The Mechanism of Respiratory Failure in Paraneoplastic Pemphigus

Abstract

ARANEOPLASTIC pemphigus 1 is an auto-immune disease that accompanies an overt or occult neoplasm and causes blisters. It is char-acterized by the presence of IgG autoantibodies that react against desmosomal and hemidesmosomal plakin proteins, 2-5 desmosomal transmembrane pro-teins (desmogleins), 6 and an unidentified 170-kd an-tigen. Blistering of stratified squamous epithelium results from acantholysis, the loss of cell–cell adhe-sion, induced by pathogenic antibodies against the desmogleins. 6 The most commonly associated neo-plasms are, in decreasing order of frequency, non-Hodgkin's lymphoma, chronic lymphocytic leuke-mia, Castleman's disease, thymoma, retroperitoneal sarcomas, and Waldenström's macroglobulinemia. Progressive respiratory failure with clinical features of bronchiolitis obliterans is frequently the cause of death among patients with paraneoplastic pemphi-gus. Possible causes of the respiratory failure in-clude infection, toxic effects induced by chemothera-py, neoplasia, and autoantibody-mediated pulmonary injury. 7-16 Deposits of IgG in the bronchial epitheli-um, which have sometimes been observed, 17 suggest that autoantibody-mediated injury has a role in this process. To define the mechanisms of the pulmonary injury further, we studied two patients with paraneoplastic pemphigus and progressive respiratory failure. We found that autoantibodies directed against plakin pro-teins may cause acantholytic changes in the respiratory epithelium, leading to respiratory failure and death.