ImmunologyTier 1Medical Sciences concept

IgG4-related disease

Core concept

IgG4-related disease (IgG4-RD): a fibro-inflammatory, multi-organ condition characterised by dense lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis on histology
Can affect almost any organ: pancreas (autoimmune pancreatitis type 1), biliary tree (IgG4-related sclerosing cholangitis, mimics cholangiocarcinoma/PSC), salivary/lacrimal glands (Mikulicz disease), retroperitoneum (retroperitoneal fibrosis), kidneys, lungs, aorta/periaortitis, and rarely the heart
Serum IgG4 is often elevated but not required for diagnosis and not specific -- normal levels do not exclude the disease, and mild elevation occurs in other conditions

Diagnosis rests on combined clinical, serological, radiological and histological features -- histology (storiform fibrosis, obliterative phlebitis, IgG4+ plasma cell infiltrate with elevated IgG4:IgG ratio) is the most specific single element
Cardiac manifestation: periaortitis/aortitis, inflammatory pseudotumour, and pericardial disease -- can mimic other large-vessel vasculitides (e.g. giant cell arteritis) or cardiac mass lesions on imaging
Excellent, often dramatic response to glucocorticoids -- a diagnostic and therapeutic clue when other overlapping conditions (malignancy, PSC) do not respond similarly

Trap: IgG4-related sclerosing cholangitis/autoimmune pancreatitis can closely mimic pancreatic or biliary malignancy radiologically -- biopsy and steroid-responsiveness help avoid unnecessary radical surgery for what is a treatable inflammatory condition
Multi-organ involvement should prompt screening of other classically affected sites (salivary glands, retroperitoneum, aorta) once one organ is diagnosed
Relapse is common after steroid taper -- rituximab used as a steroid-sparing/relapse-prevention agent given the B-cell/plasma-cell-driven pathology

Autoimmune pancreatitis type 1 (IgG4-related) is distinguished from type 2 (idiopathic duct-centric, no IgG4 association, associated with IBD) -- same organ, different disease
Retroperitoneal fibrosis overlaps differentially with malignancy and other vasculitides -- IgG4-RD is increasingly recognised as a major cause of previously "idiopathic" retroperitoneal fibrosis
Contrast with Sjogren's syndrome for salivary/lacrimal gland swelling -- different serology (anti-Ro/La vs elevated IgG4/tissue IgG4 plasma cells) and different histology

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