The Mysteries of Systemic Juvenile Idiopathic Arthritis

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Unanswered questions remain, but researchers are learning more about systemic juvenile idiopathic arthritis (SJIA) and why it’s different from other types of juvenile arthritis.

The word “idiopathic” in systemic juvenile idiopathic arthritis means the cause isn't known. Although that’s true, researchers have made great progress in understanding many aspects of SJIA, including how it differs from other types of juvenile arthritis. They also have learned what chemicals in the body trigger inflammation, which has led to targeted therapeutic approaches to the treatment of the disease.

How Systemic Juvenile Idiopathic Arthritis Is Different

Unlike other forms of juvenile idiopathic arthritis (JIA) in which most children have arthritis as their main problem, children with SJIA typically also have systemic symptoms—problems throughout the body, including fever, rash, and inflammation of organs such as the liver or spleen. Arthritis may not occur until weeks or months later and can persist long after the fever and other systemic symptoms have disappeared. A rare, life-threatening complication called macrophage activation syndrome (MAS) is closely associated with SJIA. MAS can occur in any rheumatic disease, but for reasons that aren't clear, an estimated 80 percent of cases are associated with SJIA. Even the disease process—and the role of the immune system itself—are unique to SJIA.

Role of the Immune System in Systemic Juvenile Idiopathic Arthritis

The body has two types of immunity—innate and adaptive. The innate immune system is fully active at birth and is the first line of defense against infection. The adaptive immune system continues to develop throughout life. Its role is to target viruses and bacteria that slip past the innate immune system. It does this by producing antibodies that attach to invading organisms so the body can destroy them.

Most forms of JIA develop when the adaptive immune system doesn't work properly. It becomes overactive, mistakenly attacking healthy cells and tissues. Disorders in which the adaptive immune system targets the body itself are called autoimmune diseases.

Until recently, SJIA was considered an autoimmune disease, like other types of JIA, but the latest research suggests SJIA may be an autoinflammatory condition instead. In autoinflammatory disorders, it’s the innate immune system that is activated, even when there is no infection to fight.

Several factors have led researchers to think that SJIA is an autoinflammatory disease. For one thing, children with SJIA usually don't have autoantibodies in their blood. Autoantibodies are formed when the adaptive immune system attacks healthy tissue instead of harmful organisms.

But kids with SJIA do have high blood levels of two powerful inflammatory proteins (cytokines) called interleukin-1 (IL-1) and interleukin-6 (IL-6). These proteins are known to cause inflammation in other autoinflammatory diseases and are believed to trigger inflammation in SJIA.  Discovering the important role cytokines play in SJIA has led to the development of drugs that block them—a targeted approach to treating the disease.

Questions That Remain About Systemic Juvenile Idiopathic Arthritis

Although understanding how SJIA works is important, there are other questions that must be answered, especially what causes it in the first place. Some experts believe an initial infection triggers the innate immune system to overreact. Others believe the disease is caused by problems with the genes that control the innate immune system. Most believe both may be involved.

Researchers are also trying to figure out why SJIA goes away in a few years in some children yet lasts well into adulthood in others, as well as why drugs that work for some children do not work for others.

For parents caring for a sick child, the details of how the immune system functions and other questions about SJIA may not seem very important. But researchers hope that learning more about this complicated disease will enable the medical community to address unmet needs among children living with SJIA.


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