Successful treatment with crisaborole for facial lesions refractory to adalimumab in a man with psoriasis: A case report
Successful treatment with crisaborole for facial lesions refractory to adalimumab in a man with psoriasis: A case report
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使用 Crisaborole 成功治疗阿达木单抗难治性牛皮癣男性面部病变：病例报告
DOI：
10.1111/dth.15424
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发表时间：
2022-03
影响因子：
3.6
通讯作者：
Wei Li
中科院分区：
文献类型：
--
作者：
Yiyuan Liu;Wei Li
尊敬的编辑：阿达木单抗是一种抗肿瘤坏死因子的全人源单克隆抗体，在治疗中重度慢性斑块状银屑病，特别是银屑病关节炎患者中显示出良好的疗效。然而，在某些情况下，仅使用阿达木单抗无法完全清除皮肤病变。局部治疗应结合生物制剂以改善皮损。局部皮质类固醇和钙调磷酸酶抑制剂是常见的选择，但鉴于其疗效和耐受性的局限性，临床实践中需要新的治疗选择。磷酸二酯酶4（PDE-4）抑制剂是治疗炎症性皮肤病的一个潜在靶点，它通过增加细胞内cAMP水平来减少细胞因子的释放。Crisaborole作为一种新型的非甾体PDE-4抑制剂，不仅能抑制白细胞介素4（IL-4）、IL-13等2型细胞因子，还能降低肿瘤坏死因子-α（TNF-α）、IL-17和IL-23等在银屑病发病过程中起重要作用的细胞因子。在这里，我们报告了一例阿达木单抗难治性面部皮疹，阿达木单抗对阿托硼洛反应良好。一名29岁男性，面部、躯干和四肢有6年斑块和鳞屑病史（图1A，B），被诊断为斑块状银屑病。他还遭受了4个月的关节疼痛。全血细胞计数、肝肾功能、抗核抗体（ANA）、人类免疫缺陷病毒（HIV）、乙型肝炎病毒（HBV）、丙型肝炎病毒（HCV）、T-SPOT、TB等实验室检查均正常或阴性。因此，开始阿达木单抗治疗以控制关节和皮肤症状。治疗1个月后，银屑病病变明显改善，而面部病变未能好转（图1C，D）。6个月后，除面部病变外，银屑病体征和症状完全缓解（图1 E）。患者因美观原因拒绝在面部进行活检，并因其潜在副作用而抵制局部皮质类固醇。然后处方局部钙调磷酸酶抑制剂他克莫司软膏，但患者因其局部刺激性而停用他克莫司。因此，采用每日两次的外用阿托硼唑来去除面部病变。两个月后，面部病变完全恢复（图1F），并且在6个月的随访期间没有复发。临床上，抗TNF生物制剂能有效控制银屑病的关节症状。但对于皮损，阿达木单抗的疗效不如抗IL-17生物制剂。因此，当阿达木单抗完全控制了关节疼痛，而局部仍存在皮损时，应联合外用治疗以改善银屑病皮损。根据指南，一线选择是局部皮质类固醇，然后是钙调磷酸酶抑制剂。但对于一些皮肤较薄或敏感部位，上述局部治疗也是可取的。Crisaborole是一种新型的非甾体、局部、抗炎PDE-4抑制剂，已被批准用于治疗儿童和成人的特应性皮炎（AD）。良好的疗效和耐受性使其适用于面部、乳房、生殖器、伸肌和擦擦间区等皮肤较薄和敏感的部位。此外，阿糖胞苷还能抑制银屑病患者血清中TNF-α、IL-17和IL-23等促炎细胞因子的产生，这些细胞因子在银屑病的发病机制中起重要作用。一项随机、双盲和媒介物对照试验评估了阿托硼洛治疗擦破性、肛门生殖器和面部银屑病的安全性和有效性。4周后，服用阿托硼洛的参与者表现出66%的改善，而安慰剂组为9%。在第8周，71%的阿托硼洛参与者达到了临床清除率。更重要的是，没有报告不良事件，表明阿托硼洛的耐受性良好。最近，有新的病例报告，关于治疗银屑病与阿托硼洛。Lee等人报告了2例面部银屑病患者，均成功接受了阿托硼洛治疗。我们最近发表的病例也证实了阿托硼洛治疗生殖器银屑病的疗效和耐受性。在我们的病例中，在阿达木单抗治疗前，患者因其病史和典型银屑病皮肤病变被诊断为斑块状银屑病。由于患者的实验室检查正常或阴性，无光敏感性，无脱发，无食物或药物过敏，排除了狼疮和特应性皮炎，我们认为面部皮疹为银屑病病变，并建议使用阿托洛尔。治疗2个月后，面部皮损明显，6个月内无复发，与以往报道和我们的最新经验一致。本研究可帮助皮肤科医师处理生物治疗，尤其是抗肿瘤坏死因子治疗效果不佳的病患。对于阿达木单抗治疗难治性病变，Crisaborole可视为一种有效且耐受性更好的外用药物，尤其是对于皮肤较薄和敏感区域，如面部和生殖器。投稿时间：2021年12月29日修订日期：2022年2月14日接受日期：2022年3月6日
Dear Editor, Adalimumab, a fully human monoclonal antibody against tumor necrosis factor, demonstrates good efficacy in the treatment of moderate-to-severe chronic plaque psoriasis, especially in the patients with psoriatic arthritis. However, in some cases, the skin lesions could not be completely cleared by using adalimumab alone. The topical therapy should now be combined with biologic to improve the skin lesions. Topical corticosteroids and calcineurin inhibitors are the common choices, but in view of their limitations of efficacy and tolerability, new treatments options are needed in clinic practice. As a potential therapeutic target for inflammatory skin diseases, phosphodiesterase 4 (PDE-4) inhibitor decrease the release of cytokines through increasing intracellular cAMP levels. As a novel nonsteroidal PDE-4 inhibitor, Crisaborole not only inhibits type 2 cytokines such as interleukin 4 (IL-4), IL13 and so on, but also reduces cytokines including tumor necrosis factor-α (TNF-α), IL-17 and IL-23, which play important roles during the pathogenesis of psoriasis. Here, we report a case with facial rashes refractory to adalimumab, which responded well to crisaborole. A 29-year-old man with 6 years history of plaques and scales on face, trunk and extremities (Figure 1A,B) was diagnosed with plaque psoriasis. He also suffered joint pain for 4 months. The laboratory tests of complete blood count, liver and renal function, antinuclear antibodies (ANAs), human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and T-SPOT.TB were all normal or negative. Therefore, adalimumab was initialed to control the joint and skin symptoms. After 1 month treatment, the psoriatic lesions improved significantly while the facial lesions failed to get better (Figure 1C,D). Six months later there was complete remission of psoriatic signs and symptoms except the lesions on the face (Figure 1E). The patient refused to take a biopsy on the face for aesthetic reasons, and resisted topical corticosteroids for its potential side effects. The topical calcineurin inhibitor tacrolimus ointment was then prescribed, but the patient discontinued tacrolimus for its local irritation. Therefore, the topical crisaborole with two times per day was introduced to remove the facial lesions. Two months later, the facial lesions were completely recovered (Figure 1F) and did not relapse during follow-up of 6 months. In clinic practice, the anti-TNF biologics could effectively control the joint symptoms of psoriasis. But to the skin lesions, adalimumab is less effective than anti-IL-17 biologics. Therefore, when adalimumab completely controls the joint pain while the skin lesions still exist in some local areas, the topical treatment should be combined to improve psoriatic lesions. According to the guideline, the first-line choice is topical corticosteroids, and then the calcineurin inhibitors. But to some thin-skinned areas or sensitive parts, the above topical treatments are not inadvisable. Crisaborole, a novel nonsteroidal, topical, anti-inflammatory PDE-4 inhibitor, is approved to treat atopic dermatitis (AD) in children and adults. The good effects and tolerance make crisaborole suitable for the thin-skinned and sensitive areas such as face, breasts, genitals, and extensor and intertriginous areas. Moreover, crisaborole could also decrease the production of proinflammatory cytokines including TNF-α, IL-17 and IL-23, which are believed to play key roles in the pathogenesis of psoriasis. A randomized, double-blind and vehicle-controlled trial has assessed the safety and efficacy of crisaborole in the treatment of intertriginous, anogenital, and facial psoriasis. After 4 weeks, participants with crisaborole demonstrated 66% improvement compared with 9% in placebo. And on week 8, 71% of participants with crisaborole achieved clinical clearance. More importantly, there were no reported adverse events, suggesting the good tolerance of crisaborole. Recently, new cases are reported about treatment of psoriasis with crisaborole. Lee et al presented two cases with facial psoriasis successfully treated by crisaborole. And our latest published cases also confirmed the efficacy and tolerance of crisaborole in the treatment for genital psoriasis. In our case, before adalimumab treatment, the patient was diagnosed plaque psoriasis for his medical history and typical psoriatic skin lesions. As the patient had normal or negative laboratory tests and had no light sensitivity, no hair loss, no food or drug allergy, which excluded lupus and atopic dermatitis, we thought the facial rashes as psoriatic lesions and recommended crisaborole. After 2 months therapy, the psoriatic lesions on the face were clear and did not recur during the following 6 months, which is consistent with previous report and our latest experience. Our report can help dermatology doctors managing the patients who have not enough efficacy with the biologic treatments, especially the anti-TNF therapy. Crisaborole could be considered as an effective and better tolerated topical drug for lesions refractory to adalimumab treatment, especially for the thin-skinned and sensitive areas such as face and genitals. Received: 29 December 2021 Revised: 14 February 2022 Accepted: 6 March 2022
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2.9
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影响因子：
2.3
作者：
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通讯作者：
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通讯作者：
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