PEDS-10: Connective Tissue Diseases and JIA — Part 1 (JIA Subtypes, ANA Uveitis Rule, Treatment Ladder, MAS) (Part 1 of 2)

Section 1: Defining JIA and the Seven ILAR Subtypes

PEDS-10 · ~04:30

Bottom line: JIA is the most common chronic rheumatic disease of childhood, defined as arthritis of unknown cause beginning before age 16 and persisting at least 6 weeks after exclusion of other causes. The 2004 ILAR system (Petty et al.) replaced the older juvenile rheumatoid arthritis (JRA) nomenclature with seven mutually exclusive subtypes, each separable by age, sex distribution, joint count, antibody profile, and uveitis risk. Oligoarticular JIA dominates at 50 to 60 percent and carries the highest uveitis risk; polyarticular RF-positive disease has the worst joint prognosis; systemic JIA (Still disease) is the autoinflammatory outlier with quotidian fever and salmon rash.

JIA is the umbrella diagnosis for chronic arthritis in childhood. The formal definition is arthritis of unknown cause beginning before age 16 years and persisting for at least 6 weeks after exclusion of other causes. Incidence is 2 to 20 per 100,000 children per year, prevalence in the United States is 70,000 to 100,000, and the overall female-to-male ratio is 2:1 to 3:1, though the ratio varies dramatically by subtype. The pathologic hallmark is pannus formation, a proliferative synovitis with granulation tissue invading cartilage and bone, analogous to the synovial pannus of adult rheumatoid arthritis. TNF-alpha drives inflammatory cell trafficking into the synovium in the non-systemic subtypes, while systemic JIA is increasingly framed as an autoinflammatory condition driven by innate immunity and the IL-1 / IL-6 axis, not by adaptive T- and B-cell autoreactivity.

The 2004 ILAR classification (Petty et al.) replaced the older JRA terminology with seven mutually exclusive subtypes: oligoarticular, polyarticular RF-negative, polyarticular RF-positive, systemic JIA (sJIA, Still disease), psoriatic, enthesitis-related arthritis (ERA), and undifferentiated. Each subtype is defined by the joint count in the first 6 months, the antibody profile, the age and sex distribution, and the pattern of extra-articular features.

Oligoarticular JIA is the most common subtype, accounting for 50 to 60 percent of JIA. The defining feature is four or fewer joints involved in the first 6 months of disease. Female predominance is striking at 5:1, peak onset is ages 1 to 5, and the knee is the most commonly involved joint, with disease that is reliably asymmetric. ANA is positive in 70 to 80 percent, RF is negative, HLA-B27 is negative. The uveitis risk is the highest of any JIA subtype at 20 to 30 percent. The articular prognosis is bifurcated: the persistent form (four or fewer joints throughout disease course) carries the best joint prognosis of any subtype, while the extended form (more than four joints after the initial 6 months) behaves more like polyarticular disease.

Polyarticular RF-negative JIA accounts for 15 to 20 percent of JIA and involves five or more joints in the first 6 months. Female predominance is 3:1, and onset shows a biphasic peak (1 to 3 years and 9 to 14 years). Symmetric large- and small-joint involvement is typical. ANA is positive in 25 to 40 percent, uveitis risk is moderate at 5 to 10 percent, and disease course is variable. Polyarticular RF-positive JIA is much rarer at 2 to 7 percent and is essentially adult-pattern rheumatoid arthritis presenting in childhood. Female predominance is striking at 9:1, peak age is late childhood and adolescence, and the disease shares the HLA-DR4 association of adult RA. ANA is positive in 40 to 50 percent. This subtype carries the worst articular prognosis of all JIA subtypes, and rheumatoid nodules are most frequent here. Uveitis risk is low.

Systemic JIA (sJIA, Still disease) accounts for 10 to 15 percent of JIA and is unique among the subtypes in pathogenesis (autoinflammatory rather than autoimmune), clinical features (prominent systemic inflammation), and treatment (IL-1 and IL-6 blockade rather than TNF inhibition). Sex ratio is roughly equal, age range is broad, and the peak is 1 to 5 years. The defining clinical features form a memorable quartet: quotidian fever (one or two daily temperature spikes to 39 degrees Celsius or higher with rapid return to baseline or below, often subnormal); an evanescent salmon-colored rash that flares with fever and fades between spikes; serositis (pericarditis, pleuritis, or peritonitis); and hepatosplenomegaly with generalized lymphadenopathy. ANA, RF, and HLA-B27 are all typically negative; the sJIA-associated HLA is **DRB1*11. Uveitis risk is very low. The hidden danger is MAS** at 10 to 15 percent, addressed in Section 4.

Enthesitis-related arthritis (ERA) accounts for 5 to 10 percent of JIA and is the pediatric spondyloarthropathy. Male predominance is striking at 7:1, onset is typically after age 6 (peak 9 to 12), HLA-B27 is positive in 60 to 80 percent, and the hallmark is enthesitis (inflammation at the tendon-to-bone insertion) at the Achilles, plantar fascia, and patellar tendon. Lower-extremity large-joint arthritis predominates early; sacroiliitis and axial disease develop later; many progress to ankylosing spondylitis in adulthood. The associated uveitis is acute, symptomatic anterior uveitis with a red painful eye, in stark contrast to the chronic asymptomatic uveitis of oligoarticular and polyarticular JIA. Psoriatic JIA (5 to 8 percent) shows bimodal onset reflecting two distinct phenotypes. Younger patients resemble oligoarticular JIA with female predominance, ANA positivity, small-joint involvement, and dactylitis (“sausage digit,” uniform swelling of an entire finger or toe). Older patients resemble adult psoriatic arthritis with roughly equal sex distribution, enthesitis, axial disease, and HLA-B27 positivity. Frank psoriasis is absent at presentation in roughly half of patients, and nail pitting and onycholysis appear in 50 to 80 percent. Undifferentiated JIA (10 to 15 percent) does not fit a single category or fits more than one.