Rambhia Pooja H, Honda Kord, Arbesman Joshua
Department of Dermatology, University Hospitals Cleveland Medical Center.
Department of Dermatology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Melanoma Res. 2018 Oct;28(5):475-477. doi: 10.1097/CMR.0000000000000477.
Immune checkpoint inhibitors targeting the programmed cell death (PD)-1 receptor have dramatically changed the landscape of metastatic melanoma treatment. Nevertheless, these immuno-modulatory agents have associated side effects, including dermatologic manifestations. To this end, we report a patient with metastatic melanoma that was treated with a PD-1 inhibitor, and subsequently developed inflammation of existing seborrheic keratosis lesions and new verrucous keratoses, a cutaneous side effect that has not been previously reported to our knowledge. The etiology of seborrheic and verrucous keratoses is not well understood, although their physical and histopathologic similarities to chronic viral-derived lesions, such as human papilloma virus, suggest a potential viral association. Chronic viral infections are known to result in T-cell tolerance because of persistent antigen stimulation. PD-1 inhibition is able to reinvigorate exhausted T cells, which are accordingly able to decrease viral load. Thus, the inflammatory reaction, seen in our patient, may be the result of PD-1 inhibition reactivating virally driven T lymphocytes.
靶向程序性细胞死亡(PD)-1受体的免疫检查点抑制剂极大地改变了转移性黑色素瘤的治疗格局。然而,这些免疫调节药物存在相关副作用,包括皮肤表现。为此,我们报告了一名转移性黑色素瘤患者,该患者接受了PD-1抑制剂治疗,随后出现了现有的脂溢性角化病病变炎症和新的疣状角化病,据我们所知,这种皮肤副作用此前尚未有报道。脂溢性和疣状角化病的病因尚不完全清楚,尽管它们在物理和组织病理学上与慢性病毒源性病变(如人乳头瘤病毒)相似,提示可能与病毒有关。已知慢性病毒感染会由于持续的抗原刺激导致T细胞耐受。PD-1抑制能够使耗竭的T细胞恢复活力,从而能够降低病毒载量。因此,在我们的患者中观察到的炎症反应可能是PD-1抑制重新激活病毒驱动的T淋巴细胞的结果。