Clinical pearls and pitfalls in inborn errors of immunity: An expert-derived framework for diagnostic pattern recognition.
Article
Vásquez Echeverri, Estefanía, Bustamante-Ogando, Juan Carlos, Castano-Jaramillo, Lina M et al. (2026). Clinical pearls and pitfalls in inborn errors of immunity: An expert-derived framework for diagnostic pattern recognition.
. Pediatric Allergy and Immunology, 37(8), e70470. 10.1111/pai.70470
Vásquez Echeverri, Estefanía, Bustamante-Ogando, Juan Carlos, Castano-Jaramillo, Lina M et al. (2026). Clinical pearls and pitfalls in inborn errors of immunity: An expert-derived framework for diagnostic pattern recognition.
. Pediatric Allergy and Immunology, 37(8), e70470. 10.1111/pai.70470
Inborn errors of immunity (IEI) encompass over 600 disorders with diverse and overlapping presentations. Clinicians rely on pattern recognition-clinical pearls-to navigate this complexity, yet this experiential knowledge is rarely systematically compiled. Through a structured expert elicitation, we aimed to capture and organize clinical pearls, pitfalls, and caveats for the differential diagnosis of IEI as a practical educational reference for trainees and non-specialist physicians. In a structured expert survey with narrative (thematic) synthesis-not a formal consensus process-twenty clinical immunologists were invited and twelve contributed (60% response). Each provided diagnostic pearls across six categories: red flags prompting IEI evaluation, signs suggestive of IEI categories, highly specific (near-pathognomonic) findings, highly sensitive findings, expected phenotype (including exclusionary findings), and practical clinical wisdom. Responses were translated (Spanish to English where necessary), coded and synthesized by theme by two investigators with disagreements resolved by consensus, reviewed for contradictions, and supplemented with established pearls from the literature, with the origin of each pearl tracked. Contributors provided over 150 diagnostic pearls. High-consensus red flags included disseminated BCG/mycobacterial disease, very early-onset inflammatory bowel disease (<6 years), and infant lymphopenia. Highly specific findings included microthrombocytopenia for Wiskott-Aldrich syndrome, catalase-positive organism infections for chronic granulomatous disease, and ataxia with telangiectasias for ataxia-telangiectasia. Important caveats emerged: normal mean platelet volume does not exclude Wiskott-Aldrich syndrome; normal IgG in older ataxia-telangiectasia patients may mask antibody deficiency due to oligoclonal production; and absence of fever during serious bacterial infection suggests IRAK4/MyD88 deficiency rather than arguing against it. Contributors emphasized that clinical phenotypes evolve over time and that patients may not fit established patterns at initial evaluation. This structured expert survey provides a practical, organized reference for IEI differential diagnosis. The compilation of pearls, pitfalls, and caveats, presented in eight tables, offers educational and hypothesis-generating guidance for clinicians and trainees navigating these rare disorders. In an exploratory, qualitative comparison, several types of experiential clinical wisdom-bedside decision rules, laboratory caveats, environmental guidance, and anticipatory management-were underrepresented in the outputs of general-purpose large language models informally queried on the same task, suggesting that expert-derived knowledge of this kind may help inform future educational and diagnostic-support efforts.
