Background: Paraneoplastic pemphigus (PNP) is an autoimmune mucocutaneous disease associated with lymphoproliferative neoplasms, and frequently with a very rare tumour, Castleman's disease.
Objectives: To analyse the clinical history, immunopathological and histopathological findings in 28 patients with a confirmed diagnosis of PNP and Castleman's disease.
Methods: Sera from all patients were assayed by indirect immunofluorescence (IF) and immunoprecipitation (IP) for plakin autoantibodies, immunoblotting for detection of plectin autoantibodies, and enzyme-linked immunosorbent assay for detection of desmoglein (Dsg)1 and Dsg3 autoantibodies.
Results: Severe oral mucositis was observed in all patients, and lichenoid cutaneous lesions were seen in 19 of 28. Twenty cases of Castleman's disease were of the hyaline vascular type, four were of plasmacytoid type and four were of mixed type. Striking findings included pulmonary destruction leading to bronchiolitis obliterans in 26 patients and fatal outcome due to respiratory failure in 22 patients with pulmonary involvement. Histological findings included lichenoid and interface dermatitis with variable intraepithelial acantholysis. Direct IF showed deposition of IgG and C3 in the mouth and skin in 24 of 28 patients. However, indirect IF detected serum IgG autoantibodies in all patients. IP revealed IgG autoantibodies against desmoplakin I, envoplakin and periplakin in all cases, and against desmoplakin II and the 170-kDa antigen in 19 patients. Dsg3 and Dsg1 autoantibodies were present in 22 and 11 patients, respectively, and plectin autoantibodies in 23 patients.
Conclusions: PNP in association with Castleman's disease presents with severe oral mucositis and cutaneous lichenoid lesions. Serum autoantibodies against plakin proteins are the most diagnostic markers. Pulmonary injury with respiratory failure is the cause of death in most cases.