This study will determine the safety of treatment of bullous pemphigoid in patients resistant to therapy with systemic corticosteroids, with rituximab plus systemic corticosteroids.

Bullous pemphigoid (BP) is an autoimmune blistering disease characterized clinically by the presence of severely itchy, tense blisters located over the trunk and extremities. BP is the most common of the autoimmune blistering diseases with an incidence of approximately 10 per 1,000,000 population(1;2). In addition, BP occurs more frequently in the elderly. Routine histopathology reveals a sub-epidermal blister most often with large numbers of eosinophils. Direct immunofluorescence of the skin of patients with BP reveals a linear band of C3 and IgG at the basement membrane zone. Examination of the sera of patients shows the presence of a circulating anti-basement membrane zone autoantibody. This antibody has been found to be directed against a 180 kd protein of the basement membrane zone type XVII collagen (BPAg2) and against a 230 kd protein (BPAg1) found in the epidermal hemi-desmosome(3;4).

BP is a severe disease most often requiring therapy with high dose systemic corticosteroids (0.75 - 1.0 mg/kg/day) often for months(5). In addition, relapses are common and the additional use of immunosuppressive drugs such as azathioprine, methotrexate, cyclosporine A and others are needed to minimize the dose of systemic corticosteroids. The 1-year mortality of BP has been estimated to range from 10 - 30%(1;6). Currently treatment of patients with BP consists of initial use of systemic corticosteroids (0.75 - 1.0 mg/kg/day). Control of symptoms and new blister formation is most often achieved within 1 month and systemic corticosteroids are then tapered. As many as 33 - 50% of patients may not be able to be tapered to clinically acceptable levels of systemic corticosteroids, requiring the addition of systemic immunosuppression often with azathioprine. Approximately 66% of patients require long term treatment with immunosuppressive medication to maintain control of their blistering.(5;7;8) The need for long term systemic corticosteroid therapy often with systemic immunosuppression in an elderly population results in a significant morbidity and mortality in patients with BP. New therapeutic interventions that would potentially allow for the more rapid discontinuation of prednisone, avoidance of systemic immuno- suppression and perhaps earlier clinical relapse would be of substantial benefit to patients with BP. The clinical and laboratory data has demonstrated that BP is an autoantibody mediated blistering disease. Taken together these observations suggest that the use of anti-CD20 antibody (Rituxan) may be useful in the treatment of patients with BP. We have previously treated a patient with BP and graft versus host disease with anti-CD20 and anti-CD25 and were able to achieve clinical and serological remission within 4 weeks of initiation of therapy(9). In addition, others and we have successfully utilized Rituxan for the treatment of pemphigus vulgaris, another autoantibody mediated, autoimmune blistering disease(10-15)

Inclusion Criteria:

• Patients with autoimmune blistering skin diseases with clinical, histologic and immunological criteria confirming the diagnosis of bullous pemphigoid
• Ongoing disease activity on 17.5 mg/day of prednisone or more

Exclusion Criteria:

• Current use of other immunosuppressive therapy such as azathioprine, cytoxan or mycophenolate mofetil within the last 4 weeks.

1 year

Adverse events related or possibly related to study drug

Open label trial of rituximab in the treatment of 7 patients with the autoimmune blistering disease bullous pemphigoid.