过敏哮喘鼻炎患者尘螨变应原皮下免疫治疗后不良反应234例分析及处理

摘要

目的 观察尘螨变应原皮下特异性免疫治疗(SCIT)的不良反应、分析可能的危险因素及防范措施.方法 通过对2003年8月至2010年5月温州医学院附属第二医院育英儿童医院呼吸科哮喘及变态反应免疫治疗中心234例SCIT患者回顾性分析,观察局部不良反应(LRs)、全身不良反应(SRs)的症状,体征,发生时间,治疗处理,变应原剂量调整等,分析可能的危险因素,并对预防措施进行评估.结果 (1)234例患者SCIT总注射7679针,LRs发生4973针,占总注射次数的64.8％,所有患者在SCIT过程均发生LRs.SRs共发生235次,占总注射次数的3.1％,累及67例,占治疗例数的28.6％.轻度SRs(EAACI标准Ⅰ级、Ⅱ级)发生212次,累计50例,占治疗例数的21.3％.严重SRs(EAACI标准Ⅲ级、Ⅳ级)发生23次,占总注射次数的0.3％,累及17例,占治疗例数的7.3％.(2)症状主要累及呼吸系统205次(88.4％),皮肤黏膜系统31.5％.(3)肾上腺素处理17次,占总注射次数的0.2％,累及14例,占治疗例数的6％.(4)95.3％的SRs发生在注射后的30 min内,≤10 min发生者19次,后者10次诊断为严重SRs.56例(83.6％)首次发生SRs的剂量为100 000 SQ-U.(5)61例SRs患者经调整变应原注射剂量完成疗程(治疗时间≥2年),其中36例通过变应原剂量经降级或者降级后再升级完成疗程；19例总剂量不变,但调整为分开两次、间隔30 min注射完成疗程；6例升级治疗.6例终止治疗.(6)≤14岁年龄组、维持治疗、哮喘患者、LRs发生次数为发生SRs的可能危险因素.(7) SCIT脱落病例共28例,患者依从比率88.1％.结论 SCIT过程中可能发生严重SRs,以注射次数计SRs发生概率0.3％,但占治疗病例数的7.3％.发生SRs的可能危险因素如高剂量变应原疫苗注射、哮喘患者等.对发生SRs的患者及时对症治疗,通过减少变应原疫苗注射总剂量或总量不变间隔30 min分次注射的方法,可较好避免后续治疗SRs的再次发生.%Objective To investigate the incidence of local reactions (LRs) and systemic reactions (SRs) of subcutaneous immunotherapy (SCIT) and to analyze the potential risk factors of such reactions in Chinese population.Method This is a retrospective study on 234 dust mite sensitized patients with allergic rhinitis and asthma who received allergen immunotherapy in our hospital from 2003 to 2010.Chart review was conducted to capture clinical data of reactions to immunotherapy.Parameters included signs and symptoms,the onset of reaction,and interventions in treating such reactions,particularly,the administration of epinephrine (EPI) and adjustment of vaccine dosage due to LRs and SRs.Result The 234 patients received a total of 7679 injections.Among them,4973 LRs (64.8％) and 235 SRs (3.1％) were observed in 67 patients (28.6％ of all patients).SRs included respiratory symptoms (205 events,88.4％) and cutaneous symptoms (31.5％).Of the total of 235 SR events,212 (90.2％) were presented as mild SRs and 23 (9.8％) were in severe SR category (grade Ⅲ and grade Ⅳ,EAACI grading system).Overall,severe SRs accounted for 0.3％ of total injections.Seventeen of the 23 SR events required epinephrine treatment (0.2％ of total injections).Of the 67 patients,61 completed the course of treatment after dose adjustment ; 36 patients had their doses decreased prior to further advancing to target dose.Nineteen subjects tolerated splitting two injections at 30 minutes interval.Six patients advanced the dose based on protocol and another 6 had to stop immunotherapy.Most of the SRs (77.4％) occurred during the maintenance phase of immunotherapy.The levels of TIgE,SIgE D1 and SIgE D2 were found to be significantly higher in patients with SRs comparing to patients without SRs (P ＜ 0.05).SRs more commonly occurred in patients with age less than 14 years than their older counterparts (95.5％ vs.85.6％,OR =3.58,95％ CI =1.040-12.322,P ＜0.01).The incidence of SRs were significantly higher in asthma patients who received SCIT than non-asthma patients (OR =2,95 ％ CI =1.136-4.624).Conclusion Our study suggests that risk factors of SRs include maintenance phase (higher allergen vaccine doses),patients with asthma,age of less than 14 years,higher levels of TIgE,and SIgE D1 and SIgE D2.Effective management includes proper dose adjustment,splitting doses into 2 injections at 30 min apart,and strictly following immunotherapy indications.