What is the management of IgG4-Related Disease (IgG4 RD)?

Management of IgG4-Related Disease (IgG4-RD)

Corticosteroids are the first-line treatment for active IgG4-RD, with prednisolone 40 mg daily for 2-4 weeks followed by a gradual taper over 8-12 weeks showing rapid and favorable disease control. 1

Diagnosis

Before initiating treatment, accurate diagnosis is essential:

• Laboratory testing:

  • Serum IgG4 levels (elevated in 50-80% of patients)
  • IgG4/IgG1 ratio >0.24 improves specificity 2
  • Complete blood count, comprehensive metabolic panel, ESR, CRP
  • Quantitative immunoglobulin levels (IgG, IgG subclasses) 2

• Imaging:

  • MRI/MRCP as first-line for pancreaticobiliary evaluation 2
  • CT for assessing other organ involvement
  • PET scanning to identify multisystem involvement 2

• Histopathology (essential for definitive diagnosis):

  • 10 IgG4+ plasma cells per high power field

  • IgG4+/IgG+ plasma cell ratio >40%
  • Lymphoplasmacytic infiltration with fibrosis
  • Storiform fibrosis
  • Obliterative phlebitis 2

Treatment Algorithm

First-Line Treatment

1. Corticosteroids:
   • Oral prednisolone 40 mg daily for 2-4 weeks
   • Taper by 5 mg every week over 8-12 weeks 1
   • Monitor clinical response (resolution of jaundice, liver biochemistry) and radiological findings
   • Repeat imaging at 4-8 weeks to evaluate improvement 1, 2

Maintenance Therapy

• Consider maintenance therapy due to high relapse rates (60% after steroid cessation) 1
• Two approaches:
  1. Maintenance steroids: Low-dose prednisolone 5-7.5 mg daily (Japanese approach)
     • Reduces relapse rate to 23% vs 58% with steroid withdrawal 1
  2. Immunomodulators: Introduce if evidence of relapse or high risk of relapse
     • Azathioprine (2 mg/kg/day)
     • Mycophenolate mofetil
     • Mercaptopurine 1, 3

Treatment for Relapsed/Refractory Disease

1. Rituximab (anti-CD20 monoclonal antibody):

   • Highly effective (>95% response rate) 1
   • Preferred for patients who fail first/second-line treatment
   • Particularly effective for multisystem or complex disease 1, 4
   • Standard regimen: 2 infusions of 1000 mg, 15 days apart 4

2. Alternative treatments with limited evidence:

   • Hydroxychloroquine
   • Thalidomide
   • Infliximab 3

3. Surgical intervention or radiotherapy:

   • Consider for localized disease
   • Associated with low recurrence rates 3

Special Considerations

• Complex cases: Refer patients with complex IgG4-SC and suspected malignancy to a specialist multidisciplinary meeting 1

• Monitoring:

  • Serum IgG4 levels may be used to monitor disease activity 4
  • Clinical response should be evaluated by:
    • Resolution of symptoms
    • Normalization of laboratory parameters
    • Improvement in radiological findings 2

• Treatment pitfalls:

  1. Lack of response: If no objective improvement in radiological abnormalities at 4-8 weeks, consider:

     • Incorrect diagnosis
     • Fibrotic, non-inflammatory phase of disease 1

  2. Malignancy exclusion: Carefully exclude malignancy as IgG4-RD can mimic various cancers 2, 5

  3. Steroid-related complications: Monitor for and manage complications, especially in elderly patients 5

• Long-term outcomes: While short-term outcomes with steroid therapy are generally good, long-term outcomes are less clear due to relapse, fibrosis, and associated malignancy 5

Disease-Modifying Antirheumatic Drugs (DMARDs)

DMARDs show limited efficacy (effective in less than half of cases) 3, but may be considered as steroid-sparing agents:

• Azathioprine
• Methotrexate
• Mycophenolate mofetil

For patients with IgG4-related sclerosing cholangitis (IgG4-SC), continued immunosuppressive therapy is strongly recommended, particularly for those with multiorgan involvement 1.