? Intravenous immunoglobin is increasingly used to treat PV, a rare, life-threatening, autoantibody-mediated blistering disease of the skin. The investigators' goal is to evaluate whether the effectiveness of IVIg can be improved by coupling it with a cytotoxic drug and examine the toxicity of this combination. The proposal is based on initial data that shows IVIg works by rapidly and selectively lowering serum level of the pemphigus antibodies that mediate the disease and that this effect is enhanced by the co-administration of a cytotoxic drug. To confirm this finding and determine whether it is associated with an improved outcome, the investigators plan to conduct a randomized trial of IVIg given with or without cyclophosphamide in patients with PV and examine the impact on serum pemphigus antibodies levels, clinical outcome and toxicity. ? ? The specific aims are to: 1) evaluate in a randomized Phase 2 trial whether the administration of IVIg together with cyclophosphamide lowers serum levels of pemphigus antibodies more rapidly than IVIg alone. These antibodies will be measured in the two groups at baseline and at defined intervals following initiation of IVIg therapy, using indirect immunofluorescence and ELISA assays. The primary endpoint will be a decrease in serum pemphigus antibodies one month after 4 IVIg cycles; 2) Evaluate whether the clinical activity of the disease is controlled more rapidly by the co-administration of IVIg and cyclophosphamide of the disease one month after four IVIg cycles, graded using a recently developed Disease Severity Index; and 3) Evaluate the toxicity of the two regimens, using conventional parameters. ? ? Successful completion of this work may provide a more effective and safer way to treat pemphigus unresponsive to conventional treatment. By improving the effectiveness of IVIg, it would also reduce the cost of this very expensive treatment and minimize its toxicity. ? ? ?
