Rare bullous pemphigoid during PD-1 inhibitor therapy: a case report

1. Abstract Immunotherapy is an important treatment modality in cancer, but it can also cause adverse reactions, with skin toxicity being the most common. The increasing number of immune checkpoint inhibitors being used in the clinic will inevitably cause an increase in the rate of adverse skin reactions that markedly affect the patient’s quality of life. A 58-year-old patient with intrahepatic cholangiocarcinoma developed bullous pemphigoid (BP) nearly a year after using immune checkpoint inhibitors, which is different from what has been reported in the literature within two weeks of treatment. Pathologically, the skin biopsy diagnosis was epidermal hyperplasia and focal sub-epidermal pustule formation, consistent with drug-induced dermatitis. The patient was treated with methylprednisolone, minocycline, colchicine, nicotinamide, triamcinolone, and traditional Chinese medicine decoction. No new blisters developed after 1 week of treatment. The medication was gradually discontinued, and BP did not recur. Clinicians should carefully consider the risk-benefit ratio when using PD-1 inhibitors, particularly with respect to rash severity. Further studies are needed to investigate relationship between adverse skin reactions and drug efficacy. 2. Introduction Immune checkpoint inhibitors, such as anti-programmed cell death 1 (PD-1), can enhance the anti-tumor function of T cells and increase the activity of the immune system. However, normal tissues and organs can be affected by an overactive immune system, causing an immune-related adverse reaction [1,2]. Adverse skin reactions are the most common side effects of immune checkpoint inhibitor treatment. However, adverse skin reactions are completely atypical [3]. We report herein a case of uncommon features of adverse skin from immunotherapy treatment. The case is the first that we have experienced to present such features since using PD-1 inhibitor treatment. 3. Case presentation In May 2017, the patient underwent right hepatectomy + cholecystectomy due to liver lesions found on physical examination. Postoperative pathology revealed intrahepatic cholangiocarcinoma, moderately differentiated tumor measuring 8×5×5 cm, blood vessel invasion, and no obvious nerve invasion. Tegafur (1.5 mg days 1-14) oral chemotherapy was administered for six cycles after surgery. Magnetic resonance imaging (MRI) on September 2019 showed liver lesions, and recurrence was considered. However, the patient was ineligible for surgery; as such, seven cycles of oxaliplatin (150 mg day 1) + gemcitabine (1 g day 1) chemotherapy combined with lenvatinib targeted therapy and with toripalimab (240 mg day 1) immunotherapy was initiated. After tumor