Autoimmune Pancreatitis: When to suspect How to Diagnose and How to Treat
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1 Autoimmune Pancreatitis: When to suspect How to Diagnose and How to Treat Suresh T. Chari, MD Head, Pancreas Interest Group Professor, Division of Gastroenterology & Hepatology Mayo Clinic College of Medicine, Rochester, MN AIP may be more than one disease! AIP subtypes: Type 1: Part of a systemic disease Histologic pattern (lymphoplasmacytic sclerosing pancreatitis (LPSP)) Type 2: Pancreas specific Histologic pattern (idiopathic duct centric pancreatitis) Am J GE Sept 2009 Type 1 AIP-Definition AIP is a systemic disease which afflicts not only the pancreas but also a variety of other organs including bile duct, salivary glands, the retroperitoneum and lymph nodes. Organs affected by AIP have lymphoplasmacytic infiltration with abundant IgG4 positive cells. The inflammatory process responds to steroid therapy. 1
2 Some Facts about AIP AIP is uncommon Of 444 consecutive patients with suspected pancreatic disease only 18 (4%) had AIP AIP is a disease of older men: 80% >age 50 years 80% men AIP is a relatively painless disease despite being a form of chronic pancreatitis Unusual for pain of AIP to require long-term narcotics Five Cardinal Features of AIP The HISORt Features Histology: Lymphoplasmacytic sclerosing pancreatitis and a + ve IgG4 immunostain Imaging: Typical (50%) Diffuse sausage-shaped gland enlargement, delayed enhancement Others: Focal enlargement, normal Rare: Low-density mass/dilated pd Serology: Elevated serum IgG4 (75%) Other organ involvement: especially biliary strictures, retroperitoneal fibrosis, salivary gland involvement (50-67%) Response to steroid therapy (~100%) Note of caution re use of serum IgG4 to screen for AIP! 2
3 Scatterplot of Serum IgG4 in Study Groups (n= 467) Am J Gastroenterol 2007;102: If the pre-test probability of AIP is low, the chances are the elevation in IgG4 is a false positive! Look for the other HISORt criteria: If they are present it is more likely to be a true positive. When to suspect AIP? 3
4 Clinical Presentations of AIP Pancreatic Predominantly Extra-pancreatic Acute Post-acute/ Late Pancreatic Presentations Acute Obstructive jaundice/pancreatic mass: Majority (75%) Pancreatitis (25% have elevated enzymes + mild pain, 80% have jaundice/ LFT) Post Acute: Asymptomatic pancreatic mass Steatorrhea with pancreatic atrophy Painless calcific pancreatitis Acute Presentation 67 yo man with 2 week history of obstructive jaundice and 30 lb weight loss. Labs: Glucose 315 mg/dl, CA 19-9 of 350 U/ml EUS: Diffusely hypoechoic gland with?mass in the head, FNA -ve 4
5 Late or Post-acute Presentation 65 yo man, obstructive jaundice 7 months ago, currently asymptomatic after biliary stenting Late or Post-acute Presentation 79 y.o. man with steatorrhea x 9 mo,25 pound weight loss, stool fat: 100 gm/day Pre-dominantly Extra-pancreatic Presentation Biliary strictures resembling those due to Pancreatic cancer Cholangiocarcinoma PSC Interstitial nephritis Retroperitoneal fibrosis Diffuse lymphadenopathy Sjogren s syndrome 5
6 Extra-pancreatic Presentation 70 yo man with steatorrhea and elevated liver enzymes referred for changes of P SC Extra-pancreatic Presentation 58 yo woman with steatorrhea x 2 yrs asymptomatic on enzyme replacement, presents with new renal failure Summary: Suspect AIP if. Patient presents with or has history of or has radiologic evidence of unexplained pancreatic disease Especially obstructive jaundice/pancreatic mass or Extra-pancreatic disease known to be associated with AIP 6
7 When not to suspect AIP Features of cancer: Narcotic requiring pain Marked anorexia/cachexia Dilated pancreatic duct/pancreatic atrophy Recurrent pancreatitis without biliary involvement Very uncommon in AIP Dyspepsia with mildly elevated pancreatic enzymes How to diagnose AIP Challenges to diagnosing AIP Closely mimics other well known diseases So need high index of suspicion! Rare compared to the diseases it mimics 2-3% of those suspected to have pancreatic cancer No single test is diagnostic Histology diagnostic but rarely available in pancreas/bile duct Price of misdiagnosis heavy AIP mistaken for cancer can result in major surgery Cancer mistaken for AIP can result in delay in surgery 7
8 AIP can be diagnosed when patient has Diagnostic Histology (LPSP) post-resection or on core biopsy Typical imaging + serology, OOI or compatible histology Atypical imaging + serology/ooi/ compatible histology + response to steroids Avoid steroids without strong collateral evidence of AIP! A) Making the Diagnosis: Histology A 65 y.o. man with dyspeptic symptoms and weight loss B D S. IgG4:150 mg/dl A EUS guided biopsy + IgG4 stain B 8
9 A After steroid therapy B D B) Making the Diagnosis: Typical Imaging + Serology 67 yo man, new-onset diabetes, 30 lb weight loss, obstructive jaundice and CA 19-9 of 350 Serum IgG4: 1200 mg/dl Serial Changes in Pancreatic Morphology At presentation 8 weeks later 8 months later 9
10 C) Making the Diagnosis: Steroid Trial 70 yo man referred for P SC Serum IgG4: 870 mg/dl 12 weeks after steroid course 10
11 Word of caution regarding steroid trial It is not to be used as a substitute for a thorough search for etiology Do not use it if there is no objective way to define response Treatment of AIP What do steroids accomplish? Steroids resolve inflammation AIP is a fibro-inflammatory disease, fibrosis may leave a scarred, atrophic organ Rapid decrease in inflammation can be diagnostic and reassuring Confirms that other organ involvement was due to same process Not sure it preserves pancreatic function 11
12 Steroid therapy Initial Treatment Regimen Most common regimen Prednisone 40 mg/day X 4 weeks Taper by 5 mg/week thereafter Rapid taper not helpful in diagnosis or treatment Steroid therapy Follow-up Re-image in 4-6 weeks Serum IgG4, CA 19-9, Liver tests Response rapid Majority can have stents removed by 4-6 weeks CA 19-9 decreases IgG4 decrease with rx of AIP, but so does false +ve IgG4! Response to steroid therapy CT 3.5 weeks after initiating rx 12
13 Steroid Responsiveness Unresectable mass 6 weeks after steroids Resolution of Distal Biliary Stricture 6 weeks After 12 weeks of prednisone 13
14 Relapse Following Steroid Treatment In up to 60%, during steroid taper or after Mostly within 3 years of presentation Could occur in the pancreas or another organ (usually bile duct) Proximal extra-hepatic or intrahepatic strictures predict relapse Normalization of IgG4 after withdrawal of steroids predicts low relapse rate Maintenance Rx Who should receive maintenance rx? Use in all vs wait for one relapse Which drugs can maintain remission? Low-dose steroids (10 mg/day) Azathioprine (2mg/kg) Mycophenalate mofetil (750 mg bid) How long? months Maintenance Rx How to monitor? CBC, liver enzymes every 3 months Relapses 25% on maintenance rx Respond to steroids? Change rx or give another steroid course and remain on same immunosuppression 14
15 Summary AIP is a multisystem disease with protean manifestations HISORt criteria can help diagnose AIP Manifestations respond to steroid therapy Relapses are common, may need long term maintenance rx 15
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