Elsevier

The Lancet

Volume 361, Issue 9364, 5 April 2003, Pages 1197-1204
The Lancet

Seminar
Psoriasis

https://doi.org/10.1016/S0140-6736(03)12954-6Get rights and content

Summary

Recent breakthroughs in the treatment of psoriasis have led to improved understanding of the pathogenesis of this disease. Activation of T lymphocytes leading to release of cytokines results in proliferation of keratinocytes. Several new biological therapies have been developed, which target specific steps in the pathogenesis of psoriasis. With these new treatments, variable degrees of clearing occur. Initial data suggest improved safety over older agents such as methotrexate and ciclosporin, but long-term data are necessary. Enhancements in topical therapy and phototherapy have also increased the armamentarium of treatments available for this disorder.

Section snippets

Epidemiology

Estimates of the prevalence of psoriasis vary from 0·5% to 4·6%, with rates varying between countries and races. Psoriasis tends to be more frequent at higher latitudes than lower latitudes and in more caucasians than in other races. These trends were confirmed in a postal survey to 50 000 households in the USA, in which 3% of 6·4 million Americans reported a diagnosis of psoriasis in 1994.1 Prevalence was almost equal in men and women, and more than twice as many whites than blacks or Asians

Diagnosis

Diagnosis of psoriasis relies almost entirely on characteristic clinical features and rarely requires histological confirmation. The presence of sharply demarcated, erythematous, scaling plaques on any part of the body should raise suspicion of psoriasis. In questionable cases, close examination of the scalp, and intergluteal cleft can show characteristic skin lesions even if the elbows and knees are clear. Pitted fingernails, subungual hyperkeratosis, or other nail changes could aid in

Clinical features

The clinical and histological features of psoriasis have been reviewed in detail.11, 12, 13 The most common form of psoriasis, plaque psoriasis, occurs in more than 80% of affected patients. This type of psoriasis is characterised by sharply demarcated, erythematous, scaling plaques that typically affect the elbows (figure 2), knees, scalp, and intergluteal cleft. Some individuals develop lesions on the palms and soles before other regions are affected, and occasionally patients will present

Genetics

The genetic basis of psoriasis has been investigated well in studies of families and twins. In an Australian study,14 concordance for psoriasis was 35% (12 of 34 pairs) in monozygotic twins and 12% (five of 43 pairs) for dizygotic twins. Results of an earlier Danish study15 showed a higher degree of concordance in monozygotic twins (18 of 32 pairs) than in dizygotic twins. Genetic factors contributed to clinical manifestations, including age of onset, type, and severity.

Most investigators

Pathogenesis

For many years psoriasis was thought to be a mainly epidermal disease. However, the discovery that immunosuppressive agents improve psoriasis has drastically changed our notions about the pathogenesis of this disease. Several lines of evidence point to a prominent role for T cells. Dermal infiltrates appear in early lesions before epidermal changes and consist of T cells and macrophages.20, 21 Reports that patients who received syngeneic bone marrow transplants from psoriatic donors developed

Treatment

Treatment of psoriasis ranges from topical therapies for mild disease to phototherapy or systemic therapy for more widespread disease (Panel). Despite their many shortcomings, topical drugs will remain the mainstay of psoriasis therapy for most patients. Topical tars were once used as an essential component of the Goeckerman regimen in which patients applied crude coal tar in the hospital for most of the day, removing the tar only before ultraviolet light treatments.26 Use of tars slowed when

Targeted treatments

Innovations in biotechnology have the potential to offer greater safety by building designer drugs that interfere with specific targets in the pathogenesis of psoriasis. Several drugs have been designed to treat this disorder by targeting specific cells, specific cytokines, or specific interactions between ligands and receptors. For example, denileukin diftitox, an interleukin 2-diphtheria toxin fusion protein mentioned above, targets activated T cells resulting in improvement of psoriasis.43

Other biological agents

Conflicting results have been obtained with some biological agents in development for psoriasis. Despite initial promise with an antibody against interleukin 8, further studies with this agent have proven disappointing. E-selectin, a vascular addressin thought to play a part in trafficking of T lymphocytes into lesional skin, was the target of a humanised monoclonal antibody. Results of a placebo-controlled trial98 showed decreased staining for E-selectin in lesional skin biopsies, but this

Search strategy and selection criteria

This review was done by PubMed searches of English language publications, emphasising the past 5 years of published work. Key words included psoriasis cross-referenced with epidemiology, gene, or biologic*. Additional searches were done with the terms psoriasis cross-referenced with pimecrolimus, anti-IL-8, B7, CTLA4Ig, medi-507, anti-Tac antibody, IL-10, infliximab, etanercept, alefacept, and efalizumab. Recent breakthroughs reported in the Book of Abstracts of the Annual Meeting of the

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