Where Does Rituximab Fit in the Treatment of Autoimmune Mucocutaneous Blistering Skin Disease?

May 2012 | Volume 11 | Issue 5 | Original Article | 622 | Copyright © May 2012

We propose rituximab as a first-line therapy for pemphigus vulgaris and steroid-dependent bullous pemphigoid with or without systemic steroids. A brief review of the literature substantiates the significant risk associated with the use of long term, high-dose prednisone, mycophenolate mofetil (MMF), and azathioprine. No head-to-head studies are available with respect to safety and efficacy of rituximab versus these therapies. When comparing the side effects of rituximab to MMF, both are found to be mild when used as monotherapy in dermatologic patients. The most severe side effects of rituximab include fatal infusion reactions and hypersensitivity, pancytopenia, infection and organ dysfunction. With MMF, malignancy, pancytopenia, infection, and organ dysfunction are the most concerning side effects. The frequencies of these observed adverse events are difficult to compare, but the side effect profiles of rituximab and MMF are clearly similar. Therefore, there is equipoise whether to use rituximab before rather than after MMF and/or systemic corticosteroids.

J Drugs Dermatol. 2012;11(5):622-625.


Scientific evidence supporting the optimal treatment for autoimmune mucocutaneous blistering diseases (AMBD) today has not been established.1 High dose systemic corticosteroids are often cited as first line therapy. Because corticosteroids alone are usually not sufficient to place some of these diseases (eg, pemphigus vulgaris) in remission, a steroid-sparing agent is often added from the outset. Because substantial evidence supports the efficacy of both mycophenolate mofetil (MMF) and azathioprine in these diseases,2 these agents are often used first or second line with or after prednisone. There presently is no consensus as to where rituximab fits in the therapeutic arsenal of AMBD. It is often regarded as a third line treatment used only in refractory disease.2
We wish to define AMBD subsets as those that might respond to agents generally accepted as being of limited risk (ie, a single course of prednisone, tetracycline and niacinamide, or dapsone) and those that failed first line therapy (ie, difficult cases of pemphigoid or pemphigus foliaceus) or those that often require long-term and/or multiple immunosuppressant medications for meaningful control (ie, pemphigus vulgaris). The four agents that formerly might have been used prior to trying rituximab are high dose prednisone, MMF, azathioprine, or intravenous immune globulin (IVIg).
We propose that rituximab be considered as first line therapy for the latter group of recalcitrant AMBD. Whether to use rituximab in conjunction with the other four agents remains a question. We base our proposal on the side effect profiles of each drug, setting aside a pharmacoeconomic analysis that might also be favourable to first-line use of rituximab. It is possible that rituximab as a first line therapy may be less costly if the goal is to minimize morbidity because the current first line agents may later necessitate adding rituximab if only partial remission is achieved.


Side effects of rituximab are frequently cited as reasons for avoiding its use. Reported side effects come mainly from disease states for which rituximab is indicated (chronic lymphocytic leukemia, non-Hodgkin's lymphoma, rheumatoid arthritis in combination with methotrexate, Wegener's granulomatosis, and microscopic polyangiitis), all of which are predisposed to severe comorbidities. Patients with AMBD—most commonly bullous pemphigoid and pemphigus vulgaris—are often relatively healthy prior to drug therapy. As it is difficult to tease away the disease state from the rituximab as the cause of a side effect, we are leery of relegating such an effective medication to last line treatment on the basis of inappropriate attribution of risk. We would expect that side effects of rituximab in, say,