Ocular involvement of any type is uncommon in patients with the systemic-onset form. Central nervous system (CNS) involvement, including seizures, has been reported but is considered rare.

The majority of deaths due to juvenile arthritis have occurred in children with the systemic-onset form. In many countries, the leading cause of death in patients with juvenile arthritis is renal failure secondary to amyloidosis. Amyloidosis appears to be significantly less common in the United States. These regional differences suggest an interplay between genetic and environmental factors in the pathogenesis of secondary amyloidosis.

Laboratory Findings. Laboratory tests may help in the diagnosis of systemic-onset arthritis, but ANA and rheumatoid factor tests are usually negative. Most patients have a modest-to-marked leukocytosis (15,000 to 25,000/mm³); occasionally, the count may be as high as 50,000/mm³. Polymorphonuclear leukocytes predominate, and there is a significant percentage of young cells. In most children, the platelet count is also elevated. Thrombocytopenia is rare. Normochromic, normocytic anemia with a normal mean corpuscular volume develops initially, but with continuing disease activity, the hemoglobin level decreases, followed by a fall in the mean corpuscular volume and development of a microcytic, hypochromic anemia. Serum levels of iron are usually low with a normal-to-high iron-binding capacity. Serum ferritin levels may be normal to significantly elevated and probably reflect the generalized inflammatory disease. Although the anemia is unresponsive to administration of iron, reticulocytosis and a rapid rise in hemoglobin value occur with disease remission. During the febrile phase, urinalysis may reveal intermittent or persistent proteinuria or increased red or white blood cell counts. Liver function may be abnormal, even before treatment with NSAIDs.

Macrophage Activation Syndrome. Macrophage activation syndrome is a potentially lethal complication of systemic-onset JIA. Children with macrophage activation syndrome commonly present with culturenegative septic shock and signs of cardiovascular collapse. Typical laboratory findings include a highly elevated serum ferritin, evidence of disseminated intravascular coagulation with elevated fibrin split products, low ESR due to fibrinogen consumption, elevated serum triglyceride levels, and thrombocytopenia. There is uncontrolled activation and proliferation of macrophages, and T lymphocytes, with a marked increase in circulating cytokines, such as interferon gamma (IFN-γ), and granulocyte-macrophage colony-stimulating factor (GM-CSF). Early recognition and treatment of this condition is necessary to prevent mortality. Macrophage activation syndrome has been described in association with systemic lupus erythematosus, Kawasaki disease, and adult-onset Still disease. It is thought to be closely related and pathophysiologically very similar to reactive (secondary) hemophagocytic lymphohistiocytosis. A bone marrow biopsy or aspirate usually shows hemophagocytosis.

ENTHESITIS-RELATED ARTHRITIS

The subgroup of enthesitis-related arthritis was created to accommodate those children with later-onset asymmetric oligoarticular presentation and a predisposition to develop sacroiliac disease. This subcategory encompasses those patients with the previously categorized seronegative spondyloarthropathies, including those with ankylosing spondylitis. In general, enthesitis-related arthritis tends to strike boys older than age 6 years. Patients may have a family history of ankylosing spondylitis, inflammatory bowel disease, or reactive arthritis. The arthritis has a predilection for the lower extremities, especially the knees, ankles, and hips, and exclusive involvement of the hip is not uncommon. Enthesitis, inflammation at the insertions of tendons or fascia into bone, commonly effects the insertion of the Achilles, iliotibial, patellar, or triceps tendons. Acute unilateral anterior uveitis with pain and redness, as opposed to the chronic asymptomatic bilateral uveitis seen in oligoarticular patients, affects 20% of patients, but the duration of inflammation is usually short.