Systemic Chemotherapy-Induced Secondary Sclerosing Cholangitis

Abstract

Introduction: Secondary sclerosing cholangitis (SSC) is a rare disease; the infrequency of its presentation poses a diagnostic challenge and highlights the importance of identifying causative factors. Typical causes of SSC include intraductal stones, surgical trauma, recurrent pancreatitis, and intra-hepatic chemotherapy. There have been no reported cases of systemic chemotherapy resulting in SSC. Methods: 64-year old woman presented to the hospital with a 2-week history of worsening right upper quadrant pain, jaundice and dark urine. She had a known diagnosis of stage 3A invasive ductal carcinoma of the left breast and had undergone modified radical mastectomy with lymph node dissection followed by four cycles of systemic chemotherapy with Adriamycin, Cytoxan followed by Paclitaxel. Her last day of chemotherapy was a month prior to presentation. Results: On admission, blood-work revealed elevated direct bilirubin of 8.0 mg/dL, alkaline phosphatase of 2,167 unit/L, AST 167 unit/L and ALT 150 unit/L with normal values three weeks prior. There was no evidence of underlying viral, metabolic or autoimmune liver disease. Ultrasonography and computed tomography revealed intrahepatic biliary ductal dilatation with mild prominence of common bile duct (CBD). An endoscopic retrograde cholangiopancreatography showed diffuse beading of the common hepatic and intrahepatic ducts with upstream ductal dilatation, consistent with sclerosing cholangitis. Endobrushings of CBD was negative for malignant cells and a liver biopsy demonstrated cholestatic hepatitis, cholangitis and evidence of biliary infarcts. She was diagnosed with sclerosing cholangitis secondary to ischemic cholangitis. She developed multiple complications throughout the hospital course, was deemed not a candidate for liver transplant and nonetheless was discharged in stable condition. Conclusion: The timeframe of the disease suggests a link with systemic chemotherapy received prior to presentation. Paclitaxel appeared to be the causal agent since the patient had previously tolerated four cycles of Adriamycin and Cytoxan. Ischemic cholangitis, a known cause of SSC can be induced by the anti-angiogenic properties of Paclitaxel, evidenced by biliary infarcts on liver biopsy. This case illustrates the potential for developing SSC in a previously normal liver with the use of Paclitaxel. To our knowledge, this is the first case reporting SSC as an adverse effect of a commonly used chemotherapy agent, Paclitaxel.Table 1: Liver function test 1 month prior to admission and on day of admissionFigure 1