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Publications

Journal Article Ahead of print 1 citation

PubMed: 42485622 DOI: 10.1093/bjd/ljag308

Eczema in inborn errors of immunity with atopy: frequency, timing, phenotypic clustering.

Br J Dermatol

Authors: Hélène Aubert, Nizar Mahlaoui, Sébastien Barbarot, Mickaël Alligon, Isabelle Pellier, Coralie Mallebranche, Jacinta Bustamante, Jérémie Rosain, Capucine Picard, Antoine Néel, Marie Bodinier, Carole Brosseau, Laura Polivka, Christine Bodemer, Caroline Thomas

Affiliations

  • Dermatology Department, Nantes University Hospital, Nantes, France.
  • Constitutive Site of the French National Referral Center for Primary Immunodeficiency Diseases (CEREDIH), Nantes University Hospital, Nantes, France.
  • UR1268, INRAE Pays de la Loire, Nantes, France.
  • CEREDIH, Necker Enfants-Malades University Hospital, Assistance Publique-Hôpitaux de Paris (APHP), Paris, France.
  • Pediatric Immuno-Hematology and Rheumatology Unit, Necker Enfants-Malades University Hospital, APHP, Paris, France.
  • Pediatric Immuno-Hematology-Oncology, CHU Angers, University of Angers, Angers, France.
  • Université d'Angers, Université de Nantes, Inserm, CNRS, CRCI2NA, SFR ICAT, Angers, France.
  • Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Paris, France.
  • Paris Cité University, Imagine Institute, INSERM U1163, Paris, France.
  • St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
  • Internal Medicine Department, Nantes University Hospital, Nantes, France.
  • Dermatology Department, Necker Enfants-Malades University Hospital, APHP, Paris Cité Université, Paris, France.
  • Pediatric Immuno-Hematology and Oncology, Nantes University Hospital, Nantes, France.

Abstract

BACKGROUND

Inborn errors of immunity with atopy (IEIs-A) are an IEI subgroup with eczema as a prominent clinical feature that can mimic atopic dermatitis (AD). However, IEIs-A-associated eczema can differ from that of classic AD, and its frequency, genotype-specific clinical patterns and temporal relationships with other IEIs-A manifestations (infections, allergic manifestations, autoimmunity) remain poorly defined.

OBJECTIVES

To characterize eczema frequency, timing and phenotypes in IEIs-A patients, and explore eczema's relationship with other clinical IEIs-A manifestations.

METHODS

This retrospective study used data from the French national IEI (CEREDIH) Registry database, focusing on patients with genetically defined IEIs-A followed in three large CEREDIH-participating centers and available clinical data. Eczema frequency and onset in relationship to other clinical events, particularly severe-or-unusual infections, was assessed, as were eczema phenotypes, concomitant allergic manifestations, treatments and autoimmunity. Clustering analyses were computed to identify distinct IEI-A-eczema-associated clinical phenotypes.

RESULTS

Among 373 IEIs-A patients, varying widely by genotype, 50.9% had eczema. All dedicator of cytokinesis-8 (DOCK8)-deficient patients were affected, followed by Forkhead box-P3 (FOXP3)-deficient patients (73.3%), and those with signal transducer and activator of transcription-1-loss-of-function (STAT3-LoF; 74.6%). Onset was usually early (median: 4 months). Eczema frequency and clinical presentation varied markedly across IEIs-A genotypes; four phenotypic clusters were identified, with particular localizations and severe pruritus being strongly associated with pathogenic STAT3 or DOCK8 variants. For children with isolated eczema at 24 months, the risk of developing IEI-related severe-or-unusual infections was lower than that of persistent isolated eczema until 6.8 years.

CONCLUSION

Eczema is a common, early IEIs-A feature, often preceding infections by years.While 38.4% of IEIs-A patients with eczema fulfilled the UK Working Party diagnostic criteria for AD, some clinical pictures may differ from that of classic AD. At a time when systemic AD treatments are rapidly advancing in pediatrics, recognizing these patterns to identify IEIs-A patients could refine diagnostic strategies, improve IEI detection among children with eczema, shorten the time to IEIs-A diagnosis, guide tailored management and ensure these patients receive the optimal care.

MeSH

Syphilis, Eczema, Phenotype, Immunity, Cluster Analysis, Genotype, Therapeutics, Dermatology, Infections, Child, Autoimmunity