S3464 Delayed Diagnosis Revisited: A Case of IgG4-Related Cholangitis Unmasked Over a Decade Later

Introduction: IgG4-related sclerosing cholangitis (IgG4-SC) is a chronic, immune-mediated fibroinflammatory condition that mimics malignancy and other hepatobiliary diseases. While treatable, its diagnosis is often delayed due to nonspecific presentations, normal serum IgG4 levels, or lack of targeted histologic staining. Here, we present a case of relapsing IgG-4 related cholangitis revealed over a decade later. Case Description/Methods: A 76-year-old man with a history of coronary artery disease, PAD, and type 2 diabetes mellitus presented with 1 week of jaundice and 1 month of pruritus. Labs on admission were remarkable for total bilirubin 6.4, alkaline phosphatase 550, ALT 184, and AST 158. Initial magnetic resonance cholangiopancreatography (MRCP) revealed minimal intrahepatic biliary dilation without choledocholithiasis. Due to worsening hyperbilirubinemia, a repeat MRCP was obtained which showed a 7 mm common bile duct (CBD) stricture with upstream dilation. Endoscopic retrograde cholangiopancreatography (ERCP) was then performed which confirmed a high-grade distal stricture, and he underwent sphincterotomy, dilation, brushing, and stent placement. Repeat ERCP 2 weeks later with SpyBite biopsy and stent exchange followed. While serum IgG4 was normal and initial pathology showed only inflammation, a second-opinion review identified an IgG4-positive plasma cell in the CBD biopsy. Further review uncovered a 2012 liver biopsy during a similar presentation—initially attributed to drug-induced liver injury—that stained positive for 33 IgG4-positive plasma cells per high-power field. This led to a diagnosis of relapsing IgG4-SC. The patient was started on prednisone and azathioprine with resolution of jaundice and pruritus. Discussion: This case highlights the diagnostic complexity of IgG4-SC, especially when serum IgG4 is normal and histology is subtle. A decade-long gap between initial symptoms and definitive diagnosis reflects how easily the disease can be missed without IgG4-specific staining. The critical role of pathology review and retrospective biopsy analysis was central to confirming the diagnosis. IgG4-SC should be considered in cases of idiopathic cholangitis, especially with relapsing LFT elevations and strictures without malignancy. Clinicians must maintain high suspicion and seek histopathologic confirmation early, as prompt steroid therapy can significantly alter the disease course and avoid unnecessary interventions.