单中心174例原发性免疫缺陷病临床预警症状的初步探讨

目的 分析并总结原发性免疫缺陷病（PID）患儿的临床感染特征和预警症状，了解预警症状对PID早期识别的应用价值。方法 参考2011年免疫学会国际联合会(IUIS)PID分类委员会公布的方案、泛美免疫缺陷病组(PAGID)和欧洲免疫缺陷病协会(ESID)提出的PID诊断和分类标准，在首都医科大学附属北京儿童医院2000年10月至2011年11月病例检索系统检索出院诊断中含有上述PID分类疾病的病历，对于诊断低丙种球蛋白血症和联合免疫缺陷的患儿除外继发性免疫缺陷病，逐份查阅病历重新诊断，并做出明确、可以和可能诊断，以明确、可以诊断的病例进行预警症状的分析。结果 ①174例PID患儿进入分析，男女比例为4.4∶1，其中抗体缺陷为主的免疫缺陷101例(58.0%)，严重联合免疫缺陷病（SCID）34例(19.5%)，吞噬细胞功能缺陷19例(10.9%)，定义明确的免疫缺陷综合征10例(5.7%)，免疫失调性疾病10例(5.7%)。②75例(43.1%)存在反复呼吸道感染，以抗体缺陷为主的免疫缺陷最为常见，与SCID间差异有统计学意义；卡介苗接种后异常反应在慢性肉芽肿病（CGD）中最多见，与抗体缺陷为主的免疫缺陷和SCID比较差异有统计学意义；腹泻病在定义明确的免疫缺陷综合征中较常见，败血症在SCID和CGD患儿中较常见，但PID各类型间比较差异无统计学意义。③72例(41.4%)患儿存在营养发育落后，PID各类型间差异无统计学意义；淋巴结、肝和脾肿大以CGD和免疫失调性疾病最为常见；鹅口疮在SCID中常见，与抗体缺陷为主的免疫缺陷差异有统计学意义；肛周脓肿以CGD多见，与其他PID类型比较差异有统计学意义。107例(61.5%)有明确微生物学证据。④PID患儿共电话随访到85例(48.8%)，其中死亡28例(32.9%)。⑤124例为明确和可以诊断PID，其中106例(85.5%)具备≥2条预警症状。静脉应用抗生素清除病灶(96.0%)、体重不增或生长发育极度迟缓(41.1%)、反复呼吸道感染(41.9%)和PID家族史(22.6%)在不同类型PID中均占有较高的比例。结论 预警症状对PID有着很好的提示作用，需要静脉应用抗生素清除病灶、体重不增或生长发育极度迟缓和PID家族史对PID有预警意义，中耳炎、中枢神经系统感染和反复呼吸道感染在抗体缺陷为主的免疫缺陷中较为多见， 深部脓肿、卡介苗接种后异常反应对CGD有预警意义。慢性反复发作性腹泻对PID预警作用值得进一步关注。

Preliminary study of the warning signs of 174 children with primary immunodeficiency diseases from a single center

Objective To analyze and summarize the clinical features and the warning signs of children with PID, in order to investigate the application value of the warning signs to early identification of PID. Methods According to the classification issued by the International Union of Immunological Societies (IUIS) Primary Immunodeficiency Diseases (PID) Classification Committee in 2011 and the diagnostic criteria made by Pan-American Group for Immunodeficiency (PAGID) and European Society for Immunodeficiencies (ESID), the cases diagnosed as PID above were retrieved . Secondary immunodeficiencies about the cases of hypogammaglobulinemia and combined T and B cell immunodeficiency were excluded. All cases screened out were read, definite, probable or possible diagnoses were made. At last, the warning signs of cases with both definite and probable diagnosis were analyzed. Results 174 children with PID were included, the boys/girls ratio was 4.4:1. Predominantly antibody deficiencies were the most frequent finding (58.0%), followed by combined T and B cell immunedeficiencies (19.5%), congenital defects of phagocyte (10.9%), other well-defined immunodeficiency syndromes (5.7%) and diseases of immune dysregulaton (5.7%). 75 children (43.1%) had a history of recurrent respiratory tract infections, which were common in predominant antibody deficiencies. Diarrheal diseases were common in other well-defined immunodeficiency syndromes. Sepsis was more common in children with SCID and CGD. The occurrence of abnormal reactions after BCG vaccination was particularly high in CGD and significantly different from other types. Malnutrition was very common in 72 children (41.4%) without significant differences. There were significant differences in signs of lymphadenectasis and hepatosplenomegaly in which CGD and diseases of immune dysregulaton were the most common. Thrush was common in SCID. Nine children (47.4%) with CGD were found presenting perianal abscess, which was more common than other types. Pathogen evidence was found in 107 children(61.5%). 85 cases (48.8%) were followed up and 28(32.9%) were dead. There were 124 cases meeting the definite or probable diagnosis, among them 106(85.5%) had 2 or more warning signs. 119 children (96.0%) needed intravenous antibiotics to clear infections. 51 children (41.1%) failed to gain weight or grow normally. 52 children (41.9%) were suffering from recurrent respiratory tract infections. 28 children(22.6%) had a family history of PID. Conclusion The warning signs can be good indictors to PID. Need for intravenous antibiotics, failure to thrive and family history are useful to early identification of PID. Otitis media, central nervous system infection, sepsis and recurrent respiratory tract infection are more common in predominant antibody deficiencies. Deep-seated infections and abnormal reaction after BCG vaccination are significant to CGD. High attention is expected to be paid to chronic recurrent diarrhea.