Key Points
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IgG4-related disease represents a chronic inflammatory disorder characterized by various systemic organ dysfunctions, such as IgG4-associated dacryoadenitis and sialadenitis (also called Mikulicz disease) and type 1 autoimmune pancreatitis
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The disease is associated with elevated serum levels of IgG4 and specific histopathological features, including abundant IgG4+ plasmacyte infiltration, and storiform fibrosis and obliterative phlebitis in the inflamed organs
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IgG4-related disease is also associated with a predominantly type 2 T-helper-cell cytokine profile, and infiltration of regulatory T cells is considered to be involved in the disease pathogenesis
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Comprehensive systemic and organ-specific diagnostic criteria have been defined for IgG4-related disease in Japanese populations, although criteria that classify the disease in other populations are not available at present
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Examination for systemic organ failure and screening for underlying malignancies is important during the diagnosis and follow-up of IgG4-related disease
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Glucocorticoids are effective in the treatment of IgG4-related disease, but the rate of relapse after tapering or discontinuing glucocorticosteroids is high
Abstract
Recognition of IgG4-related disease as an independent chronic inflammatory disorder is a relatively new concept; previously, the condition was thought to represent a subtype of Sjögren's syndrome. IgG4-related disease is characterized by elevated serum levels of IgG4 and inflammation of various organs, with abundant infiltration of IgG4-bearing plasma cells, storiform fibrosis and obliterative phlebitis representing the major histopathological features of the swollen organs. The aetiology and pathogenesis of this disorder remain unclear, but inflammation and subsequent fibrosis occur due to excess production of type 2 T-helper-cell and regulatory T-cell cytokines. The disease can comprise various organ manifestations, such as dacryoadenitis and sialadenitis (also called Mikulicz disease), type 1 autoimmune pancreatitis, kidney dysfunction and lung disease. Early intervention using glucocorticoids can improve IgG4-related organ dysfunction; however, patients often relapse when doses of these agents are tapered. The disease has also been associated with an increased incidence of certain malignancies. Increased awareness of IgG4-related disease might lead to consultation with rheumatologists owing to its clinical, and potentially pathogenetic, similarities with certain rheumatic disorders. With this in mind, we describe the pathogenic mechanisms of IgG4-related disease, and outline considerations for diagnosis and treatment of the condition.
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M. Yamamoto researched the data for the article, decided on the content and wrote the manuscript. H. Takahashi and Y. Shinomura made substantial contributions to review/editing of the manuscript before submission.
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Yamamoto, M., Takahashi, H. & Shinomura, Y. Mechanisms and assessment of IgG4-related disease: lessons for the rheumatologist. Nat Rev Rheumatol 10, 148–159 (2014). https://doi.org/10.1038/nrrheum.2013.183
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DOI: https://doi.org/10.1038/nrrheum.2013.183
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