Inborn errors of immunity in adulthood

TLDR

Inborn errors of immunity are immune system disorders that were once considered mainly pediatric but now account for over half of new cases in adults, with delayed diagnosis and phenocopies contributing to late recognition. The article aims to prompt timely referral to immunology for precise molecular diagnosis and targeted therapy in adult IEI patients. It provides a primer on adult IEIs, including pathophysiology, epidemiology, clinical vignettes, and a laboratory evaluation framework to aid clinicians in diagnosis and initial treatment.

Abstract

Inborn errors of immunity (IEIs) are a group of conditions whereby parts of the immune system are missing or dysfunctional. Once thought to primarily be a pediatric disorder, it is now estimated that more than 50% of worldwide incident IEI cases are accounted for by adults. Delayed diagnosis, late symptom onset, and IEI phenocopies can all lead to adult-onset recognition of IEIs. Lack of awareness regarding the diversity of IEI manifestations in adults contributes to diagnostic and treatment delays. Prompt referral to immunology is critical so that patients can receive a precise molecular diagnosis and targeted therapy when available. This article serves as a primer on IEIs in adulthood, highlighting the pathophysiology, epidemiology and clinical features. We present clinical vignettes of three key IEIs to assist clinicians in building illness scripts on their presentations. We provide a framework for the laboratory evaluation of IEIs and their initial treatment, with the aim of improving recognition and management of these conditions.