IgG4-related disease
Formal Definition
IgG4-related disease (IgG4-RD) — a recently recognized multisystem fibroinflammatory condition characterized by infiltration of affected organs with IgG4-positive plasma cells, dense lymphoplasmacytic infiltrate, storiform fibrosis, and often elevated serum IgG4 levels; can affect virtually any organ system but typically presents with tumefactive (mass-like) lesions in pancreas (autoimmune pancreatitis type 1), salivary glands (sclerosing sialadenitis / Mikulicz disease), lacrimal glands (dacryoadenitis), retroperitoneum (retroperitoneal fibrosis), aorta (aortitis), thyroid (Riedel thyroiditis), lymph nodes, kidneys (tubulointerstitial nephritis), meninges, lung, and biliary tree; response to glucocorticoids is characteristic and dramatic.
How It's Used on the Ward
"IgG4-RD" — the "can mimic any disease" fibroinflammatory disorder of middle-aged men often presenting as a mass lesion that gets mistaken for cancer; biopsy shows the characteristic triad (lymphoplasmacytic infiltrate, storiform fibrosis, obliterative phlebitis) — but it's treatable with steroids and rituximab rather than surgery; think of it when you see a pancreatic mass that's not cancer, a salivary gland that's not a tumor, or retroperitoneal fibrosis in the right demographic.
Example
""67-year-old man with 3 months of progressive painless bilateral submandibular gland swelling and dry eyes. Also reports mild abdominal discomfort. CT: symmetric bilateral submandibular gland enlargement with diffuse cervical lymphadenopathy; pancreatic head fullness with diffuse pancreatic enlargement and peripancreatic halo. Incisional submandibular biopsy: dense lymphoplasmacytic infiltrate with storiform fibrosis and obliterative phlebitis; IgG4-positive plasma cells >50/HPF. Serum IgG4 480 mg/dL (elevated). Diagnosis: IgG4-related disease affecting salivary glands, pancreas (type 1 autoimmune pancreatitis), and lymph nodes. Started prednisone 30 mg daily with rapid improvement; tapering over months.""
Clinical Context
Histopathologic triad (now refined to consensus criteria): (1) dense lymphoplasmacytic infiltrate with IgG4-positive plasma cells (>10/HPF and IgG4/IgG ratio >40%); (2) storiform (cartwheel-like) fibrosis; (3) obliterative phlebitis. Specialty "lookalikes" that are often IgG4-RD: autoimmune pancreatitis type 1, Mikulicz disease (salivary + lacrimal), Riedel thyroiditis, idiopathic retroperitoneal fibrosis, eosinophilic angiocentric fibrosis (nose/sinuses), tumefactive fibrotic lesions. Diagnostic workup: serology (serum IgG4 — elevated in ~70% but not specific), biopsy of affected organ with immunohistochemistry for IgG4 staining, exclude infection and malignancy before immunosuppression. Imaging: PET or CT for extent of disease (can be multifocal at presentation). Treatment: glucocorticoids (prednisone 30-40 mg daily) — most patients respond rapidly; steroid-sparing agents for relapsed/refractory (azathioprine, mycophenolate, rituximab). Rituximab is now recognized as a very effective targeted therapy (anti-CD20 depletes B cells). Differentiating from malignancy is critical: many IgG4-RD patients undergo unnecessary surgeries before diagnosis. Multidisciplinary care: rheumatology (often primary), pathology, oncology consult for pancreatic mass to rule out adenocarcinoma, ophthalmology, ENT, gastroenterology.