Paraneoplastic pemphigus resembling linear IgA bullous dermatosis

A 69‐year‐old Chinese man presented in 2001 with a blistering eruption over the upper and lower limbs associated with oral ulceration for 1 month. He had stage IIIA follicular small cell cleaved non‐Hodgkin's lymphoma diagnosed 5 years previously, and had received several lines of palliative chemotherapy, including two courses of chlorambucil, six cycles of cyclophosphamide, adriamycin, vincristine, and prednisolone (CHOP), and two four‐cycle courses of rituximab, with disease stabilization at the time of presentation. Examination revealed erythematous, annular plaques with raised, urticarial borders studded with tense bullae and vesicles over the thighs. Some lesions were arciform and annular, with vesicles arranged in a ring at the border ( Fig. 1). There was involvement of the feet with desquamation at the tips of the toes ( Fig. 2). Severe erosions with hemorrhagic crusts on the lips, tongue, and buccal mucosa were seen. 1Arciform and annular lesions on the posterior thigh, with vesicles arranged in a ring at the border, resembling the “crown of jewels” seen in linear IgA dermatosis2Vesicles, pustules, and bullae present on both feet and ankles Herpes simplex virus serology was negative. A biopsy specimen from a vesicle on the left thigh showed suprabasal acantholysis ( Fig. 3), some apoptotic keratinocytes ( Fig. 4), satellite cell necrosis in the epidermis, and a superficial perivascular infiltrate of lymphocytes and eosinophils. Direct immunofluorescence showed intercellular immunoglobulin G (IgG) and C3 within the epidermis and along the basement membrane zone. Indirect immunofluorescence on monkey esophagus was positive for anti‐intercellular antibody at a titre of 1/160 and positive on rat bladder at a titre of 1/80. A presumptive diagnosis of paraneoplastic pemphigus was made. This was later confirmed by the presence of antibodies against envoplakin (210 kDa), periplakin (190 kDa), and desmoglein 1 on immunoprecipitation studies. 3Suprabasal acantholysis of the epidermis (arrow). The blister cavity contains fibrin, red blood cells, nuclear debris, and acantholytic keratinocytes (hematoxylin and eosin stain; magnification, ×400)4A few apoptotic keratinocytes seen in the epidermis (thin arrows). Early suprabasal acantholysis of keratinocytes is present (thick arrows) (hematoxylin and eosin, ×400) He was started on prednisolone 60 mg/day (1 mg/kg/day), with complete resolution of skin lesions within 1 week, but persistence of oral ulcers. Cyclophosphamide was added at a low dose of 1 mg/kg/day as he had baseline leukopenia. Cyclosporine was later added to a maximum of 4 mg/kg/day with only mild improvement of the oral lesions. He declined rituximab therapy. He died 2 months later from fulminant pneumonia.