What is the recommended initial therapy for IgG4‑related disease in an adult patient?

Initial Treatment for IgG4-Related Disease

Start oral prednisolone at 0.6 mg/kg/day (typically 40 mg daily) for 2-4 weeks as first-line therapy, then taper gradually by 5 mg weekly over 8-12 weeks to reach a maintenance dose of 2.5-5 mg/day. 1, 2

Induction Phase

• Begin with prednisolone 0.6 mg/kg/day (typically 40 mg daily) for the initial 2-4 weeks to induce remission 1, 3
• Evaluate treatment response after 2-4 weeks using clinical criteria (resolution of jaundice, symptom improvement), biochemical markers (liver function tests), and radiological findings (mass lesion resolution, organ size reduction) 1, 2
• Lack of objective radiological improvement by weeks 4-8 suggests either misdiagnosis or fibrotic non-inflammatory disease phase rather than treatment failure 1, 2

Dosing Nuances

Research suggests that the optimal initial prednisolone dose range is 0.4-0.69 mg/kg/day, as doses below 0.39 mg/kg/day or above 0.7 mg/kg/day are associated with higher relapse rates 4. However, guidelines consistently recommend 0.6 mg/kg/day as the standard starting dose 1, 3.

Tapering and Maintenance Phase

• Taper prednisolone by 5 mg weekly over 8-12 weeks to reach a maintenance dose of 2.5-5 mg/day over 2-3 months 1, 2, 3
• The tapering speed is critical: reduce by less than 0.4 mg/day to minimize relapse risk, as faster reduction (>0.4 mg/day) significantly increases relapse rates 4
• Maintenance therapy with prednisolone 5-7.5 mg daily reduces relapse rates to 23% at 3 years compared to 58% with complete steroid withdrawal 1, 2

Steroid-Sparing Immunosuppression

All patients with IgG4-RD should be considered for continued immunosuppressive therapy given the 60% relapse rate after steroid cessation. 1, 2, 5

• Start steroid-sparing agents (azathioprine 2 mg/kg/day, 6-mercaptopurine, or mycophenolate mofetil) during prednisolone tapering to reduce relapse risk 1
• Continue immunosuppression for up to 3 years, potentially longer in patients with multiorgan involvement 1
• Maintenance glucocorticoid dosage should exceed 6.25 mg/day when used as monotherapy; combining with immunosuppressants allows lower glucocorticoid doses 6

Common Pitfall

Do not attempt complete drug withdrawal in the first 3 years, as this is an independent risk factor for relapse 6. The relapse rates are 10.66% at 12 months, 22.95% at 24 months, and 27.87% at 36 months 6.

Rituximab for Refractory or Relapsing Disease

Rituximab is the preferred treatment for patients who fail first-line therapy or experience disease flares on steroid withdrawal, with >95% response rates. 1, 2, 5

• Standard dosing: 2 infusions of 1000 mg rituximab 15 days apart, repeated every 6 months for maintenance 1, 5, 7
• Include premedication with methylprednisolone and antihistamines to minimize infusion reactions 1
• Rituximab is particularly indicated for multisystem disease or steroid-dependent patients 1, 5, 8
• Serial rituximab treatments lead to progressive declines in serum IgG4 concentrations and improved disease control 8

Monitoring and Predictors of Relapse

• Do not use serum IgG4 levels to guide treatment decisions or monitor response, though falling levels may correlate with improvement 1, 2, 7
• High-risk features for relapse include: higher baseline serum IgG4 concentrations, involvement of multiple organs, higher IgG4-RD Responder Index scores, eosinophil elevation, and re-elevation of serum IgG4 during follow-up 6
• Patients with perihilar and intrahepatic bile duct involvement have higher relapse rates and warrant sustained immunosuppressive therapy 1

Critical Monitoring Point

Re-elevation of serum IgG4 levels during follow-up is significantly associated with clinical relapse; adding glucocorticoids or immunosuppressants at this stage can prevent later disease relapse 6.

Specialist Referral

• Refer patients with complex multiorgan IgG4-RD, suspected malignancy, or treatment-refractory disease to specialist multidisciplinary teams with IgG4-RD experience 1, 2, 7
• Coordination with organ-specific specialists (rheumatology, gastroenterology, ophthalmology) is essential for optimal management 2