A case of leucocytoclastic vasculitis as a complication of IgG4-related skin disease

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IgG4‐related disease (IgG4‐RD) is a recently established immune‐mediated systemic disorder characterized by tissue infiltration of IgG4‐positive plasma cells and high serum levels of IgG4. The clinical manifestations of IgG4‐RD involve a variety of organs and glands, including salivary, lacrimal and thyroid glands, and pancreas, kidney, lung and skin. Recently, Tokura et al. classified the skin manifestations of IgG4‐RD into seven subtypes.1 We report a patient with a rare clinical manifestation of hypergammaglobulinaemic purpura as a skin lesion of IgG4‐RD. A 54‐year‐old Japanese man presented to the Division of Gastroenterology of our clinic with a 1‐month history of anorexia and weight loss (5.3 kg), and a 2‐week history of jaundice. Blood tests revealed a high serum level of conjugated bilirubin (7.4 mg/dL, normal range < 0.5 mg/dL), high serum IgG4 level of 1140 mg/dL (normal range 4.8–105 mg/dL), low serum complement levels and high level of antinuclear antibody (ANA) (1 : 1280; normal range < 1 : 40). Biopsy of the Vater papilla revealed lymphocyte and plasma cell infiltration of the mucosa, and additional immunohistochemistry revealed 22 IgG4‐positive cells per high‐power field (HPF) and 55.4% (31/56) IgG4+/IgG+ plasma cells infiltrating the tissue (Fig. 1a,b). (a) Plasma cells and lymphocytes infiltrating the interstitial tissue of the Vater papilla (haematoxylin and eosin, original magnification × 400). (b) Immunohistochemistry showed that the infiltrating plasma cells were positive for IgG4, with 22 IgG4‐positive cells observed per high‐power field (original magnification × 400). The diagnosis was IgG4‐RD according to the Japanese comprehensive diagnostic criteria for IgG4‐RD,2 and treatment was scheduled. Prior to treatment commencement, the patient was referred to our department for a consultation because of the appearance of multiple asymptomatic palpable purpuric papules on his legs (Fig. 2a). Tests for antineutrophilic cytoplasmic antibodies were negative. We suspected the palpable purpura as a manifestation of IgG4‐RD, and took a skin biopsy. (a) Multiple asymptomatic palpable purpuric papules on the limbs. (b) Leucocytoclastic vasculitis (haematoxylin and eosin, original magnification × 400). (c) Direct immunofluorescence test identified deposition of IgG4 in the walls of the small vessels of the upper dermis (white arrows). The white broken line represents the basal cell layer of the epidermis (original magnification × 400). Histological examination reveled swelling of vessel walls in the papillary dermis, with nuclear dust that represented leucocytoclastic vasculitis (Fig. 2b). Direct immunofluorescence identified deposition of IgG, IgM and IgA in the walls of the small vessels of the upper dermis, as well as IgG4 positivity (Fig. 2c). There was no vasculitis involvement in other organs. We diagnosed this skin manifestation as IgG4‐RD. IgG4‐RD is relatively rare, although the precise incidence remains unknown. Tokura et al. defined IgG4‐related skin disease by pathological features, separating the lesion types into primary and secondary types. Primary skin lesions are caused by direct infiltration of plasma cells, with a ratio of IgG4+/IgG+ plasma cells of > 40%, with > 10 IgG4+ plasma cells/HPF. Secondary skin lesions are caused by IgG4 deposition with IgG4+ plasma cells (IgG4+/total IgG+, > 40%) and/or perivascular IgG4 deposition.1 The vasculitic lesions of our patient fulfill the histopathological criteria of IgG4‐RD. Low serum complement level and ANA positivity are also common in IgG4‐RD. Taking into consideration that these skin lesions manifested along with IgG4‐related pancreatitis, we were confident that the patient had IgG4‐RD. The complete mechanism and pathology of IgG4‐RD remain elusive. There are several reports suggesting that the skin and systemic vasculitis lesions possibly coincide with IgG4‐RD. Collectively, these reported findings indicate the need for increased knowledge of IgG4‐RD for a better understanding of the underlying mechanisms of this disease. We thank A. Oikawa for generating the histological sections and M. Baldry for expert review of the manuscript. Conflict of interest: the authors declare that they have no conflicts of interest.

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