Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory disorder that begins in 1 or more organs as inflammatory
tumors that progress toward
fibrosis. It is often accompanied by elevated serum
IgG4.
IgG4-RD was first described in 2003 as a new concept encompassing a number of immunoallergic diseases that had previously been considered unrelated.
IgG4-RD mainly affects middleaged and older men. It consists of upregulation and expansion of CD4+ cytotoxic T lymphocytes, oligoclonal plasmablasts, and other inflammatory cells that infiltrate affected tissues and induce
inflammation, organ dysfunction, and
fibrosis. Symptoms depend on the location, severity, and extent of the disease. Virtually any organ can be affected, including the pancreas, salivary glands, lacrimal glands, thyroid gland, retro-orbital tissue, lymph nodes, retroperitoneum, mediastinum, lung, kidney, aorta, serosal surfaces, and meninges. Patients with widespread disease may present general symptoms. At least 30%-40% of patients are atopic or display atopic traits such as
eosinophilia and elevated serum
IgE levels. Additional laboratory features include increased serum
IgG4 concentrations, increased blood IgG4-plasmablasts,
hypergammaglobulinemia, and hypocomplementemia. Diagnosis of
IgG4-RD is based on a clinicopathological correlation. Lymphoplasmacytic infiltrate with abundant IgG4-positive plasma cells, storiform-type
fibrosis, obliterative
phlebitis, and tissue
eosinophilia are the pathological hallmarks.
Therapy for
IgG4-RD is based primarily on
corticosteroids but may include additional
immunomodulatory drugs and
monoclonal antibodies such as
rituximab. In individuals with allergic features,
IgG4-RD should be suspected when a history of unexplained swelling is observed in 1 or more organs, particularly if they respond to
corticosteroids and the patients are men in the sixth decade of life and beyond.