| Oligoarticular JIA |
Most common JIA subtype; onset typically at 2–4 years, predominantly in girls; ≤4 joints involved in the first 6 months, mainly large lower−limb joints (knees, ankles); high ANA positivity and the greatest risk of chronic anterior uveitis (21, 22). |
Accounts for over half of JIA in many cohorts; particularly frequent in Europe and parts of the Middle East (23–26). |
Strong associations with HLA−DRB111:03/04, HLA−DRB108:01 and HLA−DPB102:01 (risk) and HLA−DRB115:01 (protection); non−HLA loci including PTPN22 C1858T, STAT4, IL2/IL2RA/IL2RB and IL6/IL6R also contribute (13, 27). |
Clusters genetically with RF−negative polyarticular JIA as early−onset ANA−positive autoimmune arthritis, with an HLA pattern distinct from the classic shared−epitope profile of adult RA (21, 28). |
Current ACR guidelines recommend intra−articular glucocorticoid injections (± NSAIDs) as initial therapy; csDMARDs (methotrexate preferred) are introduced for poor−prognosis features or IAGC failure, with escalation to TNF inhibitors or other bDMARDs in refractory or extended disease, following a treat−to−target approach and minimizing systemic glucocorticoids (29–31). |
| RF−negative polyarticular JIA |
Onset within 6 months with involvement of ≥5 joints, most often school−age girls; symmetric small−joint and some large−joint arthritis, RF and ACPA negative; overall prognosis better than RF−positive disease (21). |
Represents roughly 30% of JIA globally, with somewhat higher proportions reported in North America (23). |
Shares an HLA risk profile with oligoarticular JIA (enrichment of HLA−DRB111:03/04, DRB108:01, DPB102:01 and protection by DRB115:01); PTPN22 C1858T confers risk across oligoarticular, RF−negative and RF−positive polyarticular JIA (27, 32). |
Genetic and transcriptomic data indicate clustering with oligoarticular JIA as early−onset ANA−positive autoimmune arthritis; although sharing several non−HLA autoimmune loci with RA and SLE, its overall genetic architecture differs from adult RA (21, 28, 33). |
For non−systemic polyarthritis, ACR guidelines recommend early csDMARD therapy (methotrexate preferred) rather than long−term NSAIDs alone; inadequate response to methotrexate prompts addition of a bDMARD (such as TNF inhibitors, abatacept or tocilizumab), usually in combination with csDMARDs, while avoiding prolonged systemic glucocorticoid use (30, 31). |
| RF−positive polyarticular JIA |
Comprises ~2–7% of JIA; typically affects adolescent girls with symmetric small−joint arthritis, marked morning stiffness, RF and/or ACPA positivity, and a high risk of erosive joint damage and disability (21, 28). |
Relatively uncommon worldwide but reported at higher prevalence in Latin America and parts of south−east Asia (23). |
Shows a strongly RA−like genetic profile, with risk alleles at shared−epitope HLA−DRB1*01 and *04, and overlap at non−HLA loci such as PTPN22, STAT4 and TNFAIP3 (21, 27, 34, 35). |
Clinical phenotype, serology and genetic architecture closely resemble adult RA, making RF−positive polyarticular JIA the closest pediatric counterpart of adult RA (21, 27, 28). |
Managed along the non−systemic polyarticular pathway, but guidelines and treat−to−target recommendations emphasize early, aggressive use of methotrexate followed by prompt escalation to TNF inhibitors or other bDMARDs in non−responders, given the highly erosive course and lower remission rates; chronic systemic glucocorticoids are discouraged (30, 31). |
| Juvenile psoriatic arthritis (JPsA) |
Accounts for ~1–7% of JIA; arthritis with psoriasis, or arthritis plus dactylitis, characteristic nail changes or a first−degree family history of psoriasis; often oligoarticular onset, may evolve to polyarticular disease; dactylitis and chronic uveitis are common; shows a bimodal age distribution (early childhood and later childhood/adolescence) (21, 28). |
Usually represents ≤10% of JIA across international and single−country cohorts, with considerable variability related to differences in classification and inclusion criteria (23–26). |
Genetic background is heterogeneous: some patients show associations with HLA class II alleles (e.g. HLA−DRB101:01, DQA101:01), while others resemble spondyloarthritis with HLA−B27−related risk; multi−omic analyses support the coexistence of an early−onset ANA−positive JIA−like subgroup and a SpA−like subgroup (27, 28, 33). |
Historically grouped with seronegative spondyloarthritis and closely related to adult psoriatic arthritis, but current data indicate only partial overlap, with some patients aligning more with early−onset ANA−positive JIA and others with adult SpA/axial PsA (21, 28). |
Current ACR recommendations manage JPsA according to predominant clinical features: peripheral oligo− or polyarthritis follows the oligo-/polyarticular JIA pathway (methotrexate then bDMARDs), whereas prominent enthesitis or sacroiliitis is treated as ERA (NSAIDs then TNF inhibitors); TNF inhibitors are the most commonly used first−line biologics when joint or skin disease is refractory, while evidence for IL−17 and IL−12/23 inhibition in children remains limited (31, 36). |
| Enthesitis−related arthritis/juvenile spondyloarthritis (ERA/JSpA) |
Defined by peripheral arthritis with enthesitis, typically in older boys; asymmetric large−joint involvement of the lower limbs with heel and plantar enthesitis; many patients later develop sacroiliitis and spinal involvement; usually RF/ACPA negative (21, 28). |
One of the most frequent subtypes in several Asian cohorts (e.g. parts of Taiwan and India), where ERA may account for more than 30% of JIA (37–39). |
Strongly associated with HLA−B27 and shares multiple susceptibility loci with adult spondyloarthritis, particularly within the IL−23/IL−17 axis (27, 28, 34). |
Widely considered the pediatric member of the spondyloarthritis family, closely resembling adult axial SpA/ankylosing spondylitis in clinical pattern (axial disease, enthesitis) and genetic background, while presenting additional growth− and development−related issues (21, 28). |
ACR guidelines recommend NSAIDs as first−line therapy for active enthesitis or sacroiliitis; persistent axial disease despite adequate NSAIDs should be escalated to TNF inhibitors rather than additional NSAIDs or csDMARDs; methotrexate or sulfasalazine may be used for predominant peripheral arthritis, but have limited efficacy for purely axial disease (30, 31, 36). |
| Systemic JIA (sJIA) |
Systemic inflammatory disease with quotidian high fevers, evanescent salmon−pink rash, lymphadenopathy, hepatosplenomegaly and/or serositis, with arthritis at or after onset; laboratory findings include markedly elevated inflammatory markers and hyperferritinaemia; macrophage activation syndrome is a life−threatening complication (21, 28, 40). |
Represents a minority of JIA overall but a relatively larger proportion in several Asian countries and regions (23, 39). |
Associated with HLA−DRB1*11 and other MHC class II alleles, but HLA contribution is smaller than in autoimmune JIA subtypes; pathobiology is dominated by innate immune activation with monocyte/macrophage and neutrophil involvement and high levels of IL−1β, IL−6 and IL−18, supporting classification as an autoinflammatory disease (21, 28, 40). |
Systematic reviews and EULAR/PReS consensus view sJIA and adult−onset Still’s disease as age−dependent manifestations of a single Still’s disease continuum, distinct from classic adult RA in clinical features, serology and inflammatory pathways (41, 42). |
The 2021 ACR guideline places IL−1 and IL−6 inhibitors as first−line therapy for active sJIA (with or without MAS), with glucocorticoids used as short−term adjuncts rather than maintenance therapy; the 2024 EULAR/PReS Still’s disease recommendations further emphasize a “biologics−first” strategy with early IL−1/IL−6 blockade and detailed algorithms for MAS management (29, 31, 42). |
| Undifferentiated JIA |
A diagnosis of exclusion encompassing chronic arthritis that fulfils criteria for no single ILAR/PRINTO category or meets criteria for ≥2 subtypes; therefore clinically heterogeneous, ranging from oligo− and polyarthritis to enthesitis−predominant or mildly systemic phenotypes (21, 28, 43). |
By definition a residual category; robust data on global or regional distribution are scarce, and most large international cohorts do not provide detailed analyses for this subgroup (23). |
Current immunogenetic studies focus mainly on “classical” subtypes (oligoarticular, RF−negative/positive polyarticular, ERA, systemic JIA, JPsA); there is no consistent evidence for a distinct HLA or non−HLA signature of undifferentiated JIA, and most cases probably inherit risk alleles of the overlapping clinical subtypes (21, 27, 28). |
Because this category reflects limitations of current classification rather than a defined biological entity, no clear adult counterpart has been established; undifferentiated JIA is better regarded as a heterogeneous group highlighting the need for biologically driven re−classification (21, 28, 44). |
ACR guidelines base recommendations on dominant clinical phenotypes rather than ILAR labels; undifferentiated JIA is therefore treated according to its main manifestations—for example, as non−systemic polyarthritis (methotrexate then bDMARDs), ERA−like disease (NSAIDs then TNF inhibitors) or Still’s disease (early IL−1/IL−6 inhibition)—in line with treat−to−target principles (29–31). |