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


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Thalhammer J., Kindle G., Nieters A., Rusch S., Seppänen M. R. J. , Fischer A., ...More

The Journal of allergy and clinical immunology, vol.148, no.5, 2021 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 148 Issue: 5
  • Publication Date: 2021
  • Doi Number: 10.1016/j.jaci.2021.04.015
  • Journal Name: The Journal of allergy and clinical immunology
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, PASCAL, BIOSIS, CAB Abstracts, EMBASE, Food Science & Technology Abstracts, International Pharmaceutical Abstracts, MEDLINE, Veterinary Science Database
  • Keywords: Primary immunodeficiency, inborn error of immunity, presenting symptom, immune dysregulation, autoimmune, inflamma-tory, syndromic, warning signs, registry, PRIMARY IMMUNODEFICIENCY DISEASES, 10 WARNING SIGNS, DEFICIENCY, REGISTRY, COMMON, TIME
  • Bursa Uludag University Affiliated: Yes

Abstract

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. (J Allergy Clin Immunol 2021;148:1332-41.)