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 as first-line therapy to induce remission, then taper gradually over 8-12 weeks to a maintenance dose of 2.5-5 mg/day. 1

Initial Induction Therapy

• Begin with oral prednisolone 0.6 mg/kg/day (approximately 40 mg daily for most adults) for 2-4 weeks to induce remission 1, 2
• This glucocorticoid regimen is the established first-line treatment regardless of which organs are affected 1, 3
• Monitor for clinical response by assessing resolution of symptoms (jaundice, organ dysfunction) and radiological improvement (mass lesions, organ enlargement) at weeks 4-8 1

Critical pitfall: If you see no objective radiological improvement by weeks 4-8, this suggests either an incorrect diagnosis or that the disease has progressed to a fibrotic, non-inflammatory phase rather than treatment failure 1

Steroid Tapering Protocol

• After the initial 2-4 week induction period, taper prednisolone by 5 mg weekly over approximately 8-12 weeks 1
• Target a maintenance dose of 2.5-5 mg/day, reaching this level over 2-3 months total 1, 2
• The gradual taper is essential to prevent disease flare while minimizing steroid-related complications 1

Maintenance Therapy Strategy

Do not discontinue immunosuppression after achieving initial remission—at least 60% of patients relapse after steroid cessation, with even higher rates in those with multiorgan involvement. 1

• Continue maintenance prednisolone at 5-7.5 mg/day, which reduces relapse rates to 23% at 3 years compared to 58% with complete steroid withdrawal 1
• All patients with IgG4-RD, particularly those with multiorgan involvement, should receive continued immunosuppressive therapy 1, 4
• Consider attempting medication cessation within 3 years in elderly patients at high risk for steroid-related complications, but only after careful risk-benefit assessment 2

Treatment of Steroid-Refractory or Relapsing Disease

Rituximab (anti-CD20 monoclonal antibody) is the preferred treatment for steroid-refractory disease, achieving response rates exceeding 95%. 1, 4

• For patients who fail to respond adequately to first-line steroids or experience disease flares during steroid withdrawal, B-cell depletion therapy with rituximab is the standard approach 4, 5
• Rituximab is effective even in patients who have failed immunomodulatory drugs 2
• Alternative immunomodulatory agents such as azathioprine or mycophenolate mofetil can be used as steroid-sparing agents for relapsing disease, though they are less effective than rituximab 2, 3

Organ-Specific Urgent Considerations

• Ocular manifestations (episcleritis, papilledema) require urgent treatment to prevent permanent vision damage 1, 4
• Pancreatic involvement may progress to exocrine insufficiency requiring enzyme replacement therapy 1
• Coordinate care with relevant specialists (rheumatology, gastroenterology, ophthalmology) for comprehensive multidisciplinary management 1, 4

Monitoring and Diagnostic Pitfalls

• Do not rely on serum IgG4 levels alone for diagnosis or treatment monitoring—they are neither sensitive nor specific enough 1
• Confirm diagnosis through combination of typical radiological findings, histopathological features (lymphoplasmacytic infiltrate, storiform fibrosis, obliterative phlebitis), and clinical context 2, 6
• Refer patients with complex multiorgan disease or suspected malignancy to specialist multidisciplinary teams 1

Treatment Algorithm Summary

1. Induction: Prednisolone 0.6 mg/kg/day × 2-4 weeks 1
2. Taper: Reduce by 5 mg weekly over 8-12 weeks 1
3. Maintenance: Continue 2.5-5 mg/day (or 5-7.5 mg/day for higher-risk patients) 1
4. Refractory/Relapse: Switch to rituximab 1, 4
5. Long-term: Consider steroid-sparing agents (azathioprine, mycophenolate) if needed 2, 3