IgG₄-Related Disease

KEY FEATURES

Essentials of Diagnosis

• 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

Demographics

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

CLINICAL FINDINGS

Symptoms and Signs

• Can affect any organ of the body

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

• Disease ranges in severity from asymptomatic to organ- or life-threatening

• Inflammatory infiltration frequently produces tumefactive masses that can be found on physical examination

  • Enlargement of submandibular glands

  • Proptosis from periorbital infiltration

  • Retroperitoneal fibrosis, mediastinal fibrosis

  • Inflammatory aortic aneurysm

  • Pancreatic mass with autoimmune pancreatitis

• Can also affect the thyroid (formerly Riedel thyroiditis), kidney, meninges, pituitary, sinuses, lung, prostate, breast, and bone

• 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

• Pancreatic cancer (pancreatic mass)

• Chronic infections (HIV, hepatitis C)

• Granulomatosis with polyangiitis (proptosis)

• Lymphoma

DIAGNOSIS

Laboratory Tests

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

Imaging Studies

• 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

TREATMENT

• Asymptomatic patients without organ-threatening disease can be monitored carefully

• Initial therapy is usually oral prednisone, 0.6 mg/kg/d, 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

OUTCOME

Prognosis

• 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 ...