DataSheet_3_Lessons Learned From the Clinical Presentation of Common Variable Immunodeficiency Disorders: A Systematic Review and Meta-Analysis.pdf

BackgroundDiagnostic delay in common variable immunodeficiency disorders (CVID) is considerable. There is no generally accepted symptom-recognition framework for its early detection.ObjectiveTo systematically review all existing data on the clinical presentation of CVID.MethodsPubMed, EMBASE and Cochrane were searched for cohort studies, published January/1999-December/2019, detailing the clinical manifestations before, at and after the CVID-diagnosis.ResultsIn 51 studies (n=8521 patients) 134 presenting and 270 total clinical manifestations were identified. Recurrent upper and/or lower respiratory infections were present at diagnosis in 75%. Many patients had suffered severe bacterial infections (osteomyelitis 4%, meningitis 6%, septicemia 8%, mastoiditis 8%). Bronchiectasis (28%), lymphadenopathy (27%), splenomegaly (13%), inflammatory bowel disease (11%), autoimmune cytopenia (10%) and idiopathic thrombocytopenia (6%) were also frequently reported. A bimodal sex distribution was found, with male predominance in children (62%) and female predominance in adults (58%). 25% of CVID-patients developed other manifestations besides infections in childhood, this percentage was much higher in adults (62%). Immune-dysregulation features, such as granulomatous-lymphocytic interstitial lung disease and inflammatory bowel disease, were more prominent in adults.ConclusionsThe shift from male predominance in childhood to female predominance in adults suggests differences in genetic and environmental etiology in CVID and has consequences for pathophysiologic studies. We confirm the high frequency of respiratory infections at presentation, but also show a high incidence of severe bacterial infections such as sepsis and meningitis, and immune dysregulation features including lymphoproliferative, gastrointestinal and autoimmune manifestations. Early detection of CVID may be improved by screening for antibody deficiency in patients with these manifestations.

背景：常见变量免疫缺陷症（CVID）的诊疗延迟问题显著。目前尚无普遍认可的早期诊断症状识别框架。目的：系统性地回顾所有关于CVID临床表现的现有数据。方法：通过PubMed、EMBASE和Cochrane数据库检索了1999年1月至2019年12月发表的相关队列研究，详细描述了CVID诊断前后临床表现的临床特征。结果：在51项研究中（n=8521例患者），共识别出134个表现型和270个总临床特征。在诊断时，75%的患者存在反复的上呼吸道和/或下呼吸道感染。许多患者曾遭受严重的细菌感染（骨髓炎4%，脑膜炎6%，败血症8%，乳突炎8%）。支气管扩张（28%），淋巴结肿大（27%），脾肿大（13%），炎症性肠病（11%），自身免疫性细胞减少症（10%）和特发性血小板减少症（6%）也常被报道。性别分布呈双峰模式，儿童期男性占主导地位（62%），成年期女性占主导地位（58%）。25%的CVID患者在儿童期除了感染外还出现其他表现，成年期这一比例显著升高（62%）。在成年患者中，免疫失调特征，如肉芽肿性淋巴细胞间质性肺病和炎症性肠病，更为突出。结论：从儿童期的男性主导转向成年期的女性主导，提示CVID的遗传和环境病因存在差异，并对病理生理学研究产生影响。我们证实了呼吸道感染的高发生率，同时揭示了败血症、脑膜炎等严重细菌感染以及淋巴增殖、胃肠道和自身免疫表现等免疫失调特征的高发病率。通过筛查具有这些表现的患者的抗体缺乏，可能提高CVID的早期诊断率。