INTRODUCTION
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.
RATIONALE
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,
