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IgG4-related disease: A relatively new concept for clinicians

  • Lilian Vasaitis
    Correspondence
    Rheumatology Clinic, Entrance 30, Uppsala University Hospital, SE-751 85 Uppsala, Sweden. Tel.: +46 18 6114486; fax +46 18 5558432.
    Affiliations
    Section of Rheumatology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden
    Search for articles by this author
Published:October 16, 2015DOI:https://doi.org/10.1016/j.ejim.2015.09.022

      Highlights

      • IgG4-related disease is a chronic fibrotic inflammation.
      • The disease affects multiple organs, is progressive, and impairs function.
      • The disorder has an allergic background and is immune-mediated.
      • Compatible clinical signs and typical pathology are the basis for the diagnosis.
      • Glucocorticoids and/or B-cell depletion induces prompt clinical response.

      Abstract

      IgG4-related disease (IgG4-RD) is a recently recognized chronic fibrotic inflammation, which can affect almost every organ, and may come to clinical attention first due to visible organ swelling or organ dysfunction, or is identified incidentally by imaging and specific biopsy. The disorder has an allergic background and is immune-mediated. Up-regulated responses of T helper 2 and T regulatory cells and their cytokines play a major role in disease progression. About 30–50% of patients are atopic or have mild eosinophilia. IgG4-RD predominantly affects middle-aged male patients. The cornerstones of diagnosis of the disease are compatible clinical features and typical histopathology. Swelling of salivary and lacrimal glands, lymphadenopathy, and type 1 autoimmune pancreatitis (AIP) are the most common manifestations of the disease. However, other tissues and organs, such as retroperitoneum, lung, kidney, aorta, upper airways, thyroid gland, meninges, heart, mesenterium and skin may be involved. Typical histopathology is lymphoplasmacytic infiltration abundant in IgG4-positive plasma cells, storiform-type fibrosis, and obliterative phlebitis. Elevated serum IgG4 concentration supports the diagnosis. Characteristic imaging features such as a "capsule-like rim" surrounding the pancreatic lesions is highly specific to type 1 AIP. 18F-fluorodeoxyglucose positron emission tomography/computed tomography enables mapping the sites of inflammation, permits evaluation of the extent of the disease, helps in guiding biopsy decision, and may be used in monitoring response to treatment. Glucocorticoids alone or in combination with B-cell depletion with rituximab induces prompt clinical response to IgG4-RD. This article reviews the current understanding, different clinical manifestations, and approaches to diagnosis and treatment of IgG4-RD.

      Keywords

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