Systemic-onset juvenile idiopathic arthritis (ORPHA:85414)
A rare pediatric rheumatological disease characterized by the variable occurrence of chronic arthritis, intermittent high spiking fever, maculopapular rash during fever episodes, hepatomegaly and/or splenomegaly, lymphadenopathy, and serositis.
Epidemiology
Juvenile idiopathic arthritis (JIA) is one of the most common pediatric chronic diseases, with a yearly incidence between 1.6 and 23 new cases per 100,000 children. Systemic-onset JIA accounts for roughly 10-20% of all JIA patients, with incidence estimated at 1/166,000 and prevalence at 1/32,000 in the prediatric population. Frequency is higher in some countries; for example in parts of Asia, sytemic-onset JIA may account for up to 30-40% of all JIA cases.
Clinical description
Onset usually occurs between 3 and 5 years of age. The clinical signs include fever with oscillating temperatures over a 24-hour period and peaks of over 39°C or more. The fever peaks are associated with the transient occurrence of an evanescent macular rash. Any joint, small or large, may be affected at disease onset, and involvement is nearly symmetrical and may be oligo- or polyarticular. Arthritis tends to increase in severity over time, and thus may not appear until later in the disease course. The course of the disease varies between individuals, ranging from a monocyclic disease course, to recurrent predominantly systemic disease course, to a progressive polyarthritis that could lead to severe and destructive joint disease.
Etiology
Whilst the underlying mechanisms and triggering factors are not fully understood, IL-1 and IL-6 play a major role in the pathogenesis of the disease.
Diagnostic methods
Diagnosis is based on clinical and biological findings in a child under the age of 16 presenting with fever for at least 3 consecutive days and 2 major criteria (arthritis and evanescent rash) or 1 major and 2 minor criteria ((1) generalized lymph node enlargement and/or hepatomegaly or splenomegaly (2) serositis (3) arthralgias lasting 2 weeks or longer (4) leukocytosis > 15.000/mm3 with neutrophilia) A confirmed diagnosis requires exclusion of other causes of the symptoms.
Differential diagnosis
The differential diagnoses is extensive and includes bacterial infections (including occult bacterial infection, brucellosis, Lyme disease, cat scratch disease, tuberculosis, and infectious mononucleosis), malaria, malignancies (such as leukemia, lymphoma, and neuroblastoma), viral infections, hereditary recurrent fever syndromes, other inflammatory diseases (such as systemic lupus erythematosus, systemic vasculitis, Kawasaki disease, Behçet disease, inflammatory bowel disease, Sweet syndrome, PFAPA, Takayasu arteritis, Castleman syndrome, rheumatic fever, and polyarteritis nodosa), connective tissue diseases, and periodic fever syndromes.
Management and treatment
Management by a specialized multidisciplinary team is required. Treatment is typically first with non-steroidal anti-inflammatory drugs (NSAIDs) and, if the inflammation is not controlled, followed by high dose corticosteroids. Treatment with cytokine inhibitors (anakinra, canakinumab, and tocilizumab) has shown to be highly effective. Furthermore, these drugs can help mitigate damage caused by the inflammatory process. Generally, complications such as macrophage activation syndrome, limitations in functional outcome by arthritis and long-term damage from chronic inflammation continue to be a major issue in patients' care, but have decreased since the use of biological treatment.
Prognosis
The disease course is long with major impact on quality of life. The risk of complications due to the illness or medication has been significantly reduced by the early use of biological treatment. Nowadays, osteopenia and osteoporosis, growth impairment, erosive arthritis, and secondary or reactive amyloidosis have almost disappeared. Currently, therapeutic strategies using anakinra (a recombinant IL-1 receptor antagonist), JAK inhibitors, and IL-6 inhibitors are also being studied. In severe case, where these is no response to these treatments or to high-dose corticosteroid therapy, intensive care becomes quickly necessary.

                            Last update: 
                            November 2020


                            - Expert reviewer(s): 
                            Dr Chantal DESLANDRE