Paraneoplastic Pemphigus: A Paraneoplastic Autoimmune Multiorgan Syndrome or Autoimmune Multiorganopathy?

Paraneoplastic pemphigus (PNP), a clinically and immunopathologically distinct mucocutaneous blistering dermatosis, is a severe form of autoimmune multiorgan syndrome generally associated with poor therapeutic outcome and high mortality. This IgG-mediated disease is initiated by an obvious or occult lymphoproliferative disorder in most cases. Clinically severe mucositis, and polymorphic blistering skin eruptions, and histologically acantholysis, keratinocyte necrosis and interface dermatitis are its hallmark features. A 58-year-old female presented with recurrent, severe, recalcitrant stomatitis and widespread erosions/blistering lesions of one-year duration. Treatment with repeated courses of systemic corticosteroids at a peripheral center would provide temporary relief. She also had fever, productive cough, odynophagia and poor oral intake, herpes zoster ophthalmicus, pain in the abdomen, and watery diarrhea. An array of investigations revealed chronic lymphocytic leukemia (CLL), mediastinal and para-aortic lymphadenopathy, bronchiolitis obliterans, and vertebral osteoporosis/fractures. With the diagnosis of CLL-associated PNP she was managed with dexamethasone-cyclophosphamide pulse (DCP) therapy for 3 cycles initially, followed by COP regimen (cyclophosphamide, vincristine, and prednisolone) for 5 cycles. Remission is being maintained with chlorambucil and prednisolone pulse therapy once in 3 weeks with complete resolution of skin lesions and adequate control of CLL. 1. Introduction Paraneoplastic pemphigus (PNP) is a mucocutaneous disease due to immunological effects of the tumor on resident immune system rather than by direct tumor infiltration or tissue damage caused by metastasis [1]. Although no age group or gender is exempt, the affected individuals in most instances are between 45 and 70 years of age and are males [2, 3]. This IgG-mediated disease is initiated by an obvious or occult lymphoproliferative disorder in most cases. Clinically severe mucositis and polymorphic blistering skin eruptions and histologically acantholysis, keratinocyte necrosis, and interface dermatitis are its hallmark features. Immunoprecipitation and immunoblot testing will detect autoantibodies directed against a complex of four polypeptides (mainly plakin family proteins and desmogleins) with different molecular weights: periplakin (210 and 190？kDa), desmoplakins-I and II (250 and 210？kDa), bullous pemphigoid antigen-1 (BPAG-I, 230？kDa), and envoplakin-I (210？kDa) [3, 4]. Pulmonary involvement as bronchiolitis obliterans is frequent, mostly irreversible and often