Systemic arthritis

Systemic arthritis (sJIA) accounts for 10–15% of children with JIA and is characterised by prominent systemic features, such as high spiking fever, skin rash and serositis. It is considered the equivalent of adult-onset Still's disease. The marked activation of the innate immune system as well as the important pathogenic role played by interleukin 1 (IL-1) and IL-6 have led to consider sJIA a polygenic autoinflammatory disease.6 Probably, as monogenic autoinflammatory diseases, sJIA does not represent a disease but rather a syndrome, the common end point of several different diseases all causing a marked and persistent activation of the innate immune system. This potential heterogeneity is suggested by the exquisite sensitivity to IL-1 blockade presented by a subset of patients7 as well as by differences in clinical course.1 ,2 Indeed, in about half of patients the disease is monocyclic or is characterised by relapses followed by intervals of remission; the arthritis usually remits when systemic features are controlled. In the other half of patients the disease follows an unremitting course; in many cases systemic symptoms eventually resolve, leaving chronic arthritis as the major long-term problem. There are, moreover, patients (who cannot by definition be classified as sJIA) who present exactly the same systemic features seen in sJIA but never develop arthritis. This subgroup of patients lacks any taxonomic definition. The superimposable systemic clinical features suggest that they have a disease strongly related to sJIA despite the lack of arthritis. This type of patient is indeed included in the definition of adult-onset Still's disease, where the presence of arthritis is not required for diagnosis. I would suggest that these patients should be included in the sJIA disease category. However, given the absence of arthritis, the term sJIA should be changed; a possible new name might be Still's disease, by analogy with the adult counterpart, adult-onset Still's disease.

Rheumatoid factor-positive polyarthritis

Rheumatoid factor (RF)-positive polyarthritis accounts for a small (≤5%) percentage of patients with JIA and is considered the equivalent of adult RF-positive rheumatoid arthritis; indeed, it is the only category in which antibodies to cyclic citrullinated peptides are found.

Enthesitis-related arthritis

Enthesitis-related arthritis accounts for about 5–10% of JIA cases and is an undifferentiated spondyloarthritis.8 Most patients are HLA-B27 positive and in a variable proportion of them, involvement of the sacroiliac joints develops during the disease course.

All the different forms of adult spondyloarthritis can be found in children (psoriatic arthritis is discussed below); the major difference is the much higher proportion of undifferentiated spondyloarthritis in childhood. The discrepancy in terminology between children and adults has been a source of confusion and it might be useful in the future to abandon the term enthesitis-related arthritis, which could suggests a form specific to childhood, and employ the same terminology used to define the adult forms of spondyloarthritis, with the prefix juvenile.

Oligoarthritis

In Western countries oligoarthritis represent up to 50% of all JIA cases; the large majority of patients belongs to a well-defined disease entity seen only in children and characterised by several common features: an asymmetric arthritis, an early onset (before 6 years of age), a female predilection, positive ANA, a high risk for developing chronic iridocyclitis and consistent HLA associations. The ILAR classification distinguishes two categories: persistent oligoarthritis in which the disease remains confined to four or fewer joints and extended oligoarthritis in which arthritis extend to more than four joints after the first 6 months of disease. It has been shown, however, that ANA-positive patients with persistent or extended oligoarthritis share the same features,9 suggesting that they represent the same disease differing just in the spread of arthritis.

Rheumatoid factor-negative polyarthritis

Rheumatoid factor-negative polyarthritis accounts for about 20% of JIA cases and is a heterogeneous category. At least two distinct clinical phenotypes can be identified: (a) one characterised by a symmetric synovitis of large and small joints, onset in school age and negative ANA; (b) a second phenotype that resembles ANA-positive, early-onset oligoarthritis. The strong similarities between this second subset and oligoarthritis led to the suggestion that they represent the same disease, the former representing a rapid spread of arthritis in the latter.5 The hypothesis was also supported by the observation that ANA-positive, RF-negative polyarthritis is seldom seen in those countries (such as Costa Rica and India) in which ANA-positive oligoarthritis is rare.5 This view has been subsequently confirmed by the demonstration that patients with ANA-positive oligoarthritis and with ANA-positive, RF-negative polyarthritis share the same features (early age at onset, asymmetric arthritis, female predominance, increased incidence of chronic iridocyclitis) and that these features are not present in patients with ANA-negative, RF-negative polyarthritis or oligoarthritis.9 ,10 Of note, Barnes and coworkers,11 studying gene expression in oligoarticular and polyarticular JIA, found that patients with early-onset arthritis (≤6 years) are characterised by a B cell signature independently from the number of joints involved; moreover, high-resolution HLA class I and class II typing has also shown similarities between early-onset oligoarticular and polyarticular JIA.12

Psoriatic arthritis

Psoriatic arthritis (PsA) is another heterogeneous JIA category, representing about 5–10% of all JIA cases. If PsA is defined according to the presence of arthritis and psoriasis or some psoriatic features (Vancouver criteria)13 two populations of patients can be identified5 ,13 ,14: (a) one that belongs to the enthesitis- related arthritis category and therefore represents, like adult PsA, a form of spondyloarthritis; (b) another that has the same above-mentioned features of ANA-positive, early-onset oligoarthritis. So, it appears that the association of psoriasis with arthritis leads to the identification of two very different groups of patients, one that is similar to adult PsA and the other that has the same characteristics as ANA-positive oligoarthritis.5 ,10 The ILAR classification criteria for PsA, in which patients with enthesitis are by definition excluded, limit the identification of those patients that have a form of PsA similar to that seen in adults.15