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

Treatment for IgG4-Related Disease

Oral prednisolone 40 mg daily for 2-4 weeks, followed by a gradual taper over 8-12 weeks, is the first-line treatment for IgG4-related disease, with maintenance immunosuppressive therapy strongly recommended due to relapse rates exceeding 60%. 1

First-Line Glucocorticoid Therapy

• Initiate oral prednisolone at 40 mg daily (or 0.6 mg/kg/day) for 2-4 weeks as induction therapy. 1, 2
• Evaluate clinical response after 2-4 weeks using clinical symptoms, biochemical markers, and radiological findings before beginning the taper. 1
• Gradually taper the dose over 8-12 weeks to a maintenance dose of 2.5-5 mg/day over 2-3 months. 1, 2
• For elderly patients or those with contraindications to high-dose steroids, lower initial doses of 10-20 mg prednisolone daily may be effective. 1

Important caveat: Lack of improvement on repeat imaging at weeks 4-8 suggests either incorrect diagnosis or a fibrotic, non-inflammatory phase of disease that will not respond to steroids alone. 1

Maintenance Therapy Strategy

• Maintenance immunosuppressive therapy should be considered in all patients due to relapse rates of ≥60% after steroid cessation, particularly in those with multiorgan involvement. 1, 3
• Maintenance options include:
  • Low-dose prednisolone (2.5-5 mg daily) 1, 2
  • Azathioprine 1
  • Mycophenolate mofetil 1
  • Mercaptopurine 1
• Cessation of glucocorticoids should be attempted within 3 years to minimize steroid-related complications, especially in elderly patients. 2

Management of Relapsed or Refractory Disease

• For disease that relapses on steroid withdrawal or fails to respond to first-line treatment, rituximab (anti-CD20 monoclonal antibody) is the preferred treatment. 3, 2
• Rituximab demonstrates >95% response rates in IgG4-RD, even in patients who failed immunomodulatory drugs. 3, 2
• Recommended rituximab dosing: 2 infusions of 1,000 mg IV given 15 days apart, repeated every 6 months for maintenance. 3
• Alternative approach for relapse: Double the current prednisone dose, slow the taper, and add azathioprine for one year if remission is maintained. 4
• If relapse occurs on azathioprine, discontinue it and switch to rituximab. 4

Alternative and Emerging Therapies

• Inebilizumab (Uplizna), another B-cell depleting agent, is FDA-approved for IgG4-RD in patients with inadequate response to steroids or active disease flares. 5
• For advanced disease with multiorgan involvement, combination therapy with rituximab, cyclophosphamide, and dexamethasone for initial therapy, followed by rituximab maintenance every 6 months, is preferred. 6
• Surgical intervention and radiotherapy for localized disease induce clinical remission with low recurrence rates. 7

Monitoring and Clinical Considerations

• Do not use serum IgG4 levels to monitor treatment response or plan further therapy—rely on clinical symptoms and radiological improvement instead. 1
• Patients with complex disease, suspected malignancy, or multiorgan involvement should be referred to specialists or centers with experience in IgG4-RD. 1, 5
• Coordinate care with rheumatology for comprehensive management of this systemic disease. 5

Critical Pitfalls to Avoid

• Failure to distinguish IgG4-RD from malignancy, infection, or other inflammatory conditions leads to inadequate treatment—histopathological confirmation is essential. 1, 2
• Inadequate duration of steroid therapy or stopping immunosuppression too early results in high relapse rates, especially with multiorgan involvement. 1
• Unrecognized IgG4-RD can lead to end-stage organ failure and death—prompt recognition and treatment are critical. 8
• Ocular manifestations including episcleritis and papilledema require urgent treatment to prevent permanent vision damage. 5