Skin Manifestations of Immunoglobulin G4-Related Disease

Immunoglobulin G4-related disease (IgG4-RD) is a fibro-inflammatory condition characterized by infiltration of IgG4+ plasma cells into one or multiple organs. The disease mostly affects middle-aged to elderly males. Recently, there has been an increased awareness of the cutaneous manifestation of IgG4-RD as an isolated lesion either as a primary or as a secondary disease from involvement by a systemic disease. Clinically, cutaneous IgG4-RD presents as papules, plaques, and subcutaneous nodules involving most commonly the head and neck region. Tissue sections characteristically show an increased infiltration of IgG4+ polyclonal plasma cells and elevated ratio of IgG4+/IgG plasma cells of more than 40%, with a storiform pattern of fibrosis. Blood tests might show eosinophilia, along with high levels of IgG4 levels. Diagnosis requires an integration of clinical, pathological, and serological studies. IgG4-RD mimics several diseases and must be distinguished from inflammatory and neoplastic processes. In this book chapter, we describe this new yet challenging entity of cutaneous IgG4-RD describing the histologic and clinical manifestations and differential diagnosis and highlighting the importance of early recognition to ensure appropriate management. Dermatologists and dermatopathologists should be aware of this rare emerging entity to avoid misinterpretation.