Have we been giving kids juvenile idiopathic arthritis inadvertently? / by Methods Man

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For the video version of this post, click here. If you’ve ever taken care of a kid with juvenile idiopathic arthritis, it sticks with you.  This disease, which is occasionally referred to as juvenile rheumatoid arthritis, isn’t fatal, but it can rob children of the ability to be active, play, and grow - the real essence of childhood. And to date, we still don’t know what causes it.  It’s clearly auto-immune, but there isn’t even a serologic test for the disease.

An article appearing in Pediatrics, from Daniel Horton, and - full disclosure - several of my former Penn colleagues - links antibiotic exposure in childhood to the subsequent development of JIA.

The researchers used the huge Health Improvement Network dataset, which captures much of the primary care activities that go on in the United Kingdom.  Examining over 140,000 children, they found 152 cases of JIA, and matched them based on age and gender to 10 controls each.  The bottom line?  88% of cases had been exposed to antibiotics.  75% of controls had been exposed.

Of course, you get antibiotics for infections. And cases were more likely to have infections as well: 93% versus 85%.  A question and an observation, then.  Question: is it the infection that causes the JIA and the antibiotics are just a bystander? Observation: man, we give a lot of antibiotics to kids.

The authors did a tremendous job putting the blame on antibiotics here.  With multivariable adjustment, infection fell away as a risk factor - antibiotics persisted. There was a dose-response finding as well - more antibiotic courses were associated with higher risk.  There was also a temporal component - there was a higher risk of JIA if antibiotics were given within a year of the index date compared to earlier time points. Finally, they tried to rule out reverse causation by considering the diagnosis of JIA whenever the first symptom (like limp or joint pain) appeared.

Bottom line? I believe that this finding is real.  Whether the offered explanation - that antibiotics affect the intestinal microflora and alter immunity - is true remains to be seen, of course.

But I want to use this study to illustrate one issue that plagues almost every study of risk factors - and that is a failure to give us a sense of the attributable risk.  In other words - how many of the cases of JIA can be explained by antibiotic use, compared to other possible risk factors (like the things that went into the multivariable adjustment)? Can every case of JIA be traced back to some antibiotic exposure? Of course not - but how much of the variation is explained by this variable.  That’s the information we need to actually counsel our patients.

One thing this study does is open the door to future research.  Given the microflora argument, that research will likely involve a lot of stool collections.  And that, my friends, is why I’m occasionally glad that I’m a nephrologist.