Knowledge on rare diseases and orphan drugs

Rheumatoid factor-negative juvenile polyarthritis represents around 15-20% of cases of juvenile idiopathic arthritis (JIA). Prevalence has been estimated at between 1 and 13 in 22,200 children, with an annual incidence of 1-26 in 700,000 children. Females are affected more often than males, with a female/male ratio of 3:1.

Rheumatoid factor negative juvenile polyarthritis is clinically heterogeneous with two patient groups distinguished by age of onset and distribution of arthritis. The early onset form typically appears between 2 and 6 years of age with asymmetrical pattern of joint involvement, possible eye inflammation (asymptomatic chronic anterior uveitis), and presence of anti-nuclear antibody. This form resembles oligoarticular juvenile idiopathic arthritis. The second group has a later onset around 10 years of age with often symmetrical distribution and distal joint involvement (commonly small joints of the hands, wrist and knees). Patients may be ANA positive or negative. This form closely resembles rheumatoid polyarthritis.

The etiology remains unknown but auto-immunity plays a role.

Rheumatoid factor-negative polyarthritis is defined as the presence of arthritis affecting five or more joints at disease onset. 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 a first-degree relative, HLA B27-positivity in males with onset of arthritis after 6 years of age, and detection of rheumatoid factor IgM in two test samples taken three months apart. 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. It is important to note that these diagnostic criteria were established in 2001 (International League of Associations for Rheumatology, Edmonton) and are currently under revision.

The differential diagnosis should include other forms of polyarthritis (associated with inflammatory or haemato-oncologic diseases).

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 nonsteroidal anti-inflammatory agents (NSAIDS), and disease-modifying antirheumatic drugs; methotrexate is used as first-line treatment and then in case of inefficacy or intolerance. Biologics such as anti-tumor necrosis factor (TNF)-alpha, tocilizumab (anti IL6 receptor) and abatacept (targeting T lymphocyte activation) could be prescribed. Rehabilitation is necessary in case of limited joint motion. Corticotherapy is used at low doses and as rarely as possible. Intraarticular injection of delayed-action corticoids (triamcinolone hexacetonide) may be recommended in case of localized persistent arthritis.

The prognosis is difficult to determine due to the heterogeneity of the condition; but the new therapeutic strategies (initial aggressive and combined therapy) seem able to improve the prognosis and the percentage of remission mainly under treatment.

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