Introduction Paraneoplastic pemphigus PNP first reported by

Introduction Paraneoplastic pemphigus (PNP), first reported by Anhalt et al in 1990, is a rare mucocutaneous disease with a very high mortality rate. Clinically, it is characterized by severe mucositis with polymorphic skin eruptions, occurring in patients with concomitant neoplasms. In the literature, most common associated neoplasms were lymphoid neoplasms, including non-Hodgkin\'s lymphoma, chronic lymphocytic leukemia, and Castleman\'s disease. In addition, several features, including: histopathologic examination showing acantholysis and interface dermatitis; positive direct immunofluorescence (DIF) findings at the keratinocyte cell surfaces and/or along the basement membrane zone (BMZ); positive indirect immunofluorescence (IIF) results using different epithelia; and serum immunoblotting (IB) revealing a complex of five ARCA of 250 kD, 230 kD, 210 kD, 190 kD, and 170 kD are demonstrated to be characteristic for PNP. Among them, the association with a lymphoid neoplasm, positive IIF results on rat bladder, and recognition of envoplakin (210 kD) and/or periplakin (190 kD) upon IB are the most sensitive and specific features in the diagnosis of PNP. However, depositions of PNP autoantibodies were found in many tissues other than skin and epithelium, including kidney, urinary bladder, and muscles. At least five different clinical and immunopathological variants have been identified, including pemphigus-like, pemphigoid-like, erythema multiforme-like, graft-versus-host disease-like, and lichen planus (LP)-like. Therefore, Nguyan et al. proposed a more encompassing term “paraneoplastic autoimmune multiorgan syndrome”. In addition, several unusual cases were reported, including patients without a underlying neoplasm, patients with lichenoid eruptions without detectable autoantibodies, and patients without mucosal involvement. All of these emphasize the complexity of the disease, the variety of mucocutaneous presentations and organ involvements, and the need for further investigations.
Materials and methods Patients with PNP treated in the National Taiwan University Hospital from 1998 to 2012 were retrospectively recruited. The diagnosis of PNP was according to the criteria proposed by Camisa and Helm, including major criteria and minor criteria. Major criteria include polymorphous mucocutaneous eruption, concurrent internal neoplasia, and characteristic serum immunoprecipitation findings. Minor criteria include positive cytoplasmic staining of rat bladder epithelium by IIF, intercellular and BMZ immunoreactants on DIF of perilesional tissue, and acantholysis in biopsy specimen from at least one anatomic site of involvement. To be diagnosed with PNP, patients must fulfill three major or two major and two minor criteria. For patients presented with the lichenoid variant of PNP not meeting the Camisa and Helm\'s criteria, we used the criteria proposed by Cummins et al, which include the following: (1) known or occult neoplasm; (2) extensive, refractory mucous membrane ulcerations; (3) histologic examination for mucosa or skin revealing lichenoid interface dermatitis; and (4) lichenoid or polymorphous blistering skin lesions and/or pulmonary involvement consistent with bronchiolitis obliterans (BO).
Results
Discussion We compared the characteristics of our PNP patients with several previously reported case series (Table 3). Similar to the design of our study, Ohyma et al and Leger et al reported PNP cases based on a hospital-based or nationwide database without selection for a specific associated neoplasm or age groups. The average ages of the patients in these two studies were similar to our study. Unlike our study, the most common associated neoplasms of these two studies were non-Hodgkin\'s lymphoma and chronic lymphocytic leukemia, respectively. Akin to our findings, polymorphic mucocutaneous manifestations are also reported in these two studies with pemphigus-like presentation as the most common mucocutaneous manifestation. Another case series reported by Choi et al describing 12 Korean patients with paraneoplastic pemphigus has a very similar result regarding the most common associated neoplasms (Table 3). However, the most common mucocutaneous presentation in that study was EM-like lesions rather than pemphigus-like lesions. Among all studies mentioned above, the mortality rate and the extents of mucosal lesions are similar except the ocular involvement, which is less frequently observed in our study.