Improving Diagnosis and Treatment in Inborn Errors of Immunity Patients After the Implementation of Systematized Interventions: A Chilean Single-Center Experience

Introduction Inborn errors of immunity (IEIs) are a heterogeneous group of primarily genetic disorders affecting the immune system, whose diagnosis can be challenging. Objective To describe the characteristics of a pediatric IEI cohort at a single tertiary center in Santiago, Chile, and to evaluate the impact of a set of systematized interventions (SIs) on diagnosis and management. Methods We analyzed patients with active follow-up for IEIs as of July 2025. Patients were grouped according to whether they were diagnosed before or after the implementation of the SIs (06/24): inclusion of an immunologist in daily clinical rounds; educational seminars on IEI for healthcare personnel; systematic review of medical records to identify suggestive clinical features; training of primary care centers for timely referral; use of the Jeffrey Modell Foundation (JMF) warning signs. Results Eleven patients were included. The mean age at diagnosis was 6.48 years (range: 0.19–15.44 years). Table 1 describes the characteristics of the cohort. After implementing the SIs, there was a tendency to reduce the time from first medical contact to diagnosis (18.61 vs. 0.02 months). Additionally, the overall time from first medical contact to treatment was shortened (22.03 vs. 1.71 months). One asymptomatic case was also identified. Compared to a similar period prior to the implementation of SIs (06/24 to 07/25 vs. 04/23 to 05/24), there was a significant increase in the number of diagnoses (6 vs. 1), including more family member screenings (3 vs. 0) and outpatient diagnoses (4 vs. 1). Conclusion This is the first report from our tertiary center in Chile on IEI. These disorders are rare and frequently underdiagnosed; the implementation of a simple set of SIs had a significant impact on improving diagnosis and treatment. Table 1.Demographic, genetic, and clinical informationPatientFamilyGenderFamily historyDeceased relatives from IEIConsanguinityDiagnosisGenetic variantIUIS groupInitial manifestationAge at Dx (years)Outpatient DxFMC to Dx (months)FMC to Tx (months)IRTAbx prophylaxisOther TxOutcomeBefore systematized interventionsP11MNoNoNoCD40L deficiencyCD40LG :c.598A>T; p.Arg200*IInfection and failure to thrive3.07No0.030.20YesYesAliveP22MYesYesNoSTAT3-HIESSTAT3 :c.1144C>T;p.Arg382TrpIIInfection and failure to thrive6.25No74.6374.70NoYesAliveP33MNoNoNoXLABTK :c.1558C>T; p.R520XIIIInfection4.35No18.2018.20YesYesAliveP44MNoNoNoXLABTK :c.894+2dup(splice site)IIIInfection and neutropenia0.99No0.200.57YesNoAliveP55FYesYesNoHAE type 1Not assessedVIIIAngioedema7.32Yes0.0016.50NoNoOn-demandAliveAfter systematized interventionsP66FNoNoNoFHL2PRF1 :c.445G>A; p.Gly149Ser c.50del; p.Leu17Argfs*34IVHLH0.19No0.000.00NoYesCyA pre HSCTAliveP77MYesNoNoHAE type 2Not assessedVIIIAngioedema15.44Yes0.003.57NoNoOn-demandAliveP84MYesNoNoXLABTK :c.894+2dup(splice site)IIIAsymptomatic0.33Yes0.000.47YesNoAliveP95FYesYesNoHAE type 1Not assessedVIIIRecurrent abdominal attacks8.50Yes0.002.17NoNoOn-demandAliveP105MYesYesNoHAE type 1Not assessedVIIIAngioedema14.48Yes0.002.17NoNoOn-demandAliveP118FYesYesNoSLE and SADIn progressNot classified yetInfection10.35No0.101.87NoYesSteroids, Aza, HCQAliveAbx: antibiotic; Aza: azathioprine; CyA: cyclosporine; Dx: diagnosis; F: female; FLH2: familial hemophagocytic lymphohistiocytosis type 2; FMC: first medical contact; HAE: hereditary angioedema; HCQ: hydroxychloroquine; HLH: hemophagocytic lymphohistiocytosis; HSCT: hematopoietic stem cell transplantation; IEI: inborn errors of immunity; IRT: immunoglobulin replacement therapy; IUIS: International Union of Immunological Societies; M: male; SAD: specific antibody deficiency; SLE: systemic lupus erythematosus; STAT3-HIES: STAT3 hyper-IgE syndrome; Tx: treatment; XLA: X-linked agammaglobulinemia.