Immunoglobulin G4-related disease (IgG4-RD) is a fibro-inflammatory disease characterized by organ enlargement and elevated serum
IgG4 levels. In 2003,
IgG4-RD was proposed as a distinct form of IgG4-related systemic disease based on a histopathological study involving patients with
autoimmune pancreatitis.
IgG4-RD occurs mainly in older men and can affect almost any organ simultaneously or metachronously. Pathophysiologically,
IgG4-RD occurs when an
autoantigen triggers an immune response characterized by Th2 predominance with increased production of
cytokines, such as
interleukin 4 (IL-4),
IL-5,
IL-10,
IL-13, and
tumor growth factor-β (TGF-β), in the affected organ.
IL-10 and TGF-β produced by the increased number of regulatory T cells induce a switch from B cells to IgG4-producing plasma cells and
fibrosis, respectively. The characteristic histological features consist of dense infiltration of lymphocytes and IgG4-positive plasma cells, storiform
fibrosis, and obliterative
phlebitis.
IgG4-RD is diagnosed based on a combination of clinical, serological, radiological, and histopathological findings. Differentiating
IgG4-RD from malignant
tumors or similar inflammatory diseases in the affected organs is important. The 2019 America College of Rheumatology/European League against
Rheumatism classification criteria for
IgG4-RD have high diagnostic sensitivity and specificity.
IgG4-RD generally responds well to treatment with
steroids, and a swift response is reassuring and provides further diagnostic confirmation. However, relapses are common during tapering or after cessation of
steroids. In Japan, low-dose
steroid maintenance
therapy is usually given to prevent a relapse. B-cell depletion with
rituximab is effective in patients resistant to or dependent on
steroids. Most patients with
IgG4-RD who receive
steroid therapy show good short-term clinical, morphological, and functional outcomes. However, long-term outcomes, such as relapse,
fibrosis development, and associated
malignancies, have not been clearly defined. Therefore, novel treatment strategies, including
rituximab, need to be tested in international randomized controlled clinical trials.