IgG4RD

IgG4-related disease (IgG4RD) is a systemic fibroinflammatory condition characterized by tissue infiltration with IgG4-positive plasma cells, storiform fibrosis, and often obliterative phlebitis. Many patients have elevated serum IgG4 levels, but normal levels do not exclude the diagnosis. The disease can involve virtually any organ and often presents as mass-forming lesions or tissue enlargement.

Common organ sites include the pancreas (autoimmune pancreatitis type 1), biliary tract (IgG4-related sclerosing cholangitis), salivary and lacrimal glands (Mikulicz-like disease), orbit and lacrimal glands, kidneys (tubulointerstitial nephritis), retroperitoneum, aorta (aortitis), lymph nodes, lungs, and meninges. Clinical manifestations depend on affected sites and may mimic malignancy or other inflammatory disorders. The disease typically affects middle-aged to older adults and shows a male predominance in many series.

Diagnosis relies on a combination of clinical presentation, elevated serum IgG4 (in many but not all cases), imaging findings, and histopathology. Key histologic features are a dense lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, storiform fibrosis, and, when present, obliterative phlebitis. Immunohistochemistry commonly uses a threshold of >10 IgG4-positive plasma cells per high-power field and a IgG4/IgG ratio exceeding 40%.

Treatment usually starts with glucocorticoids, which often yield a rapid response. Relapses are common, requiring maintenance therapy or alternatives such as rituximab, azathioprine, or mycophenolate. Early recognition and organ-specific management help prevent irreversible damage from fibrosis or obstruction.