DataSheet_4_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：在常见变量免疫缺陷病（CVID）中，诊断前的诊断延迟现象较为显著。目前尚无广泛认可的早期诊断症状识别框架。目标：系统性地回顾关于CVID临床表现的现有所有数据。方法：在PubMed、EMBASE和Cochrane数据库中搜索了1999年1月至2019年12月发表的队列研究，详细描述了CVID诊断前、诊断时以及诊断后的临床表现。结果：在51项研究中（n=8521患者），共识别出134种临床表现和270种总临床表现。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%）、自身免疫性血细胞减少症（10%）和特发性血小板减少症（6%）也被频繁报道。性别分布呈双峰分布，儿童中男性占主导地位（62%），成人中女性占主导地位（58%）。25%的CVID患者在儿童时期除了感染外还出现其他表现，这一比例在成人中要高得多（62%）。在成人中，免疫失调特征，如肉芽肿性淋巴细胞间质性肺疾病和炎症性肠病，更为突出。结论：从儿童期男性主导到成人期女性主导的转变，表明CVID在遗传和环境病因学上存在差异，并对病理生理学研究产生了影响。我们证实了呼吸感染的发病率较高，同时也显示严重细菌感染如败血症和脑膜炎的发病率较高，以及包括淋巴增殖性、胃肠道和自身免疫性表现的免疫失调特征。通过筛查具有这些表现的患者的抗体缺陷，可能有助于提高CVID的早期诊断。