Are the number of joints involved or the presence of psoriasis still useful tools to identify homogeneous disease entities in juvenile idiopathic arthritis?

1900 Juvenile idiopathic arthritis (JIA) represents a heterogeneous group of disorders of unknown etiology whose classification relies mainly on clinical grounds. A number of classification systems have been developed over the years, the most recent being that proposed by the International League Against Rheumatism (ILAR)1 (Table 1). This classification has several important features of merit: (1) It has solved the problem of the previous heterogeneity in nomenclature and criteria between Europe and North America. (2) It wisely includes, for each JIA subset, a list of additional features, called descriptors, that may be useful in future studies to better dissect each disease category. (3) It is intended to represent a “work in progress” whose main aim is to find homogeneous disease groups suitable for etiopathogenetic studies2. Some of the disease categories identified by the ILAR classification seem indeed to have peculiar features. Systemic arthritis, although probably still a heterogeneous condition, has some distinctive markers that set it apart from the other JIA subsets. It is characterized, with respect to the other JIA forms, not only by prominent systemic features such as high spiking fever, but also by some peculiar aspects of the inflammatory process, such as an apparent major role for interleukin 6 and a marked activation of the macrophage system3. On clinical, genetic, and laboratory grounds rheumatoid factor (RF) positive polyarticular JIA is identical to adult RF positive rheumatoid arthritis (RA) and is considered its equivalent in childhood. Enthesitis related arthritis on several clinical (i.e., enthesitis) and laboratory (i.e., marked increased prevalence of HLA-B27) features is assumed to belong to the spondyloarthropathy group. Although the oligoarticular onset category as a whole is probably heterogeneous, by far the largest group of patients is represented by a quite well defined form of JIA. This form, which is typical of children and is not observed in adults, is characterized by an asymmetric arthritis, an early onset (usually before 6 years of age), a female predilection, a high frequency of positive antinuclear antibodies (ANA), and a high risk for developing chronic anterior uveitis. In confirmation that these patients may represent a homogeneous entity, a strong association with some HLA alleles and in particular with DRB1*0801 (DRw8) has been found4-6; of interest, correlation with DRw8 is independent from the ethnic group of patients7. Patients with these characteristics represent, in Western countries, the great majority of the oligoarthritis group independently from the fact that arthritis remains confined to a few joints (the oligoarticular persistent subgroup) or involves more than 4 joints after the first 6 months of disease (the oligoarticular extended subgroup)8,9, a feature that occurs in up to 50% of cases10. The 2 other JIA categories, polyarticular RF negative and psoriatic, include disease entities that appear more heterogeneous. Although seronegative polyarticular JIA is found at all ages, 2 peaks are usually observed, one during the first years of life (mainly girls) and the other in the preadolescent age11, with about half of patients having disease onset before 5 years of age8,9,12. About 20 to 40% of patients are ANA positive8,9,12-14. ANA positivity is strongly associated with early age at onset; the specificity against the 45 kDa DEK nuclear antigen, which has been found in early-onset, ANA positive oligoarticular disease, has also been observed in ANA positive seronegative polyarticular JIA15. Chronic anterior uveitis is observed in seronegative polyarticular disease, with a frequency ranging from 5 to 20%12,16 and, as in oligoarticular disease, is strongly associated with early age at onset, female sex, and ANA positivity. HLA association studies have provided quite inconsistent results in seronegative polyarthritis as a whole. However, several groups8,9,12,17 have reported an increase in DRB1*0801 (DRw8) in seronegative polyarticular patients with early age at onset, Editorial