Juvenile idiopathic arthritis (JIA), a cluster of chronic joint conditions affecting children, was once termed “juvenile rheumatoid arthritis.” So it’s little wonder that it was often considered a pint-sized version of rheumatoid arthritis. However, the relationship between JIA and RA is much more complex.
Moreover, if you browse the Internet, you can find plenty of references suggesting that kids eventually “outgrow” JIA. “At our first meeting with parents, we try to remove that misperception,” says Robert P. Sundel, MD, director of rheumatology at Boston Children’s Hospital. The truth is, says Dr. Sundel, that in most people with JIA, the symptoms may wax and wane over time but will likely require treatment into adulthood.
The joint pain, swelling, fatigue and other symptoms of JIA can fade away over months or years in a small portion of patients, usually in children diagnosed at a very young age with mild oligoarthritis (the most common form of childhood arthritis, which affects fewer than five joints and is usually diagnosed in girls 8 or younger). However, these patients may still develop inflammation of the eyes, known as uveitis, which can last into adulthood and require regular exams by an ophthalmologist. That hints at a stark reality: JIA is not simply a kid’s version of RA.
More Than Junior RA
By age 17 or 18, most people with juvenile idiopathic arthritis stop seeing a pediatric rheumatologist and get a referral to a rheumatologist who treats adults. The doctor may informally use the term “rheumatoid arthritis” to describe the condition of his or her new patient. But “it’s still juvenile arthritis,” says nurse practitioner Janalee Taylor, associate clinical director of rheumatology at Cincinnati Children’s Hospital. Taylor explains that age of onset is the important factor in determining what to call the condition. So if a man or woman grew up with JIA, he or she is best described as an adult with a history of juvenile arthritis, says Taylor.
There are good reasons to make that distinction, she notes. “Juvenile idiopathic arthritis is probably a different disease from rheumatoid arthritis,” says Taylor. Doctors remain somewhat mystified by JIA – the word “idiopathic” means “of unknown origin” – and researchers are still trying to understand its precise relationship with RA. But while the two diseases may share some similarities, they also have striking differences – in most cases.
Like RA, JIA is brought on by chronic, runaway inflammation that makes joints stiff and sore, and can become disabling if left untreated. But JIA isn’t a single disease – it’s actually several different related conditions that fall under one umbrella name. The various types of JIA are distinguished by their features, such as how many joints are affected (just a few or many) and their accompanying symptoms, which can include severe skin scaling and pitting of fingernails (psoriatic arthritis) or a salmon-colored skin rash and high fever (systemic arthritis).
Doctors diagnose JIA when a child of 16 or younger develops persistent joint pain and related symptoms that last for six months or longer. A small number of these children – about 5 percent – actually have RA, says rheumatologist Timothy Beukelman, MD, an associate professor of pediatrics at the University of Alabama at Birmingham. The typical patient who falls into this category is a post-pubescent teenage girl with five or more tender, stiff joints, usually in matching pairs on both sides of the body (such as both wrists), which are common symptoms of RA. Also, blood tests will reveal that she has high levels of antibodies (proteins produced by the immune system) called rheumatoid factor (RF), which is true of most adults who have RA.
Although this girl’s symptoms strongly resemble RA, a pediatric rheumatologist will most likely diagnose her with a form of JIA known as RF-positive polyarthritis. “On the other hand, when a patient develops arthritis at age 20, she’ll see an adult rheumatologist and get diagnosed with RA,” says Dr. Beukelman. “Biologically speaking, once children go through puberty, they’re more or less adults. But as far as we can tell, these two patients really have the same disease.”
Beukelman stresses that the vast majority of children diagnosed with JIA do not have RA, nor do they have elevated RF antibodies.
A Disease in Transition
Adults with RA and JIA both appear to have an increased risk for heart disease, as well as lymphoma and related forms of cancer. However, adults with JA can develop associated health issues that are uncommon in people with RA. As mentioned earlier, an eye condition called uveitis that’s virtually nonexistent in adults with RA can afflict some people with JIA; past research indicates that about one in five patients with this eye condition will eventually develop cataracts, glaucoma, or partial blindness.
What’s more, the combination of chronic inflammation and treatment with corticosteroids in youth can stunt bone growth; past studies have shown that about half of adults who were diagnosed with systemic arthritis as children are significantly shorter than their peers. People with JA tend to have fragile bones, too, probably due to a combination of the disease, the use of corticosteroids, and lack of exercise. A 1999 study found that 7 percent of young adults with JIA (average age: 32) already had osteoporosis, which usually doesn’t emerge until midlife.
Disability is common among adults with JIA today. “We have patients who are anywhere from 30 to 60 years old who have many, many damaged joints,” says rheumatologist Peter Nigrovic, MD, director of the Center for Adults with Pediatric Rheumatic Illness (CAPRI) at Boston’s Brigham and Women’s Hospital.
That can affect a patient’s personal life: In the past, studies have revealed that adults with JA are less likely to marry and have children, and often struggle to find jobs. But that may be changing. “This is all data from older studies, when these patients were very commonly deformed,” says Dr. Nigrovic. “That’s just not the case very much anymore.”
What’s changed? JIA has important similarity with RA: Both conditions respond well to disease-modifying anti-rheumatic drugs (DMARDs) that have become available in recent years, including methotrexate and the various biologic agents, such as the tumor necrosis factor (TNF) inhibitors etanercept (Enbrel), adalimumab (Humira), and others.
These medications have brightened the long-term outlook for children with JIA, to say the least. When Taylor began treating children with arthritis 32 years ago, it wasn’t unusual for some boys and girls to end up in wheelchairs. That’s almost unheard of today. “Studies show that the majority of kids who receive adequate medical therapy – 70 to 90 percent – have satisfying outcomes and no disability,” says Taylor.
However, while treatment plans are similar for adults with both diseases, at least one form of JIA seems to respond best to a medication that’s infrequently used to treat RA. A Dutch study published online in Annals of the Rheumatic Diseases last June found that children with systemic JIA whose arthritis wasn’t well controlled with etanercept improved more if they took anakinra (Kineret) instead of adding another TNF inhibitor.
Taylor explains that while the inflammation causing RA seems to be driven largely by TNF, systemic arthritis is probably triggered by another class of cytokines known as interleukins, which anakinra stifles. Earlier studies found that another drug that blocks interleukins, tocilizumab (Actemra), is effective for JIA, too.
Whether taking DMARDs from a young age for many years will cause ill effects in adulthood is still unclear. “We don’t have any data that there’s a problem there,” says Dr. Nigrovic. “We just don’t know.” As the first generation of patients with JIA who have access to these new and greatly improved medications grows up, doctors will undoubtedly learn more.