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Metal dust as a possible inducer of immunoglobulin G4‐related skin nodules

Typically, immunoglobulin G4-related disease (IgG4-RD) leads to the development of pseudotumours or organ swellings in a single or several sites. However, to date, clinical expertise on this phenomenon is relatively vague. Laboratory tests and increased IgG4 levels in the serum are not specific for the diagnosis. The gold standard for diagnosis of IgG4-RD is typical histopathology and compatible clinical features. Consequently, histopathological analysis should be obligatory for ultimate IgG4-RD diagnosis. So far, only a few case reports have been published on IgG4related skin lesions. According to those sparse case reports, infiltrations rich in IgG4 plasma cells in the skin might occur as multiple red-brown nodules, plaques or tumours. In this issue of the BJD, Kondo et al. have reported a case of IgG4-RD presenting as nodules, which possibly originated because of a chronic local sensitization to inorganic metal dust. Different antigens have been proposed to be the cause for IgG4-RD, but this has not been confirmed, and no specific antibodies have yet been described. Kondo et al. have shown that their patient, a factory worker exposed to metal dust, developed fibro-inflammatory nodules, rich in IgG4 plasma cell and eosinophil infiltration. The nodules were localized on both ears, the places exposed to daily mechanical friction by straps of the mask. Interestingly, the patient had also expressed positive reactions to a skin patch test with zinc and manganese. The chronic sensitization to zinc and/or manganese has been suggested as the origin of the inflammatory nodules. Based on these findings, a hypothesis has been drawn on the possible importance of zinc/manganese to the pathogenesis of IgG4-related skin nodules. To my knowledge, this is the first report describing a case that demonstrates that continuous mechanical stimulation by inorganic metal dust may lead to localized IgG4-RD. It is not clear if zinc alone or in combination with manganese, in this case, has been acting as an antigen/hapten or an irritant-inducing fibroinflammatory reaction. On the other hand, it is known that inorganic manganese compounds do not penetrate the skin. In contrast to this, different zinc compounds or metallic zinc can give skin irritancy characterized by parakeratosis, hyperkeratosis, inflammatory changes in the epidermis and superficial dermis. At the present, the function of IgG4 antibodies is not yet elucidated. The patient’s skin lesions, in the case described by Kondo et al., are plausibly caused by a cell-mediated contact allergic reaction to zinc and/or manganese. As IgG4 antibodies have previously been proposed to be involved in downregulation of immune response, one may speculate that the presence of IgG4 antibodies in the reported case may reflect the involvement of B cells in the control of the inflammation caused by T cells in a contact allergic reaction. Future larger epidemiological and also experimental animal model studies are needed to explore a possible pathogenic relationship between metal dust and localized IgG4-related skin disease in genetically susceptible individuals.