IgG4 Pancreatitis Dr Chan Lok Lam Laura United Christian Hospital JHSGR 6 th Aug, 2011

IgG4 pancreatitis Recently described disorder with protean manifestations Important diagnostic consideration in patients with obstructive jaundice associated with pancreatic mass lesion Mimics pancreatic cancer clinically and radiologically Dramatic response to steroid Correct diagnosis allows medical treatment and avoids major surgery

IgG4 pancreatitis = autoimmune pancreatitis? In previous literature  YES! Concept evolving Autoimmune pancreatitis (AIP) Type I AIP (IgG4 pancreatitis)Pancreatic manifestation of systemic IgG4- related disease Type II AIP Specific pancreatic disease occasional association with ulcerative colitis

IgG4 pancreatitis Chronic inflammatory disease of presumed autoimmune origin Pathogenesis not well understood Lymphoplasmacytic infiltration with abundant IgG4 positive cells Inflammatory process responds well to steroid therapy

Epidemiology Uncommon 0.82 per 100,000 patients in a Japanese nationwide survey (2002) 4.6-6% in patients with chronic pancreatitis 3-5% undergoing pancreatic resection for suspected pancreatic cancer

Epidemiology Elderly Male

Extra-pancreatic manifestations Biliary strictures Sclerosing sialadenitis Retroperitoneal fibrosis Sclerosing cholecystitis Interstitial nephritis Diffuse lymphadenopathy Characteristic lymphoplasmacytic infiltrate rich in IgG4-positive cells Can precede/ accompany / follow pancreatic involvement

Clinical presentation Painless obstructive jaundice (65%) Vague abdominal pain Weight loss Exocrine insufficiency (88%) Endocrine dysfunction (67%)

Laboratory findings Amylase/ lipase: normal/ mildly elevated Gamma globulin, total IgG, IgG4 Commonly elevated Serum IgG4 : 140 mg/dl: Sensitivity 76%; Specificity 93% 280 mg/dl: Sensitivity 53%; Specificity 99% Elevated in 7-10% cases of Pancreatic CA (usually mild) Autoantibodies ANA, RF: elevated (non-specific)

Radiological CT/ MRI: Diffuse enlargement of the entire pancreas ‘sausage-like’ Low density capsule-like rim due to inflammation and fibrosis Delayed contrast enhancement

CT/ MRI Focally enlarged pancreas ‘inflammatory mass’

ERCP/ MRCP Diffuse narrowing of main pancreatic duct

ERCP/ MRCP Segmental narrowing of main pancreatic duct Biliary stricture ( can occur anywhere )

Differentiation IgG4 PancreatitisCA Pancreas Narrowing of MPD > 1/3 or > 3cm Pancreatic duct dilatation Skipped, narrow lesions of MPD Abrupt pancreatic duct cut- off Side branches from narrow portion of MPD Upstream pancreatic atrophy Stricture of intrahepatic ducts

EUS guided FNAC Detecting adenocarcinoma Sensitivity 70-90% Negative bx does not rule out CA Not for diagnosis of IgG4 pancreatitis Inadequate cells Lack of architecture

EUS guided core biopsy Allow diagnosis of IgG4 pancreatitis Technically difficult Increased risk of bleeding Not widely available

Biopsy of extra-pancreatic site Bile ducts, major duodenal papilla 80% pancreatic head involvement had IgG4-positive cells on biopsy of the major duodenal papilla

Response to steroid Dramatic

Response to steroid Radiographic response seen at 2-3 wks and normalization at 4-6 wks

Response to steroid Steroid trial controversial No response within 2 weeks makes IgG4 pancreatitis unlikely Failed response to steroid Prompt re-evaluation of diagnosis Consider surgery to look for cancer

Making the correct diagnosis is challenging Rare disease Mimic the more common pancreaticobiliary malignancy No single diagnostic test available Price of misdiagnosis is heavy Unnecessary surgery for benign disease Delay potentially curative surgery

Japanese Diagnostic Criteria 1. Imaging - Diffuse/ segmental narrowing of main pancreatic duct - Diffuse/ localized enlargement of pancreas 2. Serology - Elevated gamma-globulin, IgG or IgG4 OR - Presence of autoantibodies eg ANA/ RF 3. Histology - Lymphoplasmacytic sclerosing pancreatitis Diagnosis: 1 + 2/3

Take Home Message Increasing recognition Important diagnostic consideration in obstructive jaundice due to pancreatic mass lesion High index of suspicion Multidisciplinary collaboration Surgeons/GI physician/Radiologist/Pathologist

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