SummaryAutoimmune bullous skin disorders are induced by autoantibodies against distinct adhesion complexes of the epidermal and dermal-epidermal junction. Since most of these disorders are characterized by a severe, potentially lethal course, they require long-term immunosuppressive treatment to reduce the de novo synthesis of pathogenic autoantibodies by B lymphocytes. Rituximab, a chimeric monoclonal antibody against CD20 on B lymphocytes, has shown promise in several case reports or cohort studies in the treatment of paraneoplastic pemphigus, refractory cases of pemphigus vulgaris and foliaceus and in other autoimmune bullous disorders.Treatment with rituximab leads to depletion of pathogenic B-cells which may last up to 12 months resulting in a reduction of plasma cells secreting pathogenic autoantibodies. Rituximab is usually administered in an adjuvant setting at a dose of 375 mg/m 2 i. v. in weekly intervals for four consecutive weeks in addition to the standard immunosuppressive treatment. The present consensus statement of German-speaking dermatologists, rheumatologists and oncologists summarizes and evaluates the current evidence for the use and mode of application of rituximab in autoimmune bullous skin disorders.

Pemphigus vulgaris (PV) is a severe autoimmune blistering disease affecting the skin and mucous membranes. Autoreactive CD4(+) T helper (Th) lymphocytes are crucial for the autoantibody response against the desmosomal adhesion molecules, desmoglein (dsg)-3 and dsg1. Eleven patients with extensive PV were treated with the anti-CD20 antibody, rituximab (375 mg per m(2) body surface area once weekly for 4 weeks). Frequencies of autoreactive CD4(+) Th cells in the peripheral blood of the PV patients were determined 0, 1, 3, 6, and 12 months after rituximab treatment. Additionally, the clinical response was evaluated and serum autoantibody titers were quantified by ELISA. Rituximab induced peripheral B-cell depletion for 6-12 months, leading to a dramatic decline of serum autoantibodies and significant clinical improvement in all PV patients. The frequencies of dsg3-specific CD4(+) Th1 and Th2 cells decreased significantly for 6 and 12 months, respectively, while the overall count of CD3(+)CD4(+) T lymphocytes and the frequency of tetanus toxoid-reactive CD4(+) Th cells remained unaffected. Our findings indicate that the response to rituximab in PV involves two mechanisms: (1) the depletion of autoreactive B cells and (2) the herein demonstrated, presumably specific downregulation of dsg3-specific CD4(+) Th cells.

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