Systemic Juvenile Idiopathic Arthritis

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Key points

  • The clinical presentation of systemic juvenile idiopathic arthritis (sJIA), often dominated by fever and systemic features, is unique in comparison to the other JIA subtypes.

  • sJIA is a diagnosis of exclusion and requires adequate consideration of infectious, oncologic, autoimmune, and autoinflammatory diseases.

  • Macrophage activation syndrome is a serious and potentially fatal complication of sJIA, characterized by sustained fever, organomegaly, cytopenias, coagulopathy, and high transaminases. It

Incidence of systemic juvenile idiopathic arthritis

JIA is the most common rheumatic disease in childhood, with an estimated prevalence of 1 to 4 per 1000 children.1, 2 sJIA accounts for approximately 10% to 20% of JIA cases, with incidence rates ranging from 0.4 to 0.8 children per 100,000 children.3

Age

Peak age of presentation is 1 to 5 years of age. However, children can present throughout childhood and adolescence.4

Gender

Male and female children are affected equally, unlike other JIA subtypes.4

Ethnicity

sJIA occurs in children of all ethnic backgrounds.5 A slightly higher prevalence rate has been reported in Japan and India than in the United States or Canada.6, 7

When to consider systemic juvenile idiopathic arthritis

The diagnosis of sJIA should be considered in children who have unexplained, prolonged fever that spikes once or twice daily, especially when it is associated with intermittent rash, arthralgias, or arthritis.

Classification Criteria

Widely accepted classification criteria for sJIA are based on the International League of Associations for Rheumatology (ILAR) classification criteria for JIA, which were revised in 2001 (Box 1).5 These criteria require that the onset of symptoms occurs before the age of 16 years, the duration of arthritis is at least 6 weeks, and that other conditions are excluded. The term adult-onset Still disease may be considered part of the spectrum of sJIA and describes patients whose symptoms begin at

Differential diagnosis or mimics of systemic juvenile idiopathic arthritis

The diagnosis of suspected sJIA may be challenging because of overlapping features with other conditions. Physicians need to carefully consider infections, malignancies, autoimmune, autoinflammatory, and other inflammatory diseases. A wide range of infectious diseases can mimic features of sJIA, so particular attention should be paid to excluding infectious endocarditis, osteomyelitis, viral infections, cat scratch disease, brucellosis, mycoplasma, and Lyme disease. Important differential

Laboratory and imaging studies for diagnosis and care

There is no pathognomonic laboratory feature that distinguishes sJIA from other conditions. The pattern of laboratory abnormalities may be supportive for the diagnosis of sJIA, but none is specific. Box 4 summarizes the list of investigations and the typical findings that would be supportive of the diagnosis. See the MAS section above for more discussion of the pattern of laboratory findings in MAS.

Pathogenesis

The cause of sJIA is not completely understood but has been attributed to a combination of environmental triggers and polygenic influences. One study investigated the role of infectious agents in triggering the disease by analyzing seasonal onset patterns of sJIA, but no consistent seasonal pattern or infectious pathogen was identified.44

Over the last decade, sJIA has increasingly been considered an autoinflammatory, rather than an autoimmune, disease,45 distinguishing it from other subtypes of

How systemic juvenile idiopathic arthritis is treated

The goal of treatment is to control active inflammation in order to alleviate symptoms and to prevent disease-related complications and comorbidities.50 Because sJIA patients often need treatment with systemic corticosteroids and are at risk for developing MAS, the authors recommend all sJIA patients be treated in conjunction with a pediatric rheumatologist. Children with new-onset sJIA, who are stable, without severe systemic symptoms or MAS, typically receive a trial of nonsteroidal

What is the prognosis for systemic juvenile idiopathic arthritis?

Before the “biologic era,” based on numerous longitudinal follow-up studies, there appeared to be 3 patterns of disease course seen in sJIA patients, leading to significantly different long-term outcomes. About half the sJIA patients followed a persistent course of disease activity, characterized by ongoing active systemic features and arthritis.70, 71 In many cases of persistent disease, the systemic symptoms eventually resolved, but the arthritis remained active72 with the potential for

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    Disclosure Statement: J.J.Y. Lee has no disclosures; R. Schneider has provided consultation for Novimmune, Novartis, and Sobi.

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