Immune checkpoint inhibitors (ICIs) are increasingly being used for various indications in cancer. However, because they affect the immune system, their use may lead to immune-related adverse events (IRAEs). The use of nivolumab is associated with the IRAE cholangitis, which has no established countermeasures [1]. The cholangioscopic findings of cholangitis are nonspecific and include erosion, ulceration, and hemorrhage [2]
[3]. We report a case of cholangitis showing circular folds on cholangioscopy.
A 68-year-old woman developed fever and elevated hepatobiliary enzymes 2 months after starting pembrolizumab treatment for lung cancer. Computed tomography and endoscopic ultrasonography showed dilation and diffuse thickening of the common bile duct (CBD) ([Fig. 1]). Magnetic resonance cholangiography showed CBD dilation without intrahepatic bile duct dilation ([Fig. 2]). Cholangiography showed dilation and shaggy appearance of the CBD ([Fig. 3]). Cholangioscopy revealed red, edematous circular folds with hemispherical protuberances in the CBD ([Video 1]). The pathological analysis of the CBD indicated lymphocytic and eosinophilic infiltration below the bile duct epithelium. CD4+ and CD8+ lymphocytes were seen in similar frequencies ([Fig. 4]). She was diagnosed with cholangitis and treated with 0.8 mg/kg/day prednisolone on day 15 after symptom onset. Thereafter, the fever and elevated hepatobiliary enzymes rapidly improved.
Fig. 1 Imaging studies showed dilation and diffuse thickening of the common bile duct (arrows). a, b Computed tomography. c Endoscopic ultrasonography.
Fig. 2 Magnetic resonance cholangiography showed dilation of the common bile duct without dilation of the intrahepatic bile duct.
Fig. 3 Cholangiography showed dilation and shaggy image of the common bile duct.
Fig. 4 Pathological findings of the common bile duct. a Chronic active inflammatory cells such as a lymphocytes, acidophiles, neutrophils in the stroma right under the epithelium were revealed with hematoxylin and eosin staining. CD4+ cells (b) and CD8+ cells (c) were seen in similar frequencies.
Notably, cholangitis may be confused with ICI-related liver injury, making diagnosis difficult based on imaging findings alone. In our patient, cholangioscopy indicated edematous circular folds of the CBD mucous membrane, and cholangiography revealed a shaggy CBD wall. Bile duct wall thickening suggests abnormal lymphocytic infiltration. In patients who develop bile duct dilation with thickness on computed tomography and/or endoscopic ultrasonography after ICI treatment, cholangioscopy with biopsy and CD4/8 staining may be helpful for the early diagnosis of cholangitis.
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Video 1 Cholangioscopy showed edematous circular folds with redness and hemispherical protuberance on the common bile duct.
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