S1506 IgG4-Related Sclerosing Cholangitis: An Important Diagnostic Consideration for Painless Jaundice

Abstract

Introduction: Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) is the biliary manifestation of IgG4-related disease, an immune-mediated fibroinflammatory condition affecting multiple organs. Histopathology reveals lymphoplasmacytic infiltrate with dense IgG4-positive plasma cells and varying degrees of fibrosis. IgG4-SC is characterized by mass lesions and/or biliary strictures and often occurs concurrently with type 1 autoimmune pancreatitis. The differential diagnosis between primary sclerosing cholangitis (PSC), and IgG4-SC is challenging due to similar clinical and imaging characteristics, leading to treatment delay, and irreversible end organ damage. Case Description/Methods: A 62-year-old man presented with 10 days of painless jaundice, light colored stools, pruritus, and 10 kg weight loss over six months. The patient had diabetes and 20 pack-year smoking history. Exam showed jaundice and scleral icterus. The abdomen was soft with no hepatosplenomegaly. Laboratory studies were significant for ALT 449 U/L, AST 302 U/L, total bilirubin 20.4 mg/dL, ALP 989 U/L, CA-19-9 2,302 U/mL, and normal pancreatic enzymes. CT abdomen and MRCP revealed dilated intrahepatic bile ducts with no masses, and cystic changes of the pancreas with chronic calcifications. ERCP revealed hilar stricture and downstream dilatation of intrahepatic ducts. Biliary brushings showed no tumor cells. Subsequent ERCPs showed diffuse beading and structuring in the bile ducts. Liver transplant evaluation was considered for presumed PSC with concerns for cholangiocarcinoma. Further workup showed an elevated total IgG level of 2,701 mg/dL and IgG-4 level of 1,160 mg/dL. The diagnosis of IgG4-SC was established. Treatment was initiated with high dose steroids, gradually tapered down, and azathioprine to prevent disease recurrence. Patient had excellent biochemical response with normalization of liver enzymes and Ca 19-9 and biliary stricture resolution on follow up ERCP. Discussion: IgG4-SC poses a diagnostic challenge for clinicians. Total IgG and IgG4 should be obtained after ruling out common causes of obstructive jaundice. Although the presentation of IgG4-SC and PSC is similar, treatment response and outcomes differ significantly, and it is essential to establish an accurate diagnosis. Elevated IgG4 exceeding 135 mg/dL is the generally accepted cutoff. Prompt recognition of IgG4-SC is crucial as the condition is responsive to steroids with excellent outcomes.Figure 1.: ERCP showing diffuse proximal intrahepatic bile duct dilation with sparing of imaging at the hilum due to IgG4 related tactile stricturing.