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

Initial Treatment for IgG4-Related Disease

Corticosteroids are the first-line treatment for IgG4-related disease, with oral prednisolone 40 mg daily for 2-4 weeks followed by a gradual taper over 8-12 weeks. 1, 2

Diagnosis Confirmation

Before initiating treatment, it's essential to confirm the diagnosis of IgG4-related disease:

• Diagnosis is based on a combination of clinical, radiological, serological, and histopathological findings 3
• Key diagnostic features include:
  • Elevated serum IgG4 levels 1
  • Histopathological findings of IgG4-positive plasma cell infiltration, storiform fibrosis, and obliterative phlebitis 3
  • Involvement of other organs (particularly pancreatic manifestations) 1
  • Prompt response to steroid therapy 1

Initial Treatment Protocol

First-Line Therapy

• Starting dose: Oral prednisolone 40 mg daily (0.6-0.8 mg/kg/day) for 2-4 weeks 1, 2
• Tapering schedule: Reduce by 5 mg every week over approximately 8-12 weeks 1, 2
• Assessment of response: Evaluate clinical response after 2-4 weeks before beginning the taper 2
  • Measure clinical symptoms, liver biochemistry, and radiological findings 1
  • Lack of improvement on repeat imaging at weeks 4-8 suggests either incorrect diagnosis or a fibrotic, non-inflammatory phase of disease 1, 2

Special Considerations

• For elderly patients or those with contraindications to high-dose steroids (e.g., insulin-dependent diabetes, severe osteoporosis), lower initial doses of 10-20 mg prednisolone daily may be effective 1, 2
• Serum IgG4 levels often fall in response to steroids but should not be used to monitor or plan further treatment 1

Maintenance Therapy

Indications for Maintenance Therapy

• Relapse after cessation of steroid treatment occurs in at least 60% of patients with IgG4-related disease 1, 2, 4
• Higher relapse rates are associated with:
  • Multiorgan involvement 1, 2
  • Involvement of perihilar and intrahepatic bile ducts 1
  • More fibrotic phenotype and multiple bile duct strictures 1

Maintenance Options

• Immunomodulators as steroid-sparing agents:
  • Azathioprine (2 mg/kg/day) 1, 5
  • Mycophenolate mofetil 1, 6
  • Mercaptopurine 1
• Low-dose corticosteroids: Maintenance prednisolone 2.5-7.5 mg daily 1, 3
• Rituximab: For patients who fail to respond to first- or second-line treatment or whose disease flares on withdrawal of steroids 1, 4, 6

Management of Relapse

Treatment Options for Relapse

• Re-administration or dose increase of corticosteroids 3
• Addition of immunomodulatory drugs 3, 5
• Rituximab (anti-CD20 monoclonal antibody) for steroid-resistant disease 1, 7, 6
• Consider other agents in refractory cases:
  • Hydroxychloroquine 4
  • Thalidomide 4
  • Infliximab 4

Monitoring and Follow-up

• Regular monitoring of clinical symptoms and biochemical markers 1
• Repeat imaging to assess radiological response 1, 2
• Evaluate for potential steroid-related complications, especially in elderly patients 3, 6
• Consider referral to specialists or centers with experience in IgG4-related disease for complex cases or suspected malignancy 1, 2

Common Pitfalls

• Failure to distinguish IgG4-related disease from malignancy, lymphoma, or other inflammatory conditions 2, 3
• Inadequate duration of steroid therapy leading to early relapse 2
• Stopping immunosuppression too early, especially in cases with multiorgan involvement 2
• Overlooking steroid-related complications in elderly patients 3, 6