Validating Inborn Error of Immunity Prevalence and Risk with Nationally-Representative EHR Data

BACKGROUND:The 10 Warning Signs (WS) of Primary Immunodeficiency were created 30 years ago to advance recognition of inborn-errors of immunity (IEI). However, no population-level assessment of their utility applied to electronic health record (EHR) data has been conducted. OBJECTIVE:We sought to quantify the value of having 2+ WS towards diagnosing IEI using a highly representative real-world US cohort. A secondary goal was estimating the US prevalence of IEI. METHODS:In this cohort study, we accessed normalized and de-identified EHR data on 152 million US lives. An IEI cohort (n=41,080) was defined by having at least 1 verifiable IEI diagnosis placed ≥2 times in their record and compared to a matched set of controls (n=250,262). WS were encoded along with relevant diagnoses, relative weights were calculated and the proportion of IEI vs controls with 2+ WS was compared. RESULTS:The proportion of IEI patients with 2+ warning signs significantly differed from controls (0.33 vs. 0.031; p < 0.0005 ChiSq). We also estimated a US IEI prevalence of 6:10,000 individuals (41,080/73,165,655; 0.056%). Warning signs 9 (2+deep-seated infections), 7(fungal infections), 5(failure to thrive) and 4(2+pneumonias in 1 year) were the most heavily weighted among the IEI cohort. CONCLUSIONS:From this nationally representative US-based cohort study, we note that WS presence, and associated clinical diagnoses, can facilitate IEI patient identification from EHR data. In addition, we estimate that 6 in 10,000 or approximately 150-200,00 persons are affected by IEI across the US.