Trisomy 21 and Juvenile Idiopathic Arthritis: Relevance of Chromosomal Aberrations for the Diagnostic Assessment of Arthritis

Rationale: Various chromosomal disorders have been suspected to increase the risk of juvenile idiopathic arthritis (JIA). In addition, especially in children with Down syndrome (trisomy 21), there is uncertainty regarding treatment with DMARDs as these patients are also at a higher risk of developing AML. Methods: In a retrospective case series of our own patients, we evaluated the typical distribution pattern and inflammatory activity of patients with trisomy 21 and JIA (T21-JIA) and their response to methotrexate as well as adverse drug reactions as compared to other patients with seronegative polyarticular JIA (SNP-JIA). Results: Eleven T21-JIA patients were included in the study (6 female/5 male) with a median age at diagnosis of 6 years (range 1-13 years). 9 T21-JIA patients (82%) had a polyarticular course of arthritis and were treated with methotrexate. T21-JIA patients had a significantly higher total joint count of active and painful arthritis at the time of diagnosis (T-21 JIA 19.9 (+/- 10.9) vs. SNP-JIA 15.5 (+/- 6.5)). 7 out of 10 (70%) T-21-JIA patients presented with SNP-JIA, which is above the expected frequency (expected percentage according to the ILAR classification: SNP 13-15%). One T21-JIA patient had systemic, one had persistent and 2 had extended oligoarticular JIA. During the follow-up period, 81% of T21-JIA patients developed joint contractures. Notably there was no T21-JIA patient with JIA-associated uveitis. Response rates to methotrexate and frequency of adverse drug reactions (ADR) were comparable between T21-JIA patients and a matched comparative sample. Conclusion: T21-JIA patients frequently have a higher joint count of active arthritis at the time of diagnosis and a decreased range of motion in the course of disease, but there is no difference in response to methotrexate and adverse drug reactions compared to patients with a normal caryotype. Patients with other chromosomal aberrations, especially Turner (monosomy XO), Klinefelter (poly-X, XXY) and Di George syndrome (del 22q11.2), are suspected to have an increased risk for JIA as well.