Juvenile idiopathic arthritis in DiGeorge syndrome: a case report and literature review

DiGeorge syndrome (DGS) is an inborn error of immunity characterized by wide phenotypic variability, with a broad spectrum of autoimmune manifestations, including autoimmune cytopenias, thyroiditis, and juvenile idiopathic arthritis (JIA). However, the clinical features of JIA in DGS are not fully understood. Here, we report a case of DGS with JIA and provide a comprehensive review to facilitate early diagnosis and management.

A 22-month-old girl had a history of frequent respiratory infections and delayed speech after birth. She also had dysmorphic facial features and developmental delay. She had undergone repair of a ventricular septal defect at 3 months of age, during which the thymus was not visualized. Genetic testing revealed a partial heterozygous deletion of 22q11.2. She presented with inflammatory polyarthritis involving bilateral knees and the left hand for 5 months. Antinuclear antibody (ANA) was positive with a titer of 1:320. Anti-cyclic citrullinated peptide antibody showed weakly positive. Magnetic resonance imaging showed synovitis of the affected joints. The patient experienced frequent respiratory infections and delayed speech after birth. Gene examination showed a partial heterozygous deletion of 22q11.2. Thus, she was diagnosed as DGS with JIA. Etanercept was initiated after 4 months of ineffective treatment with naproxen and methotrexate, and remission was observed after 6 months of treatment. Literature review showed a female predominance (62.7%, 32/51) in this population; 80.4% (41/51) were diagnosed before 6 years of age and 62.7% (32/51) had polyarticular involvement. Moreover, 54.2% (26/48) were positive for ANA. Tumor necrosis factor inhibitors (TNFis), mainly etanercept or adalimumab, were used in 20 cases, with more than half of patients responding well to biologics.

The disease has an early onset and polyarthritis is the most common type. Clinicians should suspect underlying DGS in a child presenting with JIA when accompanied by dysmorphic facial features, recurrent infections, congenital heart disease, hypoparathyroidism with hypocalcemia and hyperphosphatemia, and/or decreased T-cell subsets. Treatment with TNFi should be considered when non-steroidal anti-inflammatory drugs and methotrexate are ineffective. Furthermore, follow-up is essential for monitoring adverse drug reactions and proposing prompt intervention.