[Phosphodiesterase 4 inhibitors in dermatology : Role in the treatment of skin diseases].

Dermatologie (Heidelberg, Germany) Pub Date : 2024-10-01 Epub Date: 2024-08-30 DOI:10.1007/s00105-024-05407-7
Morna F Schmidt, Nicole Albuscheit, Amir S Yazdi
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Abstract

Background: Chronic inflammatory skin diseases are of great social and medical importance and require effective drug therapy. Phosphodiesterase 4 (PDE4) inhibitors represent a possible therapeutic option by regulating inflammatory processes. PDEs cause the release of proinflammatory cytokines by interfering with signaling pathways. The PDE4 inhibitors apremilast (treatment of psoriasis and Behçet's disease), roflumilast (treatment of chronic obstructive pulmonary disease), and crisaborole (treatment of atopic dermatitis) are currently approved in Europe.

Psoriasis: Apremilast is used for second-line treatment of plaque psoriasis and psoriatic arthritis and has a favorable side effect profile. Topical PDE4 inhibitors are currently being researched and have not yet been approved by the European Medicines Agency (EMA).

Atopic dermatitis: The topical PDE4 inhibitor crisaborole was approved by the EMA in 2020 as a topical treatment alternative to glucocorticoids and calcineurin inhibitors. Although the substance has shown good tolerability in studies and also alleviates the accompanying itching, it did not find its way onto the German market. BEHçET'S DISEASE: Apremilast is approved for the treatment of Behçet's disease in adults with refractory, severe oral ulcers.

Outlook: Case studies have also demonstrated the efficacy of systemic PDE4 inhibition in other skin diseases (including blistering autoimmune dermatoses, lichen planus, and acantholytic genodermatoses). The substances are also being researched and used to treat extracutaneous inflammatory diseases.

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[皮肤病学中的磷酸二酯酶 4 抑制剂:在治疗皮肤病中的作用]。
背景:慢性炎症性皮肤病具有重要的社会和医疗意义,需要有效的药物治疗。磷酸二酯酶 4 (PDE4) 抑制剂通过调节炎症过程成为一种可能的治疗选择。磷酸二酯酶通过干扰信号通路导致促炎细胞因子的释放。PDE4 抑制剂阿普司特(治疗银屑病和白塞氏病)、罗氟司特(治疗慢性阻塞性肺病)和 crisaborole(治疗特应性皮炎)目前已在欧洲获得批准:银屑病:阿普仑司特用于斑块状银屑病和银屑病关节炎的二线治疗,具有良好的副作用。外用 PDE4 抑制剂目前正在研究中,尚未获得欧洲药品管理局 (EMA) 批准:外用 PDE4 抑制剂 crisaborole 于 2020 年获得 EMA 批准,可作为糖皮质激素和降钙素抑制剂的外用治疗替代药物。尽管该药物在研究中显示出良好的耐受性,并能减轻伴随的瘙痒,但它并未进入德国市场。贝赫切特氏病:阿普司特被批准用于治疗患有难治性严重口腔溃疡的成人贝赫切特氏病:病例研究也证明了全身性 PDE4 抑制剂对其他皮肤病(包括大疱性自身免疫性皮肤病、扁平苔藓和棘层溶解性遗传性皮肤病)的疗效。目前还在研究将这些物质用于治疗皮肤外炎症性疾病。
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