S3348 The Yellow Herring: IgG4-SC Disguised as Malignancy

Introduction: IgG4-related sclerosing cholangitis (IgG4-SC) is a rare autoimmune disorder that can clinically mimic primary sclerosing cholangitis (PSC) or cholangiocarcinoma, posing a diagnostic challenge. Distinguishing IgG4-SC is critical, given its favorable response to corticosteroids and markedly different prognosis. Case Description/Methods: An 85-year-old woman presented with 2 weeks of progressive painless jaundice, dark urine, pale stools, pruritus, and profound fatigue. On exam, she was visibly jaundiced with scleral icterus. Labs revealed a cholestatic pattern: ALP 425 U/L, total bilirubin 11.3 mg/dL (direct 8.7), AST 89, ALT 48, and INR 1.1. Computed tomography imaging demonstrated hepatic steatosis without focal lesions. Magnetic resonance cholangiopancreatography (MRCP) showed no obstructive lesion but revealed periportal fibrosis and diffuse biliary ductal wall edema. Given the absence of clear obstruction, autoimmune and infectious workup was initiated. ANA, AMA, ASMA, and viral hepatitis panels were negative. Alpha-1 antitrypsin was 80 mg/dL (heterozygous phenotype), and AFP was mildly elevated at 7 ng/mL. Notably, IgG4 levels were elevated at 435 mg/dL. Endoscopic ultrasound revealed a non-dilated biliary tree with no masses or stones. Liver biopsy was initially equivocal showing stage 1 portal/periportal fibrosis, acute cholangitis, ductular proliferation, and hepatocellular cholestasis, raising concern for early PSC or obstructive pathology. However, a second biopsy demonstrated bile duct injury, neutrophilic cholangitis, and a dense infiltrate rich in plasma cells, suggestive of IgG4-related cholangitis. The patient was started on prednisone 40 mg daily with marked improvement in bilirubin and ALP within 3 weeks. Naltrexone was used for symptomatic relief of pruritus with moderate success. Follow-up IgG4 levels showed a downward trend, and imaging at 6 weeks revealed resolution of ductal edema. Discussion: This case shows the diagnostic difficulty in distinguishing IgG4-SC from other hepatobiliary pathologies in patients presenting with obstructive jaundice. Initial imaging and histology may be misleading, especially in the absence of classic autoimmune markers. The elevated IgG4 level and steroid responsiveness were pivotal in confirming the diagnosis. Early recognition is essential, as untreated IgG4-SC can progress to irreversible fibrosis, while appropriate immunosuppressive therapy can lead to remission. Clinicians must keep a high index of suspicion for IgG4-SC in atypical presentations of cholestasis, when initial evaluations are inconclusive.