IgG4-related disease

The term “IgG4-related disease” encompasses several disorders described many years ago under various designations depending on the organ or system involved (e.g., Mikulicz syndrome, Riedel's thyroiditis, and retroperitoneal fibrosis). The clinical presentation varies widely, as one or more organs may be affected, usually in the same region of the body and either synchronously or metachronously. The main targets are the pancreas, bile ducts, salivary glands, lachrymal glands, mediastinal lymph nodes, and retroperitoneum. IgG4-related disease is rare, with an estimated incidence of 0.2 to 1/100 000 in Japan and no available incidence data in occidental countries. Men older than 50 years are predominantly affected. Serum IgG4 levels are often greater than 1.35 g/L. Enlargement of the involved organs, which may be pseudotumoral, is due to a combination of infiltration by T cells and IgG4-expressing plasma cells, storiform fibrosis, and obliterative thrombophlebitis. Glucocorticoid therapy is effective but may be followed by relapses requiring the use of immunomodulating agents such as azathioprine, methotrexate and, more recently, rituximab. IgG4-related disease is not an autoimmune condition related to IgG4 autoantibodies, and neither does it involve immune complexes. Specific joint involvement has been reported in a very small number of patients.