Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.
Laboratory for Investigative Dermatology, Rockefeller University, New York, NY; Department of Dermatology and the Laboratory for Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, NY.
J Allergy Clin Immunol. 2016 Jul;138(1):169-178. doi: 10.1016/j.jaci.2015.12.1323. Epub 2016 Mar 2.
Topical glucocorticosteroids are considered an efficient treatment option for atopic dermatitis (AD), but a global assessment of glucocorticosteroid responses on key disease circuits upon weeks to months of treatment is currently lacking.
We sought to assess short (4 weeks) and long-term (16 weeks) application of topical glucocorticosteroids on AD skin and define response biomarkers.
The effects of triamcinolone acetonide cream 0.025% were assessed based on gene expression and immunohistochemistry studies at baseline, 4 weeks, and 16 weeks in biopsy specimens from 15 patients with moderate-to-severe AD.
At 16 weeks, only 3 patients were clinical responders (by using SCORAD50 criteria), but 6 patients qualified as responders based on histologic criteria. Baseline characteristics indicated more severe disease in nonresponders. While 3 of 15 patients experienced only transient benefit after 4 weeks, others showed progressive improvements toward 16 weeks. Topical glucocorticosteroid use in patients with AD resulted in improvements of the AD genomic signature of 25.6% at 4 weeks and 71.8% at 16 weeks, respectively, and even 123.9% in the histologic responder group. Cytokines (IL-12p40, IL-13, IL-22, CCL17, CCL18, peptidase inhibitor 3 [PI3]/elafin, and S100As) showed consistent decreases from baseline toward 16 weeks with corresponding improvements in epidermal disease hallmarks (keratin 16 and loricrin) in lesional skin from responders (P < .05). Nonresponders largely showed lesser/nonsignificant reductions in key inflammatory and barrier markers (keratin 16, IL-13, IL-22, CCL17, CCL18, PI3/elafin, S100As, and loricrin). The combination of IL-21 and IFN-γ baseline expression closely predicted individual clinical glucocorticosteroid responses at 16 weeks of treatment.
Our study indicates that even low-potency glucocorticosteroids can broadly affect immune and barrier responses in patients with moderate-to-severe AD, associating higher baseline severity with increased steroid resistance in patients with AD.
局部糖皮质激素被认为是特应性皮炎（AD）的有效治疗选择，但目前缺乏对治疗数周到数月后关键疾病回路中糖皮质激素反应的全球评估。
我们旨在评估短期（4 周）和长期（16 周）应用局部糖皮质激素对 AD 皮肤的影响，并定义反应生物标志物。
根据 15 例中重度 AD 患者的活检标本在基线、4 周和 16 周时的基因表达和免疫组织化学研究，评估曲安奈德丙酮缩醇乳膏 0.025%的效果。
在 16 周时，只有 3 名患者（根据 SCORAD50 标准）为临床应答者，但根据组织学标准，有 6 名患者为应答者。无应答者的基线特征表明疾病更严重。虽然 15 例患者中有 3 例在 4 周后仅获得短暂缓解，但其他患者在 16 周时逐渐改善。AD 患者使用局部糖皮质激素可使 AD 基因组特征分别在 4 周时改善 25.6%，16 周时改善 71.8%，甚至在组织学应答者组中改善 123.9%。细胞因子（IL-12p40、IL-13、IL-22、CCL17、CCL18、肽酶抑制剂 3[PI3]/elafin 和 S100As）从基线开始持续下降，与应答者病变皮肤中表皮疾病标志（角质蛋白 16 和桥粒芯糖蛋白）的相应改善一致（P <.05）。无应答者主要表现为关键炎症和屏障标志物（角质蛋白 16、IL-13、IL-22、CCL17、CCL18、PI3/elafin、S100As 和桥粒芯糖蛋白）的减少幅度较小/无显著减少。IL-21 和 IFN-γ 的基线表达联合可很好地预测治疗 16 周时个体临床糖皮质激素反应。
我们的研究表明，即使是低效糖皮质激素也可以广泛影响中重度 AD 患者的免疫和屏障反应，AD 患者基线严重程度较高与糖皮质激素抵抗增加相关。
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