Down syndrome (DS) is associated with increased infections and immune dysregulation, yet contemporary large-scale United States (U.S.) data quantifying immune diagnoses, infection burden, and immunoglobulin (IgG) use are limited. We aimed to characterize these patterns using the Epic Cosmos nationwide dataset.
We performed a retrospective cross-sectional analysis of individuals with DS (ICD-10 Q90*) in Epic Cosmos (2015–2024). Immune diagnoses, infection codes, and IgG administration encounters were extracted and summarized descriptively.
We identified 209,751 individuals with DS and U.S. residence. Sex distribution was 50.5% males and 49.5% females. Age groups included 20.1% <10 years, 22.3% 10–19 years, and 57.6% ≥20 years. Race/ethnicity was predominantly White (72.0%) and Black (13.4%), with 18.2% Hispanic/Latino. Humoral immune diagnoses included hypogammaglobulinemia in 1,323 patients (0.63%), common variable immunodeficiency in 456 (0.22%), and selective IgA deficiency in 232 (0.11%); hemophagocytic lymphohistiocytosis was identified in 155 (0.07%).
The infectious burden was substantial. Respiratory infections included acute upper respiratory infections in 25.2% (62,010 encounters), pneumonia in 21.1% (103,338 encounters), otitis media in 14.2% (77,950 encounters), and sinusitis in 10.5% (48,886 encounters). Skin and mucocutaneous infections were also frequent, including cellulitis (11.3%; 33,929 encounters), abscess (9.3%; 32,316 encounters), and candidiasis (9.0%; 31,541 encounters). Serious infections included bacterial sepsis (2.7%), osteomyelitis (0.26%), endocarditis (0.10%), and bacterial meningitis (0.09%). IgG replacement was recorded for 2,296 patients (1.1%), primarily through intravenous administration.
Although formal humoral immune diagnoses were found in fewer than 1% of individuals with DS, these codes still represented more than 1,300 patients nationwide, suggesting a meaningful subgroup with immune dysfunction. Infection burden was strikingly high, with many infections occurring repeatedly, as reflected by encounter counts exceeding patient counts two- to threefold. Despite this, only 1.1% received IgG replacement therapy. These findings suggest substantial under-recognition or under-treatment of immune dysfunction in DS and highlight the need for standardized approaches to immune evaluation and infection management in this population.
