Cholangioscopic appearance of circular folds in immune-related adverse event cholangitis

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.

Endoscopy_UCTN_Code_CCL_1AZ_2AZ

Video 1 Cholangioscopy showed edematous circular folds with redness and hemispherical protuberance on the common bile duct.

Competing interests

The authors declare that they have no conflict of interest.

• References

• 1 Kawakami H, Tanizaki J, Tanaka K. et al. Imaging and clinicopathological features of nivolumab-related cholangitis in patients with non-small cell lung cancer. Invest New Drugs 2017; 35: 529-536
• 2 Kuraoka N, Hara K, Terai S. et al. Peroral cholangioscopy of nivolumab-related (induced) ulcerative cholangitis in a patient with non-small cell lung cancer. Endoscopy 2018; 50: E259-E261
• 3 Hashimoto Y, Kumahara K, Ueda Y. et al. Cholangioscopic finding of severe hemorrhagic cholangitis associated with immune-related adverse events. Gastrointest Endosc 2021; 94: 859-860

Publication History

Article published online:
10 March 2022