A rare case of immunotherapy-induced cholangitis and gastritis
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CASE REPORT
A rare case of immunotherapy‑induced cholangitis and gastritis Masakuni Fujii1 · Toshiki Ozato1 · Sho Mizukawa1 · Junichiro Nasu1 · Haruyuki Kawai1 · Shin‑ichi Fujioka1 · Masao Yoshioka1 · Junji Shiode1 · Kazuhide Yamamoto1 Received: 2 April 2020 / Accepted: 26 August 2020 © Japanese Society of Gastroenterology 2020
Abstract Immune checkpoint inhibitor-related liver injury usually appears as a hepatitis pattern, with a cholangitis pattern being a rare immune-related adverse event. We report a Japanese man in his fifties with immune checkpoint inhibitor–induced cholangitis and gastritis. The patient had been treated for approximately 7 months with carboplatin, pemetrexed sodium hydrate, and bevacizumab for an undifferentiated cancer of unknown primary, with metastases to the right pleura and nasolacrimal duct. The patient was then treated with immune checkpoint inhibitors, including 2 months of atezolizumab followed by 1 month of ramucirumab and docetaxel. Laboratory examinations showed elevated levels of biliary tract enzymes. He complained of generalized fatigue. Computed tomography revealed thickening of the gallbladder and external hepatic bile duct walls and the periportal collar sign. Endoscopic retrograde cholangiopancreatography was negative for bile duct obstruction but showed diffuse asymmetric irregular findings from the hilar region to the distal bile duct. Upper endoscopy showed diffuse irregular erosions and redness. Histopathological examination of specimens of bile duct and gastric mucosa revealed CD8predominant inflammatory cell infiltrates. We diagnosed the findings as immunotherapy-induced cholangitis and gastritis. Because there are no published reports on immunotherapyinduced cholangitis combined with gastritis, we here report our patient as a rare case. Keywords Immune-related adverse event · Immunotherapy-induced cholangitis · Immunotherapy-induced gastritis
Introduction Checkpoint inhibitors including nivolumab and atezolizumab inhibit the interaction between the programmed cell death-1 (PD-1) receptor and its ligands (PD-L1 and PD-L2) and restore antitumor immunity [1–3]. Based on evidence of their antitumor effects, immune checkpoint inhibitors have been approved for the treatment of various advanced malignancies such as melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), squamous cell carcinoma of the head and neck, Hodgkin lymphoma, and gastric cancer [4–9]. However, specific immune-related adverse events (irAEs) caused by dysregulation of the host immune system occasionally occur during treatment [3, 10].
* Masakuni Fujii [email protected] 1
Department of Internal Medicine, Okayama Saiseikai General Hospital, 2‑25 Kokutai‑cho Kita‑ku, Okayama‑City 700‑ 8511, Japan
IrAEs are sometimes serious; therefore, their management is extremely important. Nivolumab is an immune checkpoint antibody inhibitor of the PD-1 receptor. Nivolumab-induced cholangitis has been reported in only 10 of 18,562 patients (0.05%) [3, 11]. In addition, there are no repor
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