What is the treatment for IgG4 (Immunoglobulin G4) cholangitis?

Treatment of IgG4 Cholangitis

Corticosteroids are the first-line treatment for IgG4-related sclerosing cholangitis, with oral prednisolone 40 mg daily for 2-4 weeks followed by gradual taper over 8-12 weeks, and most patients will require continued immunosuppressive therapy due to relapse rates exceeding 60%. 1

Initial Treatment Approach

First-Line Corticosteroid Therapy

• Start oral prednisolone 40 mg daily for 2-4 weeks as the standard induction regimen 1, 2
• Taper by 5 mg weekly over 8-12 weeks after the initial high-dose period 1
• Measure treatment response through clinical improvement (resolution of jaundice), normalization of liver biochemistry, and radiological improvement on repeat imaging at weeks 4-8 1, 3
• Steroid therapy normalizes liver enzyme levels in approximately 61% of patients and allows biliary stent removal in most cases 3

Response Assessment

• Lack of objective radiological improvement at weeks 4-8 suggests either incorrect diagnosis or fibrotic, non-inflammatory disease 1
• Monitor clinical symptoms and liver biochemistry rather than serum IgG4 levels, as IgG4 is not used to guide ongoing treatment decisions 1
• Initial steroid response is typically rapid and favorable in IgG4-SC, unlike primary sclerosing cholangitis which shows no benefit from steroids 1

Maintenance Immunosuppression

High Relapse Risk

• At least 60% of patients relapse after steroid cessation, with even higher rates in those with multiorgan involvement 1, 4
• Relapse is more common with proximal extrahepatic/intrahepatic strictures compared to isolated intrapancreatic strictures 3
• All patients with IgG4-SC should be considered for continued immunosuppressive therapy to prevent relapse 1, 4

Maintenance Options

• Low-dose prednisolone 5-7.5 mg daily: A randomized study showed relapse rates of 23% at 3 years with maintenance prednisolone versus 58% with steroid withdrawal 1
• Azathioprine 2 mg/kg/day with or without low-dose steroids as steroid-sparing maintenance 1
• Alternative immunomodulators include mercaptopurine or mycophenolate mofetil 1, 2

Treatment for Relapse or Refractory Disease

Rituximab as Second-Line Therapy

• Rituximab is the preferred treatment for patients who fail first-line therapy or whose disease flares on steroid withdrawal, particularly with multisystem involvement 1, 4
• More than 95% of patients with IgG4-related disease respond to rituximab (anti-CD20 monoclonal antibody) 1, 4
• Standard dosing: 2 infusions of 1000 mg rituximab 15 days apart, repeated every 6 months for maintenance 4
• Rituximab has demonstrated sustained efficacy with good disease control when administered every 8-9 months in maintenance regimens 4

Management of Steroid-Refractory Cases

• For patients with inadequate response to steroids, consider early transition to rituximab rather than prolonged high-dose corticosteroid exposure 5
• Coordinate care with rheumatology for multisystem disease management 5

Critical Diagnostic Considerations

Distinguishing from Primary Sclerosing Cholangitis

• IgG4-SC patients are typically older (mean age 62 years) and predominantly male (85%) compared to PSC patients who present at age 30-40 6, 3
• IgG4-SC is not associated with inflammatory bowel disease, unlike PSC 6
• Serum IgG4 >4× upper limit of normal is highly diagnostic for IgG4-SC 7
• Histology shows >10 IgG4-positive plasma cells per high-power field with IgG4+/IgG+ ratio >40% 8

Avoiding Misdiagnosis

• Screen serum IgG4 levels in all patients with unexplained biliary strictures or previously diagnosed PSC, as misdiagnosis can lead to years of inappropriate management 8
• IgG4-SC can mimic cholangiocarcinoma or pancreatic carcinoma, potentially leading to unnecessary surgical resections 7, 6
• Refer complex cases or those with suspected malignancy to specialist multidisciplinary teams with IgG4-related disease experience 1

Common Pitfalls

• Premature steroid withdrawal leads to high relapse rates—ensure adequate maintenance therapy rather than complete cessation 3, 9
• Do not use serum IgG4 levels to monitor treatment response or guide therapy adjustments, as levels may not correlate with disease activity 1
• Inadequate initial steroid duration (less than 8-12 weeks of tapering) increases relapse risk 9
• Failure to recognize multiorgan involvement, particularly autoimmune pancreatitis (present in 92% of cases), which increases relapse risk and necessitates more aggressive maintenance therapy 3