Jaber Samer H, Cowen Edward W, Haworth Leah R, Booher Susan L, Berman David M, Rosenberg Steven A, Hwang Sam T
Dermatology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-1908, USA.
Arch Dermatol. 2006 Feb;142(2):166-72. doi: 10.1001/archderm.142.2.166.
To describe the clinical and histologic manifestations of skin reactions incidentally noted in patients with stage IV melanoma who were treated with up to 9 mg/kg of a humanized monoclonal antibody reactive against human cytotoxic T-lymphocyte antigen 4 (anti-CTLA-4) as a single agent every 3 weeks.
Single-institution prospective study.
Patients treated with anti-CTLA-4 as a sole agent were prospectively referred for clinicopathologic characterization of skin reactions occurring during treatment.
Specific clinicopathologic features were determined by means of a detailed history, a physical examination, conventional histologic analysis, antibody staining, and complete blood cell counts.
Nine (14%) of 63 consecutive patients treated with anti-CTLA-4 as a sole agent developed skin eruptions that were attributed to anti-CTLA-4 in 8 of them. Skin lesions consisted primarily of discrete, pruritic, erythematous, minimally scaly papules that typically coalesced into thin plaques on the trunk and extensor surfaces of the extremities. Extensive alopecia was also noted in 1 patient. Histologically, a superficial, perivascular CD4+-predominant T-cell infiltrate with eosinophils in the dermis, rare dyskeratotic cells, and mild epidermal spongiosis were present. An increase (compared with pretreatment values) in the peripheral blood eosinophil frequency was observed in patients at the time of skin eruptions (P = .006).
Specific features of the skin eruption dermatitis with increased tissue and peripheral blood eosinophil levels in a subset of treated patients. Specific features of skin eruption associated with anti-CTLA-4 resemble those described for maculopapular reactions to medications.
描述接受高达9 mg/kg人源化抗人细胞毒性T淋巴细胞抗原4单克隆抗体（抗CTLA-4）治疗、每3周1次的IV期黑色素瘤患者偶然出现的皮肤反应的临床和组织学表现。
单机构前瞻性研究。
将接受抗CTLA-4单药治疗的患者前瞻性地转诊，以对治疗期间出现的皮肤反应进行临床病理特征分析。
通过详细病史、体格检查、传统组织学分析、抗体染色和全血细胞计数确定特定的临床病理特征。
63例连续接受抗CTLA-4单药治疗的患者中有9例（14%）出现皮疹，其中8例归因于抗CTLA-4。皮肤病变主要由离散的、瘙痒性、红斑性、轻度鳞屑性丘疹组成，这些丘疹通常在躯干和四肢伸侧融合成薄斑块。1例患者还出现广泛脱发。组织学上，真皮浅层血管周围以CD4+为主的T细胞浸润，伴有嗜酸性粒细胞，罕见角化异常细胞，轻度表皮海绵形成。在出现皮疹时，患者外周血嗜酸性粒细胞频率较治疗前增加（P = 0.006）。
部分接受治疗的患者出现皮疹性皮炎的特定特征，组织和外周血嗜酸性粒细胞水平升高。与抗CTLA-4相关的皮疹的特定特征类似于药物斑丘疹反应所描述的特征。
