What is the diagnosis and treatment approach for a patient with autoimmune pancreatitis?

Autoimmune Pancreatitis: Diagnosis and Treatment

Diagnostic Approach

Autoimmune pancreatitis must be definitively distinguished from pancreatic cancer before treatment, as it is a benign, corticosteroid-responsive disease that can present with identical features to malignancy including jaundice, weight loss, elevated CA 19-9, and pancreatic masses. 1, 2

Laboratory Testing

• Measure serum IgG4 levels as the first-line diagnostic test, with levels >280 mg/dL being the most sensitive and specific marker for type 1 AIP 3, 2
• Check lipase and amylase (may be normal or only mildly elevated, unlike acute pancreatitis) 3
• Obtain liver function tests including bilirubin, AST, ALT, and alkaline phosphatase to assess for biliary obstruction 3
• Measure total serum IgG levels (elevated in AIP but less specific than IgG4) 1

Imaging Studies

• Obtain CT or MRI with MRCP to evaluate pancreatic morphology and biliary involvement 3
• Classic finding: diffuse "sausage-shaped" pancreatic enlargement with capsule-like peripheral rim (though focal enlargement mimicking malignancy occurs in some cases) 1, 3, 2
• MRCP evaluates for bile duct strictures, pancreatic duct narrowing, and associated organ involvement 3

Histological Confirmation

• Obtain EUS-guided FNA biopsy (preferred over CT-guided due to lower peritoneal seeding risk) when malignancy cannot be excluded 1
• Look for prominent lymphoplasmacytic infiltration with associated fibrosis 1, 2
• If initial biopsy is negative but clinical suspicion remains high, repeat EUS-FNA at least once 1

Critical Pitfall: Never proceed to pancreatic resection without definitively excluding AIP—this is a benign disease effectively treated with corticosteroids, and unnecessary surgery causes significant morbidity 2

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Treatment Protocol

Initial Corticosteroid Therapy

Start prednisolone 40 mg daily (or 0.6 mg/kg/day) for 4 weeks as first-line treatment. 3, 4, 2

• Alternative lower-dose approach of 10-20 mg daily may be equally effective for elderly patients or those with insulin-dependent diabetes or severe osteoporosis 4, 2
• After 2-4 weeks, evaluate treatment response before initiating taper 4
• Reduce dose by 5 mg every 1-2 weeks based on clinical response, biochemical markers, and imaging 4
• Taper over 2-3 months to maintenance dose of 2.5-5 mg/day 4, 2

Steroid-Sparing Maintenance Therapy

Add azathioprine (up to 2 mg/kg/day) during prednisolone tapering to prevent relapse, particularly for patients with biliary involvement. 3, 4, 2

• For patients with biliary stricture involvement specifically, maintain azathioprine at 2 mg/kg/day as steroid-free monotherapy (83% remission rate over median 67-month follow-up) 3, 4
• Consider TPMT genotyping or enzyme activity measurement before starting azathioprine to predict toxicity risk and optimize dosing 4
• Continue maintenance therapy for up to 3 years and potentially beyond 4
• Alternative steroid-sparing agents include mycophenolate mofetil 4, 2

Adjunctive Therapies

• Add ursodeoxycholic acid (UDCA) 10-15 mg/kg/day for anticholestatic and anti-inflammatory effects in patients with biliary involvement 4
• Consider endoscopic balloon dilatation for distal or hilar bile duct strictures unresponsive to medical treatment 4

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Monitoring Protocol

During Active Treatment

• Monitor every 3-6 months with complete blood count to detect cytopenias (azathioprine's primary toxicity) 3, 4
• Check liver function tests to detect disease relapse or drug hepatotoxicity 3, 4
• Measure serum IgG4 levels as a biomarker for disease activity (elevation may precede clinical relapse) 3, 4

Long-Term Surveillance

• Perform imaging (MRCP or CT) annually or if symptoms recur to assess biliary stricture progression 3, 4
• Never attempt treatment withdrawal in patients with biliary strictures due to high relapse risk (50% relapse rate after azathioprine withdrawal at median 7 years) 4
• Screen for diabetes within 3-6 months following diagnosis and annually thereafter, as pancreatic damage can lead to postpancreatitis diabetes mellitus 1

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Management of Relapse

If relapse occurs during or after prednisone tapering, restart high-dose corticosteroids (40 mg daily) and add maintenance immunosuppression. 4, 2

• Taper to low-dose maintenance (2.5-10 mg daily prednisolone) plus azathioprine or mycophenolate mofetil 4, 2
• Consider rituximab for induction and maintenance therapy in relapsing type 1 AIP 4, 5
• For type 2 AIP relapses or steroid dependence, anti-TNF therapy is a well-tolerated second-line option 5

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Special Considerations

Biliary Obstruction Management

• Obtain brush cytology and/or endoscopic biopsy during ERCP to exclude malignancy 4
• Administer perioperative antibiotics to prevent cholangitis when instrumenting an obstructed duct 4
• Patients with proximal extrahepatic and intrahepatic bile duct involvement have substantially higher relapse rates and require indefinite immunosuppression 4

Type 1 vs Type 2 AIP

• Type 1 AIP is associated with elevated IgG4 and systemic manifestations (part of IgG4-related disease) 5, 6, 7
• Type 2 AIP is pancreas-specific, not IgG4-related, and associated with inflammatory bowel disease in ~25% of cases 5, 7
• Both types respond well to corticosteroids, but relapse is common in type 1 (requiring maintenance therapy) and rare in type 2 5, 7

Long-Term Prognosis

• With appropriate maintenance immunosuppression, long-term survival is excellent 4, 7
• Disease flares can occur even after years of remission, requiring continuous monitoring 4
• Treatment goal: normalized transaminases, IgG4 levels, and stable or improved biliary strictures on imaging 4