IgG₄-Related Disease

Key Features

Essentials of Diagnosis

• Predominantly affects men (75% of patients); average age > 50 years

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

• Subacute onset; fever, 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

• Granulomatosis with polyangiitis

• Retroperitoneal fibrosis and mediastinal fibrosis

• Lymphoma

Diagnosis

Laboratory Findings

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

Imaging

• 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

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

• Because corticosteroid monotherapy may fail to control the disease and can cause significant long-term toxicity, immunosuppressants such as rituximab, mycophenolate mofetil, or azathioprine are often used

Outcome

Prognosis

• 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

References