A case of anti-p200 pemphigoid: evidence for a different pathway in neutrophil recruitment compared with bullous pemphigoid
Authors: H. Iwata, Y. Hiramitsu, Y. Aoyama, Y. Kitajima
Journal: British Journal of Dermatology (2008)

Conflicts of interest: none declared. Sir, Anti‐p200 pemphigoid was first described in 1996 by Zillikens et al. as a subepidermal blistering disease that involves autoantibodies directed against a 200‐kDa component (p200) of the basement membrane zone (BMZ).1 Although p200 is known to be an acidic noncollagenous N‐linked glycoprotein, which localizes to the lower lamina lucida of the BMZ, the nature of this molecule had not been elucidated for a long time.1 Currently, it is reported that patient sera react with laminin γ1, which is a component of the lamina densa, suggesting that p200 may be laminin γ1.2 In patients with anti‐p200 pemphigoid, histopathological examination reveals subepidermal blisters and infiltration predominantly by neutrophils, but occasionally also by eosinophils.3 Interleukin (IL)‐8 is a major chemotactic cytokine for neutrophils and has been implicated in the inflammatory process of bullous pemphigoid (BP).4 A 75‐year‐old Japanese man presented with bullae and pustules on his palms, which had arisen suddenly, then spread over the whole body (Fig. 1a). Mucous membranes, including the oral mucosa and conjunctiva, were also affected. Both flaccid and tense blisters were found. Nikolsky’s sign was negative. Milia arose after blister healing in some cases. Blood tests showed a white blood count of 11·85 × 109 L−1 (normal 3·3–9·2 × 109) and a neutrophil ratio of 81·2% (normal 45·3–73·2%). Complement C3 and C4 and immunoglobulin (including IgG and IgA) levels were within the normal range. Histopathological examination of a skin biopsy specimen from the neck revealed the presence of subepidermal bullae containing many neutrophils and some eosinophils (Fig. 1b). Direct immunofluorescence (DIF) revealed linear deposits of IgG and C3 at the BMZ. Indirect immunofluorescence (IIF) using 1 mol L−1 salt‐split skin showed that IgG antibody bound on the dermal side (Fig. 1c). Immunoblotting with dermal extracts showed that the patient’s IgG autoantibodies reacted with a 200‐kDa protein (Fig. 1d). The titre of autoantibody determined by IIF was 1 : 160. IgG subclass of autoantibodies against the BMZ was determined by DIF and IIF. The results of DIF showed linear deposits of IgG2, but not IgG1, IgG3 and IgG4 (Fig. 1e). The deposition of IgG2 autoantibody, but not IgG1, IgG3 and IgG4, was detected on the basement membrane by IIF (Fig. 1e). An indirect complement fixation test with patient serum revealed weak C3 deposits along the basement membrane (Fig. 1f). Enzyme‐linked immunosorbent assay (ELISA) revealed that the concentrations of antibodies against BP180, BP230 and desmoglein 1 and 3 were all within the normal range. The patient was diagnosed as having anti‐p200 pemphigoid and was initially treated with oral prednisolone 10 mg daily, but serum levels of autoantibodies, as determined by IIF, continued to increase, and the clinical symptoms worsened. In response to a treatment regimen of prednisolone 30 mg daily, dapsone 50 mg daily and azathioprine 100 mg daily, the blisters gradually disappeared. As the clinical symptoms resolved, the autoantibody titre against p200, as determined by IIF, also decreased gradually. At 7 months after onset, prednisolone therapy was tapered to 20 mg daily, but at this time the patient died due to sepsis, which was probably caused by aspiration pneumonia.