Department of Pediatric Allergy and Clinical Immunology, Cleveland Clinic, 9500 Euclid Avenue, R3, Cleveland, OH, 44195, USA.
Rainbow Babies and Children's Hospital Case Medical Center, Cleveland, OH, USA.
J Clin Immunol. 2019 Jan;39(1):90-98. doi: 10.1007/s10875-018-0582-z. Epub 2019 Jan 4.
Primary immunodeficiency (PID) represents disorders with a spectrum of clinical presentations. The medical community seeks clinical features to prompt evaluation for immunodeficiency given improved prognosis with early identification. We hoped to identify clinical characteristics that would improve the diagnostic accuracy of the widely disseminated Jeffrey Modell Foundation warning signs for immunodeficiency.
We performed a retrospective chart review in a two-center North American cohort of patients with PID. Charts of 137 pediatric and 400 adult patients with PID were evaluated for the presence of these warning signs and compared to controls with normal preliminary biochemical immune evaluation.
Fewer than 45% of adults with PID presented with ≥ 2 warning signs, while diagnostic utility was improved in the pediatric population where the warning signs were found to be 64% sensitive. The warning signs found in a significantly increased proportion compared to controls differed for pediatric PID patients (recurrent pneumonia (OR 2.9, p < 0.001), failure to thrive (OR 2.1, p < 0.001), need for IV antibiotics (OR 2.1, p < 0.001), serious bacterial infection (OR 4.8, p < 0.001), recurrent otitis media (OR 1.5, p = 0.027)), versus adult PID patients (recurrent otitis media (OR 2.9, p < 0.001), recurrent sinusitis (OR 2.1, p < 0.001), diarrhea with weight loss (OR 2.2, p < 0.001), recurrent viral infection (OR 3.3 p < 0.001)). In evaluation for additional criteria to promote identification of immunodeficiency, linear regression models showed slightly improved diagnostic accuracy of the warning signs with the addition of autoimmunity in our pediatric PID cohort (8.7% v 2.8%, p < 0.001, ROC 0.58). Adult PID patients demonstrated atopy more frequently than controls (48.0% vs 40.3%, p = 0.011), while atopy was found to have a negative association with the presence of PID in the pediatric age group (OR 0.3, p < 0.01). No improvement in diagnostic accuracy of the warning signs was found with the addition of allergic disease, autoimmunity, or malignant and benign proliferative disease in the adult cohort.
We demonstrate poor diagnostic performance of warning signs for immunodeficiency in patients with PID in a retrospective chart review. Divergent warning signs of statistically significant diagnostic utility were found in pediatric versus adult patients. We suggest education of physicians on differing presentations of possible immunodeficiency between age groups, and expansion of the warning signs to include non-infectious comorbidities such as autoimmunity in pediatric patients.
原发性免疫缺陷（PID）代表了具有一系列临床表现的疾病。鉴于早期识别可改善预后，医学界正在寻找可提示免疫缺陷评估的临床特征。我们希望确定可提高广泛传播的 Jeffrey Modell 基金会免疫缺陷警告标志诊断准确性的临床特征。
我们对来自北美两个中心的 PID 患儿和成年患者进行了回顾性图表审查。评估了 137 名儿科和 400 名成年 PID 患者的这些警告标志，并将其与初步生化免疫评估正常的对照组进行了比较。
不到 45%的成年 PID 患者出现≥2 个警告标志，而儿科患者的诊断效能有所提高，这些警告标志的敏感性为 64%。与对照组相比，在儿科 PID 患者中发现的警告标志比例显著增加（复发性肺炎（OR 2.9，p<0.001）、生长发育不良（OR 2.1，p<0.001）、需要静脉用抗生素（OR 2.1，p<0.001）、严重细菌感染（OR 4.8，p<0.001）、复发性中耳炎（OR 1.5，p=0.027）），而在成年 PID 患者中发现的警告标志（复发性中耳炎（OR 2.9，p<0.001）、复发性鼻窦炎（OR 2.1，p<0.001）、腹泻伴体重减轻（OR 2.2，p<0.001）、复发性病毒感染（OR 3.3，p<0.001））。在评估促进识别免疫缺陷的其他标准时，线性回归模型显示，在我们的儿科 PID 队列中，自身免疫的加入略微提高了警告标志的诊断准确性（8.7%比 2.8%，p<0.001，ROC 0.58）。成年 PID 患者比对照组更常出现特应性（48.0%比 40.3%，p=0.011），而在儿科年龄组中，特应性与 PID 的存在呈负相关（OR 0.3，p<0.01）。在成年患者队列中，添加过敏、自身免疫或恶性和良性增殖性疾病并未发现警告标志诊断准确性的提高。
我们在回顾性图表审查中证明了 PID 患者的免疫缺陷警告标志的诊断性能不佳。在儿科和成年患者中发现了具有统计学意义的诊断效用的不同警告标志。我们建议医生了解不同年龄段可能免疫缺陷的不同表现，并扩大警告标志范围，将自身免疫等非传染性合并症纳入儿科患者。
