Department of Dermatology, College of Medicine University of Florida, Gainesville, FL, USA.
Department of Biostatistics, Public Health and Health Professions and School of Medicine, University of Florida, Gainesville, FL, USA.
Exp Dermatol. 2020 Dec;29(12):1171-1175. doi: 10.1111/exd.14201. Epub 2020 Oct 15.
Atopic Dermatitis (AD) is characterized by skin barrier disruption and an aberrant immune response. Doxycycline is tetracycline antibiotics broadly used systemically to treat inflammatory dermatologic conditions. Several studies have shown doxycycline has anti-inflammatory and pro-healing properties, mainly by blocking tissue proteolytic activity. It is our hypothesis that daily application of a novel doxycycline topical formulation in AD subjects will reduce severity of the disease, by blocking cutaneous proteases activity and restoring skin barrier function and inflammation. To test this hypothesis, we performed a proof of concept, open-label clinical study. Subjects enrolled in the study (n = 15) applied NanoDOX Hydrogel 1% daily for 4 weeks on a chosen eczematous area. Investigational drug was well tolerated, and no local or systemic adverse events due to investigational drug were reported. Notably, a significant clinical improvement was observed based on a modified Eczema Area & Severity Index (EASI) score of the treated area from start of treatment to 14 and 28 days post-treatment (P < .001). A significant improvement of pruritus was also observed (P = .02). This proof of concept clinical trial is first to explore the impact of a non-systemic doxycycline treatment on AD patients. Our results provide evidence to investigate novel AD treatment strategies targeting cutaneous proteases activity.
特应性皮炎（AD）的特征是皮肤屏障破坏和异常免疫反应。多西环素是一种广泛用于全身治疗炎症性皮肤病的四环素抗生素。几项研究表明，多西环素有抗炎和促进愈合的特性，主要通过抑制组织蛋白水解活性。我们假设，在 AD 患者中每天应用一种新型的多西环素局部制剂将通过阻断皮肤蛋白酶活性以及恢复皮肤屏障功能和炎症来减轻疾病的严重程度。为了验证这一假设，我们进行了一项概念验证、开放性临床试验。入组本研究的受试者（n=15）在选定的湿疹区域每天应用 1%的 NanoDOX 水凝胶，持续 4 周。研究药物耐受性良好，未报告因研究药物引起的局部或全身不良事件。值得注意的是，根据治疗开始至治疗后 14 天和 28 天治疗区域改良的湿疹面积和严重程度指数（EASI）评分，观察到显著的临床改善（P<0.001）。瘙痒也明显改善（P=0.02）。这是第一项探索非系统性多西环素治疗对 AD 患者影响的概念验证临床试验。我们的结果为探索针对皮肤蛋白酶活性的新型 AD 治疗策略提供了证据。
