Paraneoplastic pemphigus with anti-desmocollin 3 autoantibodies and chronic lymphocytic leukemia

Paraneoplastic pemphigus (PNP) is an autoimmune blistering disorder coexisting with certain neoplasms, most commonly non-Hodgkin lymphoma, chronic lymphocytic leukemia (CLL) and Castleman’s disease [1]. The clinical presentation of PNP consists of painful mucosal erosions, polymorphic cutaneous lesions and systemic involvement. The PNP is characterized by various autoantibodies directed mainly to desmosomal proteins, particularly various plakin family proteins [2]. Recently the 170 kDa 2-macroglobulin-like protein 1 was identified as another PNP antigen [3]. In addition, novel ELISA of mammalian recombinant proteins (RP)s detected autoantibodies to desmocollins 1 (Dsc1) to Dsc3 in 67% of PNP cases [4]. Herein, we report an unusual case of PNP associated with CLL, mediated by antibodies against Dsc3.
In July 2013, a 50-year-old man was admitted to our department with a 6-week history of painful erosions in the oral cavity (Figure 1 A) and significant weight loss (6 kg within 1 month). Direct immunofluorescence (IF) of oral mucosal biopsy and indirect IF of monkey esophagus and human skin showed negative results. The diagnosis of Stevens-Johnson syndrome was made and the patient was treated with prednisolone 40 mg/day and acyclovir 400 mg/day for 1 month with no improvement. After systemic corticosteroids started the patient developed vegetating oral mucosal lesions (Figure 1 B). However, repeated direct IF for oral mucosal lesions remained negative.
Five weeks later the patient presented extensive erosive lesions both in the oral and on the genital mucosa (Figure 1 C). Subsequently, the patient developed disseminated vesicular skin lesions on the trunk and the upper extremities and damaged finger nails (Figure 1 D). A blood test performed at that time disclosed leukocytosis of 20,000 U/l with lymphocytosis. The immunopathological studies were repeated. Direct IF of perilesional skin showed IgG and C3 deposits both on keratinocyte cell surfaces and linearly along the epidermal basement membrane zone (BMZ) (Figure 2 A). Indirect IF of normal human skin, monkey esophagus and guinea pig disclosed circulating IgG anti-cell surface antibodies. Indirect IF of rat bladder also showed positive reaction with transitional epithelia (Figure 2 B). However, indirect IF of 1 M NaCl-split normal human skin showed negative results. Immunoblot (IB) studies were performed using a battery of antigen sources. mmunoblot of normal human epidermal extract was...


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