What is the treatment approach for a patient with IgG4-related disease (Immunoglobulin G4-related disease)?

Treatment of IgG4-Related Disease

First-Line Treatment

Corticosteroids are the first-line treatment for active IgG4-related disease, with oral prednisolone 40 mg daily for 2-4 weeks, followed by gradual tapering by 5 mg weekly over 8-12 weeks. 1, 2

• Treatment response should be assessed through clinical improvement (resolution of symptoms, normalization of liver biochemistry) and radiological improvement on repeat imaging at weeks 4-8. 1, 2
• Lack of objective radiological improvement by weeks 4-8 suggests either incorrect diagnosis or a fibrotic, non-inflammatory phase of disease. 1
• Serum IgG4 levels should NOT be used to monitor treatment response or guide therapy adjustments, as levels do not reliably correlate with disease activity. 1, 2

Maintenance Immunosuppression Strategy

All patients with IgG4-related disease should be considered for continued immunosuppressive therapy due to the high relapse rate of at least 60% after steroid cessation. 1, 3

Maintenance Options:

• Low-dose prednisolone 5-7.5 mg daily: A randomized study demonstrated relapse rates of 23% at 3 years with maintenance prednisolone versus 58% with steroid withdrawal. 1, 2

• Immunomodulators (azathioprine 2 mg/kg/day, mercaptopurine, or mycophenolate): These agents are commonly introduced in Europe and North America for patients with evidence of relapse or high relapse risk. 1

• The choice between maintenance steroids versus immunomodulators remains debated, with Japanese experts favoring maintenance steroids while European/North American practice often employs immunomodulators. 1

Treatment for Relapsed or Refractory Disease

Rituximab is the preferred treatment for patients who fail first- or second-line treatment, or whose disease flares on steroid withdrawal, particularly in those with multisystem or complex disease. 1, 3

• Over 95% of patients with IgG4-RD respond to rituximab (anti-CD20 monoclonal antibody therapy). 1, 3

• Standard rituximab dosing: 2 infusions of 1000 mg administered 15 days apart, repeated every 6 months for maintenance. 3, 2

• Rituximab has demonstrated efficacy even in patients who failed immunomodulatory drug therapy. 4

• Appropriate premedication should be administered to minimize infusion reactions. 3

Specialist Referral Indications

Patients with complex IgG4-related disease, multiorgan involvement, or suspected malignancy should be referred to specialists or centers with IgG4-RD experience. 1, 2

• The complexity of management necessitates multidisciplinary team involvement for diagnosis establishment, treatment planning, and clinical trial recruitment. 1

Treatment Algorithm Summary

1. Initial therapy: Prednisolone 40 mg daily × 2-4 weeks, then taper over 8-12 weeks 1, 2
2. Assess response: Clinical improvement + radiological improvement at weeks 4-8 1, 2
3. Maintenance therapy: Either low-dose prednisolone (5-7.5 mg daily) OR immunomodulator (azathioprine 2 mg/kg/day) 1, 2
4. For relapse/refractory disease: Rituximab 1000 mg × 2 doses (15 days apart), repeated every 6 months 3, 2

Critical Pitfalls to Avoid

• Do not rely on serum IgG4 levels alone for diagnosis or treatment monitoring - they lack sufficient sensitivity and specificity. 2, 5
• Do not withhold maintenance therapy - the 60% relapse rate after steroid cessation mandates continued immunosuppression in most patients. 1, 3
• Do not delay rituximab in steroid-refractory or frequently relapsing disease - early B-cell depletion therapy prevents cumulative steroid toxicity and organ damage. 1, 3
• Do not miss malignancy - IgG4-RD can mimic malignant tumors; biopsy confirmation is strongly preferred before initiating treatment. 5, 4