Knowledge on rare diseases and orphan drugs

The disorder occurs worldwide with regional variation in occurrence; prevalence in juvenile populations ranges from 1/10,000-350,000, and incidence ranges between 1/140,000-1,000,000. The disorder is less frequent in Asian populations. Females are predominantly affect with a female-to-male ratio of 8-9:1.

The disease is considered as the childhood onset of seropositive adult rheumatoid arthritis; it represents about 10% of all cases of JIA. Patients are frequently diagnosed in late childhood/adolescence, typically between the 10-12 years of age. As with adult rheumatoid arthritis (RA), patients have a chronic symmetric, erosive polyarticular arthritis. To have polyarticular RF-positive disease, the ILAR classification requires the involvement of 5 or more joints. Also, by definition, patients must have two positive tests for IgM rheumatoid factor (RF). Although anti-cyclic-citrullinated peptide (anti-CCP) antibody status is not part of the ILAR criteria, children with childhood-onset RA also commonly have anti-CCP antibodies.

Rheumatoid factor-positive polyarthritis is an autoimmune inflammatory disease associated with enhanced lymphocyte activity and production of proinflammatory cytokines (IL1, IL6 and TNF alpha).

The international diagnostic criteria rely on the clinical, biological and radiological (joint erosion) features of the disease. Rheumatoid factor-positive polyarthritis is defined as the presence of arthritis affecting five or more joints at disease onset and by detection of rheumatoid factor in two tests carried out in the first six months of the disease course. Exclusion criteria are the presence of systemic arthritis or psoriasis in the patient, or a family history of psoriasis in one of the parents or first-degree relative, and HLA B27-positivity in males with onset of arthritis after 6 years of age. Other exclusion criteria include: the presence of ankylosing spondylarthritis, enthesitis and arthritis, sacroiliitis with an inflammatory enteropathy or acute anterior uveitis in the patient, or a family history of one of these conditions in a parent or first-degree relative.

The differential diagnosis should include other polyarticular diseases: connective tissue disorders (lupus, dermatomyositis) and hematological diseases (notably, acute leukemia).

Patients should be managed by a multidisciplinary team, incorporating expertise in pediatric rheumatology, physiotherapy, psychology and infantile orthopedic care. Treatment is based on the association of nonsteroidal anti-inflammatory agents (NSAIDS), disease-modifying antirheumatic drugs (DMARDs) and rehabilitation. Methotrexate is used as first-line treatment and then in case of inefficacy or intolerance , biologics (anti-tumor necrosis factor (TNF)-alpha, tocilizumab (anti-IL6 receptor) or abatacept (targeting T lymphocyte activation) could be prescribed. Corticotherapy, at low doses, can be used while waiting for the effectiveness of DMARDs. Rehabilitation will be associated if necessary to avoid joint limitation or amyotrophy. Intra-articular injection of delayed-action corticoids (triamcinolone hexacetonide) may be recommended in case of persistent localized arthritis.

Remission is rare during adulthood (10% of cases). In the vast majority of cases, the disease remains progressive and requires follow-up treatment. The risk of cartilage and bone damage has been significantly reduced with the use of rapid and more aggressive therapeutic strategies.

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