Knowledge on rare diseases and orphan drugs

The incidence of juvenile idiopathic arthritis (JIA) in Caucasians is 8.3/100,000. Enthesitis-related juvenile idiopathic arthritis accounts for 10%-20% of these cases. Males account for approximately 60% of cases.

JIA describes a clinically heterogeneous group of diseases, characterized by arthritis beginning before the age of 16 years, involving one or more joints, and lasting for at least 6 weeks. The enthesitis-related category describes a clinically heterogeneous group of children including some who have predominately enthesitis, enthesitis and arthritis, or axial involvement (sacro iliac or dorsal or lumbosacral pain), or inflammatory bowel disease-associated arthropathy. Onset typically occurs in late childhood or adolescence with a peak age of onset between 10 and 12 years. In the first 6 months of disease, oligoarticular disease is most common.

The etiology is unknown.

Diagnosis is established by the presence of enthesitis and arthritis, or by the presence of arthritis and at least two of the following: sacroiliac pain and/or spinal inflammation, acute anterior uveitis, presence of the HLA-B27 antigen, a family history of uveitis, and spondylarthropathy, or sacroiliitis with inflammatory bowel disease in a first-degree relative. Arthritis and enthesitis are typically diagnosed by clinical findings of localized pain, tenderness, and swelling; when clinical findings are difficult to assess, echography or MRI could help. Exclusion criteria include the presence of psoriasis in the patient or a family history of psoriasis in a first-degree relative, detection of Rheumatoid Factor IgM in two tests taken at a 3-month interval, and the presence of systemic arthritis in the patient.

Differential diagnosis should include other types of juvenile idiopathic arthritis, infectious arthritis, other inflammatory diseases, and hemato-oncologic diseases that may lead to arthritis (in particular connective tissue diseases and acute leukemia).

Treatment typically revolves around monotherapy or combination therapy of nonsteroidal anti-inflammatory drugs (NSAIDs), and biologic anti-TNF agents such as etanercept and adalimumab. Use of biological DMARDs (disease modifying anti-rheumatic drugs) are only recommended in severe, refractory cases. NSAID monotherapy may be appropriate for children with low disease activity and without features of poor prognosis, although continuation of this approach for longer than 2 months may require routine laboratory studies to monitor for hepatic and renal toxicity. In order to manage pain associated with enthesitis in the foot, padded heel inserts may be recommended.

Progression to axial disease can occur in children with enthesitis-related JIA. In the majority of cases, the disease progressively evolves into spondylarthritis. By 5 years after disease onset, 92% of children with spondylarthritis develop sacroiliitis. Tarsitis, and hip arthritis within the first 6 months, are associated with worse prognosis. In comparison with other JIA categories, enthesitis-related JIA is associated with worse function, quality of life, and pain. Disease remission is often obtain with biological DMARDs when NSAIDs are insufficient; without treatment, remission occurs in less than 20% of children 5 years after diagnosis.

Last update: August 2020 - Expert reviewer(s): Dr Chantal DESLANDRE