先天性无丙种球蛋白血症静脉丙种球蛋白替代治疗114例现状分析

Intravenous immunoglobulin replacement therapy in 114 cases of congenital agammaglobulinemia

目的探讨先天性无丙种球蛋白血症静脉丙种球蛋白的治疗现状,为合理规范的治疗提供依据。方法回顾性分析1988年1月至2020年4月重庆医科大学附属儿童医院就诊的114例先天性无丙种球蛋白患儿的基本信息、临床特征、实验室检查、治疗转归等情况,比较规律输注与不规律输注丙种球蛋白患儿临床表现的改善情况,分别将患儿分为无咳嗽、短期咳嗽与长期咳嗽组,慢性肺病与非慢性肺病组,关节炎与非关节炎组,分析各组起病年龄、诊断年龄、诊断耗时、首次丙种球蛋白年龄、每个月丙种球蛋白剂量、IgG谷浓度等指标,组间比较采用χ^(2)检验、t检验、方差分析或非参数检验。结果114例患儿均为男性,起病年龄(22±18)月龄,确诊年龄(89±54)月龄,诊断延迟(63±46)个月,首次丙种球蛋白年龄(75±45)月龄。66例患儿随访至2020年4月,随访时间(54±41)个月,42例(63.6%)规律输注,每个月丙种球蛋白剂量(538±105)mg/kg,IgG谷浓度(5.8±1.5)g/L,24例(36.4%)不规律输注。规律与不规律输注组患儿发热、咳嗽、鼻窦炎、腹泻、中耳炎、关节炎的改善情况差异均无统计学意义(均P>0.05)。66例中61例(92.4%)输注前有发热,输注后发热次数明显减少,差异有统计学意义[5(2,12)比0(0,1)次/年,Z=-6.436,P<0.01];60例(90.9%)治疗前有湿性咳嗽,治疗后36例有湿性咳嗽(54.5%),长期咳嗽(27例)、短期咳嗽(9例)与无咳嗽组(18例)相比,首次丙种球蛋白年龄差异有统计学意义[(97±51)比(64±41)比(63±42)月龄,F=3.554,P=0.035]。29例(43.9%)诊断慢性肺病,慢性肺病组(29例)比非慢性肺病组(37例)确诊年龄大[103(75,142)比47(31,68)月龄,Z=-3.486 P<0.01]、诊断耗时长[91(55,129)比29(10,41)个月,Z=-4.386,P<0.01]、首次丙种球蛋白年龄大[103(75,144)比46(26,64)月龄,Z=-4.330,P<0.01],差异均有统计学意义。32例(48.5%)诊断关节炎,关节炎组(32例)比非关节炎组(34例)诊断耗时长[(74±49)比(44±40)个月,t=2.600,P=0.010],首次丙种球蛋白年龄大[(98±51)比(58±39)月龄,t=3.420,P=0.001],差异均有统计学意义。结论静脉丙种球蛋白治疗后患儿发热、鼻窦炎、腹泻、中耳炎等临床症状较前均有不同程度改善,但湿性咳嗽、慢性肺病、关节炎仍是突出临床问题,规范的丙种球蛋白治疗使得部分患儿病情得到有效控制。

Objective To analyze the clinical characteristics of congenital agammaglobulinemia and the efficacy of intravenous immunoglobulin(IVIG)replacement therapy for this disease.Methods The basic characteristics,clinical manifestations,laboratory examinations,and outcomes of 114 patients with congenital agammaglobulinemia diagnosed in Children′s Hospital of Chongqing Medical University from January 1988 to April 2020 were retrospectively analyzed.The efficacy of IVIG in improving the clinical symptoms between regular and irregular treatment groups were compared byχ^(2) test.To explore the clinical characteristics associated with delayed diagnosis and treatment,the patients were also stratified into following subgroups:non-cough,short-term cough and long-term cough groups,chronic lung disease and non-chronic lung disease groups,and arthritis and non-arthritis groups.The age at onset,age at diagnosis,time consumed for diagnosis,initial time of immunoglobulin replacement,dose of IVIG,IgG trough level between the above groups were compared by t test,F test or non-parametric test.Results All the 114 patients were male,with the onset age of(22±18)months.The age at diagnosis was(89±54)months,time consumed in diagnosis was(63±46)months,and the initial time of immunoglobulin replacement was(75±45)months.A total of 66 patients had been followed up to April 2020,with a follow-up period of(54±41)months.Among these children,42(63.6%)received regular infusion,whose monthly IVIG dose was(538±105)mg/kg and IgG trough level was(5.8±1.5)g/L,whereas 24 patients(36.4%)were treated irregularly.There was no significant difference in the improvement rate of fever,cough,sinusitis,diarrhea,otitis media and arthritis between regular and irregular IVIG replacement groups(all P>0.05).Sixty-one out of the 66 patients(92.4%)had fever before IVIG treatment,whose fever episodes were significantly decreased after IVIG treatment(5(2,12)vs.0(0,1)per year,Z=-6.436,P<0.01).Sixty patients(90.9%)suffered from wet cough before treatment and 36(54.5%)after treatment.Initial time of immunoglobulin replacement was significantly delayed in the long-term cough(27 cases)and short-term cough groups(9 cases)compared with non-cough group(18 cases)((97±51)vs.(64±41)vs.(63±42)months,F=3.554,P=0.035).Twenty-nine patients(43.9%)were diagnosed with chronic lung disease,whose initial time of immunoglobulin replacement(103(75,144)vs.46(26,64)months,Z=-4.330,P<0.01),age at diagnosis(103(75,142)vs.47(31,68)months,Z=-3.486,P<0.01),and time consumed in diagnosis(91(55,129)vs.29(10,41)months,Z=-4.386,P<0.01)were significantly later and longer than those in children without chronic lung disease(37 cases).In addition,thirty-two patients(48.5%)were diagnosed with arthritis,whose initial time of immunoglobulin replacement((98±51)vs.(58±39)months,t=3.420,P=0.001)and time consumed in diagnosis((74±49)vs.(44±40)months,t=2.600,P=0.010)were also significantly later and longer than those in children without arthritis(34 cases).Conclusions After immunoglobulin replacement therapy,the clinical symptoms such as fever,sinusitis,diarrhea,and otitis media can be improved more or less.However,long-term wet cough,chronic lung disease,and arthritis are still prominent clinical problems,which could be controlled by standard immunoglobulin replacement therapy in some patients.