Centre Méditerranéen de Médecine Moléculaire (C3M), Université Côte d'Azur, Nice, France.
Department of Dermatology, CHU Nice, Université Côte d'Azur, Nice, France.
Exp Dermatol. 2022 Nov;31(11):1764-1778. doi: 10.1111/exd.14657. Epub 2022 Aug 19.
Psoriasis is a chronic inflammatory disease whereby long-term disease control remains a challenge for the patients. Latest evidence suggests that combined topical treatment with steroids and vitamin D analogue foam (Calcipotriol/Betamethasone) is efficient in long-term management of the disease and reducing the number of relapses. Its effects on cellular inflammation and cytokine production remain to be explored. We set out to examine the effect of topical therapies on cellular infiltrate and cytokine profile in the lesional skin of psoriasis patients. This was a monocentric, double-blind, randomized trial with 30 patients. Patients were treated with the combined Calcipotriol/Betamethasone foam, Betamethasone foam alone, Clobetasol Propionate ointment or placebo. 4 mm skin biopsies from lesional and non-lesional sites were taken before and 4 weeks after treatment. Cellular infiltrate, IFNγ and IL-17 were studied by immunofluorescence. Each patient was their own control. Evolution in skin inflammation was studied in parallel with changes in patient's epidermal thickness and their tPASI clinical score. Lesional skin was characterized by increased epidermal thickness, increased number of IL-17 and IFNγ producing CD8+ T cells, NK cells and neutrophils. All treatment reduced epidermal thickness and improved patients tPASI scores. Only the combined Calcipotriol/Betamethasone foam completely abolished epidermal and dermal influx of CD8+ T cells, reduced number of CD8 + IFNγ+ cells (but not CD8 + IL-17+ cells) and significantly reduced the number of MPO+ neutrophils which were predominantly IL-17+. None of the treatments had effect on NK cells. We have shown the combined topical treatment with Calcipotriol/Betamethasone foam to be effective in reducing cellular influx into lesional skin of psoriasis patients and this effect to be superior to emollient or Betamethasone alone. Its previously described efficacy in the clinic may be attributed to its unique and rapid ability to inhibit both adaptive CD8+ T cell and innate immune neutrophilia influx into the skin, which was not observed for the other treatments.
银屑病是一种慢性炎症性疾病，长期控制疾病对患者来说仍是一个挑战。最新的证据表明，皮质类固醇和维生素 D 类似物泡沫（卡泊三醇/倍他米松）联合外用治疗在疾病的长期管理和减少复发方面是有效的。其对细胞炎症和细胞因子产生的影响仍有待探索。我们着手研究局部治疗对银屑病患者皮损皮肤细胞浸润和细胞因子谱的影响。这是一项单中心、双盲、随机试验，共纳入 30 名患者。患者接受卡泊三醇/倍他米松泡沫、倍他米松泡沫、丙酸氯倍他索软膏或安慰剂治疗。在治疗前和治疗后 4 周，从皮损和非皮损部位取 4mm 皮肤活检。通过免疫荧光法研究细胞浸润、IFNγ 和 IL-17。每位患者均为自身对照。皮肤炎症的演变与患者表皮厚度和 tPASI 临床评分的变化同时进行研究。皮损皮肤表现为表皮厚度增加、IL-17 和 IFNγ 产生的 CD8+T 细胞、NK 细胞和中性粒细胞数量增加。所有治疗均减少表皮厚度并改善患者 tPASI 评分。只有卡泊三醇/倍他米松泡沫联合治疗完全消除了 CD8+T 细胞在表皮和真皮中的浸润，减少了 CD8+IFNγ+细胞的数量（但不减少 CD8+IL-17+细胞），并显著减少了主要为 IL-17+的 MPO+中性粒细胞数量。没有一种治疗方法对 NK 细胞有影响。我们已经证明，卡泊三醇/倍他米松泡沫联合外用治疗可有效减少银屑病患者皮损皮肤的细胞浸润，其效果优于保湿剂或单独使用倍他米松。其在临床上已被证实的疗效可能归因于其独特而迅速的抑制适应性 CD8+T 细胞和固有免疫性中性粒细胞浸润皮肤的能力，而其他治疗方法则观察不到这一点。
