Kids with Down syndrome have an increased risk of arthritis 1060636728

Delayed diagnosis leads to joint damage

By Katie Bell

Arthritis in Down syndrome, or Down syndrome arthropathy, remains underrecognized, according to research from Kansas City, Missouri, that found that while treatment with several classes of medications leads to a significant reduction in active and limited joints, treatment approach, optimal therapy, and escalation are unclear.

“There is a nineteen-month average delay in diagnosis of Down syndrome arthropathy from symptom onset,” said lead author Jordan T. Jones, DO, MS, assistant professor of pediatrics in the Division of Rheumatology at Children’s Mercy Hospital in Kansas City. “Due to the delay, many patients present with bony changes seen on imaging studies and irreversible joint damage, which contributes to worse prognoses with functional limitations in a population that is already at risk for delayed motor skills and functional limitations.”

Awareness of the link between Down syndrome and arthritis among both practitioners and parents is generally low, and is a major reason for under-recognition, he suggested. “Additionally, the matter is made more complex by the underlying risk of delayed motor skills and functional limitations due to hypotonia and ligamentous laxity that are commonly seen in children with Down syndrome,” Jones said.

He and his colleagues completed a retrospective chart review at two tertiary care hospitals, identifying through a decade of electronic medical records (1995-2015) patients younger than 18 years with both Down syndrome and juvenile idiopathic arthritis (JIA). The 43 patients (58% female) included in the study had a mean age of 7.4 years at onset of musculoskeletal symptoms, with a mean 19 months to JIA diagnosis.

At JIA diagnosis, 63% of participants presented with polyarticular rheumatoid factor negative disease; 70% reported morning stiffness, with an average of 15 active joints; and 14 presented with limited joints. The mean physician global assessment of disease activity was 4.5 (out of 10).

Down syndrome arthropathy is rarely recognized at symptom onset and remains underdiagnosed.

Most patients (93%) were prescribed nonsteroidal anti-inflammatory drugs (NSAIDs) at diagnosis, with 28% simultaneously starting a disease-modifying anti-rheumatic drug (DMARD) and 5% a biologic. Over the course of disease, 74% of participants used a DMARD (94% of these took methotrexate) and 47% a biologic (83% received etanercept). Meanwhile, 25% and 39% of patients had at least one change in DMARD or biologic therapy, respectively.

At the last visit (mean follow-up of 6 years), there were significantly fewer active and limited joints, and mean physician assessment of global disease activity was 1.3. Among those prescribed DMARD therapy, 60% discontinued it due to side effects, while 39% of those prescribed a biologic had an inadequate response. Jones noted that kids with Down syndrome had more issues with adverse effects and were more likely than children with JIA alone to have an inadequate response to therapy. The findings were presented in October at the American College of Rheumatology annual meeting in Chicago.

A study presented last year at the British Society for Rheumatology’s annual conference also found that Down syndrome arthropathy is rarely recognized at onset and remains underdiagnosed. Additionally, first author and pediatric rheumatology fellow Charlene Foley, MBBS, BSc, MRCPCH, and her colleagues at Our Lady’s Children’s Hospital in Dublin, Ireland, observed that Down syndrome arthritis is more prevalent than JIA and has distinct clinical and radiographic features.

Foley and her colleagues in their clinic screened 503 children with Down syndrome for arthritis, diagnosing 22 new cases. Combining those cases with cases in clinic predating the start of the study brought the total to 33 children. “This suggests the prevalence of Down syndrome arthropathy in Ireland is eighteen to twenty-one in a thousand,” said Foley. The estimated prevalence of JIA is 1/1000.

Foley and colleagues, who included in the study a convenience sample of 33 children with JIA, found a significant delay in Down syndrome arthropathy diagnosis compared with JIA diagnosis, 1.7 years versus 0.7 years, respectively. Small joint involvement of the hands was significantly higher with Down syndrome arthropathy than in JIA. Those with Down syndrome arthropathy also had more erosive changes than those with JIA, 29.2% and 9.5%, respectively. As with the current study, the Irish researchers noted methotrexate nausea as a barrier to treatment in Down syndrome arthropathy.

“In terms of arthritis, small joint and wrist involvement were most common in children with Down syndrome arthropathy. However, this was followed by involvement of the knees and ankles. This could there-fore have consequences in terms of achieving ambulation in a cohort that often has delayed ambulation compared to children without Down syndrome arthropathy,” Foley said.

“We advocate that all children with Down syndrome have an annual musculoskeletal examination as part of their health surveillance program,” she added. Education aimed at providers and families about Down syndrome arthritis may also lead to early identification and referral for therapy, said Jones.

“Currently, there is no great way to screen patients for Down syndrome arthritis. The best option is a combination of history about morning stiffness, joint swelling or limitation, a good musculoskeletal exam to identify any abnormality, and basic blood tests looking for inflammation,” he said. “It would be helpful to get physical therapy involved earlier to identify and treat the mechanical issues these patients are at risk of developing.”

Katie Bell is a freelance writer based in New York City.


Jones JT, Talib N, Lovell DJ, Becker ML. Treatment and response of Down syndrome arthropathy [abstract]. Arthritis Rheumatol 2018;70(suppl 10).
Foley C, MacDermott E, Killeen O. G269 Down’s arthropathy – Clinical and radiological features of arthritis in children with trisomy 21. Arch Disease Childhood 2017;102:A106.

This entry was posted in Pediatric Clinical News, December, 2018. Bookmark the permalink.

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