Calabrese Laura, D'Onghia Martina, Lazzeri Laura, Rubegni Giovanni, Cinotti Elisa
Dermatology Unit, Department of Medical, Surgical and Neurological Sciences, University of Siena, 53100 Siena, Italy.
Institute of Dermatology, Catholic University of the Sacred Heart, 00168 Rome, Italy.
J Pers Med. 2024 Jul 22;14(7):775. doi: 10.3390/jpm14070775.
Atopic dermatitis (AD) is an immune-mediated skin disorder with a chronic-relapsing course and a multifactorial pathogenesis. In contrast to the traditional concept of AD as solely a type 2 immune-activated disease, new findings highlight the disease as highly heterogeneous, as it can be classified into variable phenotypes based on clinical/epidemiological or molecular parameters. For many years, the only therapeutic option for moderate-severe AD was traditional immunosuppressive drugs. Recently, the area of systemic therapy of AD has significantly flourished, and many new substances are now marketed, licensed, or in the last step of clinical development. Biological agents and small molecules have enriched the therapeutic armamentarium of moderate-to-severe AD, such as dupilumab, tralokinumab, lebrikizumab (monoclonal antibodies targeting the IL-4/13 pathway), abrocitinib, upadacitinib, and baricitinib (JAK inhibitors). Indeed, the AD treatment paradigm is now split into two main approaches: targeting the IL-4/13 axis or the JAK/STAT pathway. Both approaches are valid and have strong evidence of preclinical and clinical efficacy. Therefore, the choice between the two can often be difficult and represents a major challenge for dermatologists. Indeed, several important factors must be taken into account, such as the heterogeneity of AD and its classification in phenotypes, patients' comorbidities, age, and personal preferences. The aim of our review is to provide an overview of the clinical and molecular heterogeneities of AD and to explore the factors and parameters that, in clinical practice, may help inform clinical decision-making.
特应性皮炎（AD）是一种免疫介导的皮肤疾病，病程呈慢性复发，发病机制具有多因素性。与传统观念中AD仅仅是一种2型免疫激活疾病不同，新的研究结果表明该疾病具有高度异质性，因为根据临床/流行病学或分子参数，它可被分为不同的表型。多年来，中度至重度AD的唯一治疗选择是传统免疫抑制药物。最近，AD的全身治疗领域显著发展，许多新物质现已上市、获得许可或处于临床开发的最后阶段。生物制剂和小分子丰富了中度至重度AD的治疗手段，如度普利尤单抗、曲罗替尼单抗、乐必妥单抗（靶向IL-4/13途径的单克隆抗体）、阿布昔替尼、乌帕替尼和巴瑞替尼（JAK抑制剂）。事实上，AD治疗模式现在分为两种主要方法：靶向IL-4/13轴或JAK/STAT途径。这两种方法都是有效的，并且有临床前和临床疗效的有力证据。因此，在两者之间做出选择往往很困难，对皮肤科医生来说是一项重大挑战。确实，必须考虑几个重要因素，如AD的异质性及其在表型中的分类、患者的合并症、年龄和个人偏好。我们综述的目的是概述AD的临床和分子异质性，并探讨在临床实践中可能有助于指导临床决策的因素和参数。
