- •
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
Systemic Juvenile Idiopathic Arthritis
Section snippets
Key points
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
References (83)
- et al.
Juvenile idiopathic arthritis
Lancet
(2011) - et al.
Juvenile rheumatoid arthritis: a general review and report of 100 patients observed for 15 years
Semin Arthritis Rheum
(1976) - et al.
Rash associated with juvenile rheumatoid arthritis
J Pediatr
(1968) Long-term outcomes and predictors of outcomes for patients with juvenile idiopathic arthritis
Best Pract Res Clin Rheumatol
(2002)- et al.
Macrophage activation syndrome and cytokine directed therapies
Best Pract Res Clin Rheumatol
(2014) - et al.
Malignancies in children who initially present with rheumatic complaints
J Pediatr
(1999) - et al.
Discrimination of acute lymphoblastic leukemia from systemic-onset juvenile idiopathic arthritis at disease onset
Clinics (Sao Paulo)
(2011) - et al.
Seasonal onset of systemic-onset juvenile rheumatoid arthritis
J Pediatr
(1996) - et al.
Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase III trial
Lancet
(2008) - et al.
Efficacy of cyclosporine A in the treatment of macrophage activation syndrome in juvenile arthritis: report of five cases
J Pediatr
(1996)
Juvenile rheumatoid arthritis: outcome and treatment for the 1990s
Rheum Dis Clin North Am
Incidence and prevalence of juvenile idiopathic arthritis among children in a managed care population, 1996-2009
J Rheumatol
Does systemic-onset juvenile idiopathic arthritis belong under juvenile idiopathic arthritis?
Rheumatology (Oxford)
Evaluation of the presentation of systemic onset juvenile rheumatoid arthritis: data from the Pennsylvania systemic onset juvenile arthritis registry (PASOJAR)
J Rheumatol
International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001
J Rheumatol
Clinical analysis of 570 cases with juvenile rheumatoid arthritis: results of a nationwide retrospective survey in Japan
Acta Paediatr Jpn
Clinico-immunological profile in juvenile rheumatoid arthritis–an Indian experience
Indian J Pediatr
Still's disease in the adult
Ann Rheum Dis
Preliminary criteria for classification of adult Still's disease
J Rheumatol
Proposal for a new set of classification criteria for adult-onset still disease
Medicine (Baltimore)
The systemic juvenile idiopathic arthritis cohort of the childhood arthritis and rheumatology research alliance registry: 2010-2013
J Rheumatol
Consensus treatment plans for new-onset systemic juvenile idiopathic arthritis
Arthritis Care Res (Hoboken)
Systemic arthritis in children: a review of clinical presentation and treatment
Int J Inflam
The rash of rheumatoid arthritis and Still's disease
Q J Med
The temporomandibular joint in juvenile idiopathic arthritis: frequently used and frequently arthritic
Pediatr Rheumatol Online J
Cervical spine involvement in patients with chronic arthritis undergoing orthopaedic surgery
Ann Rheum Dis
Systemic onset juvenile chronic arthritis, polyarticular pattern and hip involvement as markers for a bad prognosis
Clin Exp Rheumatol
Long-term follow-up of 246 adults with juvenile idiopathic arthritis: functional outcome
Rheumatology
Still’s disease can cause neutrophilic meningitis
Neurology
Nasal septal perforation: a novel clinical manifestation of systemic juvenile idiopathic arthritis/adult onset Still's disease
J Rheumatol
Pulmonary hypertension and other potentially fatal pulmonary complications in systemic juvenile idiopathic arthritis
Arthritis Care Res (Hoboken)
Macrophage activation syndrome and reactive hemophagocytic lymphohistiocytosis: the same entities?
Curr Opin Rheumatol
Macrophage activation syndrome: a potentially fatal complication of rheumatic disorders
Arch Dis Child
Occult macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis
J Rheumatol
Mutations in the perforin gene can be linked to macrophage activation syndrome in patients with systemic onset juvenile idiopathic arthritis
Rheumatology
Mutations of the hemophagocytic lymphohistiocytosis-associated gene UNC13D in a patient with systemic juvenile idiopathic arthritis
Arthritis Rheum
Macrophage activation syndrome as part of systemic juvenile idiopathic arthritis: diagnosis, genetics, pathophysiology and treatment
Genes Immun
Pathogenesis of macrophage activation syndrome and potential for cytokine-directed therapies
Annu Rev Med
Marrow assessment for hemophagocytic lymphohistiocytosis demonstrates poor correlation with disease probability
Am J Clin Pathol
2016 classification criteria for macrophage activation syndrome complicating systemic juvenile idiopathic arthritis: a European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organisation collaborative initiative
Ann Rheum Dis
Cited by (0)
Disclosure Statement: J.J.Y. Lee has no disclosures; R. Schneider has provided consultation for Novimmune, Novartis, and Sobi.