Thalhammer, J;
Kindle, G;
Nieters, A;
Rusch, S;
Seppänen, MRJ;
Fischer, A;
Grimbacher, B;
... European Society for Immunodeficiencies Registry Working Party; + view all
(2021)
Initial presenting manifestations in 16,486 patients with inborn errors of immunity include infections and noninfectious manifestations.
Journal of Allergy and Clinical Immunology
, 148
(5)
1332-1341.e5.
10.1016/j.jaci.2021.04.015.
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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. Whilst increased infection susceptibility is a well-known initial IEI manifestation, less is known about the frequency of other presenting manifestations. / Objective: 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 (ESID) registry. Patients with autoinflammatory diseases were excluded due to 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 due to family history only and 0.8% presented with malignancy. Two thirds of IEI patients presented before the age of 6 years, but a quarter of patients only developed initial symptoms as adults. Immune dysregulation was most frequently recognized as an initial IEI manifestation between 6 and 25 years of age with male predominance until age 10, shifting to female predominance after age 40. Infections were most prevalent as a first manifestation in patients presenting after age 30. / Conclusion: An exclusive focus on infection-centered warning signs would have missed around 25% of IEI patients that initially present with other manifestations. / Clinical implications: We provide a data-based rationale to add immune dysregulation and syndromic features to the IEI warning signs, which may significantly improve early IEI diagnosis.
| Type: | Article |
|---|---|
| Title: | Initial presenting manifestations in 16,486 patients with inborn errors of immunity include infections and noninfectious manifestations |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.jaci.2021.04.015 |
| Publisher version: | https://doi.org/10.1016/j.jaci.2021.04.015 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Primary Immunodeficiency; inborn error of immunity; presenting symptom; immune dysregulation; autoimmune; inflammatory; syndromic; warning signs; registry |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10126811 |
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