What is the treatment approach for IgG4 (Immunoglobulin G4) disease?

Treatment of IgG4-Related Disease

Start oral prednisolone at 0.6 mg/kg/day (typically 40 mg daily) for 2-4 weeks to induce remission, then taper gradually over 8-12 weeks to a maintenance dose of 2.5-5 mg/day. 1

Initial Corticosteroid Therapy

The cornerstone of IgG4-RD treatment is systemic glucocorticoids, which achieve rapid response in most patients 1, 2, 3:

• Induction dosing: Begin prednisolone at 0.6-0.8 mg/kg/day (30-40 mg daily for most adults) for 2-4 weeks 1, 3
• Tapering schedule: Reduce by 5 mg weekly over 8-12 weeks until reaching maintenance dose of 2.5-5 mg/day over 2-3 months 1, 2
• Response assessment: Evaluate clinical improvement (resolution of jaundice, organ dysfunction) and radiological changes (reduction in mass lesions, organ enlargement) at weeks 2-4 and again at weeks 4-8 1, 3

Critical Pitfall: Interpreting Treatment Response

If no objective radiological improvement occurs by weeks 4-8, this indicates either misdiagnosis or fibrotic (non-inflammatory) disease phase rather than treatment failure 1. Do not simply increase steroid doses—reconsider the diagnosis and obtain histopathological confirmation 4, 1.

Maintenance Therapy and Relapse Prevention

At least 60% of patients relapse after steroid cessation, making maintenance immunosuppression essential 1:

• A randomized study demonstrated 23% relapse at 3 years with maintenance prednisolone 5-7.5 mg versus 58% relapse with complete steroid withdrawal 1
• All patients with IgG4-RD, particularly those with multiorgan involvement, should receive continued immunosuppressive therapy 4, 1
• Maintenance duration typically extends 2-3 years, though cessation should be attempted within 3 years in elderly patients at high risk for steroid complications 2

Adding Steroid-Sparing Agents

For patients experiencing relapse during steroid taper or requiring prolonged high-dose steroids 2, 3, 5:

• Azathioprine and mycophenolate mofetil are the most commonly used immunomodulatory agents 5
• Add these agents when disease relapses during the initial 3-month treatment period 3
• Drug combinations demonstrate superior efficacy compared to monotherapy across multiple studies 5

Treatment of Refractory or Relapsing Disease

Rituximab (anti-CD20 monoclonal antibody) achieves >95% response rates and is the preferred treatment for steroid-refractory IgG4-RD 1:

• Effective even in patients who failed immunomodulatory drugs 2
• B-cell depletion therapy represents standard of care for patients failing first-line steroids or experiencing flares upon steroid withdrawal 6
• Dosing should follow FDA-approved regimens for IgG4-RD 6

Alternative biologics for severe/refractory cases include adalimumab and ruxolitinib, though evidence is limited 5.

Organ-Specific Urgent Considerations

Certain manifestations require immediate aggressive treatment 1:

• Ocular involvement (episcleritis, papilledema): Urgent treatment necessary to prevent permanent vision loss 1
• Obstructive jaundice: Immediate indication for glucocorticoid therapy 3
• Pancreatic involvement: May lead to exocrine insufficiency requiring enzyme replacement 1

Specialist Referral Indications

Refer patients with complex IgG4-RD and suspected malignancy to specialist multidisciplinary teams 4, 1:

• Coordination with rheumatology, gastroenterology, and ophthalmology is essential for systemic disease management 1, 6
• Multidisciplinary review is particularly important for IgG4-related sclerosing cholangitis to distinguish from primary sclerosing cholangitis and malignancy 4

Critical Diagnostic and Monitoring Pitfalls

Do not rely on serum IgG4 levels alone for diagnosis or treatment monitoring 4, 1:

• Elevated serum IgG4 supports clinically suspected disease but cannot definitively diagnose IgG4-RD or distinguish it from mimickers 4
• Histopathological confirmation showing abundant IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis remains the diagnostic gold standard 4, 2
• Assessment of other organ involvement (particularly pancreatic manifestations) provides crucial diagnostic information 4

Do not discontinue all immunosuppression after initial response—relapse rates exceed 60% without maintenance therapy 1, 7.