Knowledge on rare diseases and orphan drugs

The incidence of juvenile idiopathic arthritis in Caucasians is 8.3/100,000. Oligoarticular juvenile idiopathic arthritis is the most common form in North America and Europe, comprising 30% to 60% of children with juvenile idiopathic arthritis. It affects girls more than boys and is rare in individuals of African, Native American or Sourthern Asian descent.

The disease is typically asymmetrical, affecting between one to four joints, predominantly those of the lower limbs (knee or foot) although the wrist and elbows could be rarely affected. Onset occurs between the ages of 2 and 4. The disease is divided into persistent oligoarthritis, in which there is no more than 4 joints involved after the first six months of illness, and extended oligoarthritis, in which there is involvement of more than 4 joints involved after the first six months. Pain is not a constant feature in young children and the most common reasons for seeking medical advice are an increase in the volume of the joint and/or limping. The association of this form of arthritis with nonsymptomatic iridocyclitis (no pain or visible redness) is a specific feature that is present in a third of cases. Systemic manifestations other than uveitis are characteristically absent. Therefore, fever, rash, or other constitutional symptoms suggest a different diagnosis.

The etiology is not currently known. All juvenile idiopathic arthritis subtypes are most likely complex genetic traits as they lack single-gene, Mendelian patterns of inheritance. Inherited risk factors for both disease susceptibility and disease severity have been reported; the highly polymorphic HLA genes confer the strongest genetic effects.

Diagnosis is based on the clinical manifestations, and exclusion of other potential causes. The presence of iridocyclitis and/or antinuclear antibodies without fever or psoriasis are strong diagnostic indicators. Exclusion criteria includes presence of systemic arthritis, psoriasis, ankylosing spondylarthritis, enthesitis and arthritis, sacroiliitis with an inflammatory enteropathy or acute anterior uveitis in the patient or a first-degree relative. In addition, HLA B27-positivity in males with onset of arthritis after 6 years of age and presence of rheumatoid factor IgM must be excluded.

Differential diagnosis principally includes the other subtypes of juvenile idiopathic arthritis as well as Lyme disease, inflammatory bowel disease, pigmented villonodular synovitis, malignancy, plant thorn synovitis, septic arthritis, osteomyelitis, or tuberculosis.

First step of treatment is non-steroidal anti-inflammatory agent (NSAID) , but their efficacy is quite rare. Intra-articular glucocorticoids injections are often necessary and effective. Methotrexate and, if ineffective, biologics are recommended for children with disease that extends to involve five or more joints or require repeat injections.

Several long-term complications may occur, the most frequent and significant ones being temporomandibular joint arthritis with retrognatism, uveitis complications (glaucoma or synechia), leg-length discrepancy in case of delayed diagnosis. Arthritis may extend to involve five or more joints within several years of diagnosis.

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