What is the recommended treatment for autoimmune pancreatitis?

Treatment of Autoimmune Pancreatitis

Corticosteroids are the first-line treatment for autoimmune pancreatitis, with prednisolone 0.6 mg/kg/day (or 30-40 mg/day) as the standard initial dose, tapered over 2-3 months to a maintenance dose of 2.5-5 mg/day. 1, 2

Initial Treatment Strategy

Indications for Steroid Therapy

• Obstructive jaundice due to bile duct stenosis 3, 2
• Symptomatic extrapancreatic lesions 3, 2
• Abdominal pain or back pain 2
• Diabetes mellitus coincidental with AIP 3

Pre-Treatment Considerations

• Biliary drainage should be performed first in patients with obstructive jaundice before initiating steroids 2
• Blood glucose must be controlled in diabetic patients prior to steroid initiation 2
• Ensure accurate diagnosis to distinguish AIP from pancreatic cancer before starting therapy 3, 4

Corticosteroid Dosing Regimen

Induction Phase

• Starting dose: 0.6 mg/kg/day prednisolone (typically 30-40 mg/day for adults) 1, 2, 4
• Alternative lower-dose approach: 10-20 mg prednisolone daily may be equally effective, particularly for elderly patients with contraindications such as insulin-dependent diabetes or severe osteoporosis 1
• Administer initial dose for 2-4 weeks 1, 2, 4

Tapering Schedule

• Reduce by 5 mg every 1-2 weeks based on clinical response, biochemical markers (liver enzymes, IgG, IgG4), and imaging findings 1, 2, 4
• Taper to maintenance dose (2.5-5 mg/day) over 2-3 months 1, 2, 4
• Treatment response should be evaluated after 2-4 weeks prior to tapering 1

Maintenance Therapy Duration

• Continue maintenance dose for at least 3 years in cases with radiological and serological improvement 1, 2
• Stopping maintenance therapy should be planned based on disease activity, with consideration for discontinuation after 6-12 months if complete remission is documented 2, 4

Steroid-Sparing Immunosuppressants

When to Add Immunosuppressants

Maintenance treatment with steroid-sparing agents is recommended for up to 3 years and potentially beyond, starting during prednisolone tapering, to reduce relapse risk. 1

First-Line Steroid-Sparing Agents

• Azathioprine (up to 2 mg/kg/day) 1
• 6-mercaptopurine 1
• Mycophenolate mofetil 1

Alternative Agents

• Cyclosporine A 1
• Tacrolimus 1

High-Risk Patients Requiring Sustained Immunosuppression

• Patients with perihilar and intrahepatic bile duct involvement (associated with higher relapse rates) 1
• Patients with more fibrotic phenotype, multiple bile duct strictures, or multi-organ involvement 1

Management of Relapse

Relapse Treatment Regimens

Three regimens are described for relapse management: 1

1. High-dose corticosteroids tapered to maintenance treatment with low-dose corticosteroids (2.5-10 mg daily prednisolone) plus a steroid-sparing agent (azathioprine or mycophenolate mofetil) 1

2. High-dose corticosteroids without maintenance treatment 1

3. Rituximab induction with or without maintenance rituximab (2 infusions of 1,000 mg rituximab 15 days apart every 6 months, including premedication with methylprednisolone and antihistamine) 1

Rituximab as Alternative

• Rituximab can be considered when relapse has occurred 1
• Rituximab is particularly effective for B-cell depletion in IgG4-related disease 5
• Re-administration or dose-up of steroid is also effective for treating AIP relapses 2

Adjunctive Therapies

Ursodeoxycholic Acid (UDCA)

• UDCA (10-15 mg/kg/day) has anticholestatic and anti-inflammatory effects in patients with IgG4-related cholangiopathy 1
• Whether UDCA has corticosteroid-sparing effects remains to be studied 1

Endoscopic Intervention

• Distal or hilar bile duct strictures unresponsive to medical treatment may require endoscopic balloon dilatation 1
• Short-term stenting if unresponsive to balloon dilatation alone 1
• Antibiotic prophylaxis before ERCP is mandatory 1

Monitoring and Follow-Up

Response Assessment Parameters

• Clinical manifestations (resolution of jaundice, abdominal pain) 2, 4
• Biochemical markers: liver enzymes, serum gamma-globulin, IgG, IgG4 levels 2, 4
• Imaging findings: ultrasound, CT, MRCP, ERCP 2, 4

Expected Response Rates

• Corticosteroid response rate ranges from 62-100% 1
• Relapse rate during tapering or after withdrawal is approximately 30% 1

Critical Pitfalls to Avoid

Diagnostic Uncertainty

• If diagnosis remains uncertain after initial evaluation, steroid therapy should be given with extreme caution 4
• Poor response to steroid therapy should raise suspicion for pancreatic cancer and prompt re-evaluation including possible laparotomy 3, 4

Premature Discontinuation

• Do not stop steroids too early; patients require careful monitoring for relapse even after apparent remission 2, 4

Inadequate Relapse Management

• Relapses are common in type 1 AIP (IgG4-related) but rare in type 2 AIP (IDCP) 6, 5
• Maintenance immunosuppression is often necessary for type 1 AIP to prevent relapses 5

Long-Term Prognosis

• Short-term prognosis with steroid therapy is excellent 2
• Long-term survival is excellent for both type 1 and type 2 AIP 5
• Long-term outcome factors remain unclear, including relapse patterns, pancreatic exocrine/endocrine dysfunction, and associated malignancy risk 2
• Overall lifetime risk of pancreatic cancer does not appear elevated despite rare reported instances 6