B-cell targeted therapy of pemphigus.

Abstract

Pemphigus is an autoimmune disease that causes blistering and erosion of the skin and mucous membranes because of autoantibodies against desmoglein, which plays an important role in adhesion between epidermal keratinocytes. Treatment of pemphigus has long been centered on corticosteroids, and the guidelines for management of pemphigus have recommended high-dose systemic corticosteroids as the first-line treatment. While guideline-based treatment has been shown to be beneficial in patients with pemphigus, it has also become clear that this treatment is accompanied by significant burden and risk. The challenge for future pemphigus treatment is to maximize efficacy while minimizing risk during the course of the disease. In this regard, treatment targeting B cells is expected to become increasingly important as autoreactive B cells in pemphigus patients are thought to play a major role in the production of autoantibodies, which form the basis of the pathogenesis. The recent expansion of insurance coverage to rituximab, a monoclonal antibody against CD20, for refractory pemphigus in the USA, Europe, and Japan has opened up a new era of pemphigus treatment by enabling treatment strategies with drugs targeting B cells in patients. Here, we discuss the current status and future prospects of pemphigus treatment, focusing on rituximab and Bruton's tyrosine kinase inhibitors, which are expected to become essential drugs for pemphigus treatment in the future.