Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
J Am Acad Dermatol. 2018 Mar;78(3 Suppl 1):S43-S52. doi: 10.1016/j.jaad.2017.11.056. Epub 2017 Dec 15.
Historically, drugs available for treating atopic dermatitis (AD) have been limited to topical corticosteroids and topical calcineurin inhibitors, with systemic immunosuppressants and phototherapy reserved for severe AD. Despite their efficacy and infrequent adverse events, phobia about the use of topical steroids and calcineurin inhibitors has limited their use. More targeted options with fewer systemic and cutaneous side effects are needed for treating AD. Phosphodiesterase 4 (PDE4) is involved in the regulation of proinflammatory cytokines via the degradation of cyclic adenosine monophosphate. PDE4 activity is increased in the inflammatory cells of patients with AD, leading to increased production of proinflammatory cytokines and chemokines. Targeting PDE4 reduces the production of these proinflammatory mediators in AD. Both topical and oral PDE4 inhibitors have a favorable safety profile. Crisaborole 2% ointment, a topical PDE4, is now US Food and Drug Administration-approved for children older than 2 years and adults in the treatment of AD. Crisaborole 2% ointment shows early and sustained improvement in disease severity and pruritus and other AD symptoms, with burning and/or stinging upon application as the only related adverse event. Other PDE4 inhibitors are currently in trials with promising efficacy and safety.
从历史上看,治疗特应性皮炎 (AD) 的药物仅限于局部皮质类固醇和局部钙调神经磷酸酶抑制剂,而全身免疫抑制剂和光疗则保留用于严重 AD。尽管它们具有疗效且不良反应罕见,但对使用局部皮质类固醇和钙调神经磷酸酶抑制剂的恐惧限制了它们的使用。需要更有针对性的、全身性和皮肤副作用更少的选择来治疗 AD。磷酸二酯酶 4 (PDE4) 通过降解环磷酸腺苷参与调节促炎细胞因子。AD 患者的炎症细胞中 PDE4 活性增加,导致促炎细胞因子和趋化因子的产生增加。靶向 PDE4 可减少 AD 中这些促炎介质的产生。局部和口服 PDE4 抑制剂均具有良好的安全性。他克莫司 2%软膏,一种局部 PDE4,现已获得美国食品和药物管理局批准,用于 2 岁以上儿童和成人治疗 AD。他克莫司 2%软膏在疾病严重程度和瘙痒以及其他 AD 症状方面显示出早期和持续的改善,仅在应用时有灼热感和/或刺痛感等相关不良事件。其他 PDE4 抑制剂目前正在进行临床试验,具有良好的疗效和安全性。