Conference Coverage

Down syndrome arthritis: Distinct from JIA and missed in the clinic



– Pediatric Down syndrome arthritis is more aggressive and severe than juvenile idiopathic arthritis (JIA), but it’s underrecognized and undertreated, according to reports at the annual meeting of the American College of Rheumatology.

Dr. Jordan Jones, University of Missouri, Kansas City M. Alexander Otto/MDedge News

Dr. Jordan Jones

“The vast majority of parents don’t know their kids are at risk for arthritis,” and a lot of doctors don’t realize it, either. Meanwhile, children show up in the clinic a year or more into the process with irreversible joint damage, said pediatric rheumatologist Jordan Jones, DO, an assistant professor at the University of Missouri, Kansas City, and the lead investigator on a review of 36 children with Down syndrome (DS) in the national Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry.

One solution is to add routine musculoskeletal exams to American Academy of Pediatrics DS guidelines, something Dr. Jones said he and his colleagues are hoping to do.

Part of the problem is that children with DS have a hard time articulating and localizing pain, and it’s easy to attribute functional issues to DS itself. Charlene Foley, MD, PhD, from the National Centre for Paediatric Rheumatology in Dublin, said she’s seen “loads of cases” in which parents were told that their children were acting up, probably because of the DS, when they didn’t want to walk down stairs anymore or hold their parent’s hand.

Dr. Charlene Foley of the National Centre for Pediatric Rheumatology in Dublin M. Alexander Otto/MDedge News

Dr. Charlene Foley

She was the lead investigator on an Irish program that screened 503 DS children, about one-third of the country’s pediatric DS population, for arthritis; 33 cases were identified, including 18 new ones. Most of the children had polyarticular, rheumatoid factor–negative arthritis, and all of them were antinuclear antibody negative.

A key take-home from the work is that DS arthritis preferentially attacks the hands and wrists and was present exclusively in the hands and wrists of about one-third of the Irish cohort. “So, if you only have a second to examine a child or you can’t get them to sit still, just go straight for the hands, and have a low threshold for imaging,” Dr. Foley said.

DS arthritis is often considered a subtype of JIA, but findings from the studies call that into question and suggest the need for novel therapeutic targets, the investigators said.

The Irish team found that 42% of their subjects (14 of 33) had joint erosions, far more than the 14% of JIA children (3 of 21) who served as controls, and Dr. Foley and colleagues didn’t think that was solely because of delayed diagnosis. Also, at about 20 cases per 1,000, they estimated that arthritis was far more prevalent in DS than was JIA in the general pediatrics population.

Disease onset was at a mean of 7.1 years in Dr. Jones’ CARRA registry review, and mean delay to diagnosis was 11.5 months. The 36 children presented with an average of four affected joints. Only 22% (8 of 36) had elevated inflammatory markers; just one-third were positive for antinuclear antibody, and 17% for human leukocyte antigen B27. It means that “these kids can present with normal labs, even with very aggressive disease. The threshold of concern for arthritis has to be very high when you evaluate these children,” Dr. Jones said.

Treatment was initiated with disease-modifying antirheumatic drugs (DMARDs) in two-thirds of the registry children, often with a concomitant biologic, most commonly etanercept. Over half had at least one switch during a mean follow-up of 4.5 years; methotrexate was a leading culprit, frequently discontinued because of nausea and other problems, and biologics were changed for lack of effect. Active joint counts and physician assessments improved, but there were no significant changes in limited joint counts and health assessments.

In short, “the current therapies for JIA appear to be poorly tolerated, more toxic, and less effective in patients with Down syndrome. These kids don’t respond the same. They have a very high disease burden despite being treated aggressively,” Dr. Jones said.

That finding adds additional weight to the idea that DS arthritis is a distinct disease entity, with unique therapeutic targets. “Down syndrome has a lot of immunologic issues associated with it; maybe that’s it. I think in the next few years, we will be able to show that this is a different disease,” Dr. Jones said.

There was a boost in that direction from benchwork, also led and presented by Dr. Foley, that found significant immunologic, histologic, and genetic differences between JIA and DS arthritis, including lower CD19- and CD20-positive B-cell counts in DS arthritis and higher interferon-gamma and tumor necrosis factor–alpha production, greater synovial lining hyperplasia, and different minor allele frequencies.

There was no industry funding for the studies, and the investigators didn’t have any industry disclosures.

SOURCES: Jones J et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 2722; Foley C et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 1817; and Foley C et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 781

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