IgG4-related disease can affect any organ of the body, can be localized or generalized, demonstrates the same distinctive histopathology at all sites of involvement, produces protean manifestations depending on location and extent of involvement, and causes disease that ranges in severity from asymptomatic to organ- or life-threatening. The inflammatory infiltration in IgG4-related disease frequently produces tumefactive masses that can be found during physical examination or on imaging. Some of the common presenting manifestations include enlargement of submandibular glands, proptosis from periorbital infiltration, retroperitoneal fibrosis, mediastinal fibrosis, inflammatory aortic aneurysm, and pancreatic mass with autoimmune pancreatitis. IgG4-related disease can also affect the thyroid (formerly Reidel thyroiditis), kidney, meninges, pituitary, sinuses, lung, prostate, breast, and bone. Most symptomatic patients with IgG4-related disease present subacutely; fever and constitutional symptoms are usually absent. Nearly half of the patients with IgG4-related disease also have allergic disorders such as sinusitis or asthma.
The infiltrating lesions in IgG4-related disease often produce tumors or fibrotic changes that are evident on CT or MRI imaging. However, the cornerstone of diagnosis is the histopathology. The key pathological findings are a dense lymphoplasmacytic infiltrate rich in IgG4 plasma cells, storiform (matted and irregularly whorled) fibrosis, and obliterative phlebitis. Serum IgG4 levels are usually, but not invariably, elevated so this finding cannot be used as the sole diagnostic criterion.