Diet and psoriasis: experimental data and clinical evidence.
Journal: Br J Dermatol. 2005 Oct;153(4):706-14.
Wolters M.

Psoriasis is considered as a T-cell-mediated inflammatory skin disease which is characterized by hyperproliferation and poor differentiation of epidermal keratinocytes. While susceptibility to psoriasis is inherited, the disease is influenced by environmental factors such as infections and stress. Diet has been suggested to play a role in the aetiology and pathogenesis of psoriasis. Fasting periods, low-energy diets and vegetarian diets improved psoriasis symptoms in some studies, and diets rich in n-3 polyunsaturated fatty acids from fish oil also showed beneficial effects. All these diets modify the polyunsaturated fatty acid metabolism and influence the eicosanoid profile, so that inflammatory processes are suppressed. Some patients with psoriasis show an elevated sensitivity to gluten. In patients with IgA and/or IgG antigliadin antibodies the symptoms have been shown to improve on a gluten-free diet. The active form of vitamin D, 1,25-dihydroxyvitamin D(3), exhibits antiproliferative and immunoregulatory effects via the vitamin D receptor, and thus is successfully used in the topical treatment of psoriasis. In this review, dietary factors which play a role in psoriasis are assessed and their potential benefit is evaluated. Furthermore, the risk of drug-nutrient interactions in psoriasis therapy is discussed.

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

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

Smoking and psoriasis.
Journal: Skinmed. 2005 May-Jun;4(3):174-6.
Behnam SM et al.

Many early studies examining the relationship between tobacco and the development of plaque-type psoriasis suggested a significant positive correlation; however, the majority of these initial studies failed to control for alcohol consumption and presented inconsistent results. The objective of this manuscript is to perform a literature review of articles assessing the relationship between smoking and psoriasis while controlling for confounders such as alcohol consumption. Alcohol-controlled studies suggest that women who are smokers have an up to 3.3-fold increased risk of developing plaque-type psoriasis. Men who are smokers do not exhibit such an increased risk, but studies have shown that smoking more than 10 cigarettes per day by men who are psoriasis patients may be associated with a more severe expression of disease in their extremities. In addition, smoking among both men and women who are psoriasis patients has been shown to reduce improvement rates. These data demonstrate the importance of discouraging smoking, particularly among psoriasis patients.

A critical review of Quality-of-Life Scales for Psoriasis.
Journal: Dermatol Clin. 2005 Oct;23(4):707-16.
Lewis VJ and Finlay AY.

Psoriasis can have a major impact on the lives of patients who have psoriasis and many different methods are described to measure this effect. This article describes four general health measures, six dermatology-specific measures, four psoriasis-specific measures, and four utility measure concepts that are used in psoriasis. For each of these, the extent of validation, including reliability of each measure and correlation with other measures, is described. The experience of use of each measure is summarized and key references listed. Advice is given concerning strategy for choosing which measures to use.

Getting under the skin: the immunogenetics of psoriasis.
Journal: Nat Rev Immunol. 2005 Sep;5(9):699-711.
Bowcock AM et al.

Psoriasis is a chronic inflammatory disorder of the skin that is mediated by T cells, dendritic cells and inflammatory cytokines. We now understand many of the cellular alterations that underlie this disease, and genomic approaches have recently been used to assess the alterations of gene expression in psoriatic skin lesions. Genetic susceptibility factors that contribute to predisposition to psoriasis are now also being identified. It is hoped that we will soon be able to correlate the cellular pathogenesis that occurs in psoriasis with these genetic factors. In this Review article, we describe what is known about genes that confer increased susceptibility to psoriasis, and we integrate this with what is known about the molecular and cellular mechanisms that occur in other inflammatory and autoimmune disorders.

Inpatient management of severe psoriasis.
Journal: J Drugs Dermatol. 2005 Sep-Oct;4(5):564-70.
Nelson AA et al.

Historically, severe psoriasis frequently required inpatient hospitalization for several weeks to reduce symptoms and prevent morbidity and mortality, Despite declining hospitalization rates there remain patients who undergo severe, acute psoriasis exacerbations requiring inpatient care. The majority of the literature describes the treatment of psoriasis in the outpatient setting. We review the inherent differences between the inpatient and outpatient management of psoriasis along several dimensions and discuss an approach to the inpatient treatment of severe psoriasis based upon therapeutic rate of onset, efficacy, and safety. The inpatient setting benefits from and lends itself to use of rapid acting, highly effective agents. Given the acute nature of psoriasis inpatient episodes, the risks associated with long-term use of a treatment are far less important in inpatient setting treatment planning than they are in the outpatient setting.

Outcome measures in psoriatic arthritis.
Journal: J Rheumatol. 2005 Nov;32(11):2262-9.
Gladman DD et al.

Recent advances in biologic therapies have provided hope for patients with psoriatic arthritis (PsA). However, studies have been hampered by the lack of acceptable and validated outcome measures. This article reviews outcome measures used in the assessment of both skin and joints in PsA, and provides a summary of the Psoriatic Arthritis Workshop during OMERACT 7. A set of domains to be included in the assessment of patients with PsA was derived, and a research agenda was developed.

Interventions for chronic palmoplantar pustulosis.
Journal: Cochrane Database Syst Rev. 2006 Jan 25;(1):CD001433.
Marsland A et al

BACKGROUND: Chronic palmoplantar pustulosis (PPP) is a chronic inflammatory skin condition characterised by crops of sterile pustules (yellow pus spots) on the palms and soles which erupt repeatedly over months or years. The affected areas tend to become red and scaly; cracks may form and these are often painful. Many different treatments have been used for palmoplantar pustulosis but none is generally accepted as being reliably effective. OBJECTIVES: To assess the effects of treatments for palmoplantar pustulosis, both in reducing disease severity and in maintaining remission once achieved. SEARCH STRATEGY: We searched the Cochrane Skin Group Specialised Register (January 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2003), MEDLINE (1966 to February 2003), EMBASE (1988 to February 2003). We also cross-checked with the Salford Database of Psoriasis Trials and reference lists of articles. We also contacted authors included trials, members of the Cochrane Skin Group and dermatologists interested in psoriasis. SELECTION CRITERIA: Any randomised controlled trial in which patients with chronic palmoplantar pustulosis were randomised to receive one or more interventions. DATA COLLECTION AND ANALYSIS: At least two reviewers independently assessed trial eligibility and quality. Study authors were contacted for additional information. Adverse effects information was collected from the trials. MAIN RESULTS: Twenty-three trials involving 724 people were included. There is evidence supporting the use of systemic retinoids (improvement rate difference 44%, 95 CI 28 to 59%), oral PUVA (improvement rate difference 44%, 95 CI 26 to 62%). However, a combination of PUVA and retinoids is better than the individual treatments. The use of topical steroid under hydrocolloid occlusion is beneficial. It would also appear that low dose ciclosporin, tetracycline antibiotics and Grenz Ray Therapy may be useful in treating PPP. Colchicine has a lot of side effects and it is unclear if it is effective and neither was topical PUVA (rate difference of 0.00, 95% CI -0.04 to +0.04). There is no evidence to suggest that short-term treatment with hydroxycarbamide (hydroxyurea) is effective. AUTHORS' CONCLUSIONS: Many different interventions were reported to produce "improvement" in PPP. There is, however, no standardised method for assessing response to treatment, and reductions in pustule counts or other empirical semi-quantitative scoring systems may be of little relevance to the patient. This review has shown that the ideal treatment for PPP remains elusive and that the standards of study design and reporting need to be improved to inform patients and those treating them of the relative merits of the many treatments available to them.

New drugs for peripheral joint psoriatic arthritis.
Journal: Drug Ther Bull. 2006 Jan;44(1):1-5.

Up to 3% of people have psoriasis, and as many as 42% of these have an associated chronic inflammatory arthritis. In up to 20% of such patients, the arthritis progresses to become severe, destructive and deforming. Traditional drug treatments include NSAIDs and disease-modifying anti-rheumatic drugs (DMARDs) used for rheumatoid arthritis. Leflunomide (Arava - Sanofi-Aventis), etanercept (Enbrel - Wyeth) inifliximab (Remicade - Schering-Plough) and adalimumab (Humira - Abbott) are licensed for the treatment of patients with peripheral joint disease in psoriatic arthritis. Here we review drug therapy for such patients, concentrating on the newer agents.

An overview of the pharmacokinetics and pharmacodynamics of efalizumab: a monoclonal antibody approved for use in psoriasis.
Journal: J Clin Pharmacol. 2006 Jan;46(1):10-20.
Joshi A et al.

Efalizumab is a recombinant humanized monoclonal IgG(1) antibody shown to be efficacious for the treatment of moderate to severe chronic plaque psoriasis. Efalizumab, a targeted inhibitor of T cell interactions, binds to the CD11a subunit of lymphocyte function-associated antigen 1 (LFA-1), thereby preventing LFA-1 binding to intercellular adhesion molecule 1 (ICAM-1). The authors review the pharmacokinetic and pharmacodynamic data from the efalizumab clinical development program and discuss how these data led to selection of the optimal weekly subcutaneous (SC) dose of efalizumab (1.0 mg/kg) in adults. Efalizumab SC dosages of 1.0 mg/kg/wk or greater exerted maximal pharmacodynamic effects for CD11a expression and available CD11a binding sites on T lymphocytes. Dosages greater than 1.0 mg/kg/wk SC did not provide additional benefits; moreover, higher doses did not alter the safety profile. During long-term administration of efalizumab, serum levels were generally stable and pharmacodynamic markers remained maximally affected.

The comorbid state of psoriasis patients in a university dermatology practice.
Journal: J Dermatolog Treat. 2005 Dec;16(5):319-23.
Pearce DJ et al 

Background: Psoriasis treatment is frequently complicated by the various types and severities of disease as well as the large number of therapies available. Another critical consideration in treatment planning is the presence of comorbid diseases. Purpose: The purpose of this study was to evaluate the relative prevalence of major comorbid disease states in patients with psoriasis and to identify significant predictors of these concurrent diseases in such patients. Methods: A retrospective chart review of 753 patients from an academic dermatology practice was performed. The patients were identified by ICD-9 code for psoriasis in billing records of patients seen between 1997 and 2000. Data on comorbidities were compiled from review of electronic chart notes from all physician visits in the university practice. Results: Comorbid diagnoses were listed in 551 out of 753 (73%) charts. As would be expected, hypertension, dyslipidaemia, diabetes and heart disease were the most common comorbidities; renal failure and hepatitis were least likely. Hepatitis was associated with use of systemic therapies (odds ratio = 2.19) and non-white race. When compared with national prevalence estimates, psoriasis patients had increased heart disease, hypertension, diabetes and emphysema; however, these findings must be interpreted with some caution. Conclusions: Comorbid diseases are common in psoriasis patients and should be taken into account during treatment planning and surveillance; they may pose unique challenges in caring for patients with psoriasis, particularly those requiring systemic therapy.

Infliximab for inpatient psoriasis management - is there a role?
Journal: J Dermatolog Treat. 2005 Dec;16(5):314-8.
Nelson AA et al

Background: While outpatient management is a realistic goal for most psoriasis patients, inpatient hospitalization may be required for severe acute exacerbations. The paradigm of inpatient psoriasis treatment has changed as reflected in an overall decline in admissions as well as the introduction of several new agents for patients with moderate to severe disease. With these changes as well as the changes in inpatient health care delivery, the costs of inpatient psoriasis therapy need to be re-examined. Purpose: To determine the mean charges and length of stay associated with inpatient admissions for psoriasis and compare these with the potential charges for infliximab administration in the inpatient setting. Methods: Inpatient psoriasis admissions were identified from the State of Maryland Health Services Cost Review Commission (HSCRC) non-confidential database from 1994 to 2003. The mean length of stay and total charges associated with psoriasis admissions were determined and adjusted to current values based upon the hospital costs component of the Consumer Price Index (CPI). The potential charges for infliximab administration were then estimated according to a presumed treatment paradigm and based on median Medicare reimbursement rates. Results: The mean length of stay for an inpatient psoriasis patient was 4.9 days, and the mean CPI adjusted total charges from 1994 to 2003 were $6736. In 2003, the mean total charges for a psoriasis admission were $7578. The total estimated charges for a 2-day inpatient hospitalization with infliximab administration were $6256. Conclusions: Although infliximab therapy is not currently approved for psoriasis therapy it does have efficacy and may be a first-line therapy for inpatient treatment. Additionally, the high cost of infliximab may be offset by a decreased overall length of stay and its use is therefore potentially justified.

Journal: Ann Dermatol Venereol. 2005 Nov;132(11 Pt 1):861-76.
Sparsa A.

Etanercept (Enbrel, Wyeth Pharmaceuticals) is a fusion protein composed of a soluble TNF alpha receptor issued from bio-technology. It is a member of TNF alpha's family with two others marked infliximab (Remicade, Scheringh Plough Laboratory), chimeric monoclonal antibody (25 p. 100 mouse) and adalimumab (Humira, Abbott France Laboratory), humanized monoclonal antibody (100 p. 100 human). In United States , etanercept is approved by Food and Drug Administration, since 1998, to treat rheumatoid arthritis showing an inadequate response to prior therapy with other disease-modifying antirheumatic drugs (DMARDS). In France , the MA (Marketing Authorization) is more recent, in 2000, etanercept to treat active rheumatoid arthritis who showed an inadequate response to others DMARDS (like methotrexate for example), with opportunity, in 2002, to administer etanercept in active, severe RA, in first line treatment without previous use of methotrexate. Others MA have been obtained in ankylosing spondylitis (2004) polyarticular-course juvenile rheumatoid arthritis (2000), and in the treatment of psoriasic arthritis (2002). Request of MA have been realised to treat cutaneous mild to severe psoriasis in adult, which failed to respond, contradication or no tolerance with systemic treatment as methotrexate, cyclosporine or phototherapy. Among the others anti-TNF therapy, only infliximab can be prescribed, in dermatology, to treat psoriatic arthritis in France . Encouraging good results were the subject of cases report, but lacking clinical trial, predicting probably administration of etanercept in others indications in future. TNF alpha is a proinflammatory cytokine and plays an important role in the physiopathology of large inflammatory diseases. Logically, in future, we should increased prescription of biotherapy, particularly anti-TNF alpha. We have to mind short or mild-term adverse events, widely described in the literature, but long-term side effects remained unknown. Moreover, these biotherapic agents have a high cost and should be estimate.

Alefacept for psoriasis and psoriatic arthritis.
Journal: Ann Rheum Dis. 2005 Nov;64 Suppl 4:iv58-60.
Gottlieb AB

Alefacept is a bioengineered fusion protein of soluble lymphocyte function antigen (LFA-3) with Fc fragments of IgG1. It is marketed in many countries for the treatment of moderate to severe psoriasis. This paper reviews the data supporting the use of alefacept in psoriasis and psoriatic arthritis.

The right dose in the right place: an overview of current prescription, instruction and application modalities for topical psoriasis treatments.
Journal: RJ Eur Acad Dermatol Venereol. 2005 Nov;19 Suppl 3:14-7.
Savary J et al

BACKGROUND: Compared to treatment success with oral medications, treatment success with topical treatments is currently difficult to achieve. AIM: To assess and compare existing methods of lesion size evaluation, prescription habits, instruction and application modalities of topical medications. METHODS: Review of current and new procedures to estimate the body surface area, to calculate the most adequate quantity of medication to be prescribed, to instruct patients and to assess the individual dosing procedures of topical treatments. RESULTS: The most accurate method to assess the body surface area remains the rule of nine, allowing, together with a recently developed calculation disc, to estimate the most adequate quantity of topical treatment (here calcitriol 3 g/g ointment) to be prescribed. Precise instructions to the patient are other important elements for the successful treatment of dermatoses. Dosing devices, such as a spatula, may help patients to dose their daily topical treatment, avoiding over- and underdosing of the medication. CONCLUSION: A correct evaluation of the lesions sizes, a precise calculation of the treatments quantity to be prescribed, clear instructions and treatment-specific individual dosing devices may help to achieve higher patient compliance and treatment success.

Early psoriatic arthritis.
Journal: Rheum Dis Clin North Am. 2005 Nov;31(4):641-57.
Kane D and Pathare S.  

In the majority of patients with psoriatic arthritis (PsA), it is a chronic progressive disease, and only 12% of patients with early PsA will be in disease-modifying antirheumatic drug-free remission at 2 years. Radiologic damage occurs in the early stages of PsA; up to 47% of patients with PsA have radiologic erosions after 2 years. This article reviews the clinical features of early PsA, pathologic insights into PsA gleaned from studies of early PsA, and the current state of diagnostic imaging and therapeutics in early PsA.    

New developments in topical sequential therapy for psoriasis.
Journal: Skin Therapy Lett. 2005 Nov;10(9):1-4. Koo JY.  

Topical agents for the treatment of psoriasis are indicated for patients whose affected area is less then 10% of their skin. However, for long-term use, their effectiveness can be limited. Topical sequential therapy involves the application of a class I corticosteroid and calcipotriene in three different phases: the clearance phase, the transition phase and the maintenance phase. It is an accepted and widely practiced technique that provides a balance between maximizing efficacy and minimizing side-effects thus offering patients rapid clearance of their psoriatic lesions and long-term maintenance of remission.    

Treating severe psoriasis: an update.
Journal: Nurs Stand. 2005 Oct 5-11;20(4):57-65; quiz 66.
Ronda L, Jones L.  

This article provides an overview of the common skin condition psoriasis, and the various treatments that are available, which include the newly available biologic drugs for severe psoriasis. It examines quality of life issues, including the rejection and stigmatisation felt by many patients, and explores coping strategies that can help patients.    

Psychologic factors in psoriasis: consequences, mechanisms, and interventions.
Journal: Dermatol Clin. 2005 Oct;23(4):681-94.
Fortune DG et al 

The article examines the English-language research literature concerning psychologic aspects of psoriasis published since 1995. The literature is concerned with (1) the consequences of psoriasis in terms of quality of life, disability, depression, anxiety, and stigmatization and factors that may predict such outcomes; (2) potential mechanisms of the interaction between psychologic factors, stress, and the pathophysiology of psoriasis; and (3) examination of the clinical utility of psychologic interventions on extent of psoriasis and psychologic distress. The implications of the findings are discussed with reference to future directions for research and practice.      

Alefacept: an expert review concerning the treatment of psoriasis.
Journal: Expert Opin Pharmacother. 2005 Oct;6(13):2327-33.
Langley RG et al 

Psoriasis is a chronic, inflammatory skin disease. Historically, phototherapy or immunosuppressive agents have been the first line of treatment for patients with severe psoriasis; however, the long-term use of these agents is limited by dose-dependent toxicities. Alefacept was the first biological agent approved in both the US and Canada for the treatment of adults with moderate-to-severe chronic plaque psoriasis. Alefacept is a remittive therapy that selectively reduces memory T cells. The efficacy and safety of up to two courses of alefacept have been demonstrated in clinical trials, and thus, this review focuses on new data to optimise the use of this biological agent. Emerging data indicates that multiple courses of alefacept for the long-term treatment of psoriasis are safe and effective. In addition, data are reviewed on the use of alefacept in combination with other agents and in other diseases, including psoriatic arthritis.    

Photodynamic therapy in dermatology: current concepts in the treatment of skin cancer.
Journal: Expert Rev Anticancer Ther. 2005 Oct;5(5):791-800.
Garcia-Zuazaga J et al

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

Efalizumab for the treatment of moderate to severe plaque psoriasis.
Journal: Ann Pharmacother. 2005 Sep;39(9):1476-82. Epub 2005 Jul 5.
Jordan JK 

OBJECTIVE: To review the pharmacology, efficacy, and safety of efalizumab for the treatment of moderate to severe plaque psoriasis. DATA SOURCES: A MEDLINE search (1966-May 2005) using the key words hu1124, anti-CD11a, efalizumab, Raptiva, Xanelim, and psoriasis was conducted. References of identified articles were reviewed for additional citations. STUDY SELECTION AND DATA EXTRACTION: Clinical trials evaluating the pharmacology, efficacy, and safety of efalizumab for treatment of moderate to severe plaque psoriasis in adults were included in our review. DATA SYNTHESIS: Efalizumab's ability to inhibit the binding of CD11a, a subunit of leukocyte function-associated antigen type 1, to intracellular adhesion molecule 1 results in decreased T-cell activation and migration, 2 key steps in the immunopathogenesis of psoriasis. Results of clinical trials have demonstrated that efalizumab administered subcutaneously is a safe and effective treatment for moderate to severe plaque psoriasis. Efalizumab was well tolerated in trials, with the majority of adverse events arising with the first dose and decreasing with subsequent doses. The high cost of this agent and lack of head-to-head trials with other drugs will likely restrict its use to patients who have failed prior systemic therapy or phototherapy. CONCLUSIONS: Efalizumab is a safe and effective therapy for treatment of moderate to severe plaque psoriasis in patients who have failed prior systemic therapy or phototherapy.    

The assessment of disease activity and outcomes in psoriatic arthritis.
Journal: Clin Exp Rheumatol. 2005 Sep-Oct;23(5 Suppl 39):S142-7.
Kavanaugh A. and Cassell S.  

Psoriatic Arthritis (PsA) is a common condition that significantly impacts affected patients. The introduction of novel therapeutic agents for PsA has generated considerable interest in both clinical trials and in clinical care. Thus, there is a great need for standardized outcome measures to assess the activity of disease and the response to therapy. Because psoriasis is a heterogeneous and multi-faceted condition, defining outcome measures has been a challenge. To date, such measures have largely been adapted from related diseases, as described in this essay. Further research is needed to further develop outcome measures for PsA to facilitate optimal treatment of patients with PsA.  

Alcohol as a risk factor for plaque-type psoriasis.
Journal: Cutis. 2005 Sep;76(3):181-5.
Behnam SM et al 

The association between alcohol and the development of plaque-type psoriasis is complex and confusing because many of the initial studies did not control for confounding factors such as tobacco use. This article presents a literature review of the epidemiologic, case-controlled, and clinical studies that examined the relationship between alcohol and plaque-type psoriasis. Early studies showed no correlation between alcohol consumption and plaque-type psoriasis. However, as researchers began to control for confounding factors, study results often illustrated a significant correlation between alcohol use and psoriasis. Some studies suggested a relative risk factor of 8.01, particularly in men. However, the studies did not document an increased risk for plaque-type psoriasis in women who drank alcohol. We recommend that clinicians discourage patients with psoriasis from consuming alcohol, especially during periods of disease exacerbation.    

Infantile psoriasis.
Journal: Cutis. 2005 Sep;76(3):173-7.
Janniger CK et al

Psoriasis is a common inherited papulosquamous dermatosis that may be a diagnostic dilemma, particularly in infants and children. The treatment of children with psoriasis should be handled with caution and tailored according to the child's age, as well as to the extent, distribution, and type of psoriasis.    

Experimental approaches to lymphocyte migration in dermatology in vitro and in vivo.
Journal: Exp Dermatol. 2005 Sep;14(9):641-66.
Radeke HH et al

Lymphocyte trafficking through the dermal compartment is part of the physiological surveillance process of the adaptive immune system. On the other hand, persistent or recurrent lymphocyte infiltrates are hallmarks of both types of chronic inflammatory skin diseases, Th1-type such as psoriasis or Th2/allergic-type like atopic dermatitis. A better understanding of the mechanisms underlying lymphocyte movements is one of the key prerequisites for developing more effective therapies. In this review, we introduce a range of simple-to-sophisticated experimental in vitro and in vivo approaches to analyze lymphocyte migration. These methods start from static in vitro adhesion and chemotaxis assays, include dynamic endothelial flow chamber, intravital dual photon, and transcutaneous live-video microscopy, and finally encompass specific genetically deficient or engineered animal models. Discussing pros and cons of these assay systems hopefully generates both state-of-the-art knowledge about the factors involved in most common chronic skin diseases as well as an improved understanding of the limitations and chances of new biologic pharmaceuticals that are currently introduced into clinical practice.    

Biologic therapy for psoriasis: an update on the tumor necrosis factor inhibitors infliximab, etanercept, and adalimumab, and the T-cell-targeted therapies efalizumab and alefacept.
Journal: J Drugs Dermatol. 2005 Sep-Oct;4(5):544-55.
Weinberg JM et al 

Psoriasis is a chronic skin disorder that affects approximately 2% of the US and European population. Over the last several years, one of the major focuses in psoriasis research has been the development of biologic therapies for this disease. The aim of these therapies is to provide selective, immunologically directed intervention with fewer side effects than traditional therapies. The goal of this article is to update the progress of the tumor necrosis inhibitors which are available, or under investigation, for clinical use in psoriasis: infliximab, etanercept, and adalimumab, as well as the T-cell-targeted therapies efalizumab and alefacept (Table 1).    

Mapping and identifying genes for asthma and psoriasis.
Journal: Philos Trans R Soc Lond B Biol Sci. 2005 Aug 29;360(1460):1551-61.
Kere J.  

Susceptibility genes for complex diseases are characterized by reduced penetrance, caused by the influence of other genes, the environment or stochastic events. Recently, positional cloning efforts have yielded several candidate susceptibility genes in different complex disorders such as Crohn's disease and asthma. Within a genetic locus, however, the identification of the effector gene may pose further challenges and require functional studies. I review two examples of such challenges: the cloning of GPR154 (GPRA) and AAA1 on chromosome 7p14 at a susceptibility locus for atopy and asthma, and the study of HLA-Cw6, CCHCR1 (HCR) and CDSN on chromosome 6p21 at PSORS1, the major susceptibility locus for psoriasis. The susceptibility locus for atopy and asthma contains two genes and only one of them is protein coding. We studied its isoform-specific expression in bronchial biopsies and in a mouse model of ovalbumin-induced inflammation of bronchial epithelia. In the PSORS1 locus, strong linkage disequilibrium between genes has made it difficult to distinguish the effects of the three nearby genes. We engineered transgenic mice with either a HCR non-risk allele or the HCR*WWCC risk allele controlled by the cytokeratin-14 promoter. The results suggested that the overexpression of HCR in mouse skin was insufficient to induce a psoriasiform phenotype, but it appeared to induce allele-specific gene expression changes that were similar to those observed in psoriatic skin.  

Treatment advances in psoriatic arthritis.
Journal: Curr Rheumatol Rep. 2005 Aug;7(4):313-8.
Ruderman EM 

Treatment of psoriatic arthritis, like the treatment of rheumatoid arthritis, now commonly includes the use of inhibitors of tumor necrosis factor in addition to traditional synthetic disease-modifying antirheumatic drugs. This paper examines the most recent data from therapeutic trials in psoriatic arthritis, with particular emphasis on the effectiveness of the tumor necrosis factor inhibitors. Recent data on potential future therapies is discussed as well, along with data on the mechanisms of current therapies that may have relevance for future treatment approaches.    

Genetic factors in psoriatic arthritis.
Journal: Curr Rheumatol Rep. 2005 Aug;7(4):306-12.
Korendowych E and McHugh N.  

The genetic factors that are associated with psoriatic arthritis (PsA) are intricately linked with those that predispose to psoriasis itself. The strongest association is with human leukocyte antigen-Cw*0602, although true susceptibility may lie with one of the neighboring genes along a disease-associated haplotype. There are a number of interesting candidate genes within the major histocompatibility complex (MHC) region with strong functional relevance that have been investigated in PsA. In addition, several areas outside the MHC complex have been highlighted as a result of genetic linkage studies in psoriasis. PsA is a complex, multifactorial disease where multiple genes are likely to influence disease susceptibility, severity, and clinical phenotype. The current evidence for genetic factors in psoriasis and PsA will be reviewed.  

A review of acitretin, a systemic retinoid for the treatment of psoriasis.
Journal: Expert Opin Pharmacother. 2005 Aug;6(10):1725-34.
Lee CS and Koo J.  

Acitretin is a second-generation, systemic retinoid that has been approved for the treatment of psoriasis since 1997. It can be considered one of the treatments of choice for pustular and erythrodermic psoriasis. However, the efficacy of acitretin as a monotherapy for plaque psoriasis is less, although it is often used in combination therapy with other systemic psoriasis therapies, especially ultraviolet B or psoralen plus ultraviolet A phototherapy, to increase efficacy. Such combination treatments may potentially minimise toxicity by using lower doses of each of the two agents. All systemic retinoids are potent teratogens. The most common side effects are mucocutanous effects such as cheilitis and hair loss, which are dose-dependent. Acitretin is not immunosuppressive, is generally safe for long-term use and has no time limit restrictions, which makes it useful in combination therapy and for maintenance therapy.    

Pimecrolimus in dermatology: atopic dermatitis and beyond.
Journal: Int J Clin Pract. 2005 Aug;59(8):969-74.
isondi P et al 

Pimecrolimus is a calcineurin inhibitor developed for the topical therapy of inflammatory skin diseases, particularly atopic dermatitis (AD). Pimecrolimus selectively targets T cells and mast cells. Pimecrolimus inhibits T-cell proliferation, as well as production and release of interleukin-2 (IL-2), IL-4, interferon-gamma and tumour necrosis factor-alpha. Moreover, pimecrolimus inhibits mast cell degranulation. In contrast to tacrolimus, pimecrolimus has no effects on the differentiation, maturation and functions of dendritic cells. In contrast to corticosteroids, pimecrolimus does not affect endothelial cells and fibroblasts and does not induce skin atrophy. Given the low capacity of pimecrolimus to permeate through the skin, it has a very low risk of systemic exposure and subsequent systemic side-effects. In different randomised controlled trials, topical pimecrolimus as cream 1% (Elidel) has been shown to be effective, well tolerated and safe in both adults and children with mild to moderate AD. In addition, pimecrolimus has been successfully used in inflammatory skin diseases other than AD, including seborrheic dermatitis, intertriginous psoriasis, lichen planus and cutaneous lupus erythematosus.  

Adalimumab: a review of side effects.
Journal: Expert Opin Drug Saf. 2005 Jul;4(4):637-41.
Scheinfeld N.  

Adalimumab (Humira) is a human monoclonal TNF-alpha antibody that blocks the effects of TNF-alpha. It is administered by subcutaneous injection. It has been approved alone or in combination with methotrexate for the treatment of rheumatoid arthritis in the EU and US. Approval for its use for the treatment of psoriasis, psoriatic arthritis and ankylosing spondylitis is expected in the near future. Its side effect profile is favourable when compared with traditional systemic treatments for these diseases. It does not require laboratory monitoring. The most common side effects of adalimumab are injection site reactions. Adalimumab increases the risk of rare serious infections. There is a two-fold risk of serious infections with the use of adalimumab, as reported in the Premier trial. This risk should not be minimised in this way. It should not be used during periods of active infection. Its most notable infectious complication is the reactivation of tuberculosis. Tuberculosis screening should be according to country standards and may or may not include purified protein derivative test or chest X-ray. Deep fungal and other serious and atypical infection can also be promoted by adalimumab. It has been associated infrequently with skin rashes. Rare side effects include: worsening or initiation of congestive heart failure, a lupus-like syndrome, a promotion of lymphoma, medically significant cytopenias, and worsening or initiation of a multiple sclerosis/neurological disease. There has been reported pancytopenia and elevated transamines with the use of adalimumab, which suggest that laboratory monitoring blood counts and liver functions, at least intermittently, are useful. In patients with any of the foregoing problems, its use should be extremely carefully considered. Adalimumab is a useful medication which can be safely used if its side effects are recognised.    

Psoriasis--recent advances in understanding its pathogenesis and treatment.
Journal: J Am Acad Dermatol. 2005 Jul;53(1 Suppl 1):S94-100.
Krueger G and Ellis CN 

Although not completely understood, there is clearly a genetic component in the development of psoriasis. Twin studies show a 67% concordance for monozygotic twins versus 18% for dizygotic twins. This lack of complete concordance in monozygotic twins suggests multifactorial inheritance and interaction between genetic predisposition and the environment. At present, 8 different psoriasis susceptibility loci have been identified in genome-wide linkage scans, including locations on 15 different chromosomes. Genetic connections have been made between psoriasis and other diseases, including atopic dermatitis, rheumatoid arthritis, and Crohn's disease. A variety of approaches are available for the treatment of psoriasis, ranging from topical agents for milder forms of the disease to phototherapy and systemic agents for severe psoriasis. Despite the importance of systemic therapies and recent advances represented by biologic agents, topical treatments will probably remain the mainstay of psoriasis therapy for most patients. The advent of new, cosmetically attractive vehicles may enhance compliance, add to the use of topical agents, and potentially improve patient outcomes.    

Involving the patient: impact of inflammatory skin disease and patient-focused care.
Journal: J Am Acad Dermatol. 2005 Jul;53(1 Suppl 1):S78-85.
Feldman S et al 

Atopic dermatitis (AD) and psoriasis are common chronic inflammatory diseases that are associated with significant psychosocial morbidity and a decrease in health-related quality of life (QOL). To better understand the effects of these two diseases on quality of life, as reported in the literature, a review of all English-language articles from 1970 to 2003 was performed using PubMed. Results from these studies and surveys illustrate the profound negative impact exerted by these conditions and the importance of early and appropriate treatment. These concerns can be incorporated into patient management strategies that focus on a new model for healthcare delivery, "patient-centered care," in which QOL plays an integral role. The impact of AD and psoriasis on physical, social, psychological, and financial aspects of life should not be trivialized and must be considered with the same importance as other chronic conditions. Because psoriasis and AD are chronic conditions that require patient and/or caregiver involvement for optimal management, the concept of patient-centered care with its emphasis on effective two-way communication is particularly important and useful for the clinician.  

A clinician's paradigm in the treatment of psoriasis.
Journal: J Am Acad Dermatol. 2005 Jul;53(1 Suppl 1):S59-69 .
Lebwohl M.

Psoriasis is a chronically recurring inflammatory disease that affects the skin, scalp, and joints. It ranges in severity from mild to severe, and patients with moderate to severe disease experience significant deterioration in quality of life. The goals of psoriasis treatment are to gain initial and rapid control of the disease process, decrease the percentage of body surface area involved, decrease plaque lesions, achieve and maintain long-term remission, minimize adverse events, and improve patient quality of life. Therapy varies depending on disease severity and spread and will shift from control of acute flares to long-term maintenance. Topical treatment for mild psoriasis includes the use of topical corticosteroids, calcipotriene, tazarotene, topical tars, anthralin, and keratolytics. Treatment of moderate to severe psoriasis includes systemic therapies, such as methotrexate, acitretin, cyclosporine, and biologic agents. Treatment can be effected using combination, rotational, or sequential regimens. Treatment algorithms developed by a 2002 consensus conference are described. Because some degree of therapy will always be necessary, ranging from maintenance of long-term remission to control of acute psoriasis flares, each patient requires an individualized plan.    

Clinical studies of a new vehicle formulation for topical corticosteroids in the treatment of psoriasis.
Journal: J Am Acad Dermatol. 2005 Jul;53(1 Suppl 1):S39-49.
Stein L.    

Topical corticosteroids have been the mainstay of topical anti-inflammatory therapy of psoriasis and are available in different treatment strengths or doses and various formulations or vehicles. Traditional formulations have included ointments, creams, and lotions. More recently, the mid-potency corticosteroid betamethasone valerate (BMV) and the ultra-high-potency corticosteroid clobetasol propionate (CP) have become available in a novel, thermolabile, low-residue foam vehicle for topical application. This review examines recent clinical studies on efficacy and safety of these two new formulations, BMV 0.12% foam (Luxiq; Connetics Corp, Palo Alto , Calif ) and CP 0.05% foam (OLUX, Connetics Corp), as treatments for scalp and nonscalp psoriasis. The studies demonstrated that BMV foam and CP foam are safe and effective treatments for psoriasis affecting scalp and nonscalp regions of the body. BMV foam and CP foam were absorbed more rapidly and demonstrated greater total absorption than their respective comparison formulations, namely BMV lotion and CP solution. The foam vehicle also appears to be associated with better compliance and improvements in quality of life. The unique nature of the foam vehicle, together with the positive findings of in vitro studies suggest these new foam formulations may expand the options currently available for combination therapy.    

Therapeutic options in the treatment of psoriasis and atopic dermatitis.
Journal: J Am Acad Dermatol. 2005 Jul;53(1 Suppl 1):S3-16.
Gottlieb AB 

A variety of therapeutic options are available to treat psoriasis and atopic dermatitis (AD). Local agents typically are used to treat localized and milder forms of disease, whereas phototherapy and systemic agents are used for more generalized and severe disease. Various combinations and sequences of topical or systemic therapies, or both, have been utilized in the treatment of psoriasis and, less frequently, of AD. Conventional systemic therapies for psoriasis, such as corticosteroids, oral calcineurin inhibitors, antimetabolites, and retinoids, are limited by their propensity to cause serious side effects. More recently, a number of immunobiologic agents, such as monoclonal antibodies, recombinant cytokines, and fusion proteins, have been approved by the Food and Drug Administration or are undergoing development as systemic antipsoriatic treatments. In many of these categories, a number of exciting new therapies are in development that may augment the existing armamentarium available to clinicians for the treatment of inflammatory skin diseases.    

Mechanisms of action of topical therapies and the rationale for combination therapy.
Journal: J Am Acad Dermatol. 2005 Jul;53(1 Suppl 1):S17-25.
Norris DA 

The advent of new topical agents such as topical calcineurin inhibitors, as well as the reformulations of older agents in new vehicles, has broadened the treatment approaches to psoriasis and atopic dermatitis. The clinician must now consider additional novel physiologic pathways and mechanisms of action as well as expanding options for combination therapy. Combination therapy is especially beneficial when the selected agents possess differing mechanisms of action that provide additive or synergistic efficacy, reducing the required doses of the individual agents compared with monotherapy and potentially limiting side effects. Therapeutic approaches also can be rotated or used in various sequences for maintenance therapy. In psoriasis, a number of trials have demonstrated the effectiveness of combination therapy. Although combination therapy has not been extensively studied in atopic dermatitis, many practitioners combine topical corticosteroids and topical calcineurin inhibitors in their clinical practice because the two drug classes have different and possibly complementary mechanisms of action. For both diseases, the decision as to what agents are combined must also be tempered by patient type, disease presentation or severity, and patient preferences.    

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

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

Update on the mechanisms and efficacy of biological therapies for psoriasis.
Journal: J Dermatol Sci. 2005 May;38(2):75-87. Epub 2005 Mar 5.
Koo J and Khera P.  

Biologically based agents (biologics) are novel therapeutic options in the treatment of moderate-to-severe psoriasis. Unlike traditional systemic anti-psoriatic drugs, which are chemically synthesized, these agents are unique in that they are derived from living organisms and hence called "biologics." In addition, they are the first group of "custom-designed" molecules that precisely target steps in the pathogenesis of psoriasis. The specificity of these biologics can theoretically avoid the side effects of the prebiologically developed systemic agents including the effects of hepatotoxicity, nephrotoxicity, and bone marrow suppression. However, there is also a tendency for a more precisely targeted agent to have a less overall efficacy. Due to the varying efficacies and high costs of the new biologic agents that are currently approved for psoriasis in the United States , the precise way they fit into the range of treatments for moderate-to-severe psoriasis should be defined pending future clinical experiences.  

Topical therapies for psoriasis: evidence-based review.
Journal: Can Fam Physician. 2005 Apr;51:519-25.
Afifi T et al 

OBJECTIVE: To review current understandings of and approaches to topical psoriasis therapies and to assess their efficacies and adverse effects. QUALITY OF EVIDENCE: Literature from 1987 to 2003, inclusive, was reviewed via MEDLINE using the search term "psoriasis" combined with "topical treatment." Articles were prioritized based on their level of evidence, favouring double-blind, randomized controlled trials over other comparison studies. Other studies were included where level I research was unavailable. No level III research was included. MAIN MESSAGE: Psoriasis is very common and causes substantial morbidity. Because most psoriasis is mild to moderate, patients are well suited to outpatient topical therapy. Advances in topical treatments for psoriasis have kept pace with a rapidly evolving comprehension of its pathogenesis, making a review of current therapies useful for those who treat psoriasis. While research supports continued reliance on corticosteroids as first-line therapy, comparable efficacy has been shown for vitamin D analogues and topical retinoids, albeit with a slight increase in adverse effects. CONCLUSION: The combination of steroids and vitamin D analogues or topical retinoids is perhaps the most promising current treatment. It seems to have increased efficacy and fewer side effects.    

Psoriasis treatment: traditional therapy.
Journal: Ann Rheum Dis. 2005 Mar;64 Suppl 2:ii83-6.
Lebwohl M et al

Even before the recent development of biological agents, a long list of effective treatments has been available for patients with psoriasis. Topical therapies such as corticosteroids, vitamin D analogues, and retinoids are used for localised disease. Phototherapy including broadband ultraviolet B (UVB), narrowband UVB, PUVA, and climatotherapy are effective for more extensive disease. Systemic therapies such as methotrexate, retinoids, and ciclosporin are effective for patients with refractory or extensive cutaneous disease.  

Psoriasis pathophysiology: current concepts of pathogenesis.
Journal: Ann Rheum Dis. 2005 Mar;64 Suppl 2:ii30-6.
Krueger JG and Bowcock A.  

Psoriasis vulgaris is a common skin disorder characterised by focal formation of inflamed, raised plaques that constantly shed scales derived from excessive growth of skin epithelial cells. The disease is defined by a series of linked cellular changes in the skin: hyperplasia of epidermal keratinocytes, vascular hyperplasia and ectasia, and infiltration of T lymphocytes, neutrophils, and other types of leucocyte in affected skin. In a relatively short period, psoriasis vulgaris has been conceptualised as a T lymphocyte mediated autoimmune disease and new biological therapies that target T cells have just entered routine clinical practice. Similarly, rapid progress has been made towards dissecting cellular and molecular pathways of inflammation that contribute to disease pathogenesis. This short review presents current pathogenic concepts that have emerged from genetic, genomic, and cellular information obtained in basic studies and from clinical studies of selective immune targeting drugs.  

Psoriasis: epidemiology, clinical features, and quality of life.
Journal: Ann Rheum Dis. 2005 Mar;64 Suppl 2:ii18-23; discussion ii24-5.
Langley RG et al 

Psoriasis is a common chronic, recurrent, immune mediated disease of the skin and joints. It can have a significant negative impact on the physical, emotional, and, psychosocial wellbeing of affected patients. Psoriasis is found worldwide but the prevalence varies among different ethnic groups. It has a strong genetic component but environmental factors such as infections can play an important role in the presentation of disease. There are several clinical cutaneous manifestations of psoriasis but most commonly the disease presents as chronic, symmetrical, erythematous, scaling papules and plaques. The epidemiology, clinical features, and impact on quality of life of psoriasis are reviewed.  

Psoriatic arthritis: epidemiology, clinical features, course, and outcome.
Journal: Ann Rheum Dis. 2005 Mar;64 Suppl 2:ii14-7.
Gladman DD et al

Psoriatic arthritis (PsA) has been defined as a unique inflammatory arthritis associated with psoriasis. Its exact prevalence is unknown, but estimates vary from 0.3% to 1% of the population. The clinical features described initially are recognised by most experienced clinicians, although they are most distinct in early disease. Initially, PsA typically presents as an oligoarticular and mild disease. However, with time PsA becomes polyarticular, and it is a severe disease in at least 20% of patients. Patients with PsA who present with polyarticular disease are at risk for disease progression. In addition to progression of clinical and radiological damage, health related quality of life is reduced among patients with PsA. It important to note that patients included in recent drug trials resemble patients followed prospectively in a clinic.  

Focus on: biologics that affect therapeutic agents in dermatology.
Journal: J Drugs Dermatol. 2005 Mar-Apr;4(2):233-45.
Saripalli YV and Gaspari AA 

Tumor necrosis factor (TNF)-alpha is one of the oldest known cytokines in human physiology. It is involved in both normal and pathologic states. Virtually every cell and organ in the body are affected by TNF-alpha. Though TNF-alpha is usually involved in inflammation as a normal host defense response, when overproduced, it can become pathologic and affect almost every organ system. In this article, we address the role of TNF-alpha in diseases such as rheumatoid arthritis, Crohn's disease, psoriasis, and ankylosing spondylitis as well as the drugs used to modulate TNF-alpha. Specifically, we look at the structure, mechanism of action, and clinical use for etanercept, infliximab, and adalimumab. Historically, we also review the drug lenercept, another TNF-alpha modulator. These drugs offer alternative effective treatments to rheumatologic and dermatologic diseases without as many of the toxic side effects of some of the traditional therapies. The traditional agents target TNF-alpha in addition to several other modes of action (disease modifying anti-rheumatic drugs [DMARDS] such as cyclosporine and methotrexate) (Table 1). Though TNF-alpha immunomodulation seems to be a very effective, promising treatment in several TNF-alpha mediated disease processes, long-term studies need to be performed to assess the risk-benefit ratio of using these drugs over an extended period of time.  

The impact of biologics on the quality of life of psoriasis patients and the economics of psoriasis care.
Journal: Semin Cutan Med Surg. 2005 Mar;24(1):52-7.
Stein KR et al 

Psoriasis has a tremendous impact on patients' lives, affecting them physically, psychologically, and socially. Thus, it is not merely a cosmetic concern and often warrants appropriately aggressive treatment. Traditional treatments for moderate-to-severe psoriasis include phototherapy, oral retinoids, methotrexate, and cyclosporine. Newer biologics combat the immunologic mechanism responsible for psoriasis and, to date, carry a more favorable side effect profile. We examined the impact on quality of life of biologics and assessed their total direct costs to psoriasis patients. Biologic treatments significantly improve the quality of life of psoriasis patients; however, they cost significantly more than traditional therapies. This difference calls for physicians to weigh the costs and benefits of biologic therapies and compare them to those of traditional treatments when considering care for psoriasis patients.    

Psoriatic arthritis and psoriasis: need for a multidisciplinary approach.
Journal: Semin Cutan Med Surg. 2005 Mar;24(1):46-51.
Qureshi AA et al

Psoriatic arthritis is a progressive and often destructive form of seronegative inflammatory arthritis that is associated with psoriasis. It can be difficult to diagnose because it can present in a number of different ways, often indistinguishable from noninflammatory arthropathies such as osteoarthritis as well as inflammatory arthritis such as gout. Severe arthritis may be observed in the absence of psoriasis, or mild arthritis may be seen in the presence of moderate-to-severe psoriasis. A high index of suspicion, screening of psoriasis patients, and close follow-up and evaluation with rheumatology often is needed to make the diagnosis. Early recognition of the disorder and timely therapy can prevent long-term complications, such as permanent joint destruction and disability. With the advent of biologic agents, we are better equipped to manage psoriatic arthritis today. Because dermatologists are on the front-line of psoriasis management, we are perfectly poised to identify and help improve care for patients who suffer from both psoriasis and psoriatic arthritis.  

Combining traditional agents and biologics for the treatment of psoriasis.
Journal: Semin Cutan Med Surg. 2005 Mar;24(1):37-45.
Cather JC and Menter A.  

Psoriasis patients deserve long-term control of their disease with optimal safety. Traditional agents (methotrexate, cyclosporine, retinoids, and photochemotherapy [PUVS]), although providing excellent short-term control, may produce acute or chronic toxicities, thus limiting their usage. Dermatologists are well versed in combination and rotational therapies for psoriasis, using these and other agents. With the advent of biologic therapies (three currently approved, and others pending), the potential for safer long-term psoriasis control is being realized. A review of the literature, plus our personal experience in using combinations of traditional agents and biologics, is presented.  

The treatment of psoriasis with etanercept.
Journal: Semin Cutan Med Surg. 2005 Mar;24(1):28-36.
Strober BE

Etanercept is a tumor necrosis factor alpha (TNF-alpha) inhibitor approved for the treatment of psoriasis. Etanercept is a soluble version of the tumor necrosis factor receptor (TNFR) that neutralizes the proinflammatory activity of TNF-alpha, a molecule central to the pathogenesis of psoriasis. Patients receiving etanercept continuously during both 12 and 24 weeks show a significant reduction in the signs of psoriasis. Further, higher doses of etanercept provide better efficacy. Both clinical trial and postmarketing experience with etanercept is extensive and, thus, etanercept has a well-defined safety and tolerability profile. With appropriate patient selection and follow-up, etanercept therapy has a very good benefit-to-risk ratio and represents a convenient option for patients with moderate-to-severe psoriasis.  

Clinical considerations of efalizumab therapy in patients with psoriasis.
Journal: Semin Cutan Med Surg. 2005 Mar;24(1):19-27.
Hamilton TK

Psoriasis is a chronic, incurable disease that often requires decades of therapy to maintain disease control. Efalizumab is a recombinant monoclonal IgG1 antibody approved for use in patients with chronic moderate-to-severe plaque psoriasis. To date, efalizumab has been evaluated extensively in more than 3500 patients, including in studies that have evaluated its efficacy and safety during extended use. Just as psoriasis fluctuates in severity, the response to treatment with efalizumab can vary among patients. On the basis of my personal experience managing patients in and out of clinical trials, most patients benefit from efalizumab. The possibility exists of intercurrent events during efalizumab therapy, such as the development of a transient localized papular eruption or mild arthralgia or, in a few patients, a generalized inflammatory flare or severe arthralgia. However, there are techniques to potentially manage these events in a manner that maximizes patient comfort and compliance. If dermatologists become comfortable recognizing the subset of patients who are overall excellent responders but develop a papular eruption or mild and manageable arthralgia, they will be able to readily incorporate this effective biologic into their daily practice. In this article, clinical trial data and case reports illustrate recommended patient management techniques and the substantial long-term benefits that psoriasis patients may realize with efalizumab therapy.  

Overview of biologic agents in medicine and dermatology.
Journal: Semin Cutan Med Surg. 2005 Mar;24(1):2-9.
Sobell JM   

Three agents have recently been approved by the Food and Drug Administration for the treatment of chronic plaque psoriasis: alefacept, efalizumab, and etanercept. The field of dermatology has now entered a new era, joining other disciplines of medicine that have been using biologic agents for decades. These new therapies offer psoriatic patients the potential for safe and effective long-term management of this disease. This article reviews how an increased understanding of the pathophysiology of psoriasis led to the development of these products.  

The psychosocial burden of psoriasis.
Journal: Am J Clin Dermatol. 2005;6(6):383-92.
Kimball AB et al 

BACKGROUND: Skin diseases such as psoriasis can profoundly influence a patient's self-image, self-esteem, and sense of well-being. Psoriasis is a multifactorial inflammatory condition with a disease burden that extends beyond the physical symptoms experienced by patients. Psoriasis affects all aspects of quality of life, including physical, psychologic, social, sexual, and occupational elements. OBJECTIVE: The goal of this article was to review the published literature on the impact of psoriasis on quality of life. METHODS: Relevant studies were identified through a comprehensive search of MEDLINE, EMBASE, and the Derwent Drug File databases of English-language articles published between 1993 and 2005 using the terms psoriasis in combination with quality of life, cost, cost-benefit analysis, economic, employment, days lost, healthcare, hospitalization, managed care, outcomes research, occupation, payers, and psychosocial. The reference lists of identified articles were checked for additional studies that might have been missed in the original searches. RESULTS: Data suggest that social stigmatization, high stress levels, physical limitations, depression, employment problems and other psychosocial co-morbidities experienced by patients with psoriasis are not always proportional to, or predicted by, other measurements of disease severity such as body surface area involvement or plaque severity. CONCLUSION: It is essential to include measures of psychosocial morbidity when assessing psoriasis severity and treatment efficacy because of the substantial role that psychosocial burden plays in patient perception of disease severity, quality of life, and disease course.  

Etanercept: a review of its use in the management of plaque psoriasis and psoriatic arthritis.
Journal: Am J Clin Dermatol. 2005;6(2):121-36.
Goldsmith DR and Wagstaff AJ 

Etanercept (Enbrel), a tumor necrosis factor-alpha antagonist produced by recombinant technology, is approved for use in the US as subcutaneous monotherapy in adults with moderate-to-severe psoriasis who are candidates for systemic therapy or phototherapy. The drug is also indicated in patients with psoriatic arthritis, in whom it may be used in combination with methotrexate. In well designed trials in patients with moderate-to-severe psoriasis, short-term etanercept therapy (typically 25 or 50 mg twice weekly) significantly increased the proportion of patients achieving a 75% reduction in the Psoriasis Area and Severity Index score compared with placebo. Similarly, in well designed trials in patients with psoriatic arthritis, treatment with short-term etanercept 25 mg twice weekly, alone or in combination with methotrexate, improved clinical features of the disease, while radiographic progression of joint damage appeared to be significantly slowed in a nonblind 1-year extension. Short-term etanercept therapy was well tolerated in patients with psoriasis or psoriatic arthritis. Etanercept is thus a valuable new option for the treatment of patients with chronic moderate-to-severe plaque psoriasis (who are candidates for systemic therapy or phototherapy or have failed other systemic therapies) or with psoriatic arthritis.  

Efalizumab.
Journal: Am J Clin Dermatol. 2005;6(2):113-8; discussion 119-20.
Wellington K and Perry CM 

Efalizumab is a humanized monoclonal antibody that binds to CD11a, the alpha-subunit of lymphocyte function-associated antigen-1, and consequently inhibits T-cell activation. In randomized, double-blind, placebo-controlled trials, efalizumab 1.0 mg/kg, administered subcutaneously once weekly for 12 weeks, significantly reduced disease activity in patients with chronic, moderate-to-severe plaque psoriasis. Significantly more efalizumab recipients had a > or =75% decrease in the Psoriasis Area and Severity Index (PASI) score [22.4-38.9%] than placebo recipients (2.4-4.9%); an additional 12 weeks of treatment resulted in sustained or increased PASI responses. The efficacy of weekly subcutaneous efalizumab was maintained during 15 months of treatment. Efalizumab significantly improved health-related quality of life in patients with chronic plaque psoriasis, with significant improvements in all the Dermatology Life Quality Index domains. Efalizumab was generally well tolerated in patients with chronic, moderate-to-severe plaque psoriasis, with few serious adverse events or treatment withdrawals. The most common adverse events were headache, chills, myalgia, pain, and fever; these most often occurred within 2 days of administration of the drug, were most frequent after the first or second dose, and decreased in frequency over time.  

The genetics of psoriasis and autoimmunity.
Journal: Annu Rev Genomics Hum Genet. 2005;6:93-122.
Bowcock AM 

Psoriasis is an inflammatory/autoimmune disease and, as with many autoimmune diseases, is associated with alleles from the major histocompatibility complex (MHC). With psoriasis and autoimmune disease, the penetrance of the MHC-associated alleles is never 100%, even for monozygotic twins. This may be because development requires additional environmental and/or genetic modifiers or requires specific T-cell receptor arrangements. Families segregating single or multilocus susceptibility alleles other than the MHC have also been reported. Overlapping genetic locations of loci for different autoimmune diseases have been known for several years and are starting to reveal common genes or genetic variants. These include genes normally involved in preventing spontaneous T-cell activation or proliferation, immune synapse formation, or cytokine production via pathways such as those mediated by NFkappaB and those involved in thymic selection. Autoimmunity may also involve dysregulation of genes or pathways regulated by the RUNX family of transcription factors. RUNX is involved in hematopoietic cell development, development of T cells in the thymus, chromatin remodeling, and gene silencing. Hence, its effect on cells of the immune system may be due to variable changes in gene expression and could account for variable body surface involvement and waxing and waning of disease.  

TNF alpha inhibitors in the treatment of psoriasis and psoriatic arthritis.
Journal: BioDrugs. 2005;19(1):47-57.
Tobin AM and Kirby B.  

Psoriasis is a chronic inflammatory skin disease that can lead to significant physical and psychologic distress for patients. Psoriatic arthritis (PsA), originally thought to be quite a mild disorder, is now recognized as a progressive and destructive arthritis. To date, therapies for both these conditions have been non-specific and unable to maintain long-lasting remission. In addition, many of the current therapies have significant adverse effects, limiting their usefulness. However, elucidation of the pathogenesis of psoriasis and PsA at a molecular level and the development of selective biologic agents have led to an enormous expansion of the armamentarium available to psoriasis patients. Two agents (infliximab and etanercept) selectively block the role of the cytokine tumor necrosis factor (TNF)-alpha and have proved effective in clinical trials in the treatment of both the skin and the joint manifestations of psoriasis. A third anti-TNF alpha agent (adalimumab Humira) is licensed for the treatment of rheumatoid arthritis; however, no studies have been published to date on its use in PsA or psoriasis. It is known that TNF alpha is elevated in both the skin and synovium of psoriatic patients and the effectiveness of its blockade by these two agents in psoriasis and PsA confirms its role in their pathogenesis. Randomized, double-blind, placebo-controlled trials have been performed with both agents in the treatment of psoriasis and PsA; in the case of etanercept these have been to support US FDA approval for use in psoriatic arthropathy. These studies are supported by smaller cohorts in open-label studies and anecdotal reports in the literature. Anti-TNF alpha therapy has proved to have disease-reducing activity in PsA and psoriasis and appears to be well tolerated. These studies have generally featured small numbers of patients and, until a larger cohort of treated patients is available, vigilance must be exercised. A considerable body of post-marketing safety data exists on the use of infliximab in rheumatoid arthritis and Crohn disease and for etanercept in rheumatoid arthritis and PsA. Certain issues, particularly the risk of infection, have emerged as features of the use of these agents. It remains to be seen whether effects seen in other disease entities may be extrapolated to psoriatic patients. More long-term data and experience are needed to define the role of anti-TNF alpha agents in the management of psoriasis and PsA. In particular, more studies are required to elucidate the finer points of co-medication; in some studies both agents have been used with other medications but there have been no formal trials of various possible combinations.    

Cutaneous adverse events of biological therapy for psoriasis: review of the literature.
Journal: Dermatology. 2005;211(3):209-17.
Thielen AM et al 

The use of biological agents is expanding worldwide as a new treatment alternative for chronic inflammatory diseases including more recently skin diseases, especially psoriasis. Although frequently observed, the knowledge about acute and chronic dermatological adverse events is limited, and potential pathogenic mechanisms still have to be identified. Exact diagnosis is required considering that dermatological adverse events raise a decisional challenge about potential treatment discontinuation. The object of this publication is to present an overview of the dermatological adverse events of these new treatment alternatives. Copyright 2005 S. Karger AG, Basel .

The psoriasis area and severity index is the adequate criterion to define severity in chronic plaque-type psoriasis.
Journal: Dermatology. 2005;210(3):194-9.
Schmitt J, Wozel G.  

BACKGROUND: Chronic plaque-type psoriasis is a major dermatosis, but a significant question is still unanswered: What defines severity in chronic plaque-type psoriasis? While objective assessments like the Psoriasis Area and Severity Index (PASI) have frequently been used in clinical trials, quality of life (QOL) questionnaires are currently becoming more and more popular. OBJECTIVE: This article summarizes the most important objective and subjective measurements of severity in psoriasis. For every dermatologist it is critically important to distinguish between severe psoriasis and psoriasis that severely affects QOL. Even if the PASI also has disadvantages, it is the most adequate instrument available to evaluate severity in plaque-type psoriasis. RESULT: We provide reasons why PASI >12 defines severe, PASI 7-12 moderate and PASI <7 mild chronic plaque-type psoriasis.  

Novel pharmacological approaches in the treatment of psoriasis.
Journal: J Eur Acad Dermatol Venereol. 2005 Jan;19(1):1-20.
Schleyer V et al

Progress in the understanding of psoriasis as a T-cell mediated inflammatory disease has led to the development of new immunomodulatory therapies. Currently the main focus is on the so-called biologics (or biological agents), including fusion proteins, monoclonal antibodies, cytokines and selective receptors. They mainly target single steps in the complex cascade of humoral and cellular inflammatory immuno-mechanisms that finally lead to the accelerated growth of epidermal and vascular cells in the psoriatic lesions. The most promising and advanced biological agents are discussed along with their influence on the critical pathophysiological steps in psoriasis, including depletion of T cells, blockade of initial T-cell activation and T-cell receptor (TCR) stimulation, blockade of costimulatory signals and T-cell proliferative signals as well as restoration of the T helper type 1 (Th1)/Th2 balance by diminishing type 1 cytokines and administration of type 2 cytokines. In addition to the biological agents, further development of 'classical' dermatological therapies, such as retinoids, or the discovery of new indications for non-dermatological agents contribute to the novel pharmacological approaches in the treatment of psoriasis.  

Alefacept is well tolerated in patients with chronic plaque psoriasis.
Journal: J Cutan Med Surg. 2004 Dec;8 Suppl 2:14-9.
Gottlieb AB 

Traditional systemic treatments for moderate to severe chronic plaque psoriasis are often poorly tolerated and are associated with safety concerns that restrict their long-term use. Alefacept is a fully human fusion protein that selectively targets memory T cells, and it is expected to provide enhanced safety over traditional nonselective agents. The safety and tolerability profile of alefacept is reviewed using data from the clinical development program. The most common adverse events were similar among alefacept and placebo groups. As expected from its mechanism of action, alefacept reduced the number of CD4(+) and CD8(+) T cells, with selectivity for the memory subsets. This reduction was not associated with an increase in the incidence of infections. Alefacept was not immunogenic. Patients have received up to 6 courses of alefacept therapy and the safety and tolerability profile over multiple courses is similar to that of a single course. Alefacept offers hope for a safer means to provide long-term management of psoriasis.  

Psoriasis: future research needs and goals for the twenty-first century.
Journal: Dermatol Clin. 2004 Oct;22(4):493-9, x.
Griffiths CE 

Psoriasis research is entering a new era. Progress in delineating immunogenetics and pathomechanisms of disease brings with it a need to understand fully the clinical spectrum of disease and integrate phenotype with genomics and proteomics. Involvement of patient groups and an understanding of the psychosocial aspects of psoriasis, particularly its significant impairment of quality of life, are keys to progress. The biologic revolution in therapy of inflammatory disease has embraced psoriasis bringing with it an urgent need for evidence-base, consensus on outcome measures, and long-term real-life studies.A concerted effort between academia, industry, and patients will take forward the understanding of, and therapy for, psoriasis.  

Quality-of-life issues in psoriasis.
Journal: Dermatol Clin. 2004 Oct;22(4):389-95, viii.
Mukhtar R et al 

Although the lesions of psoriasis might be "skin deep," the disease has dramatic physical,mental, social and financial ramifications for those it afflicts. Clinicians should be able to assess the impact of psoriasis on quality of life (QOL) to measure disease severity,monitor improvement, and ensure equitable funding for research and reimbursement.The development of various clinical tools to assess health-related QOL has led to increasing awareness of the extent of patient morbidity. The fact that psoriasis causes disability comparable to that seen in other major systemic diseases has important implications for how it should be viewed and treated.  

An update on the genetics of psoriasis.
Journal: Dermatol Clin. 2004 Oct;22(4):339-47, vii.
Capon F et al 

Psoriasis is a complex inflammatory disorder whose pathogenesis is likely to require the contribution of several genes and environmental triggers. Despite the difficulties posed by the study of multifactorial conditions, significant progress has been achieved in relation to the molecular genetic basis of psoriasis. It has long been recognized that the major histocompatibility complex (MHC) region on chromosome 6p21 harbors the main determinant conferring psoriasis susceptibility. The identification of non-MHC susceptibility regions across the genome has been hindered by the likely occurrence of genetic heterogeneity. Nonetheless, evidence for the assignment of a number of non-MHC loci has been achieved through studies, including the collaborative analysis of large patient cohorts, and also through the observation of overlap between psoriasis and atopic dermatitis susceptibility regions.     Etanercept in psoriasis. Journal: Expert Opin Pharmacother. 2004 Oct;5(10):2139-46. Papp KA   Psoriasis is a chronic skin disorder that affects approximately 2% of the US and European populations. Several lines of evidence have demonstrated the correlation between elevated levels of TNF and psoriasis, suggesting that interfering with the inflammatory effects of TNF may help resolve psoriatic lesions. The biological agent, etanercept, is a fully human soluble TNF-receptor fusion protein with proven efficacy in the treatment of rheumatoid arthritis, ankylosing spondylitis, juvenile rheumatoid arthritis, and psoriatic arthritis. In several well-controlled clinical trials, etanercept showed sustained efficacy in reducing the signs and symptoms of psoriasis in patients with moderate-to-severe disease. With the exception of injection site reactions, adverse event rates were similar to placebo and did not increase across higher doses. No opportunistic infections, including tuberculosis, were reported. From analysis of the available clinical trials, etanercept appears to be an effective and well-tolerated agent for the treatment of moderate-to-severe psoriasis.  

Psoriasis: a complex clinical and genetic disorder.
Journal: Curr Rheumatol Rep. 2004 Aug;6(4):314-6.
Valdimarsson H et al

Psoriasis is associated with arthritis in approximately 10% of patients. The skin disease and arthritis have a strong but complex genetic component. Several susceptibility loci have been reported including one major locus that maps very close to the human leukocyte antigen-C gene on chromosome 6p. No causative gene has so far been conclusively identified. A recent genetic analysis that only included patients with psoriatic arthritis revealed a highly significant susceptibility locus on chromosome 16q approximately 20 cM from the NOD2 gene that has been associated with Crohn's disease. This locus was barely detectable when the entire cohort of psoriasis patients was analyzed as a homogeneous entity. A further clinical stratification of psoriasis patients has revealed novel strongly suggestive loci and also increased the logarithm of the odds scores of some previously reported loci. It is concluded that a careful documentation of clinical features and phenotypic stratification may help to analyze complex genetic disorders.  

Epidemiology of psoriasis.
Journal: Curr Drug Targets Inflamm Allergy. 2004 Jun;3(2):121-8.
Naldi L.  

The prevalence of psoriasis is relatively high in the general population, ranging between 0.6% and 4.8%, mainly as a result of chronicity and the absence of a cure. Although genetic-environmental interaction has been proposed as a model for the causation of psoriasis, the evidence for environmental factors is rather scarce. Risk factors, which have been documented in epidemiological studies include smoking, alcohol consumption, diet, infection, drugs, and stressful life events. Psoriasis affects the quality of life to substantial degree. Apart from a few cross-sectional surveys of large series of psoriatic patients, there have been no formal studies of the natural history and prognosis of established psoriasis. By imposing methodologic control and a numerate approach, epidemiology can offer a major contribution to understand psoriasis.

Acknowledgments
We acknowledge Jinny James and Rao N. Saladi, M.D. for the above content.

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