Down Syndrome-Associated Arthritis (DA): Diagnostic and Management Challenges

Down syndrome (DS) is one of the most common birth defects in the United States, the most common genomic disorder of intellectual disability, and results from trisomy 21. This chromosome disorder causes an extensive, heterogenous phenotype that results in a broad presentation of symptoms that includes atlantoaxial instability, congenital heart defects, muscle hypotonia, hypothyroidism, hematologic disorders, recurrent infections, and autoimmune diseases. The autoimmune diseases are caused by immune system dysregulation that results in increased pro-inflammatory cytokines, along with other innate and adaptive immune system dysregulation. This is the likely cause of the increased risk of inflammatory arthritis or Down syndrome-associated arthritis (DA) seen in individuals with DS. Most individuals with DA present with polyarticular (five or more joints with arthritis at presentation of disease), rheumatoid factor and anti-nuclear antibody negative disease that is aggressive with bone and joint damage at presentation. There is notable delay in diagnosis of DA as there are no formal guidelines on screening or monitoring for inflammatory arthritis in individuals with DS. Once diagnosed, and despite aggressive therapy with disease modifying antirheumatic drugs, disease burden is high for those with DA. Therapy can also be challenging for those with DA as many require second and third-line disease modifying therapies. Many also struggle with medication toxicity and ineffectiveness that further causes challenges with management and outcomes. The purpose of this current review is to provide an up-to-date summary of the literature related to DA in children and adolescents with focus on presentation, diagnosis, and management considerations, along with current barriers that inhibit optimal care.