Paraneoplastic pemphigus associated with Castleman tumor, myasthenia gravis, and bronchiolitis obliterans

Background: Cases of paraneoplastic pemphigus (PNP) have been reported asso ciated with various lymphoproliferative malignancies and benign Castleman t umors, with the most severe course and fatal outcome seen in patients with bronchiolitis obliterans. Objective: The aim was to establish immunologic associations by coexistence of Castleman tumor, myasthenia gravis, and bronchiolitis obliterans and to evaluate tht treatment modalities. Methods: Clinical studies included computed tomography of the mediastinum, computed tomograph and magnetic resonance imaging of the abdominal cavity a nd quantitative electromyography Direct and indirect immunofluorescence on various substrates, immunoblot analysis, immunoprecipitation. and specific enzyme-linked immunosorbent assay using recombinant desmogleins (Dsg) were performed as immunologic assays. Results: Direct and indirect immunofluorescence including rat bladder showe d intercellular antibodies. Immunoblotting disclosed antibodies to envoplak in (210 kd protein) and periplakin (190 kd protein); in addition, immunopre cipitation detected antibodies to desmoplakin I (250 kd protein). Antibodie s to Dsg3 (pemphigus vulgaris antigen) were detected by specific enzyme-lin ktd immunosorbent assay. Myasthenia gravis was controlled by drugs; however , mucocutaneous changes were not fully responsive to corticosteroids and c yclophosphamide pulses: cyclosporine, and intravenous immunoglobulins. The surgical removal of Castleman tumor did not change the course of the diseas e. The fatal outcome was the result of bronchiolitis obliterans that occurr ed after the surgery and was only transitionally controlled by plasmapheres is. Conclusion: This is the first case of paraneoplastic pemphigus associated w ith Castleman tumor, myasthenia gravis, and bronchiolitis obliterans. Despi te a benign character of the tumor tilt: patient died, as do all patients w ith bronchiolitis obliterans. Massive plasmapheresis has only a transient e ffect. We confirmed the presence of antibodies to Dsg 3, in addition to the set of specific paraneoplastic pemphigus antibodies against various protei ns of plakin family.