For most forms of juvenile arthritis (JA), the cause is unknown (idiopathic), which is why the disease is sometimes called juvenile idiopathic arthritis.

For forms such as juvenile reactive arthritis, an infection may trigger the inflammation in joints, but the reasons are not well understood. Although the immune system attacks the tissue in the joints, no one knows what triggers such an attack. Some researchers think that the child may have some genetic component that increases the susceptibility to developing JA, but that some outside factor (e.g., virus) or a combination of factors triggers the initial inflammation.

JA often appears after an infection or injury, though neither of these events is a direct cause of the arthritis. Some physicians theorize that these events can cause the immune system to respond inappropriately and mistake something in the body for an infection, even when the infection has passed. This reaction may cause the continuing inflammation.

Studies show that a genetic marker called HLA-B27 can be found in some people with certain forms of arthritis and other autoimmune conditions. About 5 to 7 percent of Caucasian people without autoimmune conditions have this gene, according to the National Institutes of Health. However, among patients with ankylosing spondylitis and Reiter's syndrome, 80 to 90 percent or more have the gene. The presence of HLA-B27 cannot predict arthritis or some other disease, but researchers are studying the association.