Daniel J. Lovell, MD, MPH: Juvenile Idiopathic Arthritis

This week, Rheumatology Network sat down with Daniel J. Lovell, MD, MPH, to discuss his study, “Prevalence of autoimmune diseases and other associated conditions in children and young adults with juvenile idiopathic arthritis.” Lovell is the professor of pediatrics at the Cincinnati Children’s Hospital Medical Center, as well as the Joseph E. Levinson Endowed Chair of Pediatric Rheumatology. During our deep dive into juvenile idiopathic arthritis (JIA), we explore which factors may impact the likelihood of developing JIA and why patients with JIA are more likely to develop coexisting autoimmune diseases and other conditions. For those who want more information, Rheumatology Network covered this study earlier in the week.

Rheumatology Network: Hi, Dr. Lovell, thank you for joining me today. To begin, what initially interested you in studying juvenile idiopathic arthritis (JIA)?

Daniel J. Lovell, MD, MPH: Well, so I'm a pediatric dermatologist and juvenile idiopathic arthritis has been the focus of my research for my entire career. But to put juvenile idiopathic arthritis in perspective, it's the most common rheumatic disease in childhood. And it's one of the more common chronic diseases of childhood. So, it was a natural focus for me to gravitate towards looking at juvenile idiopathic arthritis.

RN: Although the causes of the disease are relatively unknown, do you have any personal theories as to what may impact the likelihood of a child developing JIA?

DL: Well, the general thought is that for many children, there's a genetic predisposition. And then exposure to something in the environment triggers that child to develop arthritis. The reason there's a two-part mechanism here is that none of the genetic associations identified to date anyway have been found exclusively in patients with JIA. E ach of them is also found in healthy children. So, there's something else that needs to be involved in the actual triggering of the disease. We haven't identified that particular environmental trigger or there may be more than 1 trigger. But that's the current theory.

RN: Why do you believe JIA patients are more likely to develop coexisting autoimmune diseases and other conditions?

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DL: Well, it's known for any given autoimmune disease that developing that 1 autoimmune disease is a permissive mechanism. So that your own immune system is supposed to only form antibodies or other immune-mediated responses against foreign tissues or tissues within your own body, they're found to be dysfunctional, like over age, red blood cells, or tumor cells, or cancer cells. So, if people develop autoimmune diseases, that immune mechanism is misdirected against your own tissues. And once that kind of immune signaling is confused that people are now making antibodies against your own tissues that can sometimes cascade into multiple cells being targeted by the immune system. So, it's been known for almost all autoimmune diseases that having 1 autoimmune disease increases your risk for having others. So that's the fact that JIAA is associated with other autoimmune diseases isn't a new finding. What's new about our studies, we took a more comprehensive look at a larger number of other diseases that might be associated than had been done in prior publications. But other publications showed that there's an increased frequency of development of autoimmune thyroiditis, psoriasis, uveitis. In fact, some of these auto other autoimmune associations are so frequent, they've actually been incorporated into the diagnostic criteria for JIA. So, for example, there is a subset of children with JIA, who have not only arthritis, but they also have psoriasis. And that happens often enough that we just made it another JIA category. Okay. So, it's not a new findings, just as this paper looked at a longer list of other autoimmune diseases of associated conditions that have been in publication previously.

RN: Can you discuss the limitations of the study?

DL: Well, it was a single-center study. Although we were able to garner a large number of cases and we were able to use the electronic medical record here at Children's to capture information on a very large number of healthy children, as well as a large number of JIA patients, it’s still a single center study. So the extent that the risk for these other autoimmune diseases is genetically influenced. The findings of this primarily white, Caucasian population may not generalize to say a study done in children from India or Japan who were very different genetic influences. And also environmental influences may play a role. So, I think that's the 1 kind of large shortcoming to study. The other one, I guess, is that we were dependent on the diagnosis listed for the patient in their electronic medical record. We sought to mitigate that weakness by requiring that the patient have JIA diagnosis listed their medical record at least twice in separate visits to try to ensure that it's, you know, kind of a persistent thought about that patient in terms of having that disease.

RN: Is your team planning on doing any further research on the topic?

DL: Yes, so the next step is since we've seen that with JIA, there's a large number of other associated diseases and associated conditions, we're now looking to see if we can figure out what might influence a particular JIA patient to get a particular other autoimmune diseases. And 1 of the things we're looking at is if exposure to certain drugs may increase the risk for JIA patients to develop certain other diseases. For example, there's data in the literature to suggest exposure to anti-TNF agents in JIA patients may increase the risk of getting psoriasis. So, we're going to test that association of this database, as well as other possible drug-related associations. And look at drugs other than just anti-TNF agent says for the JIA patients, we have the full history of all the drug exposure that any 1 patient can have. We can use that robust data, drug exposure history to assess risk for other autoimmune diseases.

RN: Is there anything else that you'd like to add about the study or JIA in general before we wrap up?

DL: Well, I think people need to understand that JIA is one of the more common chronic diseases in children. And lots of data has shown that the critical piece for improving the short-term and long-term outcome of children with JIA is early treatment and early effective treatment to control the disease so that there is a window of opportunity in terms of treatment, that if the disease is brought under excellent control during that window of opportunity, then it has both short-term and long-term impacts on the outcome of the child. So, it's very important that these children be referred quickly into the care of a person who's experienced in treating JIA so the appropriate treatments are introduced in a timely fashion. So that's the I think key take home message for JIA as if you think a child has JIA, get them to a person experienced in the treatment of those patients quickly.

RN: Well said. Well, Dr. Lovell, thank you so much for joining me today. I really appreciate it.

DL: You're welcome.