Systemic Inflammatory Diseases in Children With Sickle Cell Disease: A French Multicenter Observational Study on Diagnostic and Therapeutic Issues

• Published in: Pediatric blood & cancer Vol. 72; no. 4; pp. e31563 - n/a
• Main Authors: Vinit, Caroline, Guitton, Corinne, De Montalembert, Mariane, Benhaim, Patricia, Amor‐Chelihi, Lahoueri, Bader‐Meunier, Brigitte, Missud, Florence, Melki, Isabelle, Gajdos, Vincent, Arnaud, Cécile, Kamden, Annie, Charara, Oussama, Hentgen, Véronique, Nathanson, Sylvie, Bloch, Coralie, Meinzer, Ulrich, Quartier, Pierre, Kone‐Paut, Isabelle, De Pontual, Loïc, Pham, Luu‐Ly
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.04.2025
• Subjects: Adolescent; Anemia, Sickle Cell - complications; Anemia, Sickle Cell - therapy; antinuclear antibody; Arthritis; Autoantibodies; autoimmune disease; Autoimmune hemolytic anemia; Child; Child, Preschool; Children; Connective tissue diseases; Diagnosis; Female; Follow-Up Studies; France - epidemiology; Granulomatous uveitis; Hematopoietic stem cells; Hemolytic anemia; Humans; Hypergammaglobulinemia; Infant; Inflammation - diagnosis; Inflammation - etiology; Inflammation - therapy; Inflammatory bowel disease; Inflammatory bowel diseases; inflammatory disease; Inflammatory diseases; Liver diseases; Lymphadenitis; Male; Mixed connective tissue disease; Myasthenia gravis; Neuromuscular junctions; Observational studies; Prognosis; Retrospective Studies; Sarcoidosis; Sickle cell disease; Sjogren's syndrome; Statistical analysis; Stem cell transplantation; Steroid hormones; systemic inflammatory disease; Systemic lupus erythematosus; Uveitis; Vasculitis; France; hypergammaglobulinemia; inflammatory disease; systemic inflammatory disease; autoimmune disease; antinuclear antibody; sickle cell disease
• ISSN: 1545-5009; 1545-5017; 1545-5017
• DOI: 10.1002/pbc.31563

ABSTRACT Background Systemic inflammatory diseases (SIDs) have been reported in patients with sickle cell disease (SCD), but clinical data in children are scarce. Objectives To identify clinical and laboratory features at diagnosis of SID in children with SCD and to describe their evolution. Methods Data from children with SCD and SIDs were retrospectively collected in a French multicenter study from 1991 to 2018. Information included clinical characteristics, inflammatory markers, autoantibodies patterns, treatments, and complications. Inflammatory marker levels were compared at SID diagnosis and at the last follow‐up. Statistical analyses were performed using Cran R software. Results Among a cohort of 3800 children with SCD, 43 SIDs were identified in 35 study participants: autoimmune liver disease (AILD, n = 13), inflammatory bowel disease (IBD, n = 7), juvenile idiopathic arthritis (JIA, n = 6), systemic lupus erythematosus (n = 4), autoimmune hemolytic anemia (n = 3), Sjögren syndrome (n = 1), histiocytic necrotizing lymphadenitis (n = 2), vasculitis (n = 2), myasthenia gravis (n = 1), sarcoidosis (n = 1), idiopathic inflammatory granulomatous uveitis (n = 1), mixed connective tissue disease (n = 2). Prevalence of SID was 0.9% in our cohort of children with SCD. The median time between initial symptoms and SID diagnosis was 10 (3–20) months, notably longer in children with JIA, IBD, and Sjögren syndrome. Sixteen patients (46%) exhibited hypergammaglobulinemia (>20 g/L) at diagnosis. No significant differences were observed for other inflammatory parameters. Twenty‐one children (60%) received systemic steroids and 13 (37%) biological therapies. Three patients (9%) underwent hematopoietic stem cell transplantation. Nine patients (26%) had severe infections; one died. Conclusion Delayed diagnosis was frequent due to overlapping clinical presentations between SCD and SID. Clinicians must be aware of warning signs associated with elevated inflammatory markers, hypergammaglobulinemia, or specific antibodies. Therapeutic strategies remain challenging.