis was associated with a lower prevalence of relevant family
history, which could increase over time, and a different pattern of anatomic
involvement, which may reflect exposure to age-associated environmental factors.
Although several patients with congenital psoriasis had severe disease, this
likely represents publication bias. Additional reports of congenital psoriasis
with extended follow-up are needed to better characterize this condition.

Psoriatic skin lesions induced by tumor necrosis factor antagonist therapy: a literature review and potential mechanisms of action. Collamer AN, Guerrero KT, Henning JS, Battafarano DF. Arthritis Rheum. 2008 Jul 15;59(7):996-1001.

OBJECTIVE: Numerous reports of the induction or worsening of psoriasis in
patients treated with tumor necrosis factor (TNF) antagonists indicate that this
is not a rare phenomenon. The etiology of this paradoxical clinical response
remains unclear. The aim of this study was to describe similar cases, conduct a
comprehensive analysis of the literature, explore possible immunologic mechanisms
of action of this perplexing reaction, and recommend management options. METHODS:
A systematic literature review was performed using the PubMed and Medline
databases (1996 to September 2007) searching the index terms “infliximab,”
“etanercept,” “adalimumab,” “tumor necrosis factor alpha inhibitor,” and “TNF
inhibitor,” combined with the terms “psoriasis,” “pustular,” “skin,” “rash,” and
“palmoplantar.” All relevant articles in English were reviewed. Pertinent
secondary references were also analyzed. RESULTS: According to the literature,
new-onset psoriasis may occur any time after initiation of TNF antagonist
therapy, is often of an uncommon morphology, may respond to psoriasis treatments,
and usually resolves with TNF discontinuation. The pathogenesis of this response
appears to involve a disruption in cytokine balance following TNF inhibition,
resulting in the up-regulation of plasmacytoid dendritic cells and the subsequent
production of unopposed interferon-alpha, following a triggering event in
predisposed individuals. CONCLUSION: TNF antagonist-induced psoriasis is a newly
recognized adverse effect of these medications that typically does not require
therapy cessation. We recommend aggressive treatment of the skin disease and
consideration of a change in the TNF antagonist if the lesions are unresponsive
to conventional psoriasis treatment.

The vitamin D pathway: a new target for control of the skin’s immune response? Schauber J, Gallo RL. Exp Dermatol. 2008 Aug;17(8):633-9. Epub 2008 Jun 28.

The surface of our skin is constantly challenged by a wide variety of microbial
pathogens, still cutaneous infections are relatively rare. Within cutaneous
innate immunity the production of antimicrobial peptides (AMPs) is a primary
system for protection against infection. Many AMPs can be found on the skin, and
these include molecules that were discovered for their antimicrobial properties,
and other peptides and proteins first known for activity as chemokines, enzymes,
enzyme inhibitors and neuropeptides. Cathelicidins were among the first families
of AMPs discovered on the skin. They are now known to have two distinct
functions; they have direct antimicrobial activity and will initiate a host
cellular response resulting in cytokine release, inflammation and angiogenesis.
Dysfunction of cathelicidin is relevant in the pathogenesis of several cutaneous
diseases including atopic dermatitis where cathelicidin induction is suppressed,
rosacea, where cathelicidin peptides are abnormally processed to forms that
induce cutaneous inflammation and a vascular response, and psoriasis, where a
cathelicidin peptide can convert self-DNA to a potent stimulus of an
autoinflammatory cascade. Recent work has unexpectedly identified vitamin D3 as a
major factor involved in the regulation of cathelicidin expression. Therapies
targeting the vitamin D3 pathway and thereby cathelicidin may provide new
treatment modalities in the management of infectious and inflammatory skin
diseases.

[Photosensitizing anticancer tetrapyrroles: or how photophysics becomes a mechanism of action] [Article in French] Prognon P, Kasselouri A, Desroches M, Blais J, Maillard P.Ann Pharm Fr. 2008 Mar;66(2):71-6. Epub 2008 May 27.

The macrocyclic tetrapyrrole derivatives used for the treatment of certain solid
tumors include porphyrins and their chlorine and bacteriochlorin derivatives.
These are highly conjugated, rigid molecules characterized by a strong absorbance
in the spectral domain from near ultra-violet to far red (350-750 nm). The
combination of tetrapyrroles plus light is called dynamic phototherapy (DPT).
This combination transforms the molecule to its triplet form which by
deactivation generates free radicals and a singlet oxygen from molecular oxygen,
causing tumor destruction. Tetrapyrroles are thus, with psoralens, used for the
treatment of psoriasis. They are the only drugs whose mechanism of action results
exclusively from their electronic and photophysical spectroscopic
characteristics. This class of anticancer agents is usually free of any specific
cytotoxic effect. We describe here the current elements linking structure and
spectroscopy and observations leading to the design of compounds with strong
tumor selectivity and optimal cytotoxic properties.

How to manage infections in the era of biologics? Saraceno R, Chimenti S. Dermatol Ther. 2008 May-Jun;21(3):180-6.

Biologic agents are immunosuppressants that target cytokines or specific immune
cell subpopulations. Many therapies interfere with the normal inflammatory
cascade and with the immune system, causing an increase in the incidence of
infections. In particular, treatment with tumor necrosis factor (TNF)-alpha
antagonists in psoriasis patients is associated with an increased risk of
infection caused by intracellular microorganisms. TNF-alpha plays an important
role in host resistance against infectious and several cases of Mycobacterium
tuberculosis, Listeria monocytogenes, and Pneumocystis carinii have been reported
with anti-TNF-alpha agents. Furthermore, B and T cells are essential to the
immune response; thus, their specific reduction or inhibition by targeting
molecules in T-cell cutaneous lymphomas and psoriasis could increase the risk for
viral, fungal, and bacterial infections. A prompt and appropriate management of
infections with the emergence of biologics is essential in clinical practice.

Research in practice: the systemic aspects of psoriasis. [Article in English, German] Boehncke WH, Boehncke S. J Dtsch Dermatol Ges. 2008 Aug;6(8):622-5. Epub 2008 Jun 16.

Psoriasis is a common, chronic inflammatory and frequently severe skin disease.
Recent epidemiologic studies have documented an increased cardio-vascular
mortality in psoriasis patients. Our own work focuses on endothelial cells as
mediators for the development of inflammatory infiltrates and more recently as a
victim of injury caused by infiltrating cells. In this context, we have measured
systemic effects of this seemingly cutaneous inflammation, which results in a
metabolic state much like that in patients developing diabetes mellitus and
insulin resistance. The latter is an important pathomechanism causing endothelial
cell dysfunction and subsequently cardiovascular diseases such as myocardial
infarction or stroke. Co-morbidities observed in psoriatic patients therefore
represent complications of the accompanying systemic inflammation and are likely
to be mediated through the mechanism of insulin resistance. As psoriasis is a
risk factor for cardiovascular diseases, its adequate management must include the
treatment of other known risk factors. Dermatologists should discuss the elevated
cardiovascular risk with their psoriasis patients and encourage them not to smoke
and to normalize their body weight.

Psoriasis and the metabolic syndrome. Gottlieb AB, Dann F, Menter A. J Drugs Dermatol. 2008 Jun;7(6):563-72.

Psoriasis is a chronic immune-inflammatory-mediated disease that can predispose
patients to other inflammatory conditions. For example, individuals with
psoriasis are at increased risk for insulin resistance, obesity, dyslipidemia,
and hypertension–components that characterize the metabolic syndrome. The
metabolic syndrome is an important driver of adverse cardiovascular outcomes.
Proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), and
other factors that are overproduced in patients with psoriasis likely contribute
to the increased risk for development of metabolic syndrome. This article reviews
the association of psoriasis with metabolic syndrome, as well as the impact of
biologic agents that are currently used to treat psoriasis (ie, TNF antagonists)
on risk factors for metabolic syndrome.

Animal models of psoriasis: a critical appraisal. Schön MP. Exp Dermatol. 2008 Aug;17(8):703-12. Epub 2008 Jun 28.

Although there is no naturally occurring disorder in laboratory animals that
mimics the complex phenotype of psoriasis, a large number of spontaneous or
genetically engineered mutations in rodents, immunological reconstitution
approaches or xenotransplantation models have shed light on specific aspects
implicated in the pathophysiology and therapy of psoriasis. Animal models have
helped to elucidate functions of inflammatory mediators or to unravel the
contribution of innate or adaptive immune mechanisms, keratinocytes or
endothelial cells to chronic hyperproliferative inflammatory skin disorders.
However, given that several distinct manipulations of molecular pathways,
resident cutaneous cell types or immigrating immunocytes result in remarkably
similar phenotypes in experimental animals, it appears that interfering with
cutaneous homeostasis in general may ultimately initiate a rather uniform
reaction pattern that mirrors some features of psoriasis. This limitation of
animal models generated without the use of human material may, at least in part,
be overcome by xenotransplantation of human skin onto immunocompromised animals.
The latter approach has been employed in preclinical investigations to study the
role of immune cells and/or to predict the efficacy of some therapeutic
compounds. This brief review delineates approaches to generate animal models of
psoriasis and discusses their strengths and limitations for psoriasis research.

Beyond wavy hairs: the epidermal growth factor receptor and its ligands in skin biology and pathology. Schneider MR, Werner S, Paus R, Wolf E. Am J Pathol. 2008 Jul;173(1):14-24. Epub 2008 Jun 13.

The epidermal growth factor receptor (EGFR) network, including its seven ligands
and four related receptors, represents one of the most complex signaling systems
in biology. In many tissues, including the skin and its appendages (notoriously
the hair follicles), its correct function is necessary for proper development and
tissue homeostasis, and its deregulation rapidly results in defects in cellular
proliferation and differentiation. The consequences are impaired wound healing,
development of psoriasis-like lesions, structural and functional defects of the
hair follicles, and tumorigenesis. In addition to in vitro experiments and data
from clinical studies, several genetically modified mouse models displaying
alterations in the interfollicular skin and hair follicles attributable to
mutations in components of the EGFR system have been reported. These animals, in
many cases representing bona fide models of known human diseases, have been
seminal in the study of the role of EGFR and its ligands in the skin and its
appendages. In this review, we take the multiple phenotypes of these animal
models as a basis to summarize and discuss the effects elicited by members of the
EGFR system in diverse aspects of skin biology and pathology, including cellular
proliferation and differentiation, wound healing, hair follicle morphogenesis,
and tumorigenesis.

Vitamin D analogs: therapeutic applications and mechanisms for selectivity. Brown AJ, Slatopolsky E. Mol Aspects Med. 2008 Dec;29(6):433-52. Epub 2008 May 1.

The vitamin D endocrine system plays a central role in mineral ion homeostasis
through the actions of the vitamin D hormone, 1,25-dihydroxyvitamin D(3)
[1,25(OH)(2)D(3)], on the intestine, bone, parathyroid gland, and kidney. The
main function of 1,25(OH)(2)D(3) is to promote the dietary absorption of calcium
and phosphate, but effects on bone, kidney and the parathyroids fine-tune the
mineral levels. In addition to these classical actions, 1,25(OH)(2)D(3) exerts
pleiotropic effects in a wide variety of target tissues and cell types, often in
an autocrine/paracrine fashion. These biological activities of 1,25(OH)(2)D(3)
have suggested a multitude of potential therapeutic applications of the vitamin D
hormone for the treatment of hyperproliferative disorders (e.g. cancer and
psoriasis), immune dysfunction (autoimmune diseases), and endocrine disorders
(e.g. hyperparathyroidism). Unfortunately, the effective therapeutic doses
required to treat these disorders can produce substantial hypercalcemia. This
limitation of 1,25(OH)(2)D(3) therapy has spurred the development of vitamin D
analogs that retain the therapeutically important properties of 1,25(OH)(2)D(3),
but with reduced calcemic activity. Analogs with improved therapeutic indices are
now available for treatment of psoriasis and secondary hyperparathyroidism in
chronic kidney disease, and research on newer analogs for these indications
continues. Other analogs are under development and in clinical trials for
treatment of various types of cancer, autoimmune disorders, and many other
diseases. Although many new analogs show tremendous promise in cell-based models,
this article will limit it focus on the development of analogs currently in use
and those that have demonstrated efficacy in animal models or in clinical trials.

Systemic therapy for psoriasis. Lee M, Kalb RE. Dermatol Nurs. 2008 Apr;20(2):105-11; quiz 112.

Psoriasis therapy has changed dramatically in the past decade with the
introduction of biologic therapy. The treatment of moderate to severe psoriasis
is reviewed. Phototherapy, conventional systemic therapy, and biologic therapy
are discussed including practical tips for administering each agent. Overall
approaches to treatment are discussed along with special circumstances where
individual therapies have advantages.

Safety and efficacy of alefacept, efalizumab, etanercept and infliximab in treating moderate to severe plaque psoriasis: a meta-analysis of randomized controlled trials. Brimhall AK, King LN, Licciardone JC, Jacobe H, Menter A. Br J Dermatol. 2008 Aug;159(2):274-85. Epub 2008 Jun 10.

BACKGROUND: The relatively recent introduction of biological agents to treat
psoriasis presents clinicians with the need to objectively compare and contrast
these agents to allow more effective treatment of their patients. OBJECTIVES: To
evaluate and compare the efficacy and safety of biological agents in the
treatment of plaque psoriasis. METHODS: (i) DATA SOURCES: Four parallel
systematic reviews conducted through July 2006, including peer-reviewed data and
U.S. Food and Drug Administration (FDA) reports. (ii) STUDY SELECTION:
Randomized, controlled, double-blind, monotherapy trials of alefacept (n = 3),
efalizumab (n = 5), etanercept (n = 4) and infliximab (n = 4); 16 studies
comprising 7931 patients met inclusion criteria. (iii) DATA EXTRACTION: Efficacy
was measured by Psoriasis Area and Severity Index (PASI) 75 achievement after
10-14 weeks of treatment, using intention-to-treat analysis. Safety was evaluated
by the incidence of one or more adverse event(s) (AEs) and serious adverse
event(s) (SAEs) during 10-30 weeks of treatment. RESULTS: Pooled relative risk
(RR) and number needed to treat (NNT) of PASI 75 achievement compared with
placebo was computed using Mantel-Haenszel methods and the random effects model.
All biological agents for psoriasis were efficacious (P < 0.001); however, there
was a graded response for achievement of PASI 75: infliximab (RR = 17.40, NNT =
2), etanercept (RR = 11.73, NNT = 3), efalizumab (RR = 7.34, NNT = 4) and
alefacept (RR = 3.70, NNT = 8). The risk of one or more AEs was evaluated by RR
and number needed to harm (NNH). This was increased in the alefacept (RR = 1.09,
P = 0.03, NNH = 15), efalizumab (RR = 1.15, P < 0.001, NNH = 9) and infliximab
(RR = 1.18, P < 0.001, NNH = 9) groups compared with placebo. SAEs were increased
in a sensitivity analysis of four efalizumab trials (n = 2443, RR = 1.92, P =
0.03, NNH = 60). CONCLUSIONS: The decreasing rank order for pooled efficacy was
infliximab, etanercept, efalizumab and alefacept when compared with placebo.
Pooling safety data revealed a previously unreported increased risk of AEs for
alefacept, efalizumab and infliximab.

Psoriasis and metabolic disease: epidemiology and pathophysiology. Azfar RS, Gelfand JM. Curr Opin Rheumatol. 2008 Jul;20(4):416-22.

PURPOSE OF REVIEW: The scientific literature linking psoriasis to metabolic
syndrome, and its components, as well as atherosclerosis and myocardial
infarction has rapidly expanded. Increasingly, epidemiological studies are
establishing the directionality of these associations and psoriasis' role as an
independent risk factor in developing these outcomes. RECENT FINDINGS: Psoriasis
is associated with metabolic syndrome, and its components, such as obesity,
diabetes, and hypertension. Obesity has been shown to be an independent risk
factor for the development of psoriasis, and is also associated with more severe
psoriasis. Psoriasis is associated with diabetes, coronary artery disease, and an
increased risk for myocardial infarction independent of traditional risk factors
for these disorders. These phenotypically diverse conditions share similar
pathologic changes such as chronic inflammation, angiogenesis, oxidative stress,
and selected susceptibility genes and loci. SUMMARY: The broad literature linking
psoriasis to metabolic disorders has led to changes in standard of care
recommendations for patients with psoriasis. In particular, practitioners are
encouraged to screen psoriasis patients, especially when disease is severe, for
metabolic disorders and cardiovascular risk factors and institute appropriate
prevention strategies. Additional studies investigating the role of psoriasis
activity and severity as an independent risk factor for developing metabolic
disorders, atherosclerosis, and myocardial infarction and the role of psoriasis
treatment in altering the risk of developing these serious morbidities are
urgently needed.

The pathobiology of psoriatic synovium. Boyle DL, Kavanaugh A. Curr Opin Rheumatol. 2008 Jul;20(4):404-7.

PURPOSE OF REVIEW: Psoriatic arthritis pathogenesis is incompletely understood
and the pathophysiologic role of the synovium is only beginning to be elucidated.
Currently, approaches similar to those applied to rheumatoid arthritis are being
applied to psoriatic arthritis synovia. RECENT FINDINGS: Synovitis is being
re-examined along with efforts to better characterize the clinical phenotype and
improve patient stratification. The dermatological perspective brings an
alternative view of autoimmunity and the role of innate immunity. A pathogenetic
basis for the differing roles of skin and synovium is suggested by a landmark
animal study that demonstrated a psoriasis-like skin disease coupled with a T
cell and B cell dependent arthritis. The histopathology of the synovio-entheseal
complex has been described. Systematic methods for evaluating synovitis have been
developed and cross-sectional evaluations of psoriatic arthritis synovia in the
context of other arthritides have been performed. Fresh looks at psoriatic
arthritis synovia suggest similarity to rheumatoid arthritis synovia. SUMMARY:
Research into the pathophysiology of psoriatic arthritis is at an early, yet
promising stage. Instruments are being developed to characterize and stratify
psoriatic arthritis. The role of synovia remains unclear, but we now have a
better understanding of the pathology of innate and adaptive immunity and are
reminded that psoriatic arthritis is a systemic disease.

Leukocyte adhesion molecules in animal models of inflammatory bowel disease. Rivera-Nieves J, Gorfu G, Ley K. Inflamm Bowel Dis. 2008 Dec;14(12):1715-35.

The dysregulated recruitment of leukocytes into the intestine is required for the
initiation and maintenance of inflammatory bowel disease (IBD). Several families
of molecules regulate the influx of these cells into sites of inflammation.
Interference with some of these molecules has already shown efficacy in the
clinics and antibodies that target the molecules involved have been approved by
the FDA for use in Crohn's disease (CD), multiple sclerosis (i.e., natalizumab),
and psoriasis (i.e., efalizumab). Here, we discuss basic aspects of the different
families of relevant molecules and compile a large body of preclinical studies
that supported the targeting of specific steps of the leukocyte adhesion cascade
for therapeutic purposes in colitis and in novel models of CD-like ileitis.

Topical therapy for the management of childhood psoriasis: part I. Cordoro KM. Skin Therapy Lett. 2008 Apr;13(3):1-3.

Psoriasis represents a potentially life-altering disease that can profoundly
impact physical, emotional and social functioning, and overall quality of life.
The majority of cases are mild and managed adequately with topical medications. A
minor subset of children present with severe, rapidly evolving disease that
requires systemic therapy. The choice of treatment in children, as in adults, is
determined by disease acuity, morphology, distribution, severity and the presence
of comorbidities such as psoriatic arthropathy. Practical considerations such as
ease of use, patient acceptability, accessibility, risk to benefit ratio, cost
and individual perceptions of disease and quality of life are factored into
treatment decisions. Part I of this 2-part series will focus on topical agents,
their varying degrees of effectiveness, potential side-effects and applications
in clinical practice.

The nexus between atopic disease and autoimmunity: a review of the epidemiological and mechanistic literature. Rabin RL, Levinson AI. Clin Exp Immunol. 2008 Jul;153(1):19-30. Epub 2008 May 26.

There has been considerable interest in defining the relationship between the
expression of allergic and autoimmune diseases in populations of patients. Are
patients with autoimmune disease 'protected' from developing allergic
(immunoglobulin E-mediated) diseases? Does the establishment of an atopic
phenotype reduce the risk of the subsequent development of autoimmune diseases?
Although there are clinical studies addressing this question, methodological
problems, particularly in identification of atopic subjects, limits their
usefulness. Moreover, an immune-based explanation of the observed epidemiological
findings has relied on a paradigm that is currently undergoing increased scrutiny
and modification to include newly defined effector cell subsets and the
interaction between genetic and environmental factors, such as early endotoxin or
mycobacterial exposure. To address this question, we reviewed a series of
clinical reports that addressed coincidence or co-prevalence of atopy with four
autoimmune diseases: psoriasis, rheumatoid arthritis, multiple sclerosis and type
I diabetes mellitus. We present a model whereby active T helper type 1 (Th1)
inflammation may suppress the development of atopy, and atopy may suppress the
severity but not necessarily the onset of autoimmunity, and then discuss our
model in the context of mechanisms of adaptive immunity with particular reference
to the Th1/Th2 paradigms. Because the ultimate goal is to ameliorate or cure
these diseases, our discussion may help to predict or interpret unexpected
consequences of novel therapeutic agents used to target autoimmune or atopic
diseases.

What you should know about psoriasis. Hanson D, Thompson PA, Langemo D, Hunter S, Tinkler J, Anderson JW. Nursing. 2008 Jun;38(6):58-9.

[Immune-mediated inflammatory diseases and psoriasis] [Article in French] Delaporte E.

The association of some immune-mediated inflammatory disease in a same patient is
known. Nevertheless, this is difficult to appreciate practically for the
psoriasis due to the absence of prospective study. The strongest link is with
Crohn's disease and the spondyloartropathies. It is sustained by, i) genetic data
obtained by genome-wide association study showing some common loci and/or genes
involved in innate immunity, ii) immunologic data, these conditions sharing
effector cells among which Th17 lymphocytes and inflammatory mediators
(TNF-alpha, IL-1,17,23...), that explain the related efficacy of some biologics
like anti-TNF-alpha, IL-12/23 antibody and others in progress and iii)
environmental triggers among which bacterial infections are probably determining
in the genesis of these diseases even if this is still only an hypothesis.

[Addictions and psoriasis: an example of the dermatologist's implication in preventive medicine ?] [Article in French] Meyer N, Viraben R, Paul C. Ann Dermatol Venereol. 2008 Feb;135 Suppl 4:S259-62.

Association between psoriasis and addictive disorders has been longtime suspected
and several studies are supporting the association of psoriasis and alcohol, and
of psoriasis and tobacco. The association of psoriasis and other addictive
disorders has not yet been reported. The association of psoriasis and alcohol is
not restricted to alcoholism (defined as excessive alcohol consumption with
psychic and/or psychic (correction of physic) dependence). It has been suggested
that psoriasis is more closely linked to alcohol misuse than it is to alcoholism.
The association of psoriasis and alcohol seems not been influenced by the gender,
and shows a dose-effect relation. The most striking link between cigarette
smoking and psoriasis has been established in palmo-plantar pustulosis. This link
also seems to exist for other forms of psoriasis, with a dose-effect relation.
Cigarette smoking could be involved in the high prevalence of lung cancer and
cardio vascular disorders in psoriatic patients. There are a number of
difficulties in the assessment of the correlation between psoriasis, cigarette
smoking, and alcohol, and even more so in establishing a causal or etiologic
relationship between the three, because of several confusion factors. This must
not occult the reality of this association and its impact of psoriatic patients'
health and the importance of detecting and preventing them. The detection and the
prevention of the complications of these addictions belong to the dermatologists.

[Depression and psoriasis] [Article in French] Bouguéon K, Misery L. Ann Dermatol Venereol. 2008 Feb;135 Suppl 4:S254-8.

Psychiatric co-morbidity is very frequently associated with psoriasis. Depression
is observed in numerous patients with psoriasis. Early detection and treatment
are very important. There is a vicious circle psoriasis- alteration of quality of
life- depression, but psoriasis improvement is not always followed by an
improvement of depression. A contrario, it is obvious that a depressive patient
has a bad observance of treatment. Links between psoriasis and depression are not
only psychopathological. Biological factors, such as increase of blood amounts of
substance P and TNF or decrease of serotonine could also explain this
association.

[Pathogenesis of the metabolic syndrome] [Article in French] Jullien D. Ann Dermatol Venereol. 2008 Feb;135 Suppl 4:S243-8.

After an initial attempt by the WHO to define metabolic syndrome (MS) on a
pathophysiologically oriented approach requiring the assessment of insulin
resistance markers, the NCEP-ATPIII and more recently the IDF proposed more
clinically oriented criteria to help, toward a preventive medicine goal, to
identify patients who are likely to have features of the MS and be at increased
risk of type 2 diabetes and cardio vascular disease. The notion of MS is built
around abnormalities of the metabolism of lipids and carbon hydrates, a rise of
blood pressure, and visceral obesity of abdominal localization. These parameters
report only partially on mechanisms leading to the development of the MS. The
physiopathology of MS is partially understood even today and likely results from
the combination of environmental, genetic and epigenetic factors. Abdominal
visceral obesity, a state of low-grade chronic inflammation and insulin
resistance are the main processes susceptible to explain the various constituents
of this syndrome.

[Psoriasis, metabolic syndrome and its components] [Article in French] Ortonne JP. Ann Dermatol Venereol. 2008 Feb;135 Suppl 4:S235-42.

The psoriasis is a chronic dermatosis which is characterized by strong
inflammation. Recent studies showed that the chronic inflammation plays an
important part in the pathogenesis of many metabolic and vascular diseases.
Moreover, the diseases mediated by lymphocytes TH1 were related to the myocardial
infarction. Epidemiologic investigations showed that psoriasis is associated at
the increased risk of Comorbidities and mortality per comparison to the general
population. Thus, the psoriatic patients have a high prevalence of metabolic
pathologies such as the diabetes, hypertension, obesity and hyperlipidemy. These
concomitant affections can complicate the treatment of psoriasis. It is important
that the dermatologist systematically seeks these concomitant pathologies among
psoriatic patients. These data also suggest that the treatments of these patients
improve not only the skin lesions, but also control the inflammation associated
with the psoriasis.

[The liver and methotrexate] [Article in French] Laharie D, Terrebonne E, Vergniol J, Chanteloup E, Chabrun E, Couzigou P, de Lédinghen V. Gastroenterol Clin Biol. 2008 Feb;32(2):134-42.

Methotrexate is proposed for the treatment of inflammatory disorders such as
rheumatoid arthritis, psoriasis and Crohn's disease. The liver toxicity of
methotrexate has been investigated and prolonged treatment can induce liver
fibrosis. Moreover, alcohol consumption, diabetes and obesity are associated with
liver fibrosis in patients treated with this drug. Therefore, liver fibrosis
associated with methotrexate could be due to associated factors instead of
methotrexate itself. Recommendations to monitor and diagnose methotrexate induced
liver damage vary depending on the disease. Frequent evaluation of liver fibrosis
with liver biopsy is recommended during therapy, especially in patients treated
for psoriasis. Noninvasive methods, such as the FibroScan, could be useful for
the assessment of liver fibrosis associated with methotrexate and hence, need
further evaluation.

Necrolytic acral erythema: case report and review of the literature. Fielder LM, Harvey VM, Kishor SI. Cutis. 2008 Apr;81(4):355-60.

Necrolytic acral erythema is a novel member of the necrolytic erythema family
found exclusively in patients with hepatitis C virus (HCV) infection. Acrally
distributed, dusky, erythematous plaques with vesiculation evolve into
hyperkeratotic lesions resembling psoriasis. Given the prevalence of chronic HCV
infection, necrolytic acral erythema probably is a commonly encountered entity
misdiagnosed as an inflammatory dermatosis. The paucity of case reports in the
United States is likely the result of unfamiliarity with the condition and its
viral association. We report a case of necrolytic acral erythema and review the
literature summarizing its diagnosis, pathogenesis, and treatment.

DNA microarray technology in dermatology. Kunz M. Semin Cutan Med Surg. 2008 Mar;27(1):16-24.

In recent years, DNA microarray technology has been used for the analysis of gene
expression patterns in a variety of skin diseases, including malignant melanoma,
psoriasis, lupus erythematosus, and systemic sclerosis. Many of the studies
described herein confirmed earlier results on individual genes or functional
groups of genes. However, a plethora of new candidate genes, gene patterns, and
regulatory pathways have been identified. Major progresses were reached by the
identification of a prognostic gene pattern in malignant melanoma, an immune
signaling cluster in psoriasis, and a so-called interferon signature in systemic
lupus erythematosus. In future, interference with genes or regulatory pathways
with the use of different RNA interference technologies or targeted therapy may
not only underscore the functional significance of microarray data but also may
open interesting therapeutic perspectives. Large-scale gene expression analyses
may also help to design more individualized treatment approaches of cutaneous
diseases.

National Psoriasis Foundation consensus statement on screening for latent tuberculosis infection in patients with psoriasis treated with systemic and biologic agents. Doherty SD, Van Voorhees A, Lebwohl MG, Korman NJ, Young MS, Hsu S, National Psoriasis Foundation. J Am Acad Dermatol. 2008 Aug;59(2):209-17. Epub 2008 May 15.

BACKGROUND: Chronic immunosuppression is a known risk factor for allowing latent
tuberculosis (TB) infection to transform into active TB.
Immunosuppressive/immunomodulatory therapies, while highly efficacious in the
treatment of psoriasis and psoriatic arthritis, may be associated with an
increased rate of active TB in patients receiving some of these therapies.
OBJECTIVE: Our aim was to arrive at a consensus on screening for latent TB
infection in psoriasis patient treated with systemic and biologic agents.
METHODS: Reports in the literature were reviewed regarding immunosuppressive
therapies and risk of TB. RESULTS: Screening patients for latent TB infection
before commencement of treatment is of utmost importance when beginning treatment
with the tumor necrosis factor-alpha inhibitors, T-cell blockers, cyclosporine,
or methotrexate. The currently recommended method for screening is the tuberculin
skin test. It is preferable that positively screened patients be treated with a
full course of latent TB infection prophylaxis before
immunosuppressive/immunomodulatory therapy is initiated. However, in the opinion
of many experts, patients may be started on the
immunosuppressive/immunomodulatory therapy after 1 to 2 months, if their clinical
condition requires, as long as they are strictly adhering to and tolerating their
prophylactic regimen. LIMITATIONS: There are few evidence-based studies on
screening for latent TB infection in psoriasis patients treated with systemic and
biologic agents. CONCLUSIONS: The biologic TNF-alpha inhibitors are very
promising in the treatment of psoriasis. However, because TNF-alpha is also an
important cytokine in preventing TB infection and in keeping latent TB infection
from becoming active disease, the use of TNF-alpha inhibitors has been associated
with an increased risk of developing active TB. A higher incidence of TB has also
been reported with other immunosuppressive/immunomodulatory treatments for
psoriasis. It is, therefore, of utmost importance to appropriately screen all
patients for latent TB infection prior to initiating any immunologic therapy.
Delaying immunologic therapy until latent TB infection prophylaxis is completed
is preferable. However, if the patient is adhering to his prophylactic regimen
and is appropriately tolerating the regimen, therapy may be started after 1 to 2
months if the clinical condition requires.

Role of curcumin in health and disease. Pari L, Tewas D, Eckel J. Arch Physiol Biochem. 2008 Apr;114(2):127-49.

Curcumin (diferuloylmethane) is an orange-yellow component of turmeric (Curcuma
longa), a spice often found in curry powder. In recent years, considerable
interest has been focused on curcumin due to its use to treat a wide variety of
disorders without any side effects. It is one of the major curcuminoids of
turmeric, which impart its characteristic yellow colour. It was used in ancient
times on the Indian subcontinent to treat various illnesses such as rheumatism,
body ache, skin diseases, intestinal worms, diarrhoea, intermittent fevers,
hepatic disorders, biliousness, urinary discharges, dyspepsia, inflammations,
constipation, leukoderma, amenorrhea, and colic. Curcumin has the potential to
treat a wide variety of inflammatory diseases including cancer, diabetes,
cardiovascular diseases, arthritis, Alzheimer's disease, psoriasis, etc, through
modulation of numerous molecular targets. This article reviews the use of
curcumin for the chemoprevention and treatment of various diseases.

Use of etanercept in the treatment of psoriasis and psoriatic arthritis. Fuchs BS, Hadi S. Rev Recent Clin Trials. 2006 Sep;1(3):259-63.

Psoriasis and psoriatic arthritis are debilitating inflammatory immunemediated
diseases which are chronic in nature and often require lifelong attention.
Traditional therapies used to combat these diseases lack sufficient long-term
efficacy and are associated with a number of toxicities. Failing to adequately
satisfy both patients and physicians, traditional therapies have proven
insufficient and have left few options. Etanercept is a tumor necrosis factor
(TNF) antagonist that reduces elevated TNF levels by competitively binding to
both TNF-alpha and TNF-beta and inhibiting the proinflammatory cascade. Providing
a valuable treatment option alone, etanercept can also be effectively
administered in conjunction with traditional treatments. Etanercept is self
administered by subcutaneous (SC) injection, making treatment less of a burden
for patients by eliminating the need for frequent office visits and laboratory
testing. Etanercept is approved in the US for the treatment of psoriasis,
psoriatic arthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, and
ankylosing spondylitis.

A review of the treatment of psoriasis with infliximab. Vamvouris T, Hadi S. Rev Recent Clin Trials. 2006 Sep;1(3):201-5.

Patients afflicted with moderate to severe psoriasis experience a reduction in
the quality of life. They not only suffer the aggravation associated with the
pain, itchiness, and bleeding of the psoriatic lesions, but also experience a
negative impact on their daily functions and social well-being. Unfortunately,
traditional therapeutic measures have not been effective enough in treating
individuals suffering from moderate to severe forms of psoriasis. Most of the
conventional medications have produced at best only partial responses. However,
the recent chimeric monoclonal TNF-alpha inhibiting antibody, infliximab, has
been proven effective for the treatment of patients with moderate to severe
psoriasis. Most patients treated with infliximab have shown rapid and remarkable
improvement in the clinical manifestations of the disease. This article will
closely examine the efficacy and safety of infliximab through the analysis of
past case reports and clinical trials.

Efalizumab: a biological agent for the treatment of psoriasis. Hodulik S, Hadi S. Rev Recent Clin Trials. 2006 May;1(2):165-8.

Efalizumab is a humanized, monoclonal IgG1 antibody that binds to the
alpha-subunit of lymphocyte function associated antigen (LFA)-1, blocking the
interaction between LFA-1 and intercellular adhesion molecule-1. The result is a
reduction in T cell activation, an inhibition of the trafficking and recruitment
of T cells to the dermis and epidermis, and a decrease in the reactivation of T
cells at several steps in the psoriasis pathogenesis. The clinical responses seen
in efalizumab trials have demonstrated that this medication is efficacious,
especially in long-term treatment. Adverse events observed in efalizumab-treated
patients have been minor. Psoriasis rebound following discontinuation of
treatment, while serious, has been controlled through transition to other
therapies. Subcutaneous injection allows for administration outside the clinic.

Alefacept - a drug review. Lev-Tov H, Hadi S. Rev Recent Clin Trials. 2006 May;1(2):163-4.

Alefacept is an immunobiologic agent that has been recently introduced in the
treatment of plaque psoriasis. The author presents a brief review of the drug,
its efficacy and safety profile. Recent case reports of the use of alefacept in
conjunction with other conditions as well as the drug's possible use for
treatment of other conditions are reviewed as well.

Epidermal stem cells - role in normal, wounded and pathological psoriatic and cancer skin. Kamstrup M, Faurschou A, Gniadecki R, Wulf HC. Curr Stem Cell Res Ther. 2008 May;3(2):146-50.

In this review we focus on epidermal stem cells in the normal regeneration of the
skin as well as in wounded and psoriatic skin. Furthermore, we discuss current
data supporting the idea of cancer stem cells in the pathogenesis of skin
carcinoma and malignant melanoma. Epidermal stem cells present in the basal layer
of the interfollicular epidermis and in the bulge region of the hair follicle
play a critical role for normal tissue maintenance. In wound healing, multipotent
epidermal stem cells contribute to re-epithelization. It is possible that defects
in growth control of either epidermal stem cells or transit amplifying cells
constitute a primary pathogenetic factor in the epidermal hyperproliferation seen
in psoriasis. In cutaneous malignancies mounting evidence supports a stem cell
origin in skin carcinoma and malignant melanoma and a possible existence of
cancer stem cells.

XToll, a recombinant chaperonin 10 as an anti-inflammatory immunomodulator. van Eden W. Curr Opin Investig Drugs. 2008 May;9(5):523-33.

CBio Ltd, under license from the University of Queensland, is developing a
recombinant form of chaperonin 10, known as XToll, for the potential
anti-inflammatory treatment of rheumatoid arthritis, psoriasis and multiple
sclerosis. All three indications have been evaluated in phase IIa clinical
trials. By May 2005, a phase IIa trial for Crohn's disease had been terminated
due to slow recruitment. The company has not disclosed plans for future
development for this indication.

ABT-874, a fully human monoclonal anti-IL-12/IL-23 antibody for the potential treatment of autoimmune diseases. Ding C, Xu J, Li J. Curr Opin Investig Drugs. 2008 May;9(5):515-22.

ABT-874, a fully human mAb that blocks the binding of IL-12 and IL-23 to their
shared IL-12 receptor beta1, is currently being developed by Abbott Laboratories
for the potential treatment of Crohn's disease and psoriasis. The compound is
currently in phase III clinical trials for psoriasis and phase II trials for
Crohn's disease. ABT-87 was previously being developed for the potential
treatment of multiple sclerosis; however, by May 2007, development for this
indication was discontinued.

Psoriasis. Nestle FO. Curr Dir Autoimmun. 2008;10:65-75.

Psoriasis is one of the most common chronic inflammatory disorders with a strong
genetic background. Recent progress in the understanding of both the
immunological as well as the genetic basis has provided an unprecedented
opportunity to move scientific insights from the bench to bedside. Based on
insights from laboratory research, targeted immunotherapies are now available for
the benefit of patients suffering from psoriasis. The success of these therapies
has validated insights into disease pathogenesis and also provides the
opportunity to increase our understanding about the pathways underpinning
autoimmune-type inflammation in the skin.

Psoriasis and vascular disease: an unsolved mystery. Shelling ML, Federman DG, Prodanovich S, Kirsner RS. Am J Med. 2008 May;121(5):360-5.

Psoriasis is an immune disease most commonly recognized for its skin and joint
manifestations. These produce significant physical, social, and psychological
distress in affected patients and resultant reductions in their quality of life.
As expected, these concerns are vital in providing symptomatic improvement and in
selecting an individualized therapy. Yet, the approach in management of these
patients is likely to change given the growing body of evidence linking psoriasis
and vascular disease. Stemming from an anecdotally described relationship, the
association between psoriasis and vascular disease has become a focus of current
research to further elucidate the pathophysiology underlying and connecting these
two diseases. This article includes a review of the classical cardiovascular risk
factors, the atherothrombotic markers, and the environmental stressors associated
with psoriasis, as well as a critical review of the observed vascular diseases,
the proposed mechanism of atherosclerosis, and the benefits of treatment of
psoriasis.

Cytokines and anticytokines in psoriasis. Pietrzak AT, Zalewska A, Chodorowska G, Krasowska D, Michalak-Stoma A, Nockowski P, Osemlak P, Paszkowski T, Roliński JM. Clin Chim Acta. 2008 Aug;394(1-2):7-21. Epub 2008 Apr 12.

BACKGROUND: Psoriasis is a chronic autoimmune hyperproliferative skin disease of
varying severity affecting approximately 2-3% of the general population in the
USA and Europe. Although the pathogenesis of psoriasis has not been fully
elucidated, an immunologic-genetic relationship is likely. Cutaneous and systemic
overexpression of various proinflammatory cytokines (TNF, interleukins,
interferon-gamma) has been demonstrated in psoriatic patients. METHODS: We
reviewed the current database literature and summarized the involvement of
cytokines and their receptors in the pathogenesis and treatment of psoriasis.
RESULTS: Although many cytokine/anti-cytokine therapies have been conducted, TNF
antagonists in the treatment of both psoriasis arthropatica and vulgaris appear
to be the most widely used clinically. Interestingly, the efficacy and
tolerability of some cytokines (rhIL-11 or ABX-IL-8,) were found to be much lower
than expected. CONCLUSIONS: Preliminary results obtained with cytokine and
anti-cytokine therapies appear promising and as such continued research is
clearly indicated.

Antimicrobial peptides and the skin immune defense system. Schauber J, Gallo RL. J Allergy Clin Immunol. 2008 Aug;122(2):261-6. Epub 2008 Apr 25.

Our skin is constantly challenged by microbes but is rarely infected. Cutaneous
production of antimicrobial peptides (AMPs) is a primary system for protection,
and expression of some AMPs further increases in response to microbial invasion.
Cathelicidins are unique AMPs that protect the skin through 2 distinct pathways:
(1) direct antimicrobial activity and (2) initiation of a host response resulting
in cytokine release, inflammation, angiogenesis, and reepithelialization.
Cathelicidin dysfunction emerges as a central factor in the pathogenesis of
several cutaneous diseases, including atopic dermatitis, in which cathelicidin is
suppressed; rosacea, in which cathelicidin peptides are abnormally processed to
forms that induce inflammation; and psoriasis, in which cathelicidin peptide
converts self-DNA to a potent stimulus in an autoinflammatory cascade. Recent
work identified vitamin D3 as a major factor involved in the regulation of
cathelicidin. Therapies targeting control of cathelicidin and other AMPs might
provide new approaches in the management of infectious and inflammatory skin
diseases.

Orthopedic manifestations and management of psoriatic arthritis. Strauss EJ, Alfonso D, Baidwan G, Di Cesare PE. Am J Orthop. 2008 Mar;37(3):138-47.

Psoriatic arthritis is a complex, chronic inflammatory disease with both skin and
joint involvement. Clinical presentation varies considerably among patients and
during the course of the disease. Assessment of patients for psoriatic arthritis
requires careful attention to patient history, a focused physical examination,
and inspection for characteristic radiographic changes. Although this disease was
once thought to be a rare and mild form of arthritis, recent studies have shown
that patients with psoriatic arthritis may develop significant disability, with
up to 20% of cases demonstrating a rapidly progressive, debilitating clinical
course. Orthopedic manifestations of the disease can be severe and can cause
significant physical disability. Although surgical intervention for psoriatic
arthritis is relatively uncommon, having an understanding of the assessment,
available treatment options, and surgical considerations allows for improved
outcome in the management of this complex patient population.

Epigenetics in human autoimmunity. Epigenetics in autoimmunity - DNA methylation in systemic lupus erythematosus and beyond. Strickland FM, Richardson BC. Autoimmunity. 2008 May;41(4):278-86.

Epigenetic mechanisms are essential for normal development and function of the
immune system. Similarly, a failure to maintain epigenetic homeostasis in the
immune response due to factors including environmental influences, leads to
aberrant gene expression, contributing to immune dysfunction and in some cases
the development of autoimmunity in genetically predisposed individuals. This is
exemplified by systemic lupus erythematosus, where environmentally induced
epigenetic changes contribute to disease pathogenesis in those genetically
predisposed. Similar interactions between genetically determined susceptibility
and environmental factors are implicated in other systemic autoimmune diseases
such as rheumatoid arthritis and scleroderma, as well as in organ specific
autoimmunity. The skin is exposed to a wide variety of environmental agents,
including UV radiation, and is prone to the development of autoimmune conditions
such as atopic dermatitis, psoriasis and some forms of vitiligo, depending on
environmental and genetic influences. Herein we review how disruption of
epigenetic mechanisms can alter immune function using lupus as an example, and
summarize how similar mechanisms may contribute to other human autoimmune
rheumatic and skin diseases.

Human Th17 cell clones and natural immune responses. Matsushita S, Higashi T. Allergol Int. 2008 Jun;57(2):135-40.

Immunomodulators such as lipopolysaccharides (LPS) and forskolin change the
nature of dendritic cells (DCs) to induce Th1 and Th2 cells, respectively,
thereby designated Th1 or Th2 adjuvants. Recent studies showed that Th17-inducing
activity can be carried by certain polysaccharides such as beta-glucan derived
from Candia albicans. Such activities can be scrutinized by using MLR, cAMP and
possibly, differential expression of Notch ligand isoforms. In this review
article, we also introduce an effective method to establish human Th17 cell
clones and a transcriptome analysis using human Th subpopulations. In vivo
relevance to human Th17 responses is discussed.

Facing psoriasis and atopic dermatitis: are there more similarities or more differences? Wilsmann-Theis D, Hagemann T, Jordan J, Bieber T, Novak N. Eur J Dermatol. 2008 Mar-Apr;18(2):172-80.

Atopic dermatitis (AD) and psoriasis vulgaris (Pso) represent the most frequent
chronic inflammatory skin diseases. It has been assumed for a long time that
these diseases have a completely different background. Recent findings about the
genetic, epidemiologic and pathophysiologic factors of both diseases have
remarkably improved our knowledge about the complex mechanisms underlying AD and
Pso. Beyond that, in view of these findings, the question arises, which
similarities and differences between AD and Pso exist. In order to address this
point, we provide an overview about the current knowledge in the field of AD and
Pso.

Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 2. Psoriatic arthritis: overview and guidelines of care for treatment with an emphasis on the biologics. Gottlieb A, Korman NJ, Gordon KB, Feldman SR, Lebwohl M, Koo JY, Van Voorhees AS, Elmets CA, Leonardi CL, Beutner KR, Bhushan R, Menter A. J Am Acad Dermatol. 2008 May;58(5):851-64.

Psoriasis is a common, chronic, inflammatory, multisystem disease with
predominantly skin and joint manifestations affecting approximately 2% of the
population. In this second of 5 sections of the guidelines of care for psoriasis,
we give an overview of psoriatic arthritis including its cardinal clinical
features, pathogenesis, prognosis, classification, assessment tools used to
evaluate psoriatic arthritis, and the approach to treatment. Although patients
with mild to moderate psoriatic arthritis may be treated with nonsteroidal
anti-inflammatory drugs and/or intra-articular steroid injections, the use of
disease-modifying antirheumatic drugs, particularly methotrexate, along with the
biologic agents, are considered the standard of care in patients with more
significant psoriatic arthritis. We will discuss the use of disease-modifying
antirheumatic drugs and the biologic therapies in the treatment of patients with
moderate to severe psoriatic arthritis.

Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. Menter A, Gottlieb A, Feldman SR, Van Voorhees AS, Leonardi CL, Gordon KB, Lebwohl M, Koo JY, Elmets CA, Korman NJ, Beutner KR, Bhushan R. J Am Acad Dermatol. 2008 May;58(5):826-50.

Psoriasis is a common, chronic, inflammatory, multisystem disease with
predominantly skin and joint manifestations affecting approximately 2% of the
population. In this first of 5 sections of the guidelines of care for psoriasis,
we discuss the classification of psoriasis; associated comorbidities including
autoimmune diseases, cardiovascular risk, psychiatric/psychologic issues, and
cancer risk; along with assessment tools for skin disease and quality-of-life
issues. Finally, we will discuss the safety and efficacy of the biologic
treatments used to treat patients with psoriasis.

MicroRNAs: novel regulators in skin inflammation. Sonkoly E, Ståhle M, Pivarcsi A. Clin Exp Dermatol. 2008 May;33(3):312-5.

Compelling evidence indicates that microRNAs (miRNAs), short, non-protein coding
RNAs, are critical for the development and survival of multicellular organisms.
Recently, miRNAs were implicated in the pathogenesis of psoriasis and atopic
eczema (AE), the two most common chronic inflammatory disorders in skin. In
particular, miR-203, the first skin-specific miRNA, showing an intriguing
expression profile being confined to skin epithelium, is specifically
overexpressed in psoriasis. MiR-146a, another miRNA showing specific upregulation
in psoriasis, is involved in the regulation of innate immune responses and the
tumour necrosis factor (TNF)-alpha pathway. Interestingly, miR-125b, another
miRNA involved in the TNF-alpha pathway, is also deregulated in psoriasis and AE.
As skin inflammation may serve as a model for chronic inflammatory disorders, it
is likely that miRNAs involved in skin inflammation will eventually emerge in
other inflammatory or autoimmune disorders, and some of these may become disease
markers and therapeutic targets. In this review we present an overview of what is
currently known about the roles of miRNAs in chronic inflammatory skin disorders.

Psoriasis: characteristics, psychosocial effects and treatment options. Ryan S. Br J Nurs. 2008 Mar 13-26;17(5):284-90.

Psoriasis is a complex chronic non-infectious inflammatory skin disease with many
different presentations. The classic presentation is of well-defined red plaques
with silver scale. The characteristic scale makes the disorder highly visible and
intrusive on the patient's lifestyle. The visible nature of the disease ensures
that psoriasis has both physical and psychosocial effects. In normal skin,
epidermal cell reproduction and proliferation takes 28 days. In psoriasis, this
process is considerably accelerated to approximately four days, resulting in the
deposit of immature cells on the skin. While the exact cause of this process is
unknown, certain environmental and genetic factors are known to be provoking
factors. Disease management will be dependent on disease severity, psychosocial
effects and the patient's lifestyle. To effectively treat this disease the nurse
must be skilled in psoriasis management, and in patient education and motivation.
This article reviews the characteristics, aetiology, psychosocial effects and
treatment strategies of psoriasis.

Grenz ray therapy in the new millennium: still a valid treatment option? Warner JA, Cruz PD Jr. Dermatitis. 2008 Mar-Apr;19(2):73-80.

Grenz ray therapy has declined in the United States during the past several
decades with respect to availability, use, and resident training. However, it
remains a simple, affordable, and effective option for managing several
refractory dermatoses, especially psoriasis, hand eczema, and allergic contact
dermatitis. Though high-dose grenz irradiation has been associated with the
development of nonmelanoma skin cancers, grenz ray therapy is considered a safe
treatment modality when administered according to the guidelines recommended
herein. We review the value of grenz irradiation in contemporary dermatology.

Safety of dermatologic drugs used in pregnant patients with psoriasis and other inflammatory skin diseases. Lam J, Polifka JE, Dohil MA. J Am Acad Dermatol. 2008 Aug;59(2):295-315. Epub 2008 Apr 14.

In patients with psoriasis, there is an increased availability of drugs for
treatment. However, there are important questions about drug safety for mothers
with psoriasis and their fetuses. Currently, there are limited safety data for
many of the medications used. In this article, we review current pregnancy risk
information for medications commonly used in the treatment of psoriasis. In
addition, a list of teratology information resources is included to help
practicing clinicians find up-to-date information regarding the safety of the
medications they prescribe.

T-helper 17 cells in psoriatic plaques and additional genetic links between IL-23 and psoriasis. Blauvelt A. J Invest Dermatol. 2008 May;128(5):1064-7.

T-helper 17 (Th17) cells are a newly appreciated T-cell subset, distinct from
both Th1 and Th2 cells, that have been implicated in the pathogenesis of
psoriasis and other autoimmune inflammatory diseases (Figure 1) (Fitch et al.,
2007; Kastelein et al., 2007). IL-23 stimulates survival and proliferation of
Th17 cells and thus serves as a key master cytokine regulator for these diseases.

From conventional to cutting edge: the new era of biologics in treatment of psoriasis. Tzu J, Kerdel F. Dermatol Ther. 2008 Mar-Apr;21(2):131-41.

Psoriasis is a chronic T-cell-mediated inflammatory disease of the skin and
joints that affects 1-3% of the world population. Conventional treatments for
moderate to severe psoriasis are associated with broadband immunosuppression
and/or organ toxicities that can be problematic when used long term. Advances in
the understanding of psoriasis pathogenesis have led to targeted therapy in the
form of biologics. These agents have gained popularity as safe, effective, and
convenient alternatives for the treatment of chronic, moderate to severe plaque
psoriasis. This review will focus on the five main biologics used in the
treatment of moderate to severe plaque psoriasis: efalizumab, alefacept,
etanercept, infliximab and adalimumab. Mechanisms of action, guidelines for
usage, efficacy data, and safety concerns will be discussed for each biologic. In
addition, the new Th17 biologics and their role in psoriasis pathogenesis will
also be examined.

Cellular and molecular mechanisms involved in the action of vitamin D analogs targeting vitiligo depigmentation. Birlea SA, Costin GE, Norris DA. Curr Drug Targets. 2008 Apr;9(4):345-59.

The active metabolite of vitamin D3 - 1,25-(OH)2D3 - exerts most of its
physiological and pharmacological actions through its nuclear receptor (VDR),
regulating the transcriptional machinery of a variety of cell types. Basic
research motivated by the detection of VDR in numerous target cells, has
indicated potential therapeutic applications of VDR ligands in osteoporosis,
cancer, secondary hyperparathyroidism and autoimmune diseases such as psoriasis,
systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes and multiple
sclerosis. In recent years vitamin D analogs, particularly calcipotriol and
tacalcitol, have been used as topical therapeutic agents in vitiligo, an
autoimmune pigmentary disorder characterized by aberrant loss of functional
melanocytes from involved epidermis. The presence of cytotoxic T cells targeting
melanocyte antigens and imbalance of the cytokine network were described as
characteristics of the disease, eventually leading to melanocyte damage and
death. Vitamin D ligands are designed to target the local immune response in
vitiligo, acting on specific T cell activation, mainly by inhibiting the
transition of T cells from early to late G1 phase and by inhibiting the
expression of several pro-inflammatory cytokines genes, such as those encoding
tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma). Vitamin
D(3) compounds are known to influence melanocyte maturation and differentiation
and also to up-regulate melanogenesis through pathways activated by specific
ligand receptors, such as endothelin receptor and c-kit. In this review we
summarize the complex pathogenetic rationale of vitamin D analogs in vitiligo
depigmentation. Understanding the cellular and molecular mechanisms through which
vitamin D targets the epidermal melanin unit is of great interest for
identification of new effective therapeutic combination(s) that might induce
repigmentation in vitiligo.

Recent clinical trials of cladribine in hematological malignancies and autoimmune disorders. Robak T, Wierzbowska A, Robak E. Rev Recent Clin Trials. 2006 Jan;1(1):15-34.

The purine nucleoside analog - cladribine (2-chlorodeoxyadenosine, 2-CdA) is a
cytotoxic agent with high activity in lymphoid and myeloid malignancies. It is
also an effective drug in some autoimmune disorders. 2-CdA is usually
administered intravenously in continuous or 2-hour infusion. Recently however,
new formulation of this agent has been developed for subcutaneous and oral
administration. 2-CdA is widely established as first line standard treatment for
hairy cell leukemia. Moreover several clinical trials have demonstrated that this
agent, used alone or in combination with other cytotoxic drugs, showed good
efficacy and acceptable toxicity profile in the treatment of chronic lymphocytic
leukemia, Waldenström macroglobulinemia, low-grade non-Hodgkin's lymphoma and
acute myeloid leukemia. Moreover, some studies indicate that 2-CdA has some
activity in progressive multiple sclerosis and other autoimmune disorders
including autoimmune hemolytic anemia, rheumatoid arthritis, systemic lupus
erythematosus, psoriasis and in patients with refractory factor VIII inhibitors.
This review article will summarize the results of recent clinical trials with
2-CdA in hematological malignancies, multiple sclerosis and other autoimmune
diseases.

The impact of physical illness on sexual dysfunction. Clayton A, Ramamurthy S. Adv Psychosom Med. 2008;29:70-88.

Sexuality is the ultimate union of mind and body. Sexual dysfunction is often the
first manifestation of physical illness but is often not inquired about on
routine review of symptoms. This is, in large part, due to the health care
providers' lack of knowledge in diagnosis and treatment of sexual impairment as
well as their discomfort with this sensitive topic. However, sexual well-being is
an important determinant of quality of life and many medically ill patients find
sexual intimacy to be an essential mode of communication with their partners.
This chapter attempts to methodically delineate physical illnesses causing sexual
dysfunction by organ system. Neurologic, endocrinologic, cardiovascular and
pelvic illnesses are discussed as to their impact on sexual health. Diagnostic
and established treatment strategies are also reviewed. Breast cancer, rheumatoid
arthritis and psoriasis are touched upon. Although not a disease, pregnancy and
its unique impact on sexuality is also discussed. Not only the disease itself but
the treatment prescribed may also cause sexual impairment. Thus, a separate
section on medications that impair sexual functioning is presented. A table of
common medications as a quick reference to their effects on each stage of the
sexual cycle is also provided.

Angiogenesis: the new potential target for the therapy of psoriasis? Heidenreich R, Röcken M, Ghoreschi K. Drug News Perspect. 2008 Mar;21(2):97-105.

Angiogenesis is a hallmark of chronic inflammation such as psoriasis. Unraveling
the pathogenesis of psoriasis shows that several proangiogenic mediators are
activated and highly expressed during psoriasis. Vascular endothelial growth
factor, hypoxia- inducible factor, tumor necrosis factor, interleukin-8 and
angiopoietins are considered to be the main players responsible for the strong
vessel formation in psoriasis. The proangiogenic milieu in the skin seems to
result from a proinflammatory immune response initiated by T helper cells.
Interestingly, several small molecules as well as modern biologics used for
systemic therapy of psoriasis have been shown to provide not only immune
regulatory effects but also influence endothelial cell biology. Thus, direct
targeting of angiogenesis may not only help to understand psoriasis pathogenesis
but also to develop new strategies to treat psoriasis with therapeutics that halt
the angiogenesis required for the inflammatory disease. Copyright 2008 Prous
Science, S.A.U. or its licensors. All rights reserved.

Disease-modifying antirheumatic drugs other than methotrexate in rheumatoid arthritis and seronegative arthritis. Nandi P, Kingsley GH, Scott DL. Curr Opin Rheumatol. 2008 May;20(3):251-6.

PURPOSE OF REVIEW: To outline recent research findings with nonmethotrexate
disease-modifying antirheumatic drugs in rheumatoid arthritis and seronegative
arthritis spanning systematic reviews, randomized controlled trials,
observational clinical practice trials and assessments of adverse effects. RECENT
FINDINGS: Systematic reviews show no important differences between methotrexate,
leflunomide and sulfasalazine monotherapies; early disease-modifying
antirheumatic drug therapy reduces erosive progression. Observational studies
show that nonmethotrexate disease-modifying antirheumatic drugs are widely
prescribed; their usage has increased in the biologic era. A systemic review also
showed patients who failed monotherapy benefited from disease-modifying
antirheumatic drug combinations without excess toxicity. Randomized controlled
trials of intensive initial disease-modifying antirheumatic drug combinations
showed they reduce synovitis and erosive damage, especially when used with
steroids. The subsequent sequence of disease-modifying antirheumatic drugs and
the value of changing disease-modifying antirheumatic drug monotherapies or
stepping-up to combination disease-modifying antirheumatic drugs are, however,
unresolved. The adverse risks of nonmethotrexate disease-modifying antirheumatic
drugs have been evaluated, including infections and lung disease; patient-related
risks seem more important than drug-related risks, though several
disease-modifying antirheumatic drugs increase both types of adverse reactions.
Two limitations of nonmethotrexate disease-modifying antirheumatic drugs are
reduced impact on comorbidities like cardiovascular disease and reduced patient
and clinician preferences for these treatments. SUMMARY: Nonmethotrexate
disease-modifying antirheumatic drugs are effective, relatively well tolerated
and widely used. Their role in intensive treatment strategies in early rheumatoid
arthritis appears of crucial importance.

Psoriasiform dermatoses. Sehgal VN, Dogra S, Srivastava G, Aggarwal AK. Indian J Dermatol Venereol Leprol. 2008 Mar-Apr;74(2):94-9.

Psoriasiform reaction pattern is a commonly encountered denominator in a wide
variety of unrelated disorders. It may be a reaction to either the internal or
the external environmental, allergic, infective, parasitic, bacterial, fungal,
viral and/or malignant stimuli. The degree of evolution of such a pattern and its
significance vary according to the dermatosis. The age of the skin lesions may
also influence the histopathological presentation and its
clinico-histopathological disparity can often bewilder an expert. However, such a
situation warrants more astute and sustained observations to unveil the exact
underlying condition(s). Thus, psoriasiform dermatoses should only be an initial
caption until an exact dermatological disorder is defined. There has been greater
number of instances of psoriasiform drug eruptions where a confirmation of the
diagnosis can be achieved after their remission by doing a provocation test.
Similarly, such instances have also been on the rise in HIV/AIDS-affected
individuals all over the world. Besides mycosis fungoides and Hodgkin's disease,
several unrelated malignancies have been preceded or accompanied by psoriasiform
skin eruptions.

Rates of new-onset psoriasis in patients with rheumatoid arthritis receiving anti-tumour necrosis factor alpha therapy: results from the British Society for Rheumatology Biologics Register. Harrison MJ, Dixon WG, Watson KD, King Y, Groves R, Hyrich KL, Symmons DP; British Society for Rheumatology Biologics Register Control Centre Consortium; BSRBR. Ann Rheum Dis. 2009 Feb;68(2):209-15. Epub 2008 Apr 2.

BACKGROUND: Anti-tumour necrosis factor (TNF)alpha treatments improve outcome in
severe rheumatoid arthritis (RA) and are efficacious in psoriasis and psoriatic
arthritis. However recent case reports describe psoriasis occurring as an adverse
event in patients with RA receiving anti-TNFalpha therapy. OBJECTIVES: We aimed
to determine whether the incidence rate of psoriasis was higher in patients with
RA treated with anti-TNFalpha therapy compared to those treated with traditional
disease-modifying antirheumatic drugs (DMARDs). We also compared the incidence
rates of psoriasis between the three anti-TNFalpha drugs licensed for RA.
METHODS: We studied 9826 anti-TNF-treated and 2880 DMARD-treated patients with
severe RA from The British Society for Rheumatology Biologics Register (BSRBR).
All patients reported with new onset psoriasis as an adverse event were included
in the analysis. Incidence rates of psoriasis were calculated as events/1000
person years and compared using incidence rate ratios (IRR). RESULTS: In all, 25
incident cases of psoriasis in patients receiving anti-TNFalpha therapy and none
in the comparison cohort were reported between January 2001 and July 2007. The
absence of any cases in the comparison cohort precluded a direct comparison;
however the crude incidence rate of psoriasis in those treated with anti-TNFalpha
therapy was elevated at 1.04 (95% CI 0.67 to 1.54) per 1000 person years compared
to the rate of 0 (upper 97.5% CI 0.71) per 1000 person years in the patients
treated with DMARDs. Patients treated with adalimumab had a significantly higher
rate of incident psoriasis compared to patients treated with etanercept (IRR 4.6,
95% CI 1.7 to 12.1) and infliximab (IRR 3.5, 95% CI 1.3 to 9.3). CONCLUSIONS:
Results from this study suggest that the incidence of psoriasis is increased in
patients treated with anti-TNFalpha therapy. Our findings also suggest that the
incidence may be higher in patients treated with adalimumab.

To test or not to test? An evidence-based assessment of the value of screening and monitoring tests when using systemic biologic agents to treat psoriasis. Huang W, Cordoro KM, Taylor SL, Feldman SR. J Am Acad Dermatol. 2008 Jun;58(6):970-7. Epub 2008 Apr 2.

The development of new treatments for psoriasis provides dermatologists novel
ways to help control the disease but raises questions about what laboratory
screening tests are required. As of yet, no consensus or guidelines exist for
dermatologists to follow and there may be misconceptions about the relative need
for screening and monitoring tests in patients treated with biologic agents.
Current practice ranges from no testing to blanket screening panels. The purposes
of this review are to (1) systematically review the literature on the use of
screening and monitoring tests when initiating and continuing biologic treatments
(adalimumab, alefacept, efalizumab, etanercept, infliximab) for moderate to
severe psoriasis or psoriatic arthritis; and (2) suggest practical guidelines for
dermatologists on which to base such testing. We searched the Cochrane
Collaborative Database (including the Cochrane Database of Systematic Reviews
[Cochrane Reviews] and the Cochrane Central Register of Controlled Trials
[Clinical Trials]) and the MEDLINE database using medical subject headings as
search terms when available or key words when appropriate. We compiled published
data on risk and risk assessment related to systemic psoriasis treatments, used
expert opinion where appropriate when published clinical data were not adequately
informative, and assigned evidence grades for various screening tests based on
standard methods of the US Preventive Services Task Force. Finally, we developed
a table of evidence grades for tests used to monitor different systemic
medications. There is not strong evidence to recommend most screening tests for
monitoring biological treatments. Neither is there strong evidence not to do such
testing. Ultimately, from a practical standpoint, it is incumbent on the
clinician to consider each patient independently and determine what screening
tests are most appropriate for each individual patient.

Risks and benefits of tumor necrosis factor-alpha inhibitors in the management of psoriatic arthritis: systematic review and metaanalysis of randomized controlled trials. Saad AA, Symmons DP, Noyce PR, Ashcroft DM. J Rheumatol. 2008 May;35(5):883-90. Epub 2008 Mar 15.

OBJECTIVE: To evaluate the efficacy and safety of tumor necrosis factor-alpha
(TNF-alpha) inhibitors in the management of psoriatic arthritis (PsA). METHODS:
We searched electronic databases to identify randomized controlled trials (RCT)
of adalimumab, etanercept, and infliximab used in patients with PsA. Random
effects metaanalysis was undertaken to produce pooled estimates of the relative
risk, risk difference, or the weighted mean difference for efficacy and safety
outcomes using Stata version 9.0. RESULTS: Six RCT met the inclusion criteria,
including 982 patients. All 3 TNF-alpha inhibitors were significantly more
effective than placebo on the basis of Psoriatic Arthritis Response Criteria
(PsARC) and American College of Rheumatology response criteria ACR20, ACR50, and
ACR70 ratings. There were no significant differences between TNF-alpha inhibitors
and placebo in the proportions of patients experiencing withdrawal for any reason
(RR 0.48, 95% CI 0.20-1.18), or withdrawal due to adverse events (RR 2.14, 95% CI
0.73-6.27), serious adverse events (RR 0.98, 95% CI 0.55-1.77), or upper
respiratory tract infections (RR 0.91, 95% CI 0.65-1.28). Pooled rates for
injection site reactions were significantly higher for adalimumab and etanercept
than for placebo (RR 2.48, 95% CI 1.16-5.29), but there was no significant
difference in the proportion of patients experiencing infusion reactions with
infliximab (RR 1.03, 95% CI 0.48-2.20) compared against placebo. Indirect
analysis did not demonstrate any significant differences between the TNF-alpha
inhibitors. CONCLUSION: TNF-alpha inhibitors are effective treatments for PsA
with no important added risks associated with their short-term use. There is
still a need for longterm risk-benefit assessment of using these drugs for the
management of PsA.

Psoriatic arthritis: genetic susceptibility and pharmacogenetics. Rahman P, O'Rielly DD. Pharmacogenomics. 2008 Feb;9(2):195-205.

Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis.
The etiology of PsA is unknown; however, there is mounting evidence for a strong
genetic contribution to PsA. A few disease-related genes have already been
identified in PsA. Cytokines associated with PsA appear to be the most promising
targets for pharmacogenetics. Blockade of TNF-alpha and IL-12/23 is associated
with a marked clinical response to PsA and/or psoriasis, implying a pivotal role
of these cytokines in the pathogenesis of these two disease entities. To date,
only the -308 variant of the TNF-alpha promoter gene has been shown to be
important in predicting response to TNF-alpha blockade in inflammatory arthritis.

Etanercept: an overview of its role in the treatment of psoriasis. Galindo MP, Bartlett BL, Gewirtzman A, Mendoza N, Tremaine AM, Tyring SK. Expert Opin Drug Metab Toxicol. 2008 Mar;4(3):305-10.

BACKGROUND: Psoriasis is a chronic and disabling disease affecting patients'
quality of life. OBJECTIVES: Over the past decade, there has been significant
growth in the knowledge of the proinflammatory pathways involved in psoriasis,
including the role of increased levels of TNF. This knowledge has led to the
increased use of biologic therapy, with such drugs as etanercept, a soluble TNF
receptor fusion protein, aimed at inhibiting the actions of TNF. The goal of
biologic generation is to provide selectively targeted therapy with fewer adverse
events than traditional therapies. METHODS: Etanercept has been studied
extensively and Phase III studies have been completed. CONCLUSION: Clinical data
reviewed for etanercept-treated moderate to severe psoriasis have shown good
efficacy, tolerability and a low adverse event profile.

[Smoking and the skin] [Article in Spanish] Just-Sarobé M. Actas Dermosifiliogr. 2008 Apr;99(3):173-84.

Smoking is the main modifiable cause of disease and death in the developed world.
Tobacco consumption is directly linked to cardiovascular disease, chronic
bronchitis, and many malignant diseases. Tobacco also has many cutaneous effects,
most of which are harmful. Smoking is closely associated with several
dermatologic diseases such as psoriasis, pustulosis palmoplantaris,
hidrosadenitis suppurativa, and systemic and discoid lupus erythematosus, as well
as cancers such as those of the lip, oral cavity, and anogenital region. A more
debatable relationship exists with melanoma, squamous cell carcinoma of the skin,
basal cell carcinoma, and acne. In contrast, smoking seems to protect against
mouth sores, rosacea, labial herpes simplex, pemphigus vulgaris, and dermatitis
herpetiformis. In addition to the influence of smoking on dermatologic diseases,
tobacco consumption is also directly responsible for certain dermatoses such as
nicotine stomatitis, black hairy tongue, periodontal disease, and some types of
urticaria and contact dermatitis. Furthermore, we should not forget that smoking
has cosmetic repercussions such as yellow fingers and fingernails, changes in
tooth color, taste and smell disorders, halitosis and hypersalivation, and early
development of facial wrinkles.

Psoriasis as the marker of underlying systemic disease. Kourosh AS, Miner A, Menter A. Skin Therapy Lett. 2008 Feb;13(1):1-5.

Psoriasis is associated with comorbidities that include metabolic syndrome and
increased cardiovascular risk. These conditions share etiologic features and
health consequences that directly correlate with the severity of psoriatic
disease. This disease, in both its skin and joint manifestations, may represent a
relevant healthcare issue as an indicator of a broader, underlying disorder of
systemic inflammation, and warrants more comprehensive study and
multidisciplinary collaboration on its pathophysiology, epidemiology, and
treatment in relation to its comorbid conditions.

Comparative effects of biological therapies on the severity of skin symptoms and health-related quality of life in patients with plaque-type psoriasis: a meta-analysis. Reich K, Sinclair R, Roberts G, Griffiths CE, Tabberer M, Barker J. Curr Med Res Opin. 2008 May;24(5):1237-54. Epub 2008 Mar 19.

BACKGROUND: The comparative effects of biological response modifiers (BRMs) on
the severity of psoriasis and its effects on health-related quality of life
(HRQoL) have not been evaluated. OBJECTIVE: To conduct a meta-analysis to assess
the effects of available biological agents on the severity of psoriasis, as well
as to provide data on the effects of these agents on HRQoL. METHODS: Medline and
other databases were searched for randomized controlled trials (>or= 10 weeks’
duration in adults) comparing biological therapies for moderate-to-severe
psoriasis with placebo. A Mantel-Haenszel fixed-effects model was employed to
estimate the pooled relative risks (RR) of patients achieving >or= 75% reduction
of baseline Psoriasis Area and Severity Index (PASI 75) after >or= 10 weeks of
treatment. Similar analyses were also conducted on PASI 50 and PASI 90. Using a
random-effects model, we estimated the likelihood of achieving PASI 50, PASI 75,
and PASI 90 at 10-12 weeks and 24 weeks. Data on the effects of different BRMs
(vs. placebo) on HRQoL were also presented. Numbers (%) of patients discontinuing
treatment were presented as a general index of drug tolerability. RESULTS:
Patients receiving infliximab 5 mg/kg intravenously at weeks 0, 2, and 6, then
every 8 weeks, had the highest RR of achieving PASI 75, with a pooled RR value of
25.48 (95% confidence interval [CI], 14.04-46.23); followed by etanercept 50 mg
administered subcutaneously (SC) twice weekly with RR = 11.92 (95% CI,
8.17-17.39); etanercept 25 mg SC twice weekly with RR = 10.68 (95% CI,
6.15-18.57); efalizumab 1-2 mg/kg SC per week with RR = 7.47 (95% CI,
5.20-10.73); and alefacept administered weekly (various doses) with RR = 3.37
(95% CI, 2.18-5.23). (All RR values were estimated vs. placebo.) Similar findings
were observed with regard to proportions of patients achieving PASI 50 and PASI
90. The random-effects analysis suggested that infliximab significantly increased
the likelihood of achieving PASI 50, PASI 75, and PASI 90 compared with placebo
at 10-12 weeks; however, there were no significant differences between biological
treatments at 24 weeks. Each BRM improved HRQoL compared with placebo according
to findings from the Dermatology Life Quality Index. Proportions of patients
discontinuing treatment were similar in active-treatment and placebo groups.
CONCLUSIONS: Infliximab significantly reduced disease severity by both fixed- and
random-effects models. All biological therapies improved HRQoL compared with
placebo, and proportions of patients discontinuing treatment were similar in
active-treatment and placebo groups. The analysis is potentially limited by
statistical factors and did not systematically account for different toxicity
profiles, but the findings establish a foundation for head-to-head comparative
trials.

Etanercept. Ducharme E, Weinberg JM. Expert Opin Biol Ther. 2008 Apr;8(4):491-502.

BACKGROUND: In some patients with psoriasis the inflammatory process fueling skin
lesions also afflicts their joints in a condition called psoriatic arthritis.
TNF-alpha has been shown to play a central role in the pathogenesis of both
cutaneous and joint disease. Etanercept is a soluble fusion protein that binds
TNF-alpha, rendering the molecule inactive and making etanercept an effective,
targeted therapeutic option for many TNF-mediated inflammatory diseases.
OBJECTIVE: To review the key clinical trials which evaluated efficacy of
etanercept for the treatment of psoriasis and psoriatic arthritis, discuss
various off-label uses for this therapeutic agent and describe the adverse events
associated with its use. METHODS: A search of Medline for relevant articles on
etanercept and psoriasis. RESULTS/CONCLUSION: Etanercept has demonstrated
efficacy in the treatment of skin and joint manifestations of psoriatic disease,
thus gaining FDA approval for use in both. A growing number of off-label
dermatological uses for etanercept have been proposed, with variable success
reported in individual cases or small series. Since its introduction little over
a decade ago, etanercept has maintained a favorable safety profile.

Vitamin D receptor agonists in the treatment of autoimmune diseases: selective targeting of myeloid but not plasmacytoid dendritic cells. Penna G, Amuchastegui S, Laverny G, Adorini L. J Bone Miner Res. 2007 Dec;22 Suppl 2:V69-73.

Vitamin D receptor (VDR) agonists are well known for their capacity to control
calcium and bone metabolism and to regulate growth and differentiation of many
cell types. More recently, it has become clear that VDR agonists possess
immunoregulatory properties and, in particular, pronounced protolerogenic
activities. These agents have been shown to be effective in several models of
autoimmune diseases and are the most used topical agents in the treatment of
psoriasis, a Th1 and Th17 cell-mediated autoimmune disease of the skin,
indicating their potential applicability in the treatment of a variety of
autoimmune diseases. VDR agonists can act directly on T cells, but dendritic
cells (DCs) seem to be their primary targets. A potentially very important
activity of VDR agonists is their capacity to induce in vitro and in vivo
tolerogenic DCs able to enhance CD4(+)CD25(+) suppressor T cells that, in turn,
inhibit effector T-cell responses. Novel data now show that VDR agonists
selectively modulate tolerogenic properties in blood myeloid but not plasmacytoid
DCs, shedding new light on the multifaceted immunoregulatory properties of these
agents.

Cell adhesion antagonists: therapeutic potential in asthma and chronic obstructive pulmonary disease. Woodside DG, Vanderslice P. BioDrugs. 2008;22(2):85-100.

Chronic obstructive pulmonary disease (COPD) and asthma are inflammatory diseases
of the lung where a hallmark feature is excessive leukocyte infiltration that
leads to tissue injury. Cell adhesion molecules (e.g. selectins and integrins)
play a key role in cell trafficking, and in the lung they regulate leukocyte
extravasation, migration within the interstitium, cellular activation, and tissue
retention. All selectin family members (including L-selectin, P-selectin, and
E-selectin) and many of the beta1 and beta2 integrins appear to be important
therapeutic targets, as numerous animal studies have demonstrated essential roles
for these cell adhesion molecules in lung inflammation. Not surprisingly, these
families of adhesion molecules have been under intense investigation by the
pharmaceutical industry for the development of novel therapeutics. Integrins are
validated drug targets, as drugs that antagonize integrin alphaIIbbeta3 (e.g.
abciximab), integrin alphaLbeta2 (efalizumab), and integrin alpha4beta1
(natalizumab) are currently US FDA-approved for acute coronary syndromes,
psoriasis, and multiple sclerosis, respectively. However, none has been approved
for indications related to asthma or COPD. Here, we provide an overview of roles
played by selectins and integrins in lung inflammation. We also describe recent
clinical results (both failures and successes) in developing adhesion molecule
antagonists, with specific emphasis on those targets that may have potential
benefit in asthma and COPD. Early clinical trials using selectin and integrin
antagonists have met with limited success. However, recent positive phase II
clinical trials with a small-molecule selectin antagonist (bimosiamose) and a
small-molecule integrin alpha4beta1 antagonist (valategrast [R411]), have
generated enthusiastic anticipation that novel strategies to treat asthma and
COPD may be forthcoming.

Translational dermatology in drug discovery: perspectives for integrating humanized xenograft models and experimental clinical studies. Petersen TK, Sørensen P. Drug Discov Today. 2008 Mar;13(5-6):240-6. Epub 2007 Nov 26.

Application of humanized xenotransplantation disease models and experimental
clinical studies in the context of translational research in drug discovery in
dermatology is an opportunity to reduce failure due to lack of efficacy in
clinical development stage.

Patient profiles in psoriatic disease: a case-based approach. Wiatrowski M, Furfaro N. Dermatol Nurs. 2007 Oct;Suppl:5-19; quiz 20-1.

Psoriasis and psoriatic arthritis are related conditions that can have numerous
untoward consequences. Moreover, appropriate management of these conditions can
be challenging, as each affected patient has unique needs that must be addressed.
With that in mind, the authors discuss three real-life cases, highlighting
principles that may facilitate the effective case-by-case management of psoriatic
disease.

Psoriatic arthritis and arthroplasty: a review of the literature. lofin I, Levine B, Badlani N, Klein GR, Jaffe WL. Bull NYU Hosp Jt Dis. 2008;66(1):41-8.

Psoriatic arthritis is an inflammatory arthropathy as- sociated with the
characteristic dermatologic lesions of psoriasis. The diagnosis of psoriatic
arthritis is quite difficult, due to the overlap of patients with osteoarthritis
(OA) or rheumatoid arthritis (RA) with concomitant non-associated psoriasis. A
nonspecific elevation in inflammatory markers (erythrocyte sedimentation rate,
ESR; antinuclear antibodies, ANA; or rheumatoid factor, RF) and characteristic
radiographic features are often present in these patients. The mainstay of
treatment is medical management, using NSAIDs, various immunosuppressants, and
anti-TNF agents, for both pain control and possibly as disease modifying agents.
Only a minority of patients require surgical intervention, leading to the limited
amount of literature concerning total joint arthroplasty and psoriatic arthritis.
While past literature has yielded high infection rates post-arthroplasty, newer
studies have found more promising results. Alternative surgical options for
treating destructive arthritis include open or arthroscopic synovectomy. While
early results are promising, recurrence rates and long-term outcomes are not yet
available.

Curcumin: from ancient medicine to current clinical trials. Hatcher H, Planalp R, Cho J, Torti FM, Torti SV. Cell Mol Life Sci. 2008 Jun;65(11):1631-52.

Curcumin is the active ingredient in the traditional herbal remedy and dietary
spice turmeric (Curcuma longa). Curcumin has a surprisingly wide range of
beneficial properties, including anti-inflammatory, antioxidant, chemopreventive
and chemotherapeutic activity. The pleiotropic activities of curcumin derive from
its complex chemistry as well as its ability to influence multiple signaling
pathways, including survival pathways such as those regulated by NF-kappaB, Akt,
and growth factors; cytoprotective pathways dependent on Nrf2; and metastatic and
angiogenic pathways. Curcumin is a free radical scavenger and hydrogen donor, and
exhibits both pro- and antioxidant activity. It also binds metals, particularly
iron and copper, and can function as an iron chelator. Curcumin is remarkably
non-toxic and exhibits limited bioavailability. Curcumin exhibits great promise
as a therapeutic agent, and is currently in human clinical trials for a variety
of conditions, including multiple myeloma, pancreatic cancer, myelodysplastic
syndromes, colon cancer, psoriasis and Alzheimer’s disease.

10 derm mistakes you don’t want to make. Fox GN. J Fam Pract. 2008 Mar;57(3):162-9.

The psychosocial and occupational impact of chronic skin disease. Hong J, Koo B, Koo J. Dermatol Ther. 2008 Jan-Feb;21(1):54-9.

Chronic skin diseases, particularly psoriasis and atopic dermatitis, have a
negative impact on patients’ quality of life. Patients often experience
significant psychological and social distress such as increased levels of
depression and fear of stigma. Skin diseases can also impact patients’
occupational lives by causing them to miss work or be less productive. Quality of
life instruments provide important information for healthcare professionals, the
general public, and those involved in distribution of healthcare resources, which
helps prevent chronic skin disease from being overlooked amidst other medical
conditions.

National Psoriasis Foundation clinical consensus on psoriasis comorbidities and recommendations for screening. Kimball AB, Gladman D, Gelfand JM, Gordon K, Horn EJ, Korman NJ, Korver G, Krueger GG, Strober BE, Lebwohl MG; National Psoriasis Foundation. J Am Acad Dermatol. 2008 Jun;58(6):1031-42. Epub 2008 Mar 4.

There have been several articles and reports in recent months about comorbidities
and risks that affect psoriasis patients in addition to their underlying disease.
This piece reviews the current literature and begins to address what should be
done with this new information by updating the clinician about what health
screening tests, preventative exams, and referrals should be considered in this
population.

Assessing the impact of psoriatic arthritis on patient function and quality of life: lessons learned from other rheumatologic conditions. Mease PJ. Semin Arthritis Rheum. 2009 Feb;38(4):320-35. Epub 2008 Mar 4.

OBJECTIVES: To identify and describe measures that can be used to assess the
impact of psoriatic arthritis (PsA) on patient functioning and health-related
quality of life (HRQOL). METHODS: A literature search of the PubMed database to
identify papers describing assessment tools for quality of life and function in
rheumatic diseases. RESULTS: Many tools have been developed that can be used to
assess the impact of rheumatic disease on patient functioning and HRQOL. Although
several disease-specific tools have been developed for rheumatoid arthritis,
ankylosing spondylitis, and psoriasis, few have been developed specifically for
PsA, a condition that affects both skin and joints. However, several have been
adopted from their use in other conditions and used in clinical trials, such as
the Health Assessment Questionnaire and Short Form 36 and have shown good
performance characteristics. The Psoriatic Arthritis Quality of Life
questionnaire, a recently developed disease-specific instrument, has good
internal consistency, validity, and reliability. Initiatives are underway by the
Group for Research and Assessment of Psoriasis and Psoriatic Arthritis to
evaluate Psoriatic Arthritis Quality of Life responsiveness to treatment in
clinical trials, in addition to other projects intended to improve the assessment
of quality of life and function in PsA. These efforts are influenced by “lessons
learned” from assessment tools in rheumatoid arthritis, ankylosing spondylitis,
and psoriasis. CONCLUSIONS: Assessing the impact of PsA and its treatment on
patient function and quality of life is critical to improving patient outcomes,
and therefore, valid and reliable tools that can be easily used in both clinical
trials and clinical practice are being developed and refined.

Genes and structure of selected cytokines involved in pathogenesis of psoriasis. Pietrzak A, Zalewska A, Chodorowska G, Nockowski P, Michalak-Stoma A, Osemlak P, Krasowska D. Folia Histochem Cytobiol. 2008;46(1):11-21.

Psoriasis is a common skin disease involving 1-4% of human population worldwide,
of strong genetic background. The following cytokines are directly involved in
psoriasis: TNF, IL-1, IL-2, IL-6, IL-7, IL-8, IL-15, IL-18, IL-19, IL-20, IL-23
whereas IL-4, IL-10, IL-12 as well as IL-11, IL-17 and IFN-gamma are rather
indirectly engaged. This work is a review of some genetic factors and structure
of selected cytokines and receptors and their genes location.

Adalimumab for the treatment of severe psoriasis and psoriatic arthritis. Papoutsaki M, Costanzo A, Chimenti MS, Chimenti S. Expert Opin Biol Ther. 2008 Mar;8(3):363-70.

BACKGROUND: Psoriasis is a chronic, genetically determined, immunomediated,
inflammatory skin disease affecting approximately 2 – 3% of the Caucasian
population. Systemic treatment is required in moderate to severe plaque-type
psoriasis forms or psoriatic arthritis. However, cumulative organ toxicity, lack
of efficacy over time and other underlying diseases may limit long-term use of
conventional treatments. OBJECTIVES: TNF-alpha, serves a key role in potentiating
inflammatory responses associated with both psoriasis and psoriatic arthritis.
Adalimumab is a fully human anti-TNF-alpha monoclonal antibody; approved for the
treatment of psoriatic arthritis and, more recently, for plaque-type psoriasis.
Methods: This review reports the latest progresses made in the clinical use of
‘biologic’ drugs for psoriasis focusing on the clinical management of adalimumab
in the treatment of plaque psoriasis and psoriatic arthritis. RESULTS: Adalimumab
was shown to be effective in treating both psoriasis and psoriatic arthritis with
a rapid onset of action and a good safety profile.

Mediators of pruritus in psoriasis. Reich A, Szepietowski JC. Mediators Inflamm. 2007;2007:64727.

The pathogenesis of pruritus in psoriasis remains unclear. Many possible
mediators were implicated to transmit or modulate this sensation in psoriasis,
but none has been clearly proven to be a causative agent of itching. The most
often discussed theory mentioned the importance of impaired innervations and
neuropeptides imbalance in psoriatic skin. Other possible causes of itching might
be increased expression of interleukin 2 or vascular abnormalities. Recent data
indicated that pruritus could be also evoked by opioid system, prostanoids,
interleukin 31, serotonin, or proteases. Whether these mechanisms are also
involved in pruritus accompanying psoriasis requires further investigation.
Limited knowledge of pruritus origin in psoriasis is responsible for the lack of
the effective antipruritic treatments for psoriatics. Here, we summarize the
current knowledge about the pathogenesis of pruritus in psoriasis and point out
possible directions of future studies aiming the pathogenesis of this symptom in
psoriasis.

Herbal remedies for psoriasis: what are our patients taking? Steele T, Rogers CJ, Jacob SE. Dermatol Nurs. 2007 Oct;19(5):448-50, 457-63.

The objective of this study was to review and explore the top 15 currently used
and the historically used herbal remedies in the treatment of psoriasis.
Articles, press releases, message boards, product marketing sites, and patient
education lines through the National Library of Medicine (www.pubmed.gov),
National Psoriasis Foundation (www.psoriasis.org), Google (www.google. com), and
Yahoo (www.yahoo.com) were reviewed. Despite widespread use of complementary and
alternative medications, specifically herbals, there is limited scientific data
regarding their benefits and interactions. Studies on the efficacy and side
effect profiles of these remedies are needed. Additionally, both providers and
patients need to be cognizant of both potential benefit distortion and
adulteration of the herbal products.

The enigmatic world of mRNA-like ncRNAs: their role in human evolution and in human diseases. Széll M, Bata-Csörgo Z, Kemény L. Semin Cancer Biol. 2008 Apr;18(2):141-8. Epub 2008 Jan 15.

Accumulating data on non-protein-coding transcripts suggest that besides the
regulatory machinery driven by proteins, another yet enigmatic regulatory network
of RNA molecules operates and has considerable impact on cell functions.
Moreover, deregulation of these non-coding RNAs (ncRNAs) has been documented in
several human diseases suggesting that they may significantly contribute to their
pathogenesis. This review summarizes our present knowledge on the role of the
so-called mRNA-like ncRNAs in the complexity of multicellular organisms. We
provide some examples to show how these mRNA-like non-coding RNAs have been
discovered, how their cellular functions and role in the pathogenesis of human
diseases have been revealed.

Siddha medicine–background and principles and the application for skin diseases. Thas JJ. Clin Dermatol. 2008 Jan-Feb;26(1):62-78.

Siddha medicine is one of the most ancient medical systems of India. Siddha is
the mother medicine of ancient Tamils/Dravidians of peninsular South India. The
word Siddha means established truth. The persons who were associated with
establishing such a Siddha school of thought were known as Siddhars. They
recorded their mystic findings in medicine, yoga, and astrology in Tamil.
Fundamental Principles of Siddha include theories of Five Elements (Aimpootham),
and Three Forces/Faults (Mukkuttram). The Eight Methods of Examination (Envakai
Thervukal) is used to determine diagnosis, etiology, treatment and prognosis.
Siddha has safe herbal and herbo mineral treatment for psoriasis, eczema,
alopecia, diabetic ulcer, warts, vitiligo, pemphigus, pompholyx, leprosy, and
many more very common and rare diseases. Lifestyle modifications including diet
are important.

Psoriasis comorbidities. Gottlieb AB, Chao C, Dann F. J Dermatolog Treat. 2008;19(1):5-21.

Psoriasis is a chronic and debilitating inflammatory disease associated with
serious comorbidities. Psoriasis can have a significant impact on a patient’s
quality of life and is associated with loss of productivity, depression, and an
increased prevalence of malignancy. Emerging comorbidities of psoriasis include
cardiovascular disease and metabolic syndrome. Psoriasis patients have an
increased prevalence of the core components of metabolic syndrome, including
obesity, dyslipidemia, and insulin resistance. The relationship between psoriasis
and comorbidities such as metabolic syndrome and cardiovascular disease is likely
linked to the underlying chronic inflammatory nature of psoriasis. The molecular
mechanisms involved in psoriasis-associated dysregulation of metabolic function
are believed to be due, in large part, to the action of increased levels of
proinflammatory factors, such as tumor necrosis factor-alpha, that are central to
the pathogenesis of psoriasis. Recent studies investigating the effects of tumor
necrosis factor antagonists on the treatment of cardiovascular disease and
metabolic syndrome support this concept.

Outside-in signaling through integrins and cadherins: a central mechanism to control epidermal growth and differentiation? Müller EJ, Williamson L, Kolly C, Suter MM. J Invest Dermatol. 2008 Mar;128(3):501-16.

The process of epidermal renewal persists throughout the entire life of an
organism. It begins when a keratinocyte progenitor leaves the stem cell
compartment, undergoes a limited number of mitotic divisions, exits the cell
cycle, and commits to terminal differentiation. At the end of this phase, the
postmitotic keratinocytes detach from the basement membrane to build up the
overlaying stratified epithelium. Although highly coordinated, this sequence of
events is endowed with a remarkable versatility, which enables the quiescent
keratinocyte to reintegrate into the cell cycle and become migratory when
necessary, for example after wounding. It is this versatility that represents the
Achilles heel of epithelial cells allowing for the development of severe
pathologies. Over the past decade, compelling evidence has been provided that
epithelial cancer cells achieve uncontrolled proliferation following hijacking of
a “survival program” with PI3K/Akt and a “proliferation program” with growth
factor receptor signaling at its core. Recent insights into adhesion receptor
signaling now propose that integrins, but also cadherins, can centrally control
these programs. It is suggested that the two types of adhesion receptors act as
sensors to transmit extracellular stimuli in an outside-in mode, to inversely
modulate epidermal growth factor receptor signaling and ensure cell survival.
Hence, cell-matrix and cell-cell adhesion receptors likely play a more powerful
and wide-ranging role than initially anticipated. This Perspective article
discusses the relevance of this emerging field for epidermal growth and
differentiation, which can be of importance for severe pathologies such as
tumorigenesis and invasive metastasis, as well as psoriasis and Pemphigus
vulgaris.

Intra and extravascular transmembrane signalling of angiopoietin-1-Tie2 receptor in health and disease. Makinde T, Agrawal DK. J Cell Mol Med. 2008 Jun;12(3):810-28. Epub 2008 Feb 4.

Angiopoietin-1 (Ang-1) is the primary agonist for Tie2 tyrosine kinase receptor
(Tie2), and the effect of Ang-1-Tie2 signalling is context-dependent. Deficiency
in either Ang-1 or Tie2 protein leads to severe microvascular defects and
subsequent embryonic lethality in murine model. Tie2 receptors are expressed in
several cell types, including endothelial cells, smooth muscle cells,
fibroblasts, epithelial cells, monocytes, neutrophils, eosinophils and glial
cells. Ang-1-Tie2 signalling induces a chemotactic effect in smooth muscle cells,
neutrophils and eosinophils, and induces differentiation of mesenchymal cells to
smooth muscle cells. Additionally, this signalling pathway induces the secretion
of serotonin, matrix metalloproteinases (MMPs) and plasmin. Ang-1 inhibits the
secretion of tissue inhibitor of matrix metalloproteinase (TIMPs). Aberrant
expression and activity of Tie2 in vascular and non-vascular cells may result in
the development of rheumatoid arthritis, cancer, hypertension and psoriasis.
Ang-1 has an anti-inflammatory effect, when co-localized with vascular
endothelial growth factor (VEGF) in the vasculature. Thus, Ang-1 could be
potentially important in the therapy of various pathological conditions such as
pulmonary hypertension, arteriosclerosis and diabetic retinopathy. In this
article, we have summarized and critically reviewed the pathophysiological role
of Ang-1-Tie2 signalling pathway.

Use of pimecrolimus cream in disorders other than atopic dermatitis. Day I, Lin AN. J Cutan Med Surg. 2008 Jan-Feb;12(1):17-26.

BACKGROUND: Pimecrolimus is indicated for treatment of atopic dermatitis and has
been evaluated in many other disorders. OBJECTIVE: To review the efficacy of
pimecrolimus in treatment of disorders other than atopic dermatitis. METHODS: We
performed a PubMed search of the English-language literature using the key word
“pimecrolimus.” We reviewed articles reporting the use of pimecrolimus in
disorders other than atopic dermatitis and classified them by the type of study
used to evaluate efficacy. RESULTS: Randomized, double-blind studies have shown
that pimecrolimus is superior to vehicle in treatment of seborrheic dermatitis,
hand dermatitis, and asteatotic eczema but have yielded conflicting results
regarding intertriginous psoriasis and vitiligo. Open-label studies involving
four or more patients have shown favorable results in many disorders, including
contact dermatitis, rosacea, lichen sclerosus, and oral and genital lichen
planus. Case reports have shown that topical pimecrolimus may be useful in
cutaneous graft-versus-host disease, lichen striatus, cutaneous lichen planus,
and many other disorders. CONCLUSIONS: Topical pimecrolimus appears to be an
effective treatment for many disorders other than atopic dermatitis, especially
seborrheic dermatitis, hand dermatitis, and asteatoic eczema. It may be effective
in many other disorders, but its role in these disorders remains to be clarified
by additional studies.

Psoriasis or crusted scabies. Goyal NN, Wong

We describe a case of a 67-year-old woman with a 1-year history of nail
thickening and a non-itchy erythematous scaly eruption on the fingertips. She was
diagnosed with psoriasis and started on methotrexate after having had no response
to topical calcipotriol. The diagnosis was reviewed after it was revealed by
another consultant that the patient’s husband had been attending dermatology
clinics for several years with chronic pruritus, which had been repeatedly
thought to be due to scabies. Our patient was found to have crusted scabies after
a positive skin scraping showed numerous mites. She was treated with topical
permethrin, keratolytics and oral ivermectin. We also review the literature on
crusted scabies and its management, with recommendations.

Potential new indications of topical calcineurin inhibitors. Luger T, Paul C. Dermatology. 2007;215 Suppl 1:45-54. Epub 2007 Dec 18.

The topical calcineurin inhibitors pimecrolimus (Elidel) and tacrolimus
(Protopic) were initially developed for the treatment of atopic eczema (atopic
dermatitis), a chronic or chronically relapsing skin condition most prevalent in
infants and children. Their main advantages compared with conventional topical
corticosteroid therapy are that they are more selective in their mode of action,
do not induce skin atrophy and are not associated with significant systemic
absorption. In addition, topical calcineurin inhibitors may represent a useful
alternative to topical corticosteroids for the treatment of a number of other
inflammatory skin diseases. Preferred sites for the use of topical calcineurin
inhibitors are areas such as the face, neck, flexures, and genital areas, which
are more susceptible to topical corticosteroid side effects. The efficacy of
topical calcineurin inhibitors has been demonstrated for flexural psoriasis,
seborrhoeic, contact and hand eczema. Preliminary data also support the efficacy
of topical calcineurin inhibitors in lichen planus, facial lupus erythematosus,
autoimmune bullous dermatosis, and vitiligo. In these latter indications,
controlled studies are needed to better understand the efficacy and safety of
topical calcineurin inhibitors and their role in disease management. Copyright
2007 S. Karger AG, Basel.

EULAR evidence-based recommendations for the diagnosis of hand osteoarthritis: report of a task force of ESCISIT. Zhang W, Doherty M, Leeb BF, Alekseeva L, Arden NK, Bijlsma JW, Dincer F, Dziedzic K, Hauselmann HJ, Kaklamanis P, Kloppenburg M, Lohmander LS, Maheu E, Martin-Mola E, Pavelka K, Punzi L, Reiter S, Smolen J, Verbruggen G, Watt I, Zimmermann-Gorska I; ESCISIT. Ann Rheum Dis. 2009 Jan;68(1):8-17. Epub 2008 Feb 4.

OBJECTIVES: To develop evidence-based recommendations for the diagnosis of hand
osteoarthritis (OA). METHODS: The multidisciplinary guideline development group,
representing 15 European countries, generated 10 key propositions regarding
diagnosis using a Delphi consensus approach. For each recommendation, research
evidence was searched for systematically. Whenever possible, the sensitivity,
specificity and likelihood ratio (LR) were calculated; relative risk and odds
ratios were estimated for risk factors for hand OA. Quality of evidence was
categorised using the European League Against Rheumatism (EULAR) hierarchy, and
strength of recommendation was assessed by the EULAR visual analogue scale.
RESULTS: Diagnostic topics included clinical manifestations, radiographic
features, subgroups, differential diagnosis, laboratory tests, risk factors and
comorbidities. The sensitivity, specificity and LR varied between tests depending
upon the cut-off level, gold standard and controls. Overall, no single test could
be used to define hand OA on its own (LR <10) but a composite of the tests
greatly increased the chance of the diagnosis. The probability of a subject
having hand OA was 20% when Heberden nodes alone were present, but this increased
to 88% when in addition the subject was over 40 years old, had a family history
of nodes and had joint space narrowing in any finger joint. CONCLUSION: Ten key
recommendations for diagnosis of hand OA were developed using research evidence
and expert consensus. Diagnosis of hand OA should be based on assessment of a
composite of features.

Perioperative management of medications for psoriasis and psoriatic arthritis: a review for the dermasurgeon. Hernandez C, Emer J, Robinson JK. Dermatol Surg. 2008 Apr;34(4):446-59. Epub 2008 Jan 31.

BACKGROUND: Psoriasis affects an estimated 3% of the world’s population. Many are
on chronic immunosuppressive therapy for the cutaneous and joint manifestations
of this disorder. The management of these medications in the perioperative period
is controversial. Psoriasis and psoriatic arthritis medications can affect wound
healing, hemostasis, and infection risk during cutaneous surgery. OBJECTIVES: The
objective of this article is to provide a critical review of various medications
used for care of the psoriatic patient and their potential effect on cutaneous
surgical procedures. CONCLUSIONS: This review summarizes current understanding of
wound healing, hemostatic effects, and infectious risks regarding many psoriasis
medications including nonsteroidal anti-inflammatory drugs, cyclooxygenase
inhibitors, corticosteroids, various immunosuppressants, and biologic response
modifiers. Recommendations vary depending on the agent in question, type of
procedure, and comorbid conditions in the patient. Caution is advised when using
many of the medications reviewed due to lack of human data of their effects in
the perioperative period.

Drug delivery and formulations for the topical treatment of psoriasis. Su YH, Fang JY. Expert Opin Drug Deliv. 2008 Feb;5(2):235-49.

BACKGROUND: Psoriasis is one of the most common human skin diseases. It is
characterised by excessive growth and aberrant differentiation of corneocytes,
but is fully reversible with appropriate therapy. OBJECTIVE: There are many drug
therapies for psoriasis via the topical delivery route. This review describes the
topically applied drugs used to treat psoriasis. METHODS: Formulations to carry
or encapsulate these drugs are introduced in this review. Enhancing approaches
such as liposome inclusion, iontophoresis and laser are also discussed.
CONCLUSION: This review summarises developments in the design of formulations in
the area of topical drug delivery for treating psoriasis.

Activator protein 1 (Fos/Jun) functions in inflammatory bone and skin disease. Zenz R, Eferl R, Scheinecker C, Redlich K, Smolen J, Schonthaler HB, Kenner L, Tschachler E, Wagner EF. Arthritis Res Ther. 2008;10(1):201. Epub 2008 Jan 18.

Activator protein 1 (AP-1) (Fos/Jun) is a transcriptional regulator composed of
members of the Fos and Jun families of DNA binding proteins. The functions of
AP-1 were initially studied in mouse development as well as in the whole organism
through conventional transgenic approaches, but also by gene targeting using
knockout strategies. The importance of AP-1 proteins in disease pathways
including the inflammatory response became fully apparent through conditional
mutagenesis in mice, in particular when employing gene inactivation in a
tissue-specific and inducible fashion. Besides the well-documented roles of Fos
and Jun proteins in oncogenesis, where these genes can function both as tumor
promoters or tumor suppressors, AP-1 proteins are being recognized as regulators
of bone and immune cells, a research area termed osteoimmunology. In the present
article, we review recent data regarding the functions of AP-1 as a regulator of
cytokine expression and an important modulator in inflammatory diseases such as
rheumatoid arthritis, psoriasis and psoriatic arthritis. These new data provide a
better molecular understanding of disease pathways and should pave the road for
the discovery of new targets for therapeutic applications.

TLR7/9 antagonists as therapeutics for immune-mediated inflammatory disorders. Sun S, Rao NL, Venable J, Thurmond R, Karlsson L. Inflamm Allergy Drug Targets. 2007 Dec;6(4):223-35.

There is an increasing interest in ligands of nucleic acid-sensing Toll-like
receptors (TLR), especially TLR7 and TLR9, for pharmacological intervention in
various diseases. The TLR7 agonist imiquimod is currently used as a topical
treatment for genital warts caused by human papillomavirus (HPV), actinic
keratosis (AK) and superficial basal cell carcinoma. Oligodeoxynucleotides (ODN)
TLR9 agonists are currently in clinical trials for use in lung cancer, as
anti-viral therapy, as adjuvants and as immune modulators in asthma and
allergies. TLR7/9 antagonists, such as the anti-malaria drugs chloroquine,
hydroxychloroquine and quinacrine, have been used since the 1950s to treat
immune-mediated inflammatory disorders (IMID) such as rheumatoid arthritis (RA),
systemic lupus erythematosus (SLE) and Sjögren’s syndrome. However, the use of
these anti-malarials in IMID is limited due to the side effects or suboptimal
efficacy. Pre-clinical animal models as well as genetic linkage studies have
indicated that TLR7/9 play a pivotal role in the aforementioned as well as other
IMID such as multiple sclerosis (MS), inflammatory bowl disease (IBD)/colitis and
psoriasis. Recent evidence has suggested that selective, specific antagonists for
TLR7 and/or 9 might be more beneficial in certain diseases, such as SLE. Thus,
the use of suppressive ODN or novel small molecule TLR7/9 inhibitors with a
larger safety window and differentiated selectivity may potentially have
significant clinical utility in these IMID. Herein, we review efforts to develop
novel TLR7/9 antagonists and the rationale for the use of such therapeutics in a
variety of IMID.

New hypotheses in the genetics of psoriasis and other ‘complex’ diseases. Guilhou JJ, Molès JP. Dermatology. 2008;216(2):87-92. Epub 2008 Jan 23.

Psoriasis is a complex genetic disorder in which the disease, according to the
current concept, is caused by the interplay of many different genes. However,
recent genetic studies indicate that the location of these genes varies
considerably among populations and families, raising the question of how the same
phenotype can be induced by such variable genetic linkages. To circumvent these
discrepancies we propose that psoriasis could be induced by the same repetitive
DNA sequence, an endogenous retroviral element present at different locations in
the genome. The occurrence of the disease could be linked to an abnormal
activation of one or more endogenous retroviral element copies due to their
location and/or to modification of their sequence. This unifying concept would
simplify our understanding of genetically complex diseases. (c) 2008 S. Karger
AG, Basel.

[Biological therapy of inflammatory diseases] [Article in French] Von Frenckell C, Henno A, De la Brassinne M, Malaise MG. Rev Med Liege. 2007;62 Spec No:55-62.

The pathophysiology and the treatment of diseases with clinical presentation so
different as rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis
and psoriasis vulgaris have been revolutionized by the discovery of common
pro-inflammatory effector mechanisms involving TNF-alpha and by the use of
targeted therapies, the anti-TNF-alpha antibodies. In the past 10 years, our
experience has helped several hundreds of patients who were treated with novel
drugs, years before they became routinely available. In parallel tools of
metrology were developped that can now be applied to the routine patient. Lastly,
clinical research on these new drugs has also generated derived research works
allowing the university hospital to satisfactorilly fullfil its specific
missions.

[Cathelicidin LL-37. A central factor in the pathogenesis of inflammatory dermatoses?] [Article in German] Schauber J, Ruzicka T, Rupec RA. Hautarzt. 2008 Jan;59(1):72-4.

Keratinocytes produce and secrete antimicrobial peptides which function as
endogenous antibiotics and as signaling molecules within the cutaneous innate
immune system. Recent studies demonstrate that the antimicrobial peptide
cathelicidin LL-37 plays an important role in the pathogenesis of atopic eczema,
rosacea and psoriasis. Whereas skin in atopic eczema shows decreased cathelicidin
expression which leads to increased susceptibility to superinfection in those
patients, overabundant expression of cathelicidin peptide fragments causes
inflammation in rosacea. Finally, in psoriasis cathelicidin peptide binds to self
DNA which triggers an autoimmune response. These studies demonstrate the role of
cathelicidin as a central factor in the pathogenesis of cutaneous inflammation.
Therapies targeting cathelicidin expression and function could lead to new
treatments for these diseases.

The occurrence of psoriatic arthritis in Denmark. Pedersen OB, Svendsen AJ, Ejstrup L, Skytthe A, Junker P. Ann Rheum Dis. 2008 Oct;67(10):1422-6. Epub 2008 Jan 21.

OBJECTIVE: To apply and compare different classification criteria on a
representative nationwide sample of psoriatic arthritis (PsA) twins and to
estimate the prevalence and incidence of PsA. METHODS: The study comprised three
Danish nationwide twin cohorts. In 1994 37 388 Danish twin individuals and in
2002 46 418 twin individuals received a questionnaire, including questions on
rheumatic diseases. Twins reporting PsA and their co-twins were classified
according to the Moll and Wright and CASPAR (ClASsification criteria for
Psoriatic ARthritis) criteria based on interview, clinical examination and
scrutiny of medical records. RESULTS: 228 twin individuals reported PsA and 164
(72%) participated in clinical validation. By using the Moll and Wright and
CASPAR criteria, 54 and 50 cases were diagnosed with PsA respectively. The
positive predictive value of self-reported PsA was 31%. According to the Moll and
Wright and CASPAR criteria the prevalence was 0.15% (95% CI: 0.13%, 0.22%) and
0.14% (95% CI: 0.11%, 0.19%) respectively. The annual incidence rate based on new
self-reported cases in 2002 was 6/100 000 person-years (95% CI: 3/100 000
person-years, 11/100 000 person-years). CONCLUSIONS: The positive predictive
value of self-reported PsA was 31%. The prevalence and incidence figures of PsA
were equivalent to the previously reported occurrence in population- and
hospital-based studies.

Economic burden of psoriatic arthritis. Ackermann C, Kavanaugh A. Pharmacoeconomics. 2008;26(2):121-9.

Psoriatic arthritis (PsA) is a chronic autoimmune disease characterized by
inflammatory arthritis in association with skin psoriasis (Ps). PsA may show a
heterogeneous and variable clinical course, with involvement of peripheral and
axial diarthrodial joints, periarticular structures such as entheses, as well as
the skin and nails. Evidence is increasing that affected patients can have
significant radiographic joint damage, functional impairment, reduced quality of
life (QOL) and long-term work disability. The economic burden of PsA can be
considerable.There is an increasing interest in pharmacoeconomic evaluations in
PsA, driven mostly by the introduction of highly effective but expensive biologic
agents, particularly inhibitors of the proinflammatory cytokine tumour necrosis
factor (TNF)-alpha. Treatment with TNFalpha inhibitors results in not only
substantial improvements in signs and symptoms of arthritis, but also
improvements in all distinct sites of the disease, such as axial arthritis,
dactylitis, enthesitis and skin disease.There is a dearth of published
pharmacoeconomic evaluations in the field of PsA. The notable clinical efficacy
of the TNFalpha inhibitors needs to be factored into a comprehensive assessment
of their value. Further analyses are needed to optimize the use of the new
biologic agents in PsA.

Duration of remission of biologic agents for chronic plaque psoriasis. Langley RG, Gordon KB. J Drugs Dermatol. 2007 Dec;6(12):1205-12.

BACKGROUND: The efficacy of biologic agents to treat psoriasis has been
established in well-designed clinical trials. The primary endpoint is usually a
75% reduction from the baseline Psoriasis Area and Severity Index, stressing
acute control of symptoms. Another important endpoint is remission, or duration
of response off therapy, which reduces exposure to immunosuppressive agents and
potentially lowers costs. METHODS: We searched the literature for randomized
controlled clinical trials of remission with biologic agents. RESULTS AND
CONCLUSIONS: Among approved biologic agents, alefacept produced the longest
posttreatment clinical benefits in responders (7 to 8.6 months after a 12-week
course), followed by infliximab (4.7 months after a 6-week, 3-dose induction
period), etanercept (2.8 to 3.5 months after 12 weeks of therapy), and efalizumab
(2.8 months after 24 weeks of therapy). Long-term response to infliximab in some
patients may be limited by neutralizing antibodies. Additional data on adalimumab
are needed.

The role of emollients in the management of diseases with chronic dry skin. Proksch E. Skin Pharmacol Physiol. 2008;21(2):75-80. Epub 2008 Jan 11.

Dry skin is a common skin condition as well as a key aspect of a number of
diseases such as atopic dermatitis and psoriasis but also of other diseases and
systemic conditions. Dry skin has an impact on the patient in terms of
discomfort, pruritus and impaired quality of life. Within the overall treatment
regimen for these diseases, the use of emollients to manage dry skin plays a
considerable role in managing skin conditions. In atopic dermatitis and
psoriasis, emollients help to improve skin condition and to reduce pruritus
alongside more potent pharmacological agents. It is important to choose an
emollient that not only soothes and rehydrates the skin but also offers numerous
other dermatological supporting roles, especially induction of proper epidermal
differentiation. This review will explain the role of emollients within the
management of diseases with dry skin as a major symptom and the components of an
ideal emollient. (c) 2008 S. Karger AG, Basel

Thematic review series: skin lipids. Peroxisome proliferator-activated receptors and liver X receptors in epidermal biology. Schmuth M, Jiang YJ, Dubrac S, Elias PM, Feingold KR. J Lipid Res. 2008 Mar;49(3):499-509. Epub 2008 Jan 8.

The epidermis is a very active site of lipid metabolism, and all peroxisome
proliferator-activated receptor (PPAR) and liver X receptor (LXR) isoforms are
expressed in the epidermis. Activation of PPARalpha, -beta/delta, or -gamma or
LXRs stimulates keratinocyte differentiation. Additionally, activation of these
receptors also improves permeability barrier homeostasis by a number of
mechanisms, including stimulating epidermal lipid synthesis, increasing lamellar
body formation and secretion, and increasing the activity of enzymes required for
the extracellular processing of lipids in the stratum corneum, leading to the
formation of lamellar membranes that mediate permeability barrier function. The
stimulation of keratinocyte differentiation and permeability barrier formation
also occurs during fetal development, resulting in accelerated epidermal
development. PPAR and LXR activation regulates keratinocyte proliferation and
apoptosis, and studies have shown that these receptors play a role in cutaneous
carcinogenesis. Lastly, PPAR and LXR activation is anti-inflammatory, reducing
inflammation in animal models of allergic and irritant contact dermatitis.
Because of their broad profile of beneficial effects on skin homeostasis, PPAR
and LXR have great potential to serve as drug targets for common skin diseases
such as psoriasis, atopic dermatitis, and skin cancer.

Progress of experimental study on treatment of psoriasis by Chinese medicinal monomer and single or compound recipe in Chinese materia medica. Zhang H, Gu J. Chin J Integr Med. 2007 Dec;13(4):312-6.

Psoriasis is a common, chronic, recurrent inflammatory skin disorder whose
etiology is still unknown. It is believed that a multiple-gene inheritance is
involved and it also involves various factors such as immunity, inflammation,
cell proliferation, apoptosis, neural media, etc. Since cytokines are key
mediators in inflammation, a number of Chinese medicines (CMs) have been reported
to have certain antagonist effects on pro-inflammatory cytokines such as tumor
necrosis factor-alpha (TNF-alpha), platelet active factor (PAF) and interleukin-8
(IL-8). Some researches on CMs have made significant breakthroughs in psoriasis
by intervening with cytokines. Abnormalities with keratinocyte proliferation and
apoptosis are considered to be present in patients with psoriasis and a number of
studies show that the mechanism of CMs on psoriasis may be through the inhibition
of the keratinocyte proliferation and induction of apoptosis. Other studies also
show that the inhibition of fibroblast-secreted cytokines could regulate
keratinocyte proliferation and differentiation and reduce the level of Calcitonin
gene-related peptide (CGRP) in plasma and in lesions so as to slow down the
process of inflammation and proliferation in psoriasis. The most commonly used
models for psoriasis are the scaled tails or the vaginal epithelium of mice in
China. They were used to observe the histopathological changes after the model
mice were treated with CMs with the inhibition on the mitosis of vaginal
epithelium or promotion of granular layer in rat tail taken as the indices of
clinical efficacy. A variety of signs occur in psoriasis patients with TCM
blood-stasis syndrome type and the effect of CMs in activating blood circulation
to remove blood stasis on psoriasis suggested that the mechanism of CMs may be
partially correlated to hemorrheology and microcirculation. Along with the
continuous development of the biosciences, some TCM theories for psoriasis have
been confirmed by laboratory studies. However, the exploration into traditional
Chinese medicines’ biomechanics in psoriasis and the therapeutic mechanism of CMs
by integrative medicine still requires further studies.

Pathophysiology of psoriasis: recent advances on IL-23 and Th17 cytokines. Fitch E, Harper E, Skorcheva I, Kurtz SE, Blauvelt A. Curr Rheumatol Rep. 2007 Dec;9(6):461-7.

T helper (Th) 17 cells, a novel T-cell subset, have been implicated in the
pathogenesis of psoriasis and other autoimmune inflammatory diseases. Interleukin
(IL)-23 stimulates survival and proliferation of Th17 cells, and thus serves as a
key master cytokine regulator for these diseases. In psoriasis, IL-23 is
overproduced by dendritic cells and keratinocytes, and this cytokine stimulates
Th17 cells within dermis to make IL-17A and IL-22. IL-22, in particular, drives
keratinocyte hyperproliferation in psoriasis. Future targeting of these key
cytokines is likely to lead to dramatic clinical improvement in patients with
psoriasis. This review focuses on the numerous recent studies on the roles of
IL-23 and Th17 cells in the pathogenesis of psoriasis.

Axial disease in psoriatic arthritis. Gladman DD. Curr Rheumatol Rep. 2007 Dec;9(6):455-60.

The definition of axial disease in psoriatic arthritis has varied from isolated
unilateral grade 2 sacroiliitis to criteria similar to those used for ankylosing
spondylitis. Depending on the definition used, the prevalence of axial disease
varies from 25% to 70% of patients with psoriatic arthritis. This article reviews
the prevalence, clinical and radiologic features, pathogenesis, prognosis, and
treatment of psoriatic spondylitis.

Psoriatic arthritis epidemiology. Setty AR, Choi HK. Curr Rheumatol Rep. 2007 Dec;9(6):449-54.

Recent studies have added to our knowledge of the epidemiology of psoriatic
arthritis (PsA) across various populations. Absence of a standard case definition
and the relative rarity of PsA may have contributed to the paucity of available
data to date. Reported prevalence estimates appear to vary more than incidence
estimates. Prevalence estimates may vary as a result of differences in genetic
factors, exposure to environmental factors, and study methods. Although
prevalence data among different subgroups and extrapolation from clinical and
laboratory data allow some inferences about the role of various potential risk
factors for PsA, only one study has investigated them specifically. Overall,
quality of life in PsA appears similar to that in rheumatoid arthritis, whereas
available data on the mortality impact of PsA are conflicting, preventing a
unified conclusion. This review summarizes recent data on PsA epidemiology.

Psoriatic arthritis: current topics. McCarey D, McInnes IB. Curr Rheumatol Rep. 2007 Dec;9(6):442-8.

Psoriatic arthritis is a common inflammatory arthropathy that occurs in
approximately 25% of psoriasis patients. Due to significant advances in
therapeutics–mainly the advent of biologic therapy–the disease has been subject
to intense investigation recently. This review summarizes recent investigations
of disease pathogenesis and clinical treatment. Clinical responses to tumor
necrosis factor-blocking agents appear robust and superior to traditional
disease-modifying drug responses, whereas other interventions, such as
costimulation blockade, require more investigation. The pathogenesis of the
disease appears related to T helper 17-polarized immune responses that target
skin, joints, and the enthesial compartment. Finally, new insights into the
disorder’s genetic antecedents are emerging as more cohorts of patients undergo
advanced genetic screening methods.

T cells in psoriatic arthritis. Choy E. Curr Rheumatol Rep. 2007

Psoriatic arthritis is characterized by chronic inflammation of the skin and
synovial joint. T cells are abundant in the inflamed joint and skin. Disease
susceptibility is associated with major histocompatibility complex, which
presents antigens to T cells. T cells in the synovial joints have an activated
phenotype and demonstrate selective T-cell receptor usage suggestive of
oligoclonal expansions. Taken together, these facts suggest that psoriatic
arthritis is driven by antigen or autoantigen-driven T-cell activation. The
therapeutic benefit of anti-T-cell agents further supports an important
pathogenic role for T cells in persistent synovial inflammation and joint damage
in psoriatic arthritis.

Tacrolimus in dermatology-pharmacokinetics, mechanism of action, drug interactions, dosages, and side effects: part I. Sehgal VN, Srivastava G, Dogra S. Skinmed. 2008 Jan-Feb;7(1):27-30.

The advent of tacrolimus at the end of the preceding century in the armamentarium
of atopic dermatitis management was hailed as a breakthrough advance. It was,
therefore, thought worthwhile to precisely review its origin and mechanism of
action. Its topical application in the form of 0.03% to 0.1% ointments is rapidly
effective and safe in pediatric and adult patients. Its use in atopic dermatitis
ever since has been approved in Japan, the United States, Europe, and the Indian
subcontinent. Thus, its local immunosuppressive action was fairly intriguing.
Accordingly, its indications/uses were extended to cover several inflammatory
dermatoses. Vitiligo, psoriasis, alopecia areata, contact hypersensitivity,
lichen planus, pyoderma gangrenosum, ichthyosis linearis circumflexa, and skin
grafting/transplant are a few unapproved indications and uses, in addition to
miscellaneous dermatoses. At present, its therapeutic efficacy other then atopic
dermatitis is confined to case studies, and large studies are warranted. At this
point in time, therefore, it is conceivable that tacrolimus use should be
carefully evaluated and used only when the conventional treatment has failed to
yield favorable results. It deserves sizable caution for use in various
dermatologic conditions pending its long-term safety and efficacy data in large
patient populations.

Cardiometabolic risk in psoriasis: differential effects of biologic agents. Kaplan MJ. Vasc Health Risk Manag. 2008;4(6):1229-35.

Psoriasis is associated to an increased risk of cardiovascular (CV)
complications. Overall, the pathogenic mechanisms involved in premature CV
complications in psoriasis appear to be complex and multifactorial, with
traditional and nontraditional risk factors possibly contributing to the
increased risk. Based on what is known about the pathogenesis of psoriasis and
extrapolating the current knowledge on CV complications in other inflammatory
diseases, studies are needed to investigate if appropriate control of the
inflammatory, immunologic and metabolic disturbances present in psoriasis can
prevent the development of this potentially lethal complication. It is clear that
there is a great need for heightened awareness of the increased risk for vascular
damage in patients with psoriasis. It is also crucial to closely monitor patients
with psoriasis for CV risk factors including obesity, hypertension, diabetes, and
hyperlipidemia. Whether treatment regimens that effectively manage systemic
inflammation will lead to prevention of CV complications in psoriasis needs to be
investigated. Clearly, studies should focus on establishing the exact mechanisms
that determine CV risk in psoriasis so that appropriate preventive strategies and
treatment guidelines can be established.

Copy number variation of beta-defensins and relevance to disease. Hollox EJ. Cytogenet Genome Res. 2008;123(1-4):148-55. Epub 2009 Mar 11.

Beta-defensins are multifunctional proteins that have an important role in the
innate immune system. A cluster of beta-defensin genes shows common and extensive
variation in copy number in humans. This copy number has been associated with
differing susceptibility to Crohn’s disease and psoriasis. In this review, I
summarise what is currently known about copy number variation (CNV) of
beta-defensins, and discuss practical considerations when studying these genes,
and copy number variation in general. I also suggest future directions for
research, with an emphasis on improvement of methods for accurately typing CNV.
Copyright 2009 S. Karger AG, Basel.

Update on the natural history and systemic treatment of psoriasis. Richardson SK, Gelfand JM. Adv Dermatol. 2008;24:171-96.

The onset of psoriatic disease and its associated comorbidities involves the
interplay among a myriad of genetic and environmental risk factors. As we gain
further insight into the immunopathogenesis of psoriasis, we hope it will provide
the basis for the development of safer, more efficacious, and more durable
therapeutics in the future. Given its enormous toll on patient health and quality
of life, steps should be taken to prevent or decrease the risk for
psoriasis-associated comorbidities through behavior modification and use of
preventative health screenings and treatments. Future studies will need to be
performed to determine if successful treatment of psoriasis will lead to a
decreased risk for developing psoriasis-associated comorbidities over time.

Management of childhood psoriasis. Cordoro KM. Adv Dermatol. 2008;24:125-69.

Treating children with psoriasis represents one of the most rewarding yet
constantly challenging endeavors in dermatology. These patients require time,
energy, enthusiasm, empathy, and current, comprehensive knowledge of the unique
clinical presentations in children and available therapies, including clinical
action spectrum, mechanism of action, potential toxicity, and monitoring.
Longitudinal trials examining the epidemiology and natural history of psoriasis,
as well as the safety and efficacy of current and emerging treatments, are
desperately needed in the pediatric population. Partner with the patient, family,
and other multidisciplinary providers to form an educational and therapeutic
alliance. Early in the course of disease, schedule frequent visits for
reinforcement of the therapeutic plan, education, clinical and treatment
monitoring, and support. As the disease and the patient’s physical, psychosocial
and emotional level of functioning evolve, so too will the requirement for
follow-up and monitoring. Patient advocacy and education groups, such as the
National Psoriasis Foundation (www.psoriasis.org; 800-723-9166) are excellent
resources and can serve as an extension of your comprehensive care.

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.

TNF-mediated inflammatory disease. Bradley JR. J Pathol. 2008 Jan;214(2):149-60.

TNF was originally described as a circulating factor that can cause necrosis of
tumours, but has since been identified as a key regulator of the inflammatory
response. This review describes the known signalling pathways and cell biological
effects of TNF, and our understanding of the role of TNF in human disease. TNF
interacts with two different receptors, designated TNFR1 and TNFR2, which are
differentially expressed on cells and tissues and initiate both distinct and
overlapping signal transduction pathways. These diverse signalling cascades lead
to a range of cellular responses, which include cell death, survival,
differentiation, proliferation and migration. Vascular endothelial cells respond
to TNF by undergoing a number of pro-inflammatory changes, which increase
leukocyte adhesion, transendothelial migration and vascular leak and promote
thrombosis. The central role of TNF in inflammation has been demonstrated by the
ability of agents that block the action of TNF to treat a range of inflammatory
conditions, including rheumatoid arthritis, ankylosing spondylitis, inflammatory
bowel disease and psoriasis. The increased incidence of infection in patients
receiving anti-TNF treatment has highlighted the physiological role of TNF in
infectious diseases. 2007 Pathological Society of Great Britain and Ireland

Hidradenitis suppurativa: an update. Lee RA, Yoon A, Kist J. Adv Dermatol. 2007;23:289-306.

HS is a chronic, debilitating inflammatory dermatosis that is often refractory to
treatment. Many medical therapies have been tried and some show efficacy. The
introduction of new immunosuppressive medications has revolutionized the
treatment of psoriasis in dermatology. These therapies have the potential to
powerfully abort the molecular signals driving inflammation in HS and perhaps
even induce a remission. This may offer patients an alternative to radical
excisional surgery. However, more studies are needed to evaluate the long-term
effects of these medications, particularly in light of their association with an
increased risk of malignancy and infection. Evaluation of treatment efficacy has
been hindered by a lack of uniform standards to track treatment response. The
classic clinical classification system has limitations but is a useful scheme to
guide selection of treatments. Further laboratory studies may be warranted,
depending on the clinical presentation (Box 3). While there are many approaches
to treating HS, the authors offer an algorithm based on disease severity (Fig.
9). It is important to address many patient-oriented concerns, such as the pain,
dampness, and smell associated with draining sinuses. Communication with the
patient about expectations is important to direct treatment. Often a
multidisciplinary approach involving dermatology, plastic surgery, gynecology,
and urology may be necessary to diagnose and treat the disease. Both medical and
surgical options should be explored before embarking on therapy.

Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Tracey D, Klareskog L, Sasso EH, Salfeld JG, Tak PP. Pharmacol Ther. 2008 Feb;117(2):244-79. Epub 2007 Oct 26.

During the past 30 years, elucidation of the pathogenesis of rheumatoid
arthritis, Crohn’s disease, psoriasis, psoriatic arthritis and ankylosing
spondylitis at the cellular and molecular levels has revealed that these diseases
share common mechanisms and are more closely related than was previously
recognized. Research on the complex biology of tumor necrosis factor (TNF) has
uncovered many mechanisms and pathways by which TNF may be involved in the
pathogenesis of these diseases. There are 3 TNF antagonists currently available:
adalimumab, a fully human monoclonal antibody; etanercept, a soluble receptor
construct; and infliximab, a chimeric monoclonal antibody. Two other TNF
antagonists, certolizumab and golimumab, are in clinical development.The
remarkable efficacy of TNF antagonists in these diseases places TNF in the center
of our understanding of the pathogenesis of many immune-mediated inflammatory
diseases. The purpose of this review is to discuss the biology of TNF and related
family members in the context of the potential mechanisms of action of TNF
antagonists in a variety of immune-mediated inflammatory diseases. Possible
mechanistic differences between TNF antagonists are addressed with regard to
their efficacy and safety profiles.

Immunopathogenesis of psoriasis. Nickoloff BJ, Qin JZ, Nestle FO. Clin Rev Allergy Immunol. 2007 Oct;33(1-2):45-56.

Investigations into the cause and treatment of psoriasis remain at the forefront
of basic and applied clinical research efforts around the world. The purpose for
this review is to provide an up-to-date synopsis of recent progress in ten
sections exploring the immunological and inflammatory basis for psoriasis. Given
the breadth of this topic in investigative skin biology and frequent paradigm
shifts, it should not be surprising that the bibliography contains more than 150
references; many of which have been published in the last 5 years. Whereas
considerable progress has been made into the immunopathogenesis of psoriasis,
many fundamentally important questions remain regarding the role of cells located
in both epidermal and dermal compartments. Attempts to characterize various
animal models of psoriasis, delineation of the mechanism of action for biological
agents, and consideration of molecular links between skin inflammation and
various extracutaneous comorbidities are likely to continue challenging
investigators and clinicians for many years to come.

Peroxisome proliferator-activated receptors (PPARs) and the human skin: importance of PPARs in skin physiology and dermatologic diseases. Sertznig P, Seifert M, Tilgen W, Reichrath J. Am J Clin Dermatol. 2008;9(1):15-31.

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear
receptor superfamily that regulate lipid, glucose, and amino acid metabolism.
More recently, PPARs and corresponding ligands have been shown in skin and other
organs to regulate important cellular functions, including cell proliferation and
differentiation, as well as inflammatory responses. These new functions identify
PPARs and corresponding ligands as potential targets for the treatment of various
skin diseases and other disorders.It has been shown that in inflammatory skin
disorders, including hyperproliferative psoriatic epidermis and the skin of
patients with atopic dermatitis, the expression of both PPARalpha and PPARgamma
is decreased. This observation suggests the possibility that PPARalpha and
PPARgamma activators, or compounds that positively regulate PPAR gene expression,
may represent novel NSAIDs for the topical or systemic treatment of common
inflammatory skin diseases such as atopic dermatitis, psoriasis, and allergic
contact dermatitis. Moreover, recent findings indicate that PPAR-signaling
pathways may act as a promising therapeutic target for the treatment of
hyperproliferative skin diseases including skin malignancies. Studies in
non-diabetic patients suggest that oral thiazolidinediones, which are synthetic
ligands of PPARgamma, not only exert an antidiabetic effect but also may be
beneficial for moderate chronic plaque psoriasis by suppressing proliferation and
inducing differentiation of keratinocytes; furthermore, they may even induce cell
growth arrest, apoptosis, and terminal differentiation in various human malignant
tumors. It has been reported that PPARalpha immunoreactivity is reduced in human
keratinocytes of squamous cell carcinoma (SCC) and actinic keratosis (AK), while
PPARdelta appears to be upregulated. Additionally, the microvessel density is
significantly higher in AK and SCC that express high levels of PPARdelta.
PPARdelta has been demonstrated to have an anti-apoptotic role and to maintain
survival and differentiation of epithelial cells, whereas PPARalpha and PPARgamma
activators induce differentiation and inhibit proliferation and regulate
apoptosis. In melanoma, the growth inhibitory effect of PPARgamma activation is
independent of apoptosis and seems to occur primarily through induction of cell
cycle arrest in the G1 phase of the cell cycle or induction of
re-differentiation. PPARalpha activation causes inhibition of migration of
melanoma cells and anchorage-independent growth, whereas primary tumor growth
remains unaltered. In clinical trials of gemfibrozil, a PPARalpha ligand,
significantly fewer patients treated with this lipid-lowering drug were diagnosed
with melanoma as compared to those in the control group.In conclusion, an
increasing body of evidence indicates that PPAR signaling pathways may represent
interesting therapeutic targets for a broad variety of skin disorders, including
inflammatory skin diseases such as psoriasis and atopic dermatitis, and skin
malignancies.

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.

Evaluating the effectiveness of psychosocial interventions for individuals with visible differences: a systematic review of the empirical literature. Bessell A, Moss TP. Body Image. 2007 Sep;4(3):227-38. Epub 2007 Jun 26.

The objective of this review was to systematically identify and evaluate all
known studies testing empirically the efficacy of psychosocial intervention
programmes for adults with visible differences. Twelve papers met the inclusion
criteria. None of the papers demonstrated adequately the clinical effectiveness
of the interventions. The review concluded that further research was needed to
demonstrate adequately the effectiveness of existing interventions, and a greater
number of Randomised Controlled Trials and experimental studies were required to
increase the methodological validity of intervention studies.

Treatment of hand and foot psoriasis with emphasis on efalizumab. Kircik L. Skin Therapy Lett. 2007 Nov;12(9):4-7.

Hand and foot psoriasis is a chronic and debilitating disease that manifests as
plaque-type or pustular-type lesions. Although the palms and soles represent only
2% of the total body surface area, psoriasis of these regions may lead to
physical dysfunctions that can greatly impair dexterity, mobility, and the
quality of life of affected individuals. Deregulation of T-lymphocyte-mediated
immune response is important in the pathophysiology of psoriasis. Efalizumab
(Raptiva, Genentech) is an anti-CD11a monoclonal antibody that disrupts the
interaction between T cells and antigen-presenting cells, thereby inhibiting
various T-cell-mediated immune processes that include activation and trafficking.
Recent evidence indicates that efalizumab may be beneficial for patients with
hand and foot psoriasis.

The effect of weight on the efficacy of biologic therapy in patients with psoriasis. Clark L, Lebwohl M. J Am Acad Dermatol. 2008 Mar;58(3):443-6. Epub 2007 Dec 20.

BACKGROUND: The prevalence of obesity is rapidly increasing in the United States.
Patients with psoriasis, in particular, tend to be above normal weight. Three of
the 5 biologics used to treat psoriasis are fixed-dosed treatments: alefacept,
etanercept, and adalimumab. Dosing regimens do not account for weight. OBJECTIVE:
We attempted to determine whether the efficacy of the biologics is affected by
weight. METHODS: We review the existing body of literature, including subgroup
analyses, relating to efficacy and weight for infliximab, efalizumab, alefacept,
and etanercept. No relevant literature was found for adalimumab. RESULTS:
Weight-based dosed medications do not seem to lose efficacy with increasing
weight. Both etanercept and alefacept may have compromised efficacy in heavier
individuals. LIMITATIONS: The data are limited to subgroup analyses and smaller
studies, often with no statistical significance reported. CONCLUSIONS: Additional
studies are warranted, specifically designed to address the issue of obesity and
response to therapy of the biologics. Alternative dosing for etanercept and
alefacept should be further evaluated in patients above normal weight.

Psoriasis: consensus on topical therapies. van de Kerkhof PC, Barker J, Griffiths CE, Kragballe K, Mason J, Menter A, Papp K. J Eur Acad Dermatol Venereol. 2008 Jul;22(7):859-70. Epub 2007 Dec 13.

OBJECTIVE: A consensus conference was convened to evaluate the topical treatment
of psoriasis. PARTICIPANTS: Members of the International Psoriasis Council (IPC)
with broad clinical experience in the treatment of psoriasis and a specialist in
meta- and pharmacoeconomic analyses were invited to participate on the consensus
panel. Those accepting the invitation convened in Saariselkä, Finland. EVIDENCE:
An advisory group on topical treatments was nominated by the organizing panel
members. All participants reported at the consensus conference on evidence based
data with respect to disease severity assessment, the available data on efficacy
and safety and on a comparative efficacy/safety analysis. CONSENSUS PROCESS: At
the consensus conference, the presentations were discussed and conclusions, which
were reached by the group, were recorded. Active participants of the group wrote
assigned sections of this consensus document with a majority of participants
agreed on the conclusions.

Infliximab in dermatological treatment: beyond psoriasis. Rigopoulos D, Korfitis C, Gregoriou S, Katsambas AD. Expert Opin Biol Ther. 2008 Jan;8(1):123-33.

Infliximab is a chimeric monoclonal antibody of the IgG1 class. Experience from
its use has been accumulated in rheumatology and gastroenterology by the
treatment of rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis
and inflammatory bowel disease, respectively. Because of its TNF-alpha binding
capacity it has been approved for the treatment of moderate-to-severe plaque
psoriasis. Moreover, it has also been evaluated in other inflammatory dermatoses
as well as systemic diseases involving the skin such as severe atopic dermatitis,
pityriasis rubra pilaris, pyoderma gangrenosum and cutaneous sarcoidosis. The
possible future uses of infliximab in dermatology are being reviewed herein.

Serotonergic drugs–a possible role in the treatment of psoriasis? Thorslund K, Nordlind K. Drug News Perspect. 2007 Oct;20(8):521-5.

Psoriasis is a chronic inflammatory skin disease, where specific immunity and/or
innate immunity may be of importance in the disease pathogenesis. Psoriasis may
be worsened by stress, which suggests that a neuroimmune interaction is
contributing to the disease. Serotonin (5-HT) is a monoamine which besides
general effects also has an impact on cell proliferation, migration and
apoptosis. 5-HT exerts its effects via several receptors. 5-HT has a role in
inflammation, and 5-HT receptors as well as its transporter protein have been
found in psoriatic skin. 5-HT 1A receptor-positive mast cells, and 5-HT 2A
receptor and serotonin reuptake transporter (SERT)-positive T lymphocytes may be
targets for therapy with serotonergic drugs in psoriasis. (c) 2007 Prous Science.
All rights reserved.

The genetics and biology of Irf5-mediated signaling in lupus. Kozyrev SV, Alarcon-Riquelme ME. Autoimmunity. 2007 Dec;40(8):591-601.

Recently much attention was attracted to the importance of the type I interferon
pathway in the initiation and development of the autoimmune disease systemic
lupus erythematosus (SLE). Many SLE patients have increased serum levels of
IFN-alpha and display an IFN gene expression “signature” characterized by strong
overexpression of IFN-responsive genes in leukocytes and target tissues.
Moreover, about 20% of cancer patients treated with IFN-alpha therapy manifest
symptoms resembling SLE and some later develop the disease. One of the key genes
of the IFN-alpha pathway, IRF5, was found to be strongly associated with SLE. Two
functional SNPs lead to alternative splicing and altered steady-state level of
IRF5 gene expression. Besides, the gene has a polymorphic inserion/deletion in
exon 6, which contributes to the diversity in the isoform pattern of IRF5.
Interestingly, recent studies have not found association of IRF5 with the other
autoimmune diseases, such as rheumatoid arthritis or psoriasis, suggesting the
unique role for IRF5 in the development of lupus. Here, we present the current
knowledge on IRF5 genetics and its biological function and discuss the possible
ways in which IRF5 contributes to susceptibility to SLE.

Clinical use of anti-TNF-alpha biological agents–a guide for GPs. Chang J, Girgis L. Aust Fam Physician. 2007 Dec;36(12):1035-8.

BACKGROUND: Tumour necrosis factor-alpha (TNF-alpha) inhibitors are a new class
of injectable drugs, under the umbrella term ‘biological agents’, now available
for the treatment of rheumatoid arthritis and other chronic inflammatory
conditions including juvenile idiopathic arthritis, Crohn disease, psoriasis and
psoriatic arthritis. OBJECTIVE: The aim of this review is to provide an overview
of TNF-alpha inhibitors and highlight the key practical issues of relevance to
general practitioners. DISCUSSION: TNF-alpha inhibitors may have a potent effect
in reducing inflammation and possibly inducing remission where conventional
disease modifying drugs have failed to do so. These drugs are associated with an
increased risk of infection as well as other potentially serious side effects.
Their use is restricted to the relevant specialist prescribing the drug and are
only available on the Pharmaceutical Benefits Scheme under strict prescribing
criteria. The role of the GP is critical in identifying patients suitable for
referral to consider commencing treatment and in monitoring patients on long term
therapy.

Anti-TNF antibodies: lessons from the past, roadmap for the future. Shealy DJ, Visvanathan S. Handb Exp Pharmacol. 2008;(181):101-29.

Tumor necrosis factor alpha (TNF) is an important cell-signaling component of the
immune system. Since its discovery over 20 years ago, much has been learned about
its functions under normal and disease conditions. Nonclinical studies suggested
a role for TNF in chronic immune-mediated inflammatory diseases, such as
rheumatoid arthritis, Crohn’s disease, and psoriasis, and therefore neutralizing
monoclonal antibodies specific to human TNF were developed for clinical
evaluation. Treatment with anti-TNF monoclonal antibodies (infliximab,
adalimumab, and certolizumab pegol) has been shown to provide substantial benefit
to patients through reductions in both localized and systemic expression of
markers associated with inflammation. In addition, there are beneficial effects
of anti-TNF treatment on markers of bone and cartilage turnover. Further
exploration of changes in these markers and their correlation with clinical
measures of efficacy will be required to allow accurate prediction of those
patients most in need of these treatments. Both the clinical and commercial
experience with these anti-TNF antibodies provide a wealth of information
regarding their pharmacological effects in humans.

Psoriasis–pathophysiology, conventional, and alternative approaches to treatment. Traub M, Marshall K. Altern Med Rev. 2007 Dec;12(4):319-30.

Psoriasis is a common T-cell-mediated immune disorder characterized by
circumscribed, red, thickened plaques with an overlying silver-white scale. It
occurs worldwide, although the incidence is lower in warmer, sunnier climates.
The primary cause of psoriasis is unknown. During an active disease state, an
underlying inflammatory mechanism is frequently involved. Many conventional
treatments focus on suppressing symptoms associated with psoriasis and have
significant side effects. This article reviews several of the researched natural
approaches to psoriasis treatment, while addressing its underlying cause.

Explaining phenotype heterogeneity in patients with psoriasis. Christophers E. Br J Dermatol. 2008 Mar;158(3):437-41. Epub 2007 Nov 28.

Psoriasis is a heterogeneous disorder with many different phenotypes. Further,
different forms may alter their morphology and course of disease in that, for
instance, plaque-type psoriasis may become pustular and vice versa. With
advancing insight in immunopathology phenotype switching can now be explained by
directional changes from T cell-mediated pathology to an inflammatory
neutrophilic pattern which is driven by innate signalling. Within this framework
not a single ‘antigen’ but various causative agents play a key role.

[Topical corticosteroids and corticosteroid sparing therapy in psoriasis management] [Article in Croatian] Sukarovska BG, Lipozencić J, Vrzogić P. Acta Med Croatica. 2007 Sep;61(4):375-81.

Psoriasis is a chronic, recurrent, genetically determined, inflammatory
dermatosis that affects the skin, scalp and joints. Psoriasis is caused by
various triggers (infections, drugs, physical and emotional factors). It ranges
in severity from mild to severe, and patients with moderate to severe disease
suffer significant deterioration in the quality of life. Clinical types of
psoriasis are psoriasis guttata, nummular psoriasis, plaque, generalized and
erythrodermic psoriasis. Skin changes affect intertriginous regions (inverse
psoriasis), and there also are special forms of pustular psoriasis and
arthropathic psoriasis. The goals of psoriasis treatment are to gain initial and
rapid control of the disease; to decrease plaque lesions and percentage of body
surface area involved, to achieve long-term remission; and to minimize adverse
events. Topical treatment for mild psoriasis includes topical corticosteroids,
calcipotriene, tazarotene, topical tars, anthralin and keratolytics, and
immunomodulators (pimecrolimus, tacrolimus). The treatment of moderate to severe
psoriasis includes systemic therapies such as methotrexate, acitretin,
cyclosporine, hydroxurea and biologicals. Topical treatment can be effective
using combination, rotational or sequential regimens for patients with more
severe disease. The aim of successful treatment of psoriasis is fast control of
the disease and regression of lesions in a short period, prolonged remission and
minimal adverse reaction. Local therapy with various topicals is administered for
mild and localized forms of the disease, with or without phototherapy (UVB).
Topical corticosteroids are used in a variety of formulations, with a potential
ranging from superpotent to least potent (class 1-7), which decrease symptoms in
tne first two weeks of treatment with improvement in subsequent weeks; D3 vitamin
analog (effective in 6-8 weeks), retinoids (effective in 1-2 weeks), tars (2-4
weeks), anthralin (2-4 weeks), and keratolytics (most effective in combination
with corticosteroids. Topical corticosteroids have been the first choice in the
treatment of and inflammatory dermatoses since 1952 to the present.
Corticosteroids are effective as monotherapy or in combination for sequential or
rotational treatment. They are effective in short time, simple for use and
inexpensive. Psoriasis is a chronic skin disease that requires long-term therapy.
For patients with mild to moderate form, intermittent corticosteroid therapy is
the most effective treatment. Every-other-day or weekend-only application may be
effective in chronic stage. Calcipotriene and tazarotene are more effective in
combination with corticosteroids in the initial weeks of therapy. Tar
preparations, anthralin and keratolytics may be used with ultraviolet light and
corticosteroids. Topical immunomodulators are effective on the face and
intertriginous psoriatic lesions.

Observations on the procedural aspects and health effects of scarification in sub-Saharan Africa. Ayeni OA, Ayeni OO, Jackson R. J Cutan Med Surg. 2007 Nov-Dec;11(6):217-21.

BACKGROUND: Scarification involves cutting or making an incision into the skin
and then allowing the wound to heal, leaving a permanent scar. The purpose of
this article is to examine the origins of scarification and its social and
medical significance in sub-Saharan Africa. METHODS: We conducted a computerized
search in the MEDLINE electronic database with combinations of the following
terms: scarification, tribal marks, keloid, hypertrophic scar, Africa, and
sub-Saharan Africa. Inclusion criteria were studies published in English
involving human participants. We reviewed the bibliography of each article that
met our inclusion criteria for additional relevant studies. We abstracted data on
the historical, social, and medical aspects of scarification from eligible
studies. RESULTS: This review of scarification in sub-Saharan Africa highlights
the complex interplay that exists between biology and society. Photographs,
artwork, and literary descriptions reveal that scarification results in
hypertrophic or atrophic scars, although these types of scars are often
mistakenly referred to as keloids. In terms of the procedural aspects of
scarification, specific tools and substances were consistently used by various
ethnic groups. Although much is known about the history of scarification as a
form of identification in Africa, it appears that the practice also had medical
applications. Scarification was used to treat conditions such as epilepsy,
although it was also known to exacerbate conditions such as sarcoidosis, lichen
planus, and psoriasis. Evolving cultural beliefs, in addition to the association
of scarification with an increased risk of contracting hepatitis B and human
immunodeficiency virus (HIV), are contemporary threats to this long-standing
practice. CONCLUSIONS: Given the remarkably consistent appearance of scars that
are described in the literature and depicted in images, scarification does not
appear to be a random or accidental occurrence. Instead, it is a deliberate
attempt to reproduce a custom that has been perfected after many years of
practice in sub-Saharan Africa.

MM-093, a recombinant human alpha-fetoprotein for the potential treatment of rheumatoid arthritis and other autoimmune diseases. Dudich E. Curr Opin Mol Ther. 2007 Dec;9(6):603-10.

Merrimack Pharmaceuticals Inc (previously Atlantic Biopharmaceuticals) is
developing MM-093 (formerly ABI-001), an injectable formulation of a recombinant
human alpha-fetoprotein, for the potential treatment of myasthenia gravis,
multiple sclerosis, rheumatoid arthritis, autoimmune uveitis and psoriasis.
MM-093 is currently undergoing phase II clinical trials for rheumatoid arthritis,
psoriasis and autoimmune uveitis.

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.

Psoriatic disease–from skin to bone. Ritchlin C. Nat Clin Pract Rheumatol. 2007 Dec;3(12):698-706.

Psoriatic arthritis is an inflammatory joint disease that is heterogeneous in
presentation and clinical course. Evidence that this disease is distinct from
rheumatoid arthritis and other spondyloarthropathies is based on data derived
from characteristic clinical features, histopathologic analyses, immunogenetic
associations and musculoskeletal imaging. Emphasis has centered previously on a
dominant role for the T lymphocyte in the inflammatory process; however, studies
provide support for a major contribution from monocyte-macrophages in the
initiation and perpetuation of joint and skin inflammation. The occurrence of
arthritis in the absence of psoriasis in a minority of patients with psoriatic
arthritis, coupled with divergent genetic risk factors, indicates that psoriatic
arthritis is distinct from psoriatic skin inflammation. A new terminology,
psoriatic disease, has emerged that encompasses the various manifestations of
tissue and organ involvement observed in many psoriasis patients, including
inflammation in the joint, eye and gut. Moreover, adverse cardiovascular and
metabolic outcomes in patients with psoriasis or psoriatic arthritis might be
directly linked to the cutaneous and musculoskeletal manifestations of these
diseases via subsets of circulating monocytes and tissue macrophages activated by
inflammatory cytokine networks that arise in the skin and possibly the joint.

[Off-label use of biologic agents in the treatment of dermatosis, Part 1: infliximab and adalimumab] [Article in Spanish] Díaz-Ley B, Guhl G, Fernández-Herrera J. Actas Dermosifiliogr. 2007 Dec;98(10):657-78.

In recent years, the therapeutic armamentarium available to dermatologists has
been extended thanks to the development of numerous biologic agents. In our
field, immunomodulators–although currently only approved for psoriasis–have
given rise to new therapeutic possibilities in a number of inflammatory skin
diseases. Since these new agents have more specific immunologic mechanisms of
action, their efficacy and safety is an improvement on traditional
immunosuppressants. Consequently, it is very likely that they will play an
important role in dermatology in the next few years. This article, the first part
of a review of off-label use of biologic agents in dermatology, describes the
anti-tumor necrosis factor-alpha antibodies, infliximab and adalimumab.

Etanercept: a review of its use in the management of ankylosing spondylitis and psoriatic arthritis. Hoy SM, Scott LJ. Drugs. 2007;67(17):2609-33.

Etanercept (Enbrel), a recombinant, dimeric, soluble tumour necrosis factor (TNF)
receptor protein, is approved in various countries for the treatment of adult
patients with ankylosing spondylitis or psoriatic arthritis.Monotherapy with
subcutaneous etanercept 25mg twice weekly or 50mg once weekly was effective and
generally well tolerated in patients with ankylosing spondylitis or psoriatic
arthritis participating in several large, well designed clinical studies.
Treatment with etanercept was more effective than placebo in reducing disease
activity and improving health-related quality of life (HR-QOL) in both patient
populations, and in delaying structural disease progression in patients with
psoriatic arthritis. The beneficial response to etanercept achieved with
shorter-term treatment was sustained in studies of up to 4 years’ total duration.
Randomised, well designed, head-to-head comparisons, including pharmacoeconomic
analyses, with other anti-TNF biological modulators are required to accurately
position etanercept and fully establish its cost effectiveness. In the meantime,
etanercept is a valuable treatment option for patients with ankylosing
spondylitis or psoriatic arthritis who are suitable candidates for therapy.

Innate immunity and antimicrobial defense systems in psoriasis. Büchau AS, Gallo RL. Clin Dermatol. 2007 Nov-Dec;25(6):616-24.

Psoriasis is a chronic inflammatory disorder that is mediated by elements of the
innate and adaptive immune systems. Its characteristic features in the skin
consist of inflammatory changes in both dermis and epidermis, with abnormal
keratinocyte differentiation and proliferation. Despite the elucidation of many
aspects of psoriasis pathogenesis, some puzzling questions remain to be answered.
A major question currently debated is whether psoriasis is a primary abnormality
of the epidermal keratinocyte or a reflection of dysregulated bone marrow-derived
immunocytes. In this review we will focus on understanding the role of the innate
immune system in psoriasis and how this provides a rational solution to address
the origin of this multifactorial disease. Innate immunity is nonspecific and
genetically based. It protects the body against the constant risk of pathogens
through the use of rapidly mobilized defenses that are able to recognize and kill
a variety of threats (bacteria, fungi, viruses, etc). The key mechanisms of
innate immune responses are the existence of receptors to recognize pathogens and
the production of factors that kill pathogens, such as antimicrobial peptides and
proteins. Any combination of excessive sensitivity of the innate detection
system, or dysregulation of the response system, can manifest both an epidermal
phenotype and an abnormal T-cell function. Thus, the multidimensional action of
the innate immune system, its triggers, and its recently understood role in
T-cell function argue for an important role for innate mechanisms of recognition
and response in the pathogenesis of psoriasis.

Triggering psoriasis: the role of infections and medications. Fry L, Baker BS. Clin Dermatol. 2007 Nov-Dec;25(6):606-15.

Psoriasis can be provoked or exacerbated by a variety of different environmental
factors, particularly infections and drugs. Strong evidence exists for the
induction of guttate psoriasis by a preceding tonsillar Streptococcus pyogenes
infection, whereas disease exacerbation has been linked with skin and/or gut
colonization by Staphylococcus aureus, Malassezia, and Candida albicans. The
role, if any, of viruses (papillomaviruses, HIV, and endogenous retroviruses)
present in lesional skin is at present unknown. The use of various drugs, such as
lithium, beta-blockers, antimalarial agents, nonsteroidal anti-inflammatory
drugs, and angiotensin-converting enzyme inhibitors, has also been associated
with induction or worsening of disease in psoriatic patients.

Animal models of psoriasis. Boehncke WH, Schön MP. Clin Dermatol. 2007 Nov-Dec;25(6):596-605.

Research into the pathogenesis of psoriasis has been severely hampered by the
lack of a naturally occurring disorder in laboratory animals that mimics the
complex phenotype and pathogenesis of the human disease. A large variety of
spontaneous mutations, genetically engineered rodents, immunological
reconstitution approaches, and xenotransplantation models have been used to study
specific aspects of the pathophysiology of psoriasis, however. Several
manipulations of resident cutaneous cell types or immigrating immunocytes appear
to result in remarkably similar hyperproliferative inflammatory phenotypes in
mice, thus suggesting that interfering with cutaneous homeostasis in general may
ultimately result in a rather uniform reaction pattern that mirrors some features
of psoriasis. Fully animal models of psoriasis have nonetheless not only shed
light on the biological functions of given inflammatory mediators or other
molecules but also tremendously contributed to the discussion on central
pathogenic questions, such as the roles of innate and adaptive immune mechanisms,
keratinocytes, and endothelial cells in psoriasis. Psoriasis research has also
been greatly nourished by xenotransplantation of diseased or unaffected human
skin onto immunocompromised recipients, an approach that has in many variations
been used to study the role of T lymphocytes and other cells and that has been
used for preclinical therapeutic studies. General approaches to generate animal
models of psoriasis, features of some specific models, their value for psoriasis
research, and their use for drug development are discussed in this article.

Psoriasis: the epidermal component. Tschachler E. Clin Dermatol. 2007 Nov-Dec;25(6):589-95.

Besides the infiltrate of immune cells in psoriatic lesions, the principal
characteristic changes in the skin are changes of the epidermal architecture and
alterations of keratinocyte differentiation, which are distinct from other
inflammatory skin diseases clinically and histologically. Several lines of
evidence suggest that 3 of the 9 psoriasis susceptibility loci identified today
might play a role in the keratinocyte differentiation program. Therefore, besides
the dysregulation of the immune system, intrinsic epidermal components are also
likely to play a role in triggering and/or sustaining the disease process and
contribute to the chronicity of psoriasis and its frequent relapses.

Resident skin cells in psoriasis: a special look at the pathogenetic functions of keratinocytes. Albanesi C, De Pità O, Girolomoni G. Clin Dermatol. 2007 Nov-Dec;25(6):581-8.

Psoriasis is a chronic inflammatory skin disease characterized by exaggerated
keratinocyte proliferation. Current paradigm indicates that psoriasis is driven
by T cell-mediated immune responses targeting keratinocytes. However, psoriasis
cannot be explained solely on the basis of T-cell activation, and it is likely
that intrinsic alterations in epidermal keratinocytes play a very relevant role
in disease expression. In particular, keratinocytes may be important in
initiating, sustaining, and amplifying the inflammatory responses by expressing
molecules involved in T-cell recruitment, retention, and activation.
Keratinocytes are also a relevant source of growth factors for angiogenesis.
Finally, intrinsic defects in cytokine and growth factor signaling in
keratinocytes may be responsible for their aberrant hyperproliferation and
differentiation to T cell-derived signals. Other skin resident cells such as
fibroblasts, mast cells, and endothelial cells also contribute to psoriasis
pathogenesis by expressing molecules involved in T-cell recruitment and
activation.

Immunopathogenesis and role of T cells in psoriasis. Ghoreschi K, Weigert C, Röcken M. Clin Dermatol. 2007 Nov-Dec;25(6):574-80.

Psoriasis is a T cell-dependent autoimmune disease of the skin and joints.
Disease manifestation is orchestrated by proinflammatory CD4-positive T helper
cells producing either interferon-gamma (Th1) or interleukin (IL)-17 (Th17).
These Th1 and Th17 cells interact with dermal dendritic cells, macrophages, mast
cells, and neutrophils. Together, they cause an inflammation that mainly involves
interferon-gamma, tumor necrosis factor, IL-8, IL-12, IL-17, IL-19, and IL-23.
New therapeutics either are directed against T cells, tumor necrosis factor, and
IL-12/IL-23 or deviate immune responses into a protective IL-4-dominated Th2
phenotype.

The cytokine and chemokine network in psoriasis. Nickoloff BJ, Xin H, Nestle FO, Qin JZ. Clin Dermatol. 2007 Nov-Dec;25(6):568-73.

Creation and maintenance of psoriatic plaques require a multicellular conspiracy
by which prepsoriatic skin becomes infiltrated by a variety of immunocytes
triggering changes in the behavior of epidermal keratinocytes and endothelial
cells. These complex cellular events require coordination in space and time to
achieve the mature plaque. Key molecular coordinators dictating behavior and
movement of cells within plaques include cytokines as well as chemokines. These
mediators of inflammation play fundamentally important roles in the
pathophysiology of psoriasis. The purpose of this chapter is to provide an
updated review of cytokine and chemokine networks in psoriatic skin lesions.

The genetic basis of psoriasis. Valdimarsson H. Clin Dermatol. 2007 Nov-Dec;25(6):563-7.

For a complex genetic disease, psoriasis has a high penetration within families
and a concordance rate of up to 70% in identical twins. Despite this and the
endeavors of many research groups for more than a decade, no susceptibility
allele has so far been unequivocally identified, although about 20 genetic loci
associated with psoriasis have been reported from linkage-based studies.
Moreover, only 1 of these linkage-based loci, PSORS1, that includes the HLA-C
gene on chromosome 6p21, has been universally confirmed. Very recent data
strongly indicate that HLA-Cw*0602 is the susceptibility allele in this locus, a
finding that is consistent with the notion that the pathogenesis of psoriasis
involves autoantigen recognition by epidermal CD8+ T lymphocytes. Several
candidate genes in some of the other 7 PSORS designated loci are currently being
evaluated. The relative lack of success in elucidating the genetic basis of
psoriasis highlights the formidable challenge of dissecting the genetic basis of
diseases with a complex mode of inheritance.

Childhood psoriasis. Benoit S, Hamm H. Clin Dermatol. 2007 Nov-Dec;25(6):555-62.

In about one third of patients, psoriasis starts in the first or second decade of
life. In the beginning, involvement is often atypical or mild, and a confident
diagnosis may be difficult to establish. Plaque psoriasis is the most frequent
type, also in children, but lesions are often smaller, thinner, and less scaly
than in adults. Treatment can be a challenge because many therapeutic options
have drawbacks or are not approved in childhood. Because psoriasis is a life-long
disease, affected children and their parents need special support and guidance.
We herein focus on the peculiarities of clinical presentations and of the
management of psoriatic children and adolescents.

Quality of life in patients with psoriasis and psoriasis arthritis with a special focus on stigmatization experience. Schmid-Ott G, Schallmayer S, Calliess IT. Clin Dermatol. 2007 Nov-Dec;25(6):547-54.

Negative impact of psoriasis and psoriasis arthritis on quality of life is a
central consequence of these diseases. Feelings of stigmatization might, for
example, already emerge with only small patches of skin being affected. Empirical
data indicate that treating dermatologists should address possible negative
effects elicited by problematic encounters with the public and in sexual
relationships even if the severity of the disease is low, because lesions on
invisible parts of the body can already cause serious adverse impairment. Such
psychosocial consequences can be reduced by attending a self-help organization
and by taking part in an interdisciplinary patient education program led by
dermatologists.

Psoriasis: epidemiology. Gudjonsson JE, Elder JT. Clin Dermatol. 2007 Nov-Dec;25(6):535-46.

Psoriasis is a chronic, inflammatory and hyperproliferative skin disease with a
genetic basis. While epidermal hyperplasia and altered keratinocyte
differentiation are prominent features, considerable evidence indicates that
psoriasis is immunologically mediated. Recently, the identification of HLA-Cw6 as
the disease allele conferring susceptibility to psoriasis has provided a focus
for elucidation of these events. In this article, we will focus on the
epidemiology of psoriasis and its associated arthritis.

Comorbidities in psoriasis. Christophers E. Clin Dermatol. 2007 Nov-Dec;25(6):529-34.

Epidemiological studies have shown that, in psoriasis patients, associated
disorders may occur more frequently than expected. Such comorbidities include
psoriatic arthritis, psoriatic pustular diseases, Crohn disease, and signs of
metabolic syndrome, which leads to atherosclerosis with coronary heart disease.
Although the disorders represent separate entities, they appear to follow
overlapping pathogenic pathways. Comorbidities often become clinically manifest
years after onset of psoriasis and are frequently seen in severe disease.
Persistent low-grade inflammation with secretion of proinflammatory cytokines
(eg, tumor necrosis factor alpha) favors the development of insulin resistance
and metabolic syndrome. In addition, biochemical and immunologic observations
point toward an inflammatory immune mechanism that uses tools of the innate
defense armamentarium.

The histopathologic spectrum of psoriasis. Murphy M, Kerr P, Grant-Kels JM. Clin Dermatol. 2007 Nov-Dec;25(6):524-8.

Psoriasis is the prototype of a group of cutaneous disorders (psoriasiform
dermatitides) that show psoriasiform epidermal hyperplasia, defined as regular
elongation of the rete ridges with preservation of the rete ridge-dermal papillae
pattern. Depending on whether the lesion is early or resolving, psoriasiform
epidermal changes may be subtle or prominent. Other histologic clues to the
diagnosis of psoriasis include more dilated and tortuous papillary blood vessels,
neutrophils within the epidermis associated with spongiosis (spongiform
pustules), neutrophils beneath the cornified layer (subcorneal pustules),
neutrophils within the cornified and parakeratotic horn, hypogranulosis, and more
keratinocytic mitotic figures above the basal cell layer.

Psoriatic arthritis: clinical spectrum and diagnostic procedures. Kleinert S, Feuchtenberger M, Kneitz C, Tony HP. Clin Dermatol. 2007 Nov-Dec;25(6):519-23.

Psoriatic arthritis presents with a broad clinical spectrum of symptoms.
Symmetrical polyarthritis with joint pain and joint swelling is one pattern of
clinical manifestations that often indicates erosive progressive disease. Unlike
in rheumatoid arthritis, the distal interphalangeal joints are regularly
involved. Sometimes, the disease focuses on the larger joints of the lower
extremities; iliosacral and intervertebral joints and tendons can also be
involved. Thus, inflammatory back pain as well as any other prolonged joint pain
in a patient with psoriasis is suspicious of psoriatic arthritis. This article
reviews the clinical spectrum and diagnostic procedures that can lead to the
diagnosis of psoriatic arthritis.

The clinical spectrum of psoriasis. Naldi L, Gambini D. Clin Dermatol. 2007 Nov-Dec;25(6):510-8.

The clinical picture of psoriasis is not uniform. Being one of the most common
chronic inflammatory skin disorders, psoriasis may present in many different
forms and may include extracutaneous manifestations. Classifications have been
proposed based on disease onset or the clinical course of psoriasis. Chronic
plaque psoriasis occurs in a variety of clinical forms primarily distinguished by
size, distribution, and dynamics of psoriatic plaques. In addition, psoriasis
inversa, localized and generalized pustular forms, erythrodermic psoriasis, as
well as a number of more uncommon forms have been recognized, a distinction on
clinical grounds that is relevant for the overall prognosis and impact on the
patients’ quality of life as well as for the choice of therapy. The broad and
rather colorful clinical spectrum of psoriasis as well as implications for
clinical practice will be comprehensively reviewed in this article.

Three decades of psoriasis research: where has it led us? Sabat R, Sterry W, Philipp S, Wolk K. Clin Dermatol. 2007 Nov-Dec;25(6):504-9.

Psoriasis is a common chronic skin disease. Its pathogenesis has intensively been
investigated in the last 3 decades. In the 1970s, the observed increased
proliferation of keratinocytes and their altered differentiation were considered
to be the most important signs and causes of psoriatic skin lesions. Since the
early 1980s, T cells slid into the focus of psoriasis research. It was then
postulated that a subpopulation of T cells, so-called T1 cells, and their
prominent cytokine interferon-gamma, had a dominant role in the pathogenesis of
psoriasis. In the last decade, new data regarding macrophages and dendritic cells
and the high therapeutic success of anti-tumor necrosis factor alpha biologics
led to the assumption that antigen-presenting cells are important not only in the
induction of psoriasis but also in its maintenance. The knowledge gained over the
past 3 decades let us postulate that psoriasis is an immunologically induced,
overshot, regeneration-like reaction of the skin in which various cells play a
dominant role at different stages. This hypothesis is also supported by the very
recent discoveries about interleukin (IL)-22, IL-20, and IL-23.

Joint remodelling in inflammatory disease. Schett G. Ann Rheum Dis. 2007 Nov;66 Suppl 3:iii42-4.

Bone and the immune system share multiple interactions. The skeleton harbours the
bone marrow and provides the niche for development of haematopoietic cells
including the immune system. The immune system provides cells as well as
molecular signals, which regulate bone homeostasis. Understanding the cellular
and molecular regulation of the tight interaction between bone and the immune
system is crucial for understanding the changes of skeletal architecture during
inflammation. Whereas a short and self-limited activation of the immune system
has no clinically meaningful effect on bone, prolonged immune activation as found
in chronic inflammatory disease inevitably leads to bone wasting.

Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2007. Furst DE, Breedveld FC, Kalden JR, Smolen JS, Burmester GR, Sieper J, Emery P, Keystone EC, Schiff MH, Mease P, van Riel PL, Fleischmann R, Weisman MH, Weinblatt ME. Ann Rheum Dis. 2007 Nov;66 Suppl 3:iii2-22.

A practical guide to scalp disorders. Grimalt R. J Investig Dermatol Symp Proc. 2007 Dec;12(2):10-4.

The scalp is unique among skin areas in humans, with high follicular density and
a high rate of sebum production. The relatively dark and warm environment on the
scalp surface provides a welcoming environment for the superficial mycotic
infections associated with many scalp conditions and for parasitic infestation.
Infections and infestations can occur when items such as fingers, combs, hats, or
styling implements come into contact with the hair and scalp and introduce
microorganisms. Inflammatory conditions may also produce changes in the scalp.
Many common scalp conditions have similar symptoms and clinical features,
complicating diagnosis, but a correct diagnosis is critical to determining proper
treatment. This paper describes the symptoms, etiology, and treatment strategies
for a number of common scalp conditions, including dandruff, seborrheic
dermatitis, tinea capitis, pediculosis capitis, and psoriasis.

Cost-effectiveness of biologic treatments for psoriasis based on subjective and objective efficacy measures assessed over a 12-week treatment period. Nelson AA, Pearce DJ, Fleischer AB Jr, Balkrishnan R, Feldman SR. J Am Acad Dermatol. 2008 Jan;58(1):125-35. Epub 2007 Nov 8.

BACKGROUND: The cost-effectiveness of biologic agents is not well delineated.
OBJECTIVE: To determine the cost-effectiveness of biologic agents in cost per
patient achieving a minimally important difference in Dermatology Life Quality
Index (DLQI MID) and cost per patient achieving a 75% improvement in Psoriasis
Area Severity Index (PASI-75), assessed over a 12-week period. METHOD: Efficacies
of the agents were determined through a literature review; treatment paradigms
and associated costs were determined. The cost-effectiveness of the agents was
determined and sensitivity analysis performed. RESULTS: Etanercept at a dose of
25 mg administered subcutaneously (SQ) once weekly was the most cost-effective
agent in cost per patient achieving DLQI minimally important difference;
infliximab at a dose of 3 mg/kg administered intravenously (IV) for 3 infusions,
adalimumab at a dose of 40 mg SQ every other week, and etanercept at a dose of 25
mg SQ twice weekly were the next most cost-effective agents in cost per patient
achieving the DLQI minimally important difference. Intravenous infliximab at a
dose of 3 mg/kg was the most cost-effective agent in terms of cost per patient
achieving PASI-75 improvement; intravenous infliximab at a dose of 5 mg/kg and
adalimumab at a dose of 40 mg SQ every other week were the next most
cost-effective agents in cost per patient achieving PASI-75 improvement.
LIMITATIONS: This study had a limited time horizon of 12 weeks; generalizing the
results to longer treatment periods may not be accurate and is not advisable.
Additionally, when sensitivity analyses were performed, multiple agents had
overlapping cost-effectiveness ratios at relatively low levels of variance; thus
it may not be accurate to differentiate the cost-effectiveness of these agents.
CONCLUSIONS: Different biologic agents for psoriasis appear to have different
cost-effectiveness values; within the limitations of the available data,
infliximab and adalimumab appear to be the most cost-effective agents.

DNA microarrays and their use in dermatology. Mlakar V, Glavac D. Acta Dermatovenerol Alp Panonica Adriat. 2007 Mar;16(1):7-12.

Multiple different DNA microarray technologies are available on the market today.
They can be used for studying either DNA or RNA with the purpose of identifying
and explaining the role of genes involved in different processes. This paper
reviews different DNA microarray platforms available for such studies and their
usage in cases of malignant melanomas, psoriasis, and exposure of keratinocytes
and melanocytes to UV illumination.

Psoriasis: advances in pathophysiology and management. MacDonald A, Burden AD. Postgrad Med J. 2007 Nov;83(985):690-7.

Psoriasis is an inflammatory skin disease that affects 1-3% of Caucasian
populations and may be persistent, disfiguring and stigmatizing. There is a range
of severity, but even when the affected body surface area is relatively limited
the impact on day-to-day activities and social interactions may be significant.
An understanding of the psychological burden and an appreciation that many
patients are currently dissatisfied with their management has driven the
development of more effective treatment. In recent years psoriasis has been the
focus of intense investigation resulting in an improved understanding of the
immunopathogenesis, and the development of new, targeted biological treatments.

Interactions between TNF and GnRH. MacEwan DJ. Neurochem Res. 2008 Apr;33(4):678-82. Epub 2007 Nov 6.

Tumour necrosis factor (TNF) ligand members and their associated TNF receptor
(TNFR) superfamilies have many diverse physiological roles. TNF is thought to
play a critical role in the pathophysiology of a range of diseases including
refractory asthma, sepsis, ankylosing spondylitis, lupus, type II diabetes,
multiple sclerosis and psoriasis. The recent continued expansion of the novel
anti-TNF therapeutic agents (etanercept and infliximab) has seen major
improvements in the treatment of some inflammatory-based human diseases including
notably rheumatoid arthritis and Crohn’s disease, with other conditions currently
being trialled using anti-TNF agents. The cellular signalling machinery used by
TNFRs to achieve their many cellular responses are discussed, as is the
gonadotrophin-releasing hormone (GnRH) receptor signalling mechanisms. TNF is
known to have many actions throughout the body including effects on the
hypothalamic-pituitary-adrenal/gonadal axes, with many anti-gonadotrophic effects
including a role in the development of endometriosis. These interactions between
TNF, GnRH and gonadotrophs are discussed.

Spinal epidural abscess in clinical practice. Sendi P, Bregenzer T, Zimmerli W. QJM. 2008 Jan;101(1):1-12. Epub 2007 Nov 3.

Spinal epidural abscess (SEA) is a rare but severe infection requiring prompt
recognition. The major prognostic factor for a favourable outcome is early
diagnosis, leading to appropriate treatment. In clinical practice, a diagnosis of
SEA is often not considered, particularly in the early stages of the disease when
neurological symptoms are not apparent. Knowledge of persons at risk, clinical
features and the required diagnostic procedures may decrease the number of
initially misdiagnosed cases. Clinical signs, duration of symptoms and the rate
of neurological deterioration show a high inter-individual variability, and the
classic triad (spinal pain, fever and neurological deficit) is often not found,
especially not at first presentation to a physician. However, most patients
complain of severe localized back pain. Inflammatory parameters in the blood are
generally elevated, but not specific. Gadolinium-enhanced magnetic resonance
imaging is the most sensitive, specific and accurate imaging method. Although
neurosurgical decompression is still the treatment of choice in the majority of
cases, less invasive procedures (e.g. computed tomography-guided needle
aspiration) or antimicrobial treatment alone can be applied in selected cases.
The choice of the most appropriate therapy should be discussed immediately after
a confirmed diagnosis in consultation with infectious disease, radiology and
spinal surgery specialists. The outcome of SEA is largely influenced by the
severity and duration of neurological deficits prior to surgery, stressing the
importance of early recognition.

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.

HLA-G in the skin–friend or foe? Urosevic M. Semin Cancer Biol. 2007 Dec;17(6):480-4. Epub 2007 Sep 19.

Skin is the largest organ of the human body that harbors a robust and versatile
immune surveillance system. Whereas impaired immune function of the skin enables
tumor growth, excessive immune activation results in different inflammatory
diseases of the skin. HLA-G is a non-classical MHC class I molecule that was
initially described to provide immunotolerogenic signals. In this context, HLA-G
was mainly investigated as a mechanism that tumor cells employ to evade and
inhibit host immune response. Expression of HLA-G in several inflammatory
conditions in the skin implicated that the (dys)function of this molecule may
also underlie excessive immune stimulation observed in these disorders. This
review focuses on the functionality of HLA-G in the skin and summarizes available
data obtained from studies performed in skin cancer and inflammatory dermatoses.

From the Medical Board of the National Psoriasis Foundation: monitoring and vaccinations in patients treated with biologics for psoriasis. Lebwohl M, Bagel J, Gelfand JM, Gladman D, Gordon KB, Hsu S, Kalb RE, Kimball AB, Korman NJ, Krueger GG, Mease P, Morison WL, Paller A, Pariser DM, Ritchlin C, Strober B, Van Voorhees A, Weinstein GD, Young M, Horn L. J Am Acad Dermatol. 2008 Jan;58(1):94-105. Epub 2007 Nov 5.

BACKGROUND: Biologics are widely used in the treatment of psoriasis and psoriatic
arthritis. OBJECTIVE: Our aim was to arrive at a consensus on the kind of
monitoring and the vaccinations that should be performed before and during
biologic therapy. METHODS: Medical literature and data presented at meetings were
reviewed and a consensus conference was held by members of the Medical Board of
the National Psoriasis Foundation. RESULTS: Consensus was established on
monitoring and vaccination practices that included discussion and recognition of
variations in those practices. History, physical examination, chemistry screen
with liver function tests, complete blood cell count, and platelet count and
tuberculosis testing are widely obtained at baseline and with variable
frequencies thereafter. Patients treated with efalizumab have platelet counts
checked more often; liver function tests are repeated more frequently in patients
treated with infliximab; patients taking tumor necrosis factor blockers undergo
tuberculosis testing more often; and patients treated with alefacept have CD4
counts checked approximately every 2 weeks. Avoidance of live vaccines during
biologic therapy and administration of essential vaccines before biologic therapy
were discussed, although vaccination is performed only to a variable degree.
There was no consistency in the measurement of antinuclear antibodies among the
experts. LIMITATIONS: There are few evidence-based studies on monitoring
practices for patients with psoriasis taking biologic therapies. CONCLUSIONS: In
patients taking biologic therapies for psoriasis, monitoring of blood
chemistries, blood counts, CD4 counts, antinuclear antibodies, tuberculin skin
tests, history, and physical examination may be warranted depending on the
particular therapy and the particular patient. Vaccination practices are also
addressed.

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.

Drug evaluation: BG-12, an immunomodulatory dimethylfumarate. Wakkee M, Thio HB. Curr Opin Investig Drugs. 2007 Nov;8(11):955-62.

Biogen Idec Inc, following its acquisition of Fumapharm AG, is developing BG-12
(Panaclar, BG-00012, FAG-201), an oral second-generation fumarate derivative, for
the potential treatment of multiple sclerosis (MS). In January 2007, a phase III
program for relapsing-remitting MS patients was initiated. The company was also
developing the drug for psoriasis and, in October 2003, Biogen Idec expected to
commence phase III trials for psoriasis in the US in the following year. In April
2005, the drug met its European phase III psoriasis trial endpoint, with the data
expected to be used to support a market authorization filing in Germany in 2005.
It was later disclosed that while an application had been filed, this was
subsequently withdrawn based on a joint decision by Fumapharm and Biogen Idec. No
further development has been reported on BG-12 for psoriasis in the US and it was
not listed as a pursued indication on Biogen Idec’s April 2007 pipeline.

Drug evaluation: CNTO-1275, a mAb against IL-12/IL-23p40 for the potential treatment of inflammatory diseases. Wittig BM. Curr Opin Investig Drugs. 2007 Nov;8(11):947-54.

Centocor Inc is developing CNTO-1275 (ustekinumab), a subcantaneous mAb against
the p40 subunit of IL-12 and IL-23, for the potential treatment of inflammatory
diseases such as psoriasis, psoriatic arthritis, multiple sclerosis (MS) and
Crohn’s disease (CD). In July 2004, a phase II trial for MS had commenced, and by
July 2006 this study was no longer recruiting patients. By May 2005, CNTO-1275
was in phase II studies for CD, and by January 2006 the antibody was in phase III
studies for psoriasis. In December 2005, a phase II trial in patients with
psoriatic arthritis had commenced and had finished recruiting by January 2007.

Biologicals in the treatment of psoriasis. Boker A, Kimball AB, Rolz-Cruz G. Curr Opin Investig Drugs. 2007 Nov;8(11):939-46.

Psoriasis is a chronic inflammatory skin disorder that can cause substantial
disability. The recognition of psoriasis as an immunologically mediated disease
led to the development of agents that specifically target key steps in the
pathological process. This review focuses on these biological agents, and
presents results from phase II and III clinical trials together with the safety
profile and approved indications for alefacept, efalizumab, etanercept,
infliximab and adalimumab. Preliminary safety and efficacy data for the newer
therapeutic agents, such as CNTO-1275 and ABT-874, are also described.

Alefacept for the treatment of psoriasis and other dermatologic diseases. Strober BE, Menon K. Dermatol Ther. 2007 Jul-Aug;20(4):270-6.

Alefacept is a novel biologic agent for the treatment of plaque psoriasis.
Alefacept is a fully human recombinant dimeric fusion protein composed of the
terminal portion of Leukocyte Functioning Antigen-3 (LFA-3) and the Fc portion of
human IgG(1). The drug likely works in part by inducing the apoptosis of memory
effector (activated) T cells that play a central role in the pathophysiology of
psoriasis. Alefacept also may interrupt the direct immunologic activation of T
cells by antigen presenting cells. Alefacept is administered as a course of 12
intramuscular injections, but other dosing strategies have been explored. After a
course of therapy, statistically more patients receiving alefacept achieve a
psoriasis area and severity index (PASI) 75 response than those receiving a
placebo. Some patients who achieve PASI 75 also experience long-term remissions
from psoriasis. The drug is well-tolerated and adverse events are rare. Off-label
use of the drug is growing and may be formally explored in the future.

Efalizumab. Chacko M, Weinberg JM. Dermatol Ther. 2007 Jul-Aug;20(4):265-9.

Efalizumab is a novel immunomodulator that blocks T-cell migration and
activation. The drug was initially approved in October 2003 for the treatment of
adult patients with chronic moderate to severe plaque psoriasis. This review will
discuss the efficacy and safety data for efalizumab in the treatment of
psoriasis. In clinical use, efalizumab has utility as a first-line biologic
therapy for plaque psoriasis, as well as a first-line choice for hand and foot
psoriasis, overweight patients, and those who have had inadequate response to a
TNF inhibitor. In addition, several off-label applications of efalizumab will be
reviewed.

TNF- alpha inhibitors. Jackson JM. Dermatol Ther. 2007 Jul-Aug;20(4):251-64.

Tumor necrosis-alpha (TNF-alpha) has been implicated in many forms of
inflammation and is an end-stage product of the inflammatory cytokine cascade. It
is an inducer of inflammation and is involved in many cutaneous and systemic
inflammatory diseases. The development of agents that block the effects of
TNF-alpha has aided in the treatment of many of these diseases. This article will
briefly discuss the production, structure, and administration of the TNF-alpha
inhibitors. There will be a focus on the mechanism of action of each of the
TNF-alpha inhibitors as well as their benefit in their FDA approved and non FDA
approved dermatologic conditions. The side effect profile and monitoring
recommendations for these agents will also be discussed.

Systemic ciclosporin and tacrolimus in dermatology. Madan V, Griffiths CE. Dermatol Ther. 2007 Jul-Aug;20(4):239-50.

Ciclosporin and tacrolimus are calcineurin inhibiting immunosuppressant agents
useful in the treatment of immune-mediated inflammatory dermatoses. Available
data and clinical experience demonstrate ciclosporin’s efficacy in treating
psoriasis, atopic dermatitis, pyoderma gangrenosum, lichen planus, autoimmune
bullous disease (in combination with corticosteroids), recalcitrant chronic
idiopathic urticaria, and chronic dermatitis of the hands and feet. Although the
role of topical tacrolimus in atopic dermatitis is well established, such
experience with the oral formulation of tacrolimus has been limited. However,
there are several case studies and anecdotal reports of the successful use of
oral tacrolimus in various dermatoses. In this article we discuss the utility of
systemic ciclosporin and tacrolimus in dermatology.

Mycophenolate mofetil. Zwerner J, Fiorentino D. Dermatol Ther. 2007 Jul-Aug;20(4):229-38.

Mycophenolate mofetil (MMF) is a relatively new systemic immunosuppressive agent
whose use is rapidly increasing within the field of dermatologic. Originally used
in the 1970s for the treatment of psoriasis, MMF has demonstrated efficacy in
multiple types of inflammatory skin diseases. Although the safety data within the
dermatologic literature is sparse, MMF’s extensive use within the field of organ
transplantation has demonstrated a favorable safety profile. MMF’s lack of
hepatic or renal toxicity is a significant advantage over immunosuppressive
medications currently used in dermatology and make MMF an attractive candidate
for multidrug regimens. In this review the present authors discuss the
pharmacology, mechanisms of action, side effects and current uses of MMF reported
within the dermatologic literature. The present authors also provide practical
information regarding the use of the MMF culled from the literature as well as
from the present authors’ own clinical experience with the medication.

New concepts in antimalarial use and mode of action in dermatology. Kalia S, Dutz JP. Dermatol Ther. 2007 Jul-Aug;20(4):160-74.

Although chloroquine, hydroxychloroquine and quinacrine were originally developed
for the treatment of malaria, these medications have been used to treat skin
disease for over 50 years. Recent clinical data have confirmed the usefulness of
these medications for the treatment of lupus erythematosus. Current research has
further enhanced our understanding of the pharmacologic mechanisms of action of
these drugs involving inhibition of endosomal toll-like receptor (TLR) signaling
limiting B cell and dendritic cell activation. With this understanding, the use
of these medications in dermatology is broadening. This article highlights the
different antimalarials used within dermatology through their pharmacologic
properties and mechanism of action, as well as indicating their clinical uses. In
addition, contraindications, adverse effects, and possible drug interactions of
antimalarials are reviewed.

Biological and clinical effects of anti-TNFalpha treatment. Valesini G, Iannuccelli C, Marocchi E, Pascoli L, Scalzi V, Di Franco M. Autoimmun Rev. 2007 Nov;7(1):35-41. Epub 2007 Mar 26.

Tumor necrosis factor alpha (TNFalpha) is implicated in the pathogenesis of many
chronic inflammatory diseases such as rheumatoid arthritis (RA), psoriasis and
psoriatic arthritis (PsA), ankylosing spondylitis (AS), Crohn’s disease,
ulcerative colitis and uveitis. The availability of new pharmacological agents
(infliximab, etanercept, adalimumab), able to selectively block the TNFalpha, has
recently offered new opportunity for the treatment of these diseases. TNFalpha
antagonists are different in the mechanism of action and are all effective agents
in the treatment of RA and several chronic inflammatory diseases as a large
number of controlled clinical trials have shown. Among biological effects of
TNFalpha antagonists, the production of autoantibodies has been emphasized. This
phenomenon is not correlated with the disease background, since anti-nuclear
antibodies (ANA) and anti-double stranded-DNA antibodies (anti-dsDNA) induction
is observed in RA as well as in spondyloarthritis (SpA) patients. Nonetheless,
recent studies had reported a significant reduction in the serum titre of
rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide antibodies
(anti-CCP) during anti-TNFalpha therapy. The TNFalpha antagonists represent a
significant advance in the therapy of active RA and other chronic inflammatory
diseases. However, they have distinct biological, clinical, and pharmacological
properties that must be considered when selecting a drug for therapy.

Inflammatory molecules: a target for treatment of systemic autoimmune diseases. Tincani A, Andreoli L, Bazzani C, Bosiso D, Sozzani S. Autoimmun Rev. 2007 Nov;7(1):1-7. Epub 2007 Mar 26.

Inflammation is a process to protect the host against infection and danger
signals. However, many pathologic conditions, including autoimmune diseases, are
sustained by perpetual activation of the inflammatory process. In the past few
years our knowledge about the molecular basis of inflammation have been uncovered
and now much is known about the primary role of pro-inflammatory cytokines such
as IL-1 and TNF. In the early ’90s, anti-cytokine therapies started and confirmed
the primary role of TNF in autoimmune diseases, such as rheumatoid arthritis,
Crohn’s Disease and psoriasis. Increasing understanding of the role of
inflammatory mediators in inflammation and diseases is opening new avenues for
the treatment of inflammatory-based diseases through selective targeting of
cytokines and lipid mediators.

[Genetic and immunological aspects of the pathogenesis of psoriasis] [Article in Polish] Reich A, Szepietowski J. Wiad Lek. 2007;60(5-6):270-6.

Psoriasis is a chronic, inflammatory skin disorder, which occurs in about 1-3% of
general population. Skin lesions are a result of hyperproliferation of epidermis
and of time shortening of the transposition of keratinocytes from basal to
corneal layer of epidermis. In healthy subjects this time is estimated on about
26-28 days, whereas in psoriatic individuals lasts only 3-4 days. Despite many
investigations, the etiopathogenesis of psoriasis still remains unclear.
Observations that psoriasis could occur in the same family members, indicated the
importance of genetic factors. Moreover, high effectiveness of immunosuppressive
drugs in the treatment of psoriasis suggested also a significant role of immune
system in the development of this disease. Here, we present the current knowledge
on the role of genetic and immunological factors in the development of psoriasis.

Skin diseases with high public health impact. Psoriasis. Barker J. Eur J Dermatol. 2007 Nov-Dec;17(6):563-4. Epub 2007 Oct 19.

Tobacco smoke causes premature skin aging. Morita A. J Dermatol Sci. 2007 Dec;48(3):169-75. Epub 2007 Oct 24.

Smoking tobacco is the most preventable cause of morbidity and is responsible for
more than three million deaths a year worldwide. In addition to a strong
association with a number of systemic diseases, smoking is also associated with
many dermatological conditions, including poor wound healing, premature skin
aging, squamous cell carcinoma, melanoma, oral cancer, acne, psoriasis, and hair
loss. This review focuses on the effects of smoking on premature skin aging. It
has been long established that smoking has deleterious effects on skin.
Epidemiological studies indicate that smoking is an important environmental
factor in premature skin aging. In vitro studies indicate that tobacco smoke
extract impairs the production of collagen and increases the production of
tropoelastin and matrix metalloproteinases (MMP), which degrade matrix proteins,
and also causes an abnormal production of elastosis material. Smoking increases
MMP levels, which leads to the degradation of collagen, elastic fibers, and
proteoglycans, suggesting an imbalance between biosynthesis and degradation in
dermal connective tissue metabolism. Reactive oxygen species are also involved in
tobacco smoke-induced premature skin aging. Scavengers of reactive oxygen species
ameliorate the induction of MMP. Tobacco smoke extract also impacts dermal
connective tissue in nude mice. Thus, in vitro and in vivo evidence indicates
that smoking tobacco leads to accelerated aging of the skin. These findings might
be useful to motivate those patients who are more concerned about their
appearance than the potential internal damage associated with smoking to stop
smoking.

Do fungi play a role in psoriatic nails? Szepietowski JC, Salomon J. Mycoses. 2007 Nov;50(6):437-42.

Onychomycosis is the most common disease of the nails and constitutes about a
half of all nail abnormalities. Some factors like increasing age, male sex,
repeated nail damage, genetic predispositions and underlying conditions, such as
diabetes, immunodeficiency or peripheral arterial disease may predispose to
develop onychomycosis. It is also suggested that abnormalities in nail morphology
are the predisposing factors to onychomycosis. Psoriasis is one of the most
common reasons of disturbed nail morphology and the spectrum of nail changes in
psoriasis is very wide. Thus, there were suggestions that dystrophic nails in
psoriatic patients lose their natural preventing barrier and therefore are more
predisposed to fungal infection. This paper summarizes the knowledge about
prevalence of onychomycosis among psoriatic patients and contains a literature
review concerning this problem. Most authors report that the prevalence of
onychomycosis in psoriatic patients is not higher than that in control
population. However, especially yeasts and maybe moulds, probably as concomitant
pathogens, are more often isolated from psoriatic patients than from
non-psoriatic population. In reasonable cases, the mycological examination is
required, especially when the clinical picture of the nails suggests the presence
of fungal infection. In these cases, antifungal treatment may be beneficial for
psoriatic patients.

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.

TNF-alpha inhibitors in dermatology. Cordoro KM, Feldman SR. Skin Therapy Lett. 2007 Sep;12(7):4-6.

To date, the US FDA has approved three tumor necrosis factor (TNF)-a inhibitors
for use in dermatology. Etanercept (Enbrel, Amgen-Wyeth), a fully human fusion
protein of TNF receptor II bound to the Fc component of human IgG1, is approved
for use in psoriasis (2004) and psoriatic arthritis (2002). Infliximab (Remicade,
Centocor) is a chimeric monoclonal antibody that is approved for use in psoriasis
(2006) and psoriatic arthritis (2005), and adalimumab (Humira, Abbott
Laboratories), a fully human monoclonal antibody, is approved for use in
psoriatic arthritis (2005). While data regarding the efficacy and safety of these
therapies is abundant, it proves nearly impossible to objectively compare and
contrast agents as there are no head-to-head trials. Clinical experience and
post-marketing reporting has allowed dermatologists to identify the relative
strengths and limitations of each agent. The well-founded enthusiasm for these
agents, because of their excellent initial efficacy and safety profile, is
reasonably tempered by concerns about declining efficacy over time, the risk of
infection, lymphoma and demyelinating disorders, and cost. The distinct and
targeted mechanism of action of the TNF inhibitors allows dermatologists to
customize therapy to match the individual needs and characteristics of patients
who are candidates for systemic or phototherapy.

Targeted UV therapy in the treatment of psoriasis. Stein KR, Pearce DJ, Feldman SR. J Dermatolog Treat. 2008;19(3):141-5.

Ultraviolet (UV) light is an effective treatment for extensive psoriasis and some
other inflammatory skin conditions. Because the predominant effect of UV is a
local one (as opposed to a systemic effect on immunity), localized delivery of
ultraviolet B radiation (UVB) may be a useful treatment for localized variants of
psoriasis and other conditions. The article reviews the literature regarding use
of localized UV therapy. A theoretical benefit of localized UV therapy is reduced
toxicity compared with whole-body therapy. Practical benefits in psoriasis
treatment include higher efficacy and more appealing cosmesis compared with
topicals. The 308-nm excimer laser is effective for psoriasis with fewer UVB
treatments and lower total UVB exposure than needed for total body UV treatment.
Other methods of localized UV delivery include quartz lamps, hand-held home UV
devices, and non-laser intense photo sources. Other conditions treated with
localized UV include vitiligo and lichen planus. Localized UV therapy is a useful
modality for the treatment of localized variants of psoriasis with growing use
for other dermatologic diseases.

Immune regulation in psoriasis and psoriatic arthritis–recent developments. Hueber AJ, McInnes IB. Immunol Lett. 2007 Dec 15;114(2):59-65. Epub 2007 Sep 25.

Psoriasis and psoriatic arthritis (PsA) are common diseases associated with
considerable morbidity and disability. Their pathophysiology comprises a
dysfunctional stromal-immune cell and cytokine network leading to inflammation of
skin, entheses and joints. Recent advances in understanding of disease
pathogenesis have led to the introduction of novel therapeutics providing the
ultimate proof of concept in defining the role of these targets in the
pathogenetic response. The pro-inflammatory cytokines TNF, IL-12/IL-23 and a
variety of co-stimulator molecules have all been identified as critical factors
in disease progression. In this short review we summarise key recent developments
in understanding of the role of cytokines, T cells, B cells in psoriatic disease
pathogenesis. We also describe the pathways that are believed to link such
inflammatory pathways to articular matrix dysregulation.

Outcomes in randomized controlled trials in psoriasis: what has changed over the last 20 years? Morsy H, Kamp S, Jemec GB. J Dermatolog Treat. 2007;18(5):261-7.

OBJECTIVE: In 1989, Marks et al. reviewed the different assessment tools employed
in the evaluation of psoriasis severity before 1986. Our objective was to
reproduce this seminal review to describe the changes over the last 20 years with
regard to the evaluation of psoriasis severity in randomized clinical trials.
DATA SOURCES: MeSH search on Pubmed for articles about psoriasis. STUDY
SELECTION: Randomized clinical trials published in Archives of Dermatology,
British Journal of Dermatology, Clinical and Experimental Dermatology and Journal
of the American Academy of Dermatology from 1 January 2004 to 31 December 2005.
DATA SYNTHESIS: Recent psoriasis trials implemented various clinical scoring
systems in an attempt to assess psoriasis severity, but this is done without any
apparent uniformity making direct comparisons between trials difficult. The
predominant difference, which has occurred in the outcomes of psoriasis trials
over the past 20 years, appears to be the introduction of an assessment of the
patients’ quality of life. CONCLUSION: The past 20 years have brought some
improvements to the field of psoriasis evaluation but they also bring emphasis to
the need for uniformity with regard to trial outcomes to ensure comparability and
make better pooling of data from different randomized clinical trials possible
for future meta-analyses.

Health-related quality of life: from health economics to bedside? Naldi L. Dermatology. 2007;215(4):273-6.

Interleukin-20 as a target in psoriasis treatment. Stenderup K, Rosada C, Worsaae A, Clausen JT, Norman Dam T. Ann N Y Acad Sci. 2007 Sep;1110:368-81.

Interleukin-20 (IL-20) is a new member of the IL-10 cytokine family discovered by
a structural algorithm. IL-20 transgenic mice displayed skin abnormalities
reminiscent of psoriasis, a finding that has prompted the investigation of this
new interleukin in relation to this disease. This article reviews the role of
IL-20 and its implication in psoriasis. It is shown that IL-20 and its receptors
are found in human skin and that IL-20 is involved in proliferation,
angiogenesis, and chemotaxis, all characteristics of psoriasis. We demonstrated
that IL-20 induced the thickening of human epidermis in vivo; however, this
thickening does not seem to be related to a direct effect of IL-20 on
hyperproliferation since the growth of normal human epidermal keratinocytes
(NHEKs) cultured in vitro was not affected by IL-20. On the other hand, in vitro,
IL-20 stimulated human peripheral blood mononuclear cells (PBMCs) to produce
proinflammatory cytokines and, in vivo, IL-20 in combination with PBMCs induced
psoriasis. This may suggest that IL-20 indirectly exerts its proliferative
effects on keratinocytes via immune cells present in the skin. Finally, we found
that blocking IL-20 signaling in psoriasis improves psoriasis, suggesting that
IL-20 is a potential target in psoriasis treatment.

Recent advances in medical dermatology. Clark LN, Lebwohl M. Int J Dermatol. 2007 Oct;46(10):1005-10.

Collectively, new developments in the field of medical dermatology will
ultimately lead to improved patient care. We review several new findings in the
dermatologic literature including the following: new questions regarding the
malignant potential of anti-tumor necrosis factor agents, which are widely used
for the treatment of moderate to severe psoriasis as well as psoriatic arthritis;
anti-interleulin-12, a promising anticytokine for the treatment of psoriasis;
diagnostic advances in the detection of latent Mycobacterium tuberculosis;
advances in the primary prevention of human papillomavirus and herpes zoster; and
new therapeutic options with existing medications for neuropathic pain and
pruritus.

Psoriasis of the face and flexures. van de Kerkhof PC, Murphy GM, Austad J, Ljungberg A, Cambazard F, Duvold LB. J Dermatolog Treat. 2007;18(6):351-60.

Facial and flexural psoriasis may impair the quality of life of psoriatic
patients considerably. For the adequate management of psoriasis it is important
to pay attention to lesions at these sensitive sites, which require an approach
different to that for lesions on other sites in several respects. An extensive
literature search was carried out to collect evidence-based data on facial and
flexural psoriasis with respect to epidemiology, clinical aspects, pathogenetic
factors and various treatments. Subsequently, a panel of experts, the Copenhagen
Psoriasis Working Group (CPWG), discussed these aspects and several
recommendations were formulated reconciling the evidence-based data. Facial
psoriasis occurs in 17-46% of psoriatics and flexural psoriasis is experienced by
6.8-36% of patients with psoriasis. Therefore, psoriasis at these sites cannot be
regarded as a rare manifestation. Facial psoriasis is a prognostic marker
indicating a poor prognosis of psoriasis. Facial and flexural psoriasis cannot be
regarded as distinct disease entities but rather as site variations. The clinical
features of facial psoriasis suggest that there are three subtypes: hairline
psoriasis, sebo-psoriasis and true facial psoriasis. Otitis externa and ocular
manifestations should not be neglected. Evidence that microbiological factors may
be relevant to facial and flexural psoriasis is virtually absent. For facial
psoriasis the response to UV radiation is variable. At least 5% of psoriatics
have photosensitive psoriasis. In these patients photosensitive diseases such as
lupus erythematodes and polymorphic light eruption have to be excluded. Based on
the literature assessment and working group discussions the CPWG concluded the
following. (1) Low-potency topical corticosteroids, vitamin D3 analogues and
calcineurin inhibitors are first choice treatments in facial and flexural
psoriasis. Evidence for the efficacy of the first two modalities is at level 3
while it is at level 1 for the third one. An individualized approach is
indicated; for example, in case of corticosteroid side effects in the past the
other two modalities should be selected and in unstable psoriasis prone to
irritation, monotherapy with vitamin D3 analogues should be avoided. (2)
Antimicrobial treatments are not indicated for facial and flexural psoriasis. (3)
Dithranol and tar treatment are not indicated as first-line treatment but only if
the first-line options fail. (4) In case topical therapies are not effective,
phototherapy and systemic treatments are indicated. (5) For future drug
development the combination of vitamin D3 analogues with low strength
corticosteroids is recommended.

Beta adrenergic receptors in keratinocytes. Sivamani RK, Lam ST, Isseroff RR. Dermatol Clin. 2007 Oct;25(4):643-53, x.

Beta2 adrenergic receptors were identified in keratinocytes more than 30 years
ago, but their function in the epidermis continues to be elucidated.
Abnormalities in their expression, signaling pathway, or in the generation of
endogenous catecholamine agonists by keratinocytes have been implicated in the
pathogenesis of cutaneous diseases such as atopic dermatitis, vitiligo, and
psoriasis. New studies also indicate that the beta2AR also modulates keratinocyte
migration, and thus can function to regulate wound reepithelialization. This
review focuses on the function of these receptors in keratinocytes and their
contribution to cutaneous physiology and disease.

Curcumin as “Curecumin”: from kitchen to clinic. Goel A, Kunnumakkara AB, Aggarwal BB. Biochem Pharmacol. 2008 Feb 15;75(4):787-809. Epub 2007 Aug 19.

Although turmeric (Curcuma longa; an Indian spice) has been described in
Ayurveda, as a treatment for inflammatory diseases and is referred by different
names in different cultures, the active principle called curcumin or
diferuloylmethane, a yellow pigment present in turmeric (curry powder) has been
shown to exhibit numerous activities. Extensive research over the last half
century has revealed several important functions of curcumin. It binds to a
variety of proteins and inhibits the activity of various kinases. By modulating
the activation of various transcription factors, curcumin regulates the
expression of inflammatory enzymes, cytokines, adhesion molecules, and cell
survival proteins. Curcumin also downregulates cyclin D1, cyclin E and MDM2; and
upregulates p21, p27, and p53. Various preclinical cell culture and animal
studies suggest that curcumin has potential as an antiproliferative,
anti-invasive, and antiangiogenic agent; as a mediator of chemoresistance and
radioresistance; as a chemopreventive agent; and as a therapeutic agent in wound
healing, diabetes, Alzheimer disease, Parkinson disease, cardiovascular disease,
pulmonary disease, and arthritis. Pilot phase I clinical trials have shown
curcumin to be safe even when consumed at a daily dose of 12g for 3 months. Other
clinical trials suggest a potential therapeutic role for curcumin in diseases
such as familial adenomatous polyposis, inflammatory bowel disease, ulcerative
colitis, colon cancer, pancreatic cancer, hypercholesteremia, atherosclerosis,
pancreatitis, psoriasis, chronic anterior uveitis and arthritis. Thus, curcumin,
a spice once relegated to the kitchen shelf, has moved into the clinic and may
prove to be “Curecumin”.

Scalp psoriasis: a review of current topical treatment options. Papp K, Berth-Jones J, Kragballe K, Wozel G, de la Brassinne M. J Eur Acad Dermatol Venereol. 2007 Oct;21(9):1151-60.

The scalp is the most common site of disease involvement at the onset and
throughout the course of psoriasis. For many patients, psoriasis of the scalp is
the most difficult aspect of their disease; yet, despite a wide range of therapy
options and an extensive literature base, scalp psoriasis remains difficult to
treat, highlighting a long-standing unmet need for the effective treatment of
scalp psoriasis. A review of past and current medical literature reveals that a
number of interesting therapeutic approaches have been used in the treatment of
scalp psoriasis. The diverse and sometimes extreme therapeutic approaches, the
marginal benefit of many topical agents, the paucity of controlled studies
evaluating the efficacy of topical agents in the treatment of scalp psoriasis and
the high level of patient dissatisfaction with currently available treatments for
psoriasis all support the need for new, effective and well-tolerated treatment
options for scalp psoriasis.

Molecular basis of atopic dermatitis. Bonness S, Bieber T. Curr Opin Allergy Clin Immunol. 2007 Oct;7(5):382-6.

PURPOSE OF REVIEW: Atopic dermatitis is a common chronic inflammatory skin
disease and there are numerous publications on this topic. This review will focus
on developments in understanding the molecular basis of atopic dermatitis while
considering the genetic background, skin barrier impairment, immune system
deviation and microbial superinfections. RECENT FINDINGS: Atopic dermatitis is a
complex genetic disease in which gene-gene and gene-environment interactions play
a key role. Surprisingly some genetic regions of interest were found to be
overlapping with loci identified to play a role in another very common
inflammatory skin disease, psoriasis, while no overlap has so far been observed
with asthma. Impairment of the skin barrier followed by antigens trespassing
seems to play an important role, favouring sensitization via transepidermal
penetration which is the focus of current investigations. Superinfections by
pathogens such as Staphylococcus aureus due to a weak innate defence seem to be
significant in atopic dermatitis as they elicit a strong inflammatory response.
SUMMARY: Atopic dermatitis is a chronic inflammatory skin disease with a high
incidence in school children and adults. Disease pathogenesis is complex and the
background is multifactorial, making the underlying predispositions elusive.
Understanding new pathogenic pathways may lead to the development of new drugs
with enhanced benefit for the patient.

Interleukin-17 in inflammatory skin disorders. van Beelen AJ, Teunissen MB, Kapsenberg ML, de Jong EC. Curr Opin Allergy Clin Immunol. 2007 Oct;7(5):374-81.

PURPOSE OF REVIEW: Recently, a novel and unique subset of interleukin
(IL)-17-producing CD4+ T helper (Th17) cells, distinct from Th1 and Th2 cells,
was discovered. The question is addressed as to what extent inflammatory skin
diseases are associated with the actions of this newly discovered Th17 cell
subset. RECENT FINDINGS: Th17 cells are involved in protection against bacterial
pathogens. In addition, it is now clear that Th17 cells may also be crucial in
the pathogenesis of various chronic inflammatory diseases that were formerly
categorized as Th1-mediated disorders. SUMMARY: In this review, we summarize the
current knowledge of IL-17 and Th17 cells and discuss the possible role of IL-17
in the pathology of psoriasis, contact hypersensitivity and atopic dermatitis.
Whereas IL-17 may play an important role in the pathogenesis of psoriasis and
contact hypersensitivity, its role in atopic dermatitis is still unclear.

Not enough vitamin D: health consequences for Canadians. Schwalfenberg G. Can Fam Physician. 2007 May;53(5):841-54.

OBJECTIVE: To review the evidence on vitamin D (VTD) insufficiency and deficiency
from a Canadian perspective and to highlight some of the known and evolving
implications of insufficiency or deficiency for health. QUALITY OF EVIDENCE:
PubMed was searched for articles on VTD insufficiency or deficiency and the role
they play in various diseases and conditions. Level I and II evidence indicates
that lack of VTD has a major role in short- and long-latency diseases. MAIN
MESSAGE: The long winters in Canada and lack of exposure to the sun contribute to
lower levels of VTD among Canadians in late winter and spring. Currently
recommended levels of fortification and supplementation are likely not high
enough to restore adequate levels of VTD in the body. Repletion and maintenance
therapy might be needed. CONCLUSION: Many Canadians are at risk of VTD
insufficiency or deficiency. Assessment of VTD status is important because
optimal levels of VTD have been determined for various conditions. Low levels of
VTD have negative implications for bone health and the health of other cell
types.

Pathogenetic and clinical rationale for TNF-blocking therapy in psoriatic arthritis. Punzi L, Podswiadek M, Sfriso P, Oliviero F, Fiocco U, Todesco S. Autoimmun Rev. 2007 Sep;6(8):524-8. Epub 2007 Jan 8.

The classical definition of psoriatic arthritis (PsA) as an inflammatory
arthritis associated with psoriasis reflects only in part the large spectrum of
musculoskeletal disorders found in patients with psoriasis. In particular,
enthesopathy, dactilytis, osteitis and axial involvement are frequently neglected
and probably account for the unsatisfactory response of PsA to traditional drugs,
such as NSAIDs, steroids and DMARDs. Furthermore, these drugs showed only a
partial ability to influence radiographic progression and psoriasis. The new
anti-TNF agents, in particular etanercept but also infliximab and adalimumab,
have demonstrated a comprehensive effectiveness on the multiple aspects of the
PsA disease, including quality of life and slowing of radiographic progression.
Despite this clear efficacy, the actual mechanisms by which TNF-blocking agents
are able to obtain all these effects are still incompletely understood. However,
the success of this therapy suggested one of the best ways for further research
in the field of PsA. In this new fashion, the most stimulating hypotheses
involving TNF are those regarding genetic predisposition, angiogenesis and
osteoclastogenesis.

Biologic therapies in psoriasis: a new therapeutic approach. Gisondi P, Girolomoni G. Autoimmun Rev. 2007 Sep;6(8):515-9. Epub 2007 Jan 9.

Chronic plaque psoriasis is an immune-mediated, inflammatory skin disease with a
heavy burden on quality of life of patients. The disease has a chronic relapsing
course and may be life long. Comorbid disorders include psoriatic arthritis,
obesity, dyslipidemia, hypertension and an increased rate of cardiovascular
disease. Conventional systemic treatments include methotrexate, cyclosporine and
acitretin, which are associated with end organ toxicity that precludes long term
therapy. Biological drugs are designed to selectively interfere with the immune
mechanisms that induce psoriasis. Efalizumab is effective for skin psoriasis but
not psoriatic arthritis. Anti-TNF-alpha agents (etanercept, infliximab and
adalimumab) are active on both psoriasis and psoriatic arthritis. Infliximab is
the most effective and rapid agent, but its safety profile may be less
favourable. Moreover, efficacy can reduce over time. Etanercept is moderately
active but has a better safety profile, and can be discontinued and re-used
without loss of efficacy. The long term safety of all these agents has not been
established.

Leflunomide in psoriatic arthritis. Kaltwasser JP. Autoimmun Rev. 2007 Sep;6(8):511-4. Epub 2007 Jan 9.

Psoriatic arthritis (PsA) is a common unique form of inflammatory arthritis
associated with psoriasis. Its exact prevalence is unknown but 5-30% of the 2-3%
of subjects of the general population affected with psoriasis are developing PsA.
Typically PsA presents as an oligoarticular asymmetrical arthritis with
predominant distal finger joint pattern, presence of spinal involvement
enthesitis and dactylitis. There is evidence that T-cells play a key role in the
immunopathology of PsA as well as Psoriasis. Leflunomide, a selective pyrimidine
synthesis inhibitor with the property to inhibit T-cell activation and
proliferation has been shown to improve both joint and skin symptoms in patients
with PsA. Significant response rates have been observed for Psoriatic Arthritis
Response Criteria (PsARC), modified ACR20 and PASI 50 after 24 weeks of treatment
with 20 mg/d Leflunomide orally in a randomised, placebo controlled multicenter
trial (TOPAS Study). Leflunomide treatment also improved quality of life and
showed a favourable safety profile. It is therefore concluded that Leflunomide
offers an efficacious, well tolerated, safe, and relatively inexpensive
therapeutic option for the treatment of actively inflamed joints and psoriatic
skin lesions in patients with PsA.

Do utilization management controls for phototherapy increase the prescription of biologics? Simpson GL, Yelverton CB, Rittenberg S, Feldman SR. J Dermatolog Treat. 2006;17(6):359-61.

The use of phototherapy for psoriasis has declined because of inconvenience,
managed care disincentives, and poor reimbursements. However, phototherapy is
safer than other options, and the efficacy rates for different methods of
photo