DADA2 diagnosed in adulthood versus childhood: A comparative study on 306 patients including a systematic literature review and 12 French cases.


Journal

Seminars in arthritis and rheumatism
ISSN: 1532-866X
Titre abrégé: Semin Arthritis Rheum
Pays: United States
ID NLM: 1306053

Informations de publication

Date de publication:
12 2021
Historique:
received: 17 05 2021
revised: 31 08 2021
accepted: 13 09 2021
pubmed: 28 9 2021
medline: 19 3 2022
entrez: 27 9 2021
Statut: ppublish

Résumé

Deficiency of adenosine deaminase 2 (DADA2) is a rare autoinflammatory disease usually presenting before the age of 10 years. Non-specific clinical features or late-onset presentation may delay its diagnosis until adulthood. To determine whether DADA2 diagnosed in adulthood is associated with specific characteristics compared to DADA2 diagnosed in childhood. We pooled a cohort of 12 adult DADA2 patients followed in France with cases identified through a systematic literature review. For each patient, we determined the type of clinical presentation and assessed six key organ involvements. A total of 306 cases were included. Among the 283 patients with available data regarding age at diagnosis, 140 were diagnosed during adulthood and 143 during childhood. The vascular presentation of DADA2 was more frequent in the adult diagnosis group (77.9% vs. 62.9%, p < 0.01), whereas the hematological presentation (bone marrow failure) prevailed in the pediatric diagnosis group (10.0% vs. 20.3% p = 0.02). In patients with vasculopathy, severe skin manifestations developed in 35% and 10% of the adult and pediatric diagnosis groups, respectively. Conversely, fewer strokes occurred in the adult group presenting with systemic vasculopathy (54% vs. 81%). Symptomatic humoral immune deficiency (HID) was rarely a clinical presentation in itself (5% and 2.8%) but accompanied other phenotypes of DADA2, especially the hematological phenotype in the adult group (33% vs. 4%). DADA2 diagnosed in adulthood presents more often with a vascular phenotype and less often with bone marrow failure than DADA2 diagnosed in childhood. Adults diagnosed with DADA2 vasculopathy display more severe skin involvement but fewer strokes.

Sections du résumé

BACKGROUND
Deficiency of adenosine deaminase 2 (DADA2) is a rare autoinflammatory disease usually presenting before the age of 10 years. Non-specific clinical features or late-onset presentation may delay its diagnosis until adulthood.
OBJECTIVE
To determine whether DADA2 diagnosed in adulthood is associated with specific characteristics compared to DADA2 diagnosed in childhood.
METHODS
We pooled a cohort of 12 adult DADA2 patients followed in France with cases identified through a systematic literature review. For each patient, we determined the type of clinical presentation and assessed six key organ involvements.
RESULTS
A total of 306 cases were included. Among the 283 patients with available data regarding age at diagnosis, 140 were diagnosed during adulthood and 143 during childhood. The vascular presentation of DADA2 was more frequent in the adult diagnosis group (77.9% vs. 62.9%, p < 0.01), whereas the hematological presentation (bone marrow failure) prevailed in the pediatric diagnosis group (10.0% vs. 20.3% p = 0.02). In patients with vasculopathy, severe skin manifestations developed in 35% and 10% of the adult and pediatric diagnosis groups, respectively. Conversely, fewer strokes occurred in the adult group presenting with systemic vasculopathy (54% vs. 81%). Symptomatic humoral immune deficiency (HID) was rarely a clinical presentation in itself (5% and 2.8%) but accompanied other phenotypes of DADA2, especially the hematological phenotype in the adult group (33% vs. 4%).
CONCLUSION
DADA2 diagnosed in adulthood presents more often with a vascular phenotype and less often with bone marrow failure than DADA2 diagnosed in childhood. Adults diagnosed with DADA2 vasculopathy display more severe skin involvement but fewer strokes.

Identifiants

pubmed: 34571400
pii: S0049-0172(21)00180-3
doi: 10.1016/j.semarthrit.2021.09.001
pii:
doi:

Substances chimiques

Intercellular Signaling Peptides and Proteins 0
Adenosine Deaminase EC 3.5.4.4

Types de publication

Journal Article Systematic Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

1170-1179

Informations de copyright

Copyright © 2021 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare no conflict of interest for this study.

Auteurs

Antoine Fayand (A)

Sorbonne Université, AP-HP, Tenon hospital, Department of Internal Medicine, Centre de référence des maladies auto-inflammatoires et des amyloses d'origine inflammatoire (CEREMAIA), Paris, France.

François Chasset (F)

Sorbonne Université, AP-HP, Tenon Hospital, Department of Dermatology, Paris, France.

David Boutboul (D)

AP-HP, Saint-Louis Hospital, Department of Clinical Immunology, Paris University, Paris, France.

Viviane Queyrel (V)

Pasteur 2 Hospital, Department of Rheumatology, Cote d'Azur University, Nice University Hospital, Nice, France.

Nathalie Tieulié (N)

Pasteur 2 Hospital, Department of Rheumatology, Cote d'Azur University, Nice University Hospital, Nice, France.

Isabelle Guichard (I)

Hôpital Nord, Department of Internal Medicine, Jean Monnet University, Saint-Etienne University Hospital, Saint-Etienne, France.

Nicolas Dupin (N)

AP-HP, Cochin Hospital, Department of Dermatology, Paris Universisty, Paris, France.

Nathalie Franck (N)

AP-HP, Cochin Hospital, Department of Dermatology, Paris Universisty, Paris, France.

Pascal Cohen (P)

Service de Médecine Interne, Centre de Référence des Maladies Auto-Immunes Systémiques Rares d'Ile de France, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France, Université de Paris, Paris F-75006, France.

Didier Bessis (D)

Saint-Eloi Hospital, Department of Dermatology, Montpellier University, Montpellier University Hospital, Montpellier, France.

Guillaume Le Guenno (GL)

Estaing Hospital, Department of Internal Medicine, Clermont-Auvergne University, Clermont Ferrand University Hospital, Clermont Ferrand, France.

Isabelle Koné-Paut (I)

AP-HP, Bicêtre Hospital, Department of Pediatric Rheumatology, Paris-Saclay University, Le-Kremlin-Bicêtre, France.

Alexandre Belot (A)

Hospices Civils de Lyon, Femme Mère Enfant Hospital, Centre de référence des rhumatismes inflammatoires et maladies autoimmunes de l'enfant (RAISE), Lyon University, Lyon, France.

Axelle Bonhomme (A)

Metz-Thionville Regional Hospital, Department of Dermatology, Metz, France.

Stéphanie Ducharme-Bénard (S)

Hôpital du Sacré-Cœur de Montréal, Department of Internal Medicine, Montreal, QC, Canada.

Gilles Grateau (G)

Sorbonne Université, AP-HP, Tenon hospital, Department of Internal Medicine, Centre de référence des maladies auto-inflammatoires et des amyloses d'origine inflammatoire (CEREMAIA), Paris, France.

Guillaume Sarrabay (G)

Arnaud de Villeneuve Hospital, Laboratory of rare and autoinflammatory genetic diseases, Centre de référence des maladies auto-Inflammatoires et des amyloses d'origine inflammatoire (CEREMAIA), Montpellier University, Montpellier University Hospital, Montpellier, France.

Isabelle Touitou (I)

Arnaud de Villeneuve Hospital, Laboratory of rare and autoinflammatory genetic diseases, Centre de référence des maladies auto-Inflammatoires et des amyloses d'origine inflammatoire (CEREMAIA), Montpellier University, Montpellier University Hospital, Montpellier, France.

Guilaine Boursier (G)

Arnaud de Villeneuve Hospital, Laboratory of rare and autoinflammatory genetic diseases, Centre de référence des maladies auto-Inflammatoires et des amyloses d'origine inflammatoire (CEREMAIA), Montpellier University, Montpellier University Hospital, Montpellier, France.

Sophie Georgin-Lavialle (S)

Sorbonne Université, AP-HP, Tenon hospital, Department of Internal Medicine, Centre de référence des maladies auto-inflammatoires et des amyloses d'origine inflammatoire (CEREMAIA), Paris, France. Electronic address: sophie.georgin-lavialle@aphp.fr.

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