Introduction: A 69-year-old Chinese woman with a history of pancreatitis, recurrent cholangitis, and allergic rhinitis presented with jaundice and epigastric pain. Labs were notable for cholestatic injury, thrombocytopenia, eosinophilia, and elevated IgE. Physical exam revealed enlarged, nontender submandibular glands. ERCP showed a stricture in the bifurcation affecting secondary and tertiary intrahepatic ducts. Stool and bile ova/parasites were negative and empiric praziquantel was ineffective. Bile duct biopsy showed chronic inflammatory infiltrate, no fibrosis, and 14 IgG4 plasma cells per high-powered field. Cytology was negative for malignancy. During a similar episode 7 months ago, serum IgG was elevated at 1890 mg/dL, with peak IgG4 of 134 mg/dL. After starting prednisone 40 mg daily, her labs normalized within 2-3 weeks. Repeat ERCP showed improvement of strictures and an 8-week follow-up MRI showed persistence of the right intrahepatic duct stricture with overall improvement in inflammation. She continues on a prednisone taper while taking 100 mg of daily azathioprine. According to adapted HISORt criteria and clinical diagnostic criteria of IgG4-SC 2012 by Ohara et al, a diagnosis of IgG4-sclerosing cholangitis is supported by 1) segmental stricture with pre-stenotic dilation, 2) bile duct wall thickening, 3) an average of >10 IgG4 positive plasma cells on histology, and 4) effective response to steroid therapy. High IgE levels and peripheral eosinophilia are seen in IgG4-related disease and concurrent thrombocytopenia has been reported. Due to the presence of eosinophilia and the patient’s background, chronic infection with Clonorchis or Opisthorchis species needed to be excluded. Negative testing, lack of response to praziquantel, and steroid response confirmed the absence of a parasitic infection. We entertained the possibility of primary sclerosing cholangitis (PSC) or cholangiocarcinoma (CC). However, steroid response is not expected in either entity. Eosinophilic cholangitis (EC) is possible, but less likely as prior cases described involved predominantly young men and included the presence of a dense eosinophilic infiltrate on biopsies. The diagnosis of isolated extrapancreatic biliary lesions as IgG4 sclerosing disease remains challenging due to an overlap of features with PSC, EC, Churg-Strauss syndrome, CC, and chronic parasitic biliary infections.Table 1