Differentiating IgG4-related Sclerosing Cholangitis from Primary Sclerosing Cholangitis: A Comprehensive Systematic Review and Meta-analysis of Diagnostic Features

INTRODUCTION: Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) and primary sclerosing cholangitis (PSC) are cholestatic disorders which may be difficult to differentiate. Importantly, PSC is an untreatable progressive fibroinflammatory disease, whereas IgG4-SC responds to immunosuppression if recognized in a timely manner. This systematic review and meta-analysis aimed to identify and define the performance of clinical, biochemical, radiographic, and histologic features to differentiate between these two diseases. METHODS: A systematic search for comparative studies of IgG4-SC and PSC through November 2023 (with repeat evaluation for interval literature in December 2024) was performed and data extraction performed in duplicate. Pooled proportions, odds ratios (OR), means, and standardized mean differences of pertinent diagnostic features were calculated using random-effects inverse-variance models. RESULTS: We identified thirty-eight studies comparing patients with IgG4-SC and PSC. IgG4-SC patients were more likely to have pancreatic disease (p <0.001) but less likely to have inflammatory bowel disease (p<0.001) than those with PSC. Serum IgG4 was significantly higher in IgG4-SC (p<0.001), as anticipated. Radiographically, IgG4-SC demonstrated long distal strictures (p=0.02) and symmetric ductal thickening (p<0.001), whereas PSC showed a beaded appearance (p=0.038). With the exception of IgG4 staining, histologic features including periductal fibrosis were similar between these entities, though sample size was limited for these features. DISCUSSION: Our meta-analysis shows that IgG4-SC and PSC present with similar clinical and radiographic features and possibly comparable histology. A history of unusual pancreatitis and elevated IgG4 (serum or tissue) prompt assessment for more specific radiographic features which if present warrant a therapeutic treatment trial.