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

Abstract

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.

The importance of multidisciplinary healthcare for paraneoplastic pemphigus

“…Paraneoplastic pemphigus (PNP) is a potentially fatal autoimmune blistering disease, first described in 1990 by Anhalt and colleagues, which is commonly associated with lymphoproliferative neoplasms . Males between 45 and 70 years of age are most commonly affected by PNP . The diagnosis of PNP is based on clinical appearance, histopathology, the detection of tissue‐bound and circulating autoantibodies, and identification of the underlying neoplasm .…”

“…In addition, there may be linear deposits of IgG and/or C3 in the basement membrane zone . However, in approximately 50% of patients with PNP, especially those with lichenoid variants, the results of DIF are negative for immunoreactants and thus, may be equivocal for diagnosis of PNP …”

“…Acantholysis, keratinocyte necrosis, and interface dermatitis are hallmark features of PNP on routine histology. 2 Direct immunoflourescence (DIF) of perilesional tissue typically reveals intercellular deposits of immunoglobulin G and complement component 3 (IgG/C3) in the epithelium consistent with pemphigus. 5 In addition, there may be linear deposits of IgG and/or C3 in the basement membrane zone.…”

“…5 However, in approximately 50% of patients with PNP, especially those with lichenoid variants, the results of DIF are negative for immunoreactants and thus, may be equivocal for diagnosis of PNP. 2 In all forms of pemphigus, indirect immunofluorescence (IIF) on monkey esophagus or rodent bladder shows characteristic intercellular binding of IgG and often C3 in the epithelium. [2][3][4][5] For PNP, IIF has higher sensitivity and specificity than DIF, 86% and 98% compared to 41% and 87%, respectively.…”

“…2 In all forms of pemphigus, indirect immunofluorescence (IIF) on monkey esophagus or rodent bladder shows characteristic intercellular binding of IgG and often C3 in the epithelium. [2][3][4][5] For PNP, IIF has higher sensitivity and specificity than DIF, 86% and 98% compared to 41% and 87%, respectively. 1 Rodent bladder contains specific PNP antigens and is the preferred substrate to differentiate PNP from PV.…”