Buquicchio Rosalba, Mastrandrea Valentina, Strippoli Sabino, Quaresmini Davide, Guida Michele, Filotico Raffaele
Dermato-Oncology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Tumori "Giovanni Paolo II", Bari, Italy.
Melanoma and Rare Tumors Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Tumori "Giovanni Paolo II", Bari, Italy.
Front Oncol. 2021 Aug 23;11:691980. doi: 10.3389/fonc.2021.691980. eCollection 2021.
Pemphigus vulgaris (PV) is a rare and severe autoimmune blistering disorder affecting the skin and mucous membranes, characterized by the production of autoantibodies against two desmosomal adhesion proteins, desmoglein 1 and 3. In patients with advanced squamous cell carcinoma of the skin unfit for surgery and radiotherapy, immune check-point inhibitors, including the anti-Programmed Death-1 (PD-1) agent cemiplimab have been successfully employed proving relevant clinical outcomes. Cemiplimab is a monoclonal antibody capable of inhibiting PD-1 signalling that has recently been approved for the treatment of patients with metastatic or locally advanced cutaneous squamous cell carcinoma. Although the peculiar setting of advanced CSCC involving elderly patients, rare and unusual skin immune-related adverse events such as PV could be observed in cemiplimab treated patients.
A 95-year-old man without a history of autoimmune disease was treated with cemiplimab for multiple and advanced squamous cell carcinomas of the head obtaining a complete response to therapy. After seven cycles of cemiplimab administered every 21 days, the patient developed a mucocutaneous blistering eruption. Clinical diagnosis of PV was suspected on the basis of the diffuse involvement of trunk and extremities with large blisters and necrotic eschar. It was carried out an ELISA test, that showed high level of circulating antibodies against desmoglein 1, thus confirming the diagnosis of PV. For this reason, cemiplimab infusion was discontinued and complete resolution of skin lesions was obtained using oral prednisone 0,8 mg/kg/daily for four weeks. Once remission was achieved, a maintenance dose of 10 mg/day was administered, observing a good control of bullous disease and low value of desmoglein 1. Response to CSCC persisted also during cemiplimab discontinuation, until obtaining a complete remission still persisting at 9 months after the last cycle of therapy.
The case we observed is the first description of PV revealed from cemiplimab therapy, thus suggesting that cemiplimab could allow the arise of underlying autoimmune PV, through a mechanism both T and B-cell-mediated.
寻常型天疱疮（PV）是一种罕见且严重的自身免疫性水疱病，累及皮肤和黏膜，其特征是产生针对两种桥粒黏附蛋白桥粒芯糖蛋白1和3的自身抗体。在不适合手术和放疗的晚期皮肤鳞状细胞癌患者中，免疫检查点抑制剂，包括抗程序性死亡蛋白1（PD-1）药物西米普利单抗已成功应用并取得了相关临床疗效。西米普利单抗是一种能够抑制PD-1信号传导的单克隆抗体，最近已被批准用于治疗转移性或局部晚期皮肤鳞状细胞癌患者。尽管晚期皮肤鳞状细胞癌的特殊情况涉及老年患者，但在接受西米普利单抗治疗的患者中可能会观察到罕见且不寻常的皮肤免疫相关不良事件，如PV。
一名95岁无自身免疫性疾病病史的男性因头部多发晚期鳞状细胞癌接受西米普利单抗治疗，治疗后获得完全缓解。每21天给予七个周期的西米普利单抗治疗后，患者出现了黏膜皮肤水疱疹。基于躯干和四肢广泛出现大疱和坏死焦痂，怀疑为PV临床诊断。进行了酶联免疫吸附测定（ELISA）试验，结果显示循环中抗桥粒芯糖蛋白1抗体水平很高，从而证实了PV的诊断。因此，停止了西米普利单抗输注，并使用每日0.8mg/kg的口服泼尼松治疗四周，皮肤病变完全消退。一旦实现缓解，给予10mg/天的维持剂量，观察到对大疱性疾病的良好控制以及桥粒芯糖蛋白1的低水平。在西米普利单抗停药期间，对皮肤鳞状细胞癌的反应持续存在，直到在最后一个治疗周期后9个月仍保持完全缓解。
我们观察到的病例是西米普利单抗治疗后出现PV的首例描述，因此表明西米普利单抗可能通过T细胞和B细胞介导的机制引发潜在的自身免疫性PV。
