Sugawara Arisa, Koga Hiroshi, Abe Toshifumi, Ishii Norito, Nakama Takekuni
Department of Dermatology, Kurume University School of Medicine, Fukuoka, Japan.
Department of Dermatology, St. Mary's Hospital, Fukuoka, Japan.
J Dermatol. 2021 Mar;48(3):401-404. doi: 10.1111/1346-8138.15693. Epub 2020 Nov 12.
Immune checkpoint inhibitors including programmed cell death protein 1 (PD-1) antibody are used in major breakthrough therapies in cancer, however they cause unique adverse events, termed immune-related adverse events (irAEs). Among the various dermatological irAEs, an autoimmune bullous disease, bullous pemphigoid (BP), the hallmarks of which are circulating autoantibodies to epidermal basement membrane zone (BMZ) including BP180, have been noted. However, the mechanism and timing of autoantibody production in PD-1 inhibition remains unclear. Herein we report the case of a lichen planus (LP)-like lesion in presence of anti-BMZ antibodies, preceding BP in a patient treated with pembrolizumab, a PD-1 antibody. A 72-year-old Japanese woman with a 3-month history (6 cycles) of pembrolizumab was referred to our department for pruritic purple-red papules or plaques. Histological finding revealed LP-like dermatitis. Although pembrolizumab was stopped because of disease progression, she developed edematous erythematous lesions and tense blisters seven weeks later. Based on histopathological findings, direct immunofluorescence (DIF) assay and positive findings on chemiluminescent enzyme immunoassay (CLEIA) for BP180, she was diagnosed with BP and administered oral prednisolone. The blisters and erythemas improved, whereas her respiratory condition worsened and she died 29 days after the development of BP. We performed DIF of formalin-fixed, paraffin-embedded specimens biopsied from the LP-like lesion and revealed IgG deposition at the epidermal BMZ. This finding showed anti-BMZ antibodies had already existed at LP-like lesion preceding development of BP; this suggests that the preceding LP-like lesion induced anti-BMZ antibody production, resulting in the development of BP.
包括程序性细胞死亡蛋白1（PD-1）抗体在内的免疫检查点抑制剂被用于癌症的重大突破性治疗中，然而它们会引发独特的不良事件，即免疫相关不良事件（irAEs）。在各种皮肤免疫相关不良事件中，一种自身免疫性大疱性疾病——大疱性类天疱疮（BP）已被注意到，其特征是存在针对包括BP180在内的表皮基底膜带（BMZ）的循环自身抗体。然而，PD-1抑制过程中自身抗体产生的机制和时间仍不清楚。在此，我们报告一例在用PD-1抗体帕博利珠单抗治疗的患者中，在BP出现之前，存在抗BMZ抗体的扁平苔藓（LP）样病变的病例。一名72岁的日本女性，有3个月（6个周期）帕博利珠单抗治疗史，因瘙痒性紫红色丘疹或斑块被转诊至我科。组织学检查发现为LP样皮炎。尽管由于疾病进展停用了帕博利珠单抗，但7周后她出现了水肿性红斑病变和紧张性水疱。基于组织病理学检查结果、直接免疫荧光（DIF）检测以及BP180化学发光酶免疫分析（CLEIA）的阳性结果，她被诊断为BP，并接受了口服泼尼松龙治疗。水疱和红斑有所改善，然而她的呼吸状况恶化，在BP出现后29天死亡。我们对从LP样病变处活检的福尔马林固定、石蜡包埋标本进行了DIF检测，发现表皮BMZ处有IgG沉积。这一发现表明在BP发生之前，LP样病变处就已经存在抗BMZ抗体；这提示先前的LP样病变诱导了抗BMZ抗体的产生，从而导致了BP的发生。
