Current treatment of pemphigus

Pemphigus is a potentially life-threatening autoimmune blistering disease. Patients with pemphigus suffer from blisters/erosions of the skin and/or mucous membranes. Autoantibodies are directed against cell-surface proteins on keratinocytes. While the pathogenic relevance of antidesmosomal autoantibodies is clearly established, the role of non-desmosomal antigens has recently been highlighted. Treatment is usually based on high doses of systemic glucocorticosteroids which are mostly combined with additional immunosuppressants such as cyclophosphamide, azathioprine and mycophenolate mofetil or immunomodulants including intravenous immunoglobulin. The combination therapy has significantly reduced both mortality and disease-related morbidity whereas adverse events lead to treatment-related morbidity in a substantial number of patients. In addition, in some patients, these regimens are not sufficient to induce remission. For these groups of patients, new treatment modalities are warranted. In recent years, immunoadsorption and the anti-CD20 antibody rituximab have successfully been applied in pemphigus. Immunoadsorption rapidly reduces the amount of circulating autoantibodies and may be most efficient in the initial phase of the therapy. Rituximab has resulted in clinical improvement in almost all of about 60 pemphigus patients reported so far. Serious adverse events, however, were also reported. Due to the increasing understanding of the pathogenic mechanisms in pemphigus and to the development of new treatment modalities for other, more frequent autoimmune diseases such as rheumatoid arthritis, lupus erythematosus, and Crohn's disease, further advances in the treatment of pemphigus can be expected.