Antoine Fayand1, François Chasset2, David Boutboul3, Viviane Queyrel4, Nathalie Tieulié4, Isabelle Guichard5, Nicolas Dupin6, Nathalie Franck6, Pascal Cohen7, Didier Bessis8, Guillaume Le Guenno9, Isabelle Koné-Paut10, Alexandre Belot11, Axelle Bonhomme12, Stéphanie Ducharme-Bénard13, Gilles Grateau1, Guillaume Sarrabay14, Isabelle Touitou14, Guilaine Boursier14, Sophie Georgin-Lavialle15. 1. 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. 2. Sorbonne Université, AP-HP, Tenon Hospital, Department of Dermatology, Paris, France. 3. AP-HP, Saint-Louis Hospital, Department of Clinical Immunology, Paris University, Paris, France. 4. Pasteur 2 Hospital, Department of Rheumatology, Cote d'Azur University, Nice University Hospital, Nice, France. 5. Hôpital Nord, Department of Internal Medicine, Jean Monnet University, Saint-Etienne University Hospital, Saint-Etienne, France. 6. AP-HP, Cochin Hospital, Department of Dermatology, Paris Universisty, Paris, France. 7. 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. 8. Saint-Eloi Hospital, Department of Dermatology, Montpellier University, Montpellier University Hospital, Montpellier, France. 9. Estaing Hospital, Department of Internal Medicine, Clermont-Auvergne University, Clermont Ferrand University Hospital, Clermont Ferrand, France. 10. AP-HP, Bicêtre Hospital, Department of Pediatric Rheumatology, Paris-Saclay University, Le-Kremlin-Bicêtre, France. 11. 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. 12. Metz-Thionville Regional Hospital, Department of Dermatology, Metz, France. 13. Hôpital du Sacré-Cœur de Montréal, Department of Internal Medicine, Montreal, QC, Canada. 14. 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. 15. 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.
Abstract
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.
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.