嗜酸性粒细胞增多相关疾病较多,其病因不同,治疗方案也不相同,非感染和非肿瘤嗜酸性粒细胞增多相关疾病的一线治疗大多为糖皮质激素,根据病情轻重可联合免疫抑制剂治疗。美泊利单抗(mepolizumab)是一种人源抗白介素-5单克隆抗体,目前已被美国FDA批准用于慢性鼻-鼻窦炎伴鼻息肉(Chronic sinusitis with nasal polyps)、嗜酸性肉芽肿多血管炎(eosinophilic granulomatosis with polyangiitis)及高嗜酸性粒细胞综合征(hypereosinophilic syndrome)的二线治疗。现就美泊利单抗治疗除支气管哮喘(bronchial asthma)外相关嗜酸性粒细胞的应用研究进展作综述。
BACKGROUND Atopic dermatitis and asthma are two diseases whose pathogenesis is largely attributable to the activation,at least in the initial stages,of T helper(Th)-2 Lymphocytes,the related cytokine axis,and B lymphocytes with antibody production.Psoriasis is conversely a pathology resulting from a recruitment of Th-17 and Th-1 lymphocytes,after an initial role of innate immunity.Mepolizumab is a humanized monoclonal antibody directed against interleukin(IL)-5,a central cytokine in the Th-2 axis,therefore involved in the pathogenesis of asthma.Several authors have described the appearance of psoriatic lesions in patients with asthma or atopic dermatitis following the therapy with dupilumab,a monoclonal antibody that blocks the interleukin(IL)-4,another Th-2 cytokine.CASE SUMMARY We present the case of a 59-year-old patient who developed psoriasiform lesions on the palms after mepolizumab therapy for asthma,for the activation of the parallel cytokine cascade after the blockade of IL-5.We successfully treated the patient with a topical calcipotriol and betamethasone ointment.CONCLUSION We should investigate with further attention the possible impact on the human immunological ecosystem put in place by the inhibition of the activity of individual inflammatory mediators,so as to be able to recognize the initial adverse effects early.
目的系统评价美泊利单抗治疗嗜酸性粒细胞性哮喘的疗效与安全性。方法计算机检索PubMed、Embase、ISI Web of Science、Cochrane CENTRAL、MEDLINE、VIP、CNKI等数据库,收集美泊利单抗治疗嗜酸性粒细胞性哮喘的随机对照试验(RCT),检索时限均为从建库至2016年10月,并追溯纳入研究的参考文献和手工检索相关会议资料。由两位研究者按照纳入与排除标准独立筛选文献、提取资料和评价质量后,采用RevMan 5.1软件进行Meta分析。结果共纳入了9个RCT,2 273例患者。Meta分析结果显示,与对照组比较,试验组治疗期间哮喘急性发作率降低[RR=0.67,95%CI(0.53,0.85),P=0.000 9],血液中嗜酸性粒细胞计数明显减少[MD=–0.22,95%CI(–0.29,–0.15),P<0.000 01],痰中嗜酸性粒细胞计数明显减少[MD=–6.37,95%CI(–9.68,–3.06),P<0.000 2],哮喘相关生活质量(ACQ)总分提高的患者比例也明显增加。两组间总不良反应发生率相似[RR=0.90,95%CI(0.71,1.14),P=0.39];严重不良反应发生率方面,美泊利单抗优于安慰剂[RR=0.45,95%CI(0.23,0.89),P=0.02];总心血管事件发生率方面,美泊利单抗与安慰剂治疗相当[RR=0.95,95%CI(0.40,2.22),P=0.90]。对于能否改善肺功能,美泊利单抗可能有一定作用,但目前观察到的效果不明显。结论美泊利单抗在哮喘治疗中可降低哮喘患者血液及痰中嗜酸性粒细胞数,减轻哮喘患者急性发作率,提高生活质量,且有较好的安全性。
