Department of Dermatology, Royal North Shore Hospital, St Leonards, New South Wales, Australia.
School of Medicine, University of New South Wales, Sydney, New South Wales, Australia.
Australas J Dermatol. 2024 Sep;65(6):491-504. doi: 10.1111/ajd.14329. Epub 2024 Jun 3.
Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions characterised by keratinocyte apoptosis, necroptosis and epidermal detachment. Several cytokines and cytotoxic proteins have been shown to be elevated in the blood and skin of SJS/TEN sufferers and biologics such as intravenous immune globulin and tumour necrosis factor (TNF)-alpha inhibitors have demonstrated good therapeutic potential. The exact pathogenic model of SJS/TEN however remains elusive. This systematic review aimed to evaluate the case-control studies of cytokines and cytotoxic proteins in the blister fluid and skin of adults with Stevens Johnson syndrome and/or toxic epidermal necrolysis. This review was registered with INPLASY and conducted in accordance with the PRISMA reporting guidelines. Potential bias was assessed using the NIH criteria. Eleven articles describing results from 96 cases and 170 controls were included. Fas, Fas ligand, Interleukin (IL)-8 and B-cell lymphoma (Bcl)-2 were elevated in SJS/TEN blister fluid and skin tissue, compared with healthy controls. IL-2, IL-6, TNF-alpha, tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon-gamma and matrix metalloproteinase-2 were elevated in SJS/TEN blister fluid compared with fluid sampled from lesional controls. Granulysin, IL-33, TGF-beta-1 and IL-13 were elevated in SJS/TEN skin tissue compared with lesional lichen planus tissue, as was IL-13, IFN-gamma, IL-2 and IL-5, when compared with erythema multiforme tissue. A wide array of cytokines and cytotoxic proteins are present at higher concentrations in the blister fluid and skin tissue of SJS/TEN patients compared with healthy and lesional controls. Our findings suggest that these proteins may be pathogenic, as well as possibly markers for diagnosis, disease severity and course. They may also prove to be useful therapeutic targets. More research is needed.
史蒂文斯-约翰逊综合征（SJS）和中毒性表皮坏死松解症（TEN）是严重的皮肤不良反应，其特征为角质形成细胞凋亡、坏死性凋亡和表皮脱落。已经证明，SJS/TEN 患者的血液和皮肤中存在几种细胞因子和细胞毒性蛋白升高，静脉注射免疫球蛋白和肿瘤坏死因子（TNF）-α抑制剂等生物制剂已显示出良好的治疗潜力。然而，SJS/TEN 的确切发病机制仍不清楚。本系统评价旨在评估成人史蒂文斯-约翰逊综合征和/或中毒性表皮坏死松解症患者水疱液和皮肤中细胞因子和细胞毒性蛋白的病例对照研究。本综述在 INPLASY 注册，并按照 PRISMA 报告指南进行。使用 NIH 标准评估潜在偏倚。纳入了 11 篇描述 96 例病例和 170 例对照结果的文章。与健康对照组相比，Fas、Fas 配体、白细胞介素（IL）-8 和 B 细胞淋巴瘤（Bcl）-2 在 SJS/TEN 水疱液和皮肤组织中升高。与取自病变对照的液体相比，IL-2、IL-6、TNF-α、肿瘤坏死因子相关凋亡诱导配体（TRAIL）、干扰素-γ和基质金属蛋白酶-2 在 SJS/TEN 水疱液中升高。与病变扁平苔藓组织相比，粒细胞酶、IL-33、TGF-β-1 和 IL-13 在 SJS/TEN 皮肤组织中升高，与多形性红斑组织相比，IL-13、IFN-γ、IL-2 和 IL-5 也升高。与健康和病变对照相比，SJS/TEN 患者水疱液和皮肤组织中存在大量细胞因子和细胞毒性蛋白，浓度较高。我们的研究结果表明，这些蛋白可能是致病的，也可能是诊断、疾病严重程度和病程的标志物。它们也可能被证明是有用的治疗靶点。需要进一步研究。
