Murata Junko, Abe Riichiro, Shimizu Hiroshi
Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
J Allergy Clin Immunol. 2008 Nov;122(5):992-1000. doi: 10.1016/j.jaci.2008.06.013. Epub 2008 Aug 9.
It is difficult to distinguish the early phase of Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) from other ordinary types of drug-induced skin reactions (ODSRs). Levels of several serum soluble factors, including soluble Fas ligand (sFasL), have been reported to be increased in patients with SJS/TEN; however, the marker to predict the onset of SJS/TEN before the development of skin detachment or mucosal lesions has not been identified.
We sought to determine whether sFasL might be a useful marker in the early stages of SJS/TEN.
Sera of 19 patients with SJS and 16 patients with TEN at 1 or multiple time points were obtained from Japanese multiple hospitals. The disease onset (day 1) was defined when erosion/ulceration of the mucocutaneous or ocular lesion first developed. For the investigation of soluble factors, including sFasL, TNF-alpha, IFN-gamma, IL-6, and sCD40 ligand, we used ELISAs and Cytometric Bead Arrays.
Before disease onset (day -4 to approximately -2), 7 samples were available, and we detected the highest concentrations of sFasL in 5 (71.4%) of 7 patients. Increased sFasL levels decreased rapidly within 5 days of disease onset. In all 32 patients with ODSRs and 33 healthy control subjects, no increase of sFasL levels was detected. Other soluble factor concentrations did not show significant difference with those seen in patients with SJS/TEN before disease onset and ODSRs.
The sFasL levels of sera in patients with SJS/TEN are significantly increased before development of skin detachment, mucosal lesions, or both.
史蒂文斯-约翰逊综合征（SJS）/中毒性表皮坏死松解症（TEN）的早期阶段很难与其他普通类型的药物性皮肤反应（ODSRs）相区分。据报道，包括可溶性Fas配体（sFasL）在内的几种血清可溶性因子水平在SJS/TEN患者中升高；然而，尚未确定在皮肤脱屑或黏膜病变出现之前预测SJS/TEN发病的标志物。
我们试图确定sFasL是否可能是SJS/TEN早期阶段的有用标志物。
从日本多家医院获取了19例SJS患者和16例TEN患者在1个或多个时间点的血清。当黏膜皮肤或眼部病变首次出现糜烂/溃疡时定义为疾病发作（第1天）。为了研究包括sFasL、肿瘤坏死因子-α（TNF-α）、干扰素-γ（IFN-γ）、白细胞介素-6（IL-6）和可溶性CD40配体在内的可溶性因子，我们使用了酶联免疫吸附测定（ELISA）和细胞计数微球阵列。
在疾病发作前（第-4天至约-2天），有7份样本可用，我们在7例患者中的5例（71.4%）检测到sFasL的最高浓度。疾病发作后5天内，sFasL水平迅速下降。在所有32例ODSRs患者和33例健康对照者中，未检测到sFasL水平升高。其他可溶性因子浓度与SJS/TEN患者疾病发作前和ODSRs患者相比无显著差异。
SJS/TEN患者血清中的sFasL水平在皮肤脱屑、黏膜病变或两者出现之前显著升高。
