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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

  • Patients who do not respond to prednisone or respond only to sustained high doses of prednisone, can be treated with rituximab, mycophenolate mofetil, or azathioprine

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

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Brito-Zerón  P,  et al. IgG4-related disease: advances in the diagnosis and treatment. Best Pract Res Clin Rheumatol. 2016 Apr;30(2):261–78.
[PubMed: 27886799]
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Brito-Zerón  P,  et al. Therapeutic approach to IgG4-related disease: a systematic review. Medicine (Baltimore). 2016 Jun;95(26):e4002.
[PubMed: 27368010]
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Ebbo  M,  et al. Long-term efficacy and safety of rituximab in IgG4-related disease: data from a French nationwide study ...

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