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Initial presenting manifestations in 16,486 patients with inborn errors of immunity include infections and noninfectious manifestations

Published:April 22, 2021DOI:https://doi.org/10.1016/j.jaci.2021.04.015

      Background

      Inborn errors of immunity (IEI) are rare diseases, which makes diagnosis a challenge. A better description of the initial presenting manifestations should improve awareness and avoid diagnostic delay. Although increased infection susceptibility is a well-known initial IEI manifestation, less is known about the frequency of other presenting manifestations.

      Objective

      We sought to analyze age-related initial presenting manifestations of IEI including different IEI disease cohorts.

      Methods

      We analyzed data on 16,486 patients of the European Society for Immunodeficiencies Registry. Patients with autoinflammatory diseases were excluded because of the limited number registered.

      Results

      Overall, 68% of patients initially presented with infections only, 9% with immune dysregulation only, and 9% with a combination of both. Syndromic features were the presenting feature in 12%, 4% had laboratory abnormalities only, 1.5% were diagnosed because of family history only, and 0.8% presented with malignancy. Two-third of patients with IEI presented before the age of 6 years, but a quarter of patients developed initial symptoms only as adults. Immune dysregulation was most frequently recognized as an initial IEI manifestation between age 6 and 25 years, with male predominance until age 10 years, shifting to female predominance after age 40 years. Infections were most prevalent as a first manifestation in patients presenting after age 30 years.

      Conclusions

      An exclusive focus on infection-centered warning signs would have missed around 25% of patients with IEI who initially present with other manifestations.

      Key words

      Abbreviations used:

      ALPS (Autoimmune lymphoproliferative disease), AT (Ataxia telangiectasia), CVID (Common variable immunodeficiency), DGS (Di-George syndrome), ESID (European Society for Immunodeficiencies), HIES (Hyper-IgE syndrome), IEI (Inborn errors of immunity), IUIS (International Union of Immunological Societies), PID (Primary immunodeficiency), SCID (Severe combined immunodeficiency), WAS (Wiskott-Aldrich syndrome)
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