Pemphigus - A Treatment Update
Sue Jessop; Nonhlanhla P. Khumalo

Abstract
Pemphigus is an uncommon but potentially life-threatening chronic autoimmune bullous disorder. Antibodies are directed against antigens (desmoglein 1 and 3) in the desmosomes linking keratinocytes and against acetylcholine receptors. Conventional treatment with high-dose corticosteroids, sometimes with adjuvant immunosuppressive agents, may be associated with very serious adverse effects. There is an urgent need to establish the evidence for the safest and most effective form of treatment. A literature review has revealed 11 controlled (9 randomized) trials of treatment for pemphigus. The numbers of participants in the individual trials are small and the data cannot be pooled as they evaluate different forms of treatment. The results of these trials suggest that very high doses of corticosteroids, either as pulse therapy or in daily dosage, are not superior to moderate daily doses.


Based on evidence from the available trials, addition of an immunosuppressive agent generally does not appear to offer substantial benefit in terms of clinical response. However, a recent study demonstrated a significant reduction in corticosteroid requirements among patients receiving immunosuppressive agents. Newer therapies, such as biologic agents (in particular rituximab), calcineurin inhibitors, or immunoadsorption appear promising but there are inadequate controlled trials to establish their role clearly. Initial open-label studies suggest that specific peptide immunotherapy may offer a safe and novel approach to the treatment of pemphigus in the future. At present, treatment of an individual patient with pemphigus requires clinical judgment and should not be based purely on guidelines or on the inadequate available evidence alone. There is an urgent need for large randomized, controlled, multicenter trials of treatment in patients with pemphigus.

Background
Pemphigus is an uncommon, autoimmune blistering disorder characterized by the presence of flaccid blisters of the skin and/or mucous membranes. It may occur at any age (peak 5060 years). In the newborn it is thought to result from passive placental transfer of pathogenic antibodies from the maternal circulation. Neonatal pemphigus is usually self-limiting, resolving with the disappearance of maternal antibodies. The recognized forms of this disease are pemphigus vulgaris (PV), pemphigus vegetans, pemphigus foliaceus (PF), IgA pemphigus, and paraneoplastic pemphigus. This article reviews only the literature relating to the two most common types (PV and PF including endemic forms).

Epidemiology and Etiology
Accurate prevalence figures are limited but it has long been recognized that PV has a relatively high prevalence in people from the Mediterranean area and among those of Jewish ancestry. The two common forms, PV and PF, show a variation in relative prevalence from one geographic area to another. PF is known to have an extraordinarily high prevalence in parts of Tunisia and Brazil (the endemic, so-called 'fogo selvagem,' form of the disorder). A genetic predisposition (HLA-DRB1*0102) has been identified.

Clinical Features
PV is characterized by the presence of flaccid blisters that rupture easily, leading to erosions and crusts. Without treatment the blisters tend to spread, showing little tendency to heal spontaneously. Skin and mucosal surfaces are often both involved, although pemphigus may initially remain at one site for months to years. PF is a more superficial condition in which the cleft occurs in the outer layers of the epidermis and frequently leads to erosive or crusted lesions rather than blisters.

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