GLASGOW (FRONTLINE MEDICAL NEWS) Children with Down syndrome are at increased risk for arthritis that often goes unrecognized and leads to treatment delays and potential chronic disability.

Research presented at the British Society for Rheumatology annual conference highlighted how Down arthropathy is not only more prevalent than idiopathic juvenile arthritis (JIA), but also has distinct clinical and radiographic features.

“Our research to date has shown that there is a significant increased risk of arthritis in children with trisomy 21, and higher than that previously reported,” said Dr. Charlene Foley, a research fellow at Our Lady’s Children’s Hospital in Dublin.

“There is a significant delay in diagnosis, which may be a cause of the x-ray changes at diagnosis, or it may be in fact that Down arthropathy is more aggressive,” than other childhood forms of arthritis, she observed.

Dr. Foley noted that Down arthropathy was first reported in the medical literature about 30 years ago and crude estimates suggested a prevalence of around 8.7 cases per 1,000 children versus 1 per 1,000 for JIA. However, the research she presented put the crude point prevalence at 18-21 per 1,000 children.

Dr. Foley presented the findings of an observational study conducted in the Republic of Ireland in which children with trisomy 21 and their families were identified from a variety of sources and invited to participate. After completion of a screening questionnaire and an appointment local to the participants, children who were suspected of having arthritis were invited to attend a consultant appointment. They underwent a clinical management pathway developed for JIA because no specific pathway had been developed for the children at that time, with follow-up appointments held every 3-6 months depending on the child’s needs.

Over an 18-month period, 503 children with trisomy 21 and a mean age of 8 years were screened. They had a range of musculoskeletal anomalies, the most common of which were flat feet in almost all the children (91.1%), inflammatory arthritis in 7.1%, and scoliosis in 4.8%. Many other problems occurred, with an incidence of 1.5% or less for each.

A total of 22 new cases of Down arthropathy have been identified to date, in addition to 11 at the clinic who predated the start of the study. About 75% have come through the screening clinics and the rest through pediatricians’ referral.

“It is a challenging disease both in terms of diagnosis and management,” Dr. Foley said. Of all the identified children, 91% had poor language skills or nonverbal communication and 15% had autism spectrum disorder.

On average, the time to diagnosis of the arthropathy was 1.7 years versus 0.74 years for a control group of 33 children with JIA. This is likely an underestimation, however, as 42% of the children or parents in the Down arthropathy cohort were unable to give a date on which symptoms had started.

Dr. Foley reported that the majority of trisomy 21 children had presented with polyarticular arthritis, mostly involving the proximal interphalangeal joints of the hands (78.6% of cases), or the wrists (53.6% of cases). There was significant small joint involvement (88% vs. 43% of the JIA cohort), and higher restricted joint counts (4.5 vs. 2.0). There were also differences in erythrocyte sedimentation rate and C-reactive protein at diagnosis, with these being “barely raised” in children with Down arthropathy versus children with JIA, so unlikely to aid a diagnosis. Children were also found to be rheumatoid factor negative.

Two-thirds of Down arthropathy cases had x-ray changes at presentation versus 24% of the JIA group, of which 29% versus 9.5% were erosive.

Treatment is complicated by drug-related side effects, with many children unable to tolerate methotrexate, Dr. Foley said. In the Irish cohort, treatment with methotrexate led to nausea in 75%, compared with 7.1% of the JIA children. Although reports are limited, methotrexate intolerance has been shown in children with trisomy 21, so there could be a genetic or metabolic reason behind this. Dr. Foley noted that they manage this problem by starting methotrexate on the lowest possible doses (10 mg/m2) and co-administering the antiemetic ondansetron. They have a low threshold for switching to an anti-TNF drug if needed, and have also started giving biologic drugs to some newly diagnosed children.

“The take-home message is to think outside of the Down syndrome box and don’t just blame everything on Down syndrome,” Dr. Foley said. As it may be challenging to examine a child, she suggested looking at the hands first because they are the most likely to be affected.

“We feel that a musculoskeletal assessment should be part of the annual surveillance for all children with Down syndrome,” she concluded.

As for who should conduct such an assessment, Dr. Foley suggested that general pediatricians who are regularly seeing these children for other health checks should perform it. However, as one delegate observed, nonrheumatology professionals may need a little training and guidance, as musculoskeletal assessments can be difficult. Looking only at the hands, and potentially the feet, may be one solution.

The study has raised a number of questions and future research will be needed to further characterize the arthritis and to determine how best to diagnose and treat it, noted Dr. Foley, who indicated that she had no conflicts of interest.


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