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For further information, see CMDT Part 20-15: IgG4-Related Disease

Key Features

Essentials of Diagnosis

  • Mainly affects men (75% of patients) > 50 years

  • Protean manifestations caused by lymphoplasmacytic infiltrates in any organ or tissue, especially the pancreas, lacrimal glands, biliary tract, and retroperitoneum

  • Subacute onset; constitutional symptoms rare

  • Diagnosis rests on specific histopathological findings that include presence of IgG4-bearing plasma cells

General Considerations

  • A systemic disorder of unknown cause

  • Any organ of the body can be affected

  • Marked by highly characteristic fibroinflammatory changes

  • Severity ranges from asymptomatic to organ- or life-threatening

Clinical Findings

Symptoms and Signs

  • Lymphoplasmacytic infiltrates, fibrosis, and phlebitis may be localized or generalized

  • Enlargement of submandibular glands

  • Proptosis from periorbital infiltration

  • Retroperitoneal fibrosis, mediastinal fibrosis

  • Inflammatory aortic aneurysm

  • Pancreatic mass with autoimmune pancreatitis

  • Fever and constitutional symptoms are usually absent

  • Nearly half of patients also have allergic disorders such as sinusitis or asthma

Differential Diagnosis

  • Sarcoidosis

  • Sjögren syndrome

  • Chronic infections (HIV, hepatitis C)

  • Granulomatosis with polyangiitis

  • Lymphoma


Laboratory Findings

  • Serum IgG4 levels are usually, but not invariably, elevated so this finding cannot be used as the sole diagnostic criterion


  • CT or MRI often show tumors or fibrotic changes produced by infiltrating lesions

Diagnostic Procedures

  • Cornerstone of diagnosis is histopathology; same distinctive histopathology demonstrated at all sites of involvement

  • The key pathologic findings are

    • A dense lymphoplasmacytic infiltrate rich in IgG4 plasma cells

    • Storiform (matted and irregularly whorled) fibrosis

    • Obliterative phlebitis


  • Initial therapy is usually oral prednisone 0.6 mg/kg/day, tapered over weeks or months depending on response

  • Given that corticosteroid monotherapy may fail to control the disease and can cause significant long-term toxicity, immunosuppressants, especially rituximab, are often used



  • Patients who are asymptomatic and have no organ-threatening disease can be monitored carefully

  • Spontaneous resolution can occur

  • The degree of fibrosis in affected organs determines the patient's responsiveness to treatment

When to Refer

  • Presence of systemic symptoms or signs

  • Symptoms or signs not responsive to prednisone

When to Admit

  • Severe systemic signs unresponsive to outpatient management


Lu  H  et al. Differences in clinical characteristics of IgG4-related disease across age groups: a prospective study of 737 patients. Rheumatology (Oxford). 2021;60:2635.
[PubMed: 33211878]  
Wallace  ZS  et al. The 2019 American College of Rheumatology/European League Against Rheumatism classification ...

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