Juvenile idiopathic arthritis (JIA) is an exclusion diagnosis that encompasses all the forms of otherwise unexplained chronic arthritis occurring under the age of 16.

Various attempts have been made to classify this heterogeneous group of diseases with the aim of identifying mutually exclusive categories suitable for etiopathogenetic studies. The classification that is currently used worldwide was proposed in 1995 by the International League of Associations for Rheumatology (ILAR) and contains seven different categories:

1. Systemic arthritis


2. Oligoarthritis


3. Polyarthritis (rheumatoid factor negative)


4. Polyarthritis (rheumatoid factor positive)


5. Psoriatic arthritis


6. Enthesitis related arthritis


7. Undifferentiated arthritis

Since then increasing evidence has accumulated suggesting that some of these categories are heterogeneous. Therefore, there is a need to revise the criteria in order to identify more homogeneous entities and to try to distinguish those diseases, if any, that are observed only in children from those that represent the childhood counterpart of adult diseases.

Differently from the ILAR classification, which was not formally validated but essentially developed by consensus, the aim of this protocol is to test the new proposed classification in a prospective collection of at least 1,000 patients at disease onset. Then a final consensus conference will be organized to analyze the collected data and formulate the final JIA classification.

Hypothesis and significance

The ILAR classification has represented a significant international step forward in the understanding of JIA. However, recent evidence calls for a reconsideration of the classification criteria in order to better identify clinically homogeneous entities.

In particular, it has been shown that two categories, RF negative polyarthritis and psoriatic arthritis, are rather heterogeneous. There is also mounting evidence, coming from clinical observations and gene expression studies, for the existence of a homogenous entity observed only in children and characterized by several common features: an asymmetric arthritis, an early onset (usually before 6 years of age), a female prevalence, positive antinuclear antibodies (ANA), a high risk of developing chronic iridocyclitis and consistent HLA association. There is also strong evidence that patients with these characteristics are, according to ILAR criteria, currently classified into three different categories: oligoarthritis, RF-negative polyarthritis and psoriatic arthritis. This appears to be the main reason for the observed heterogeneity of the RF negative polyarthritis and psoriatic arthritis categories. Indeed, if the above-mentioned group of patients would be grouped together in a new, separate category, RF negative polyarthritis and psoriatic arthritis will probably be much more homogeneous and very similar to their adult counterpart.

In more general terms, it appears reasonable to think that, once this new category identifying a form of arthritis observed only in children, will be defined, the other categories of chronic arthritis observed in children will represent the childhood onset form of diseases observed also in adults. It appears also reasonable to reconsider the classification of systemic JIA. This condition should probably be classified separately from JIA and includes also patients without arthritis as it occurs in its adult equivalent, adult onset Still’s disease.

New advances (such as anti-CCP antibodies) in classification and nomenclature of the corresponding adult disease should also be considered in defining the new criteria.

Preliminary data

In December 2015 an international consensus conference has been convened by researchers of the IRCCS G Gaslini (PRINTO headquarter) in order to reach a consensus on the new PRINTO JIA classification criteria. The consensus panel (13 panelists) proposed the following distinct 6 PRINTO JIA categories:

a)         Systemic arthritis: the main modification is that the definition now allows the inclusion also of patients with fever but without arthritis, as in the adult equivalent, adult onset Still disease.

b)         RF positive arthritis: anti-CCP antibodies have been added to the definition

c)         Enthesitis/spondylitis related JIA: definition and nomenclature have been made more similar to those of the adult counterpart

d)        Early onset ANA+: this represents the major novelty. It has been recognized that this entity, which in the ILAR classification is split into different categories, represents a homogeneous form of chronic arthritis, which is typical of children

e)         Other JIA: Does not fit the disorders a. to d. Arthritis >= 6 weeks.

f)         Unclassified JIA: Fits more than 1 disorder a. to d. Arthritis >= 6 weeks

 

It has been recognized that the number of joints involved, as well as the presence of psoriasis, are not useful in children to define homogeneous entities. The previous oligo, poly and psoriatic categories were therefore abandoned and it has been decided to lump together in the other or unclassified categories all those forms of arthritis that do not fit the criteria of the diseases mentioned above.

However, a number of descriptors have been defined that will be useful in the prospective data collection (see below), to try to identify homogeneous entities.

Data collection

 Prospective collection of 1,000 JIA new patients at disease onset including biologic samples

The project includes the enrollment of a prospective cohort of at least 1,000 JIA patients, evaluated at onset and at 4 times points since the disease onset (within the first and after at least 3 months the second and then at least annually up to year 5). Related biologic samples will be collected at the first 2 time points (ANA, anti CCP, RF, HLA B27). The left over of the HLA B27 samples will be used for additional genetic analysis providing the family/patient consent/assent and additional approval by the ethics committee (if needed). This phase represents the core of the validation process. It will also include ultrasound evaluation (limited to few selected centres to be identified) at each visit in order to examine the potential added value that might be provided to the new classification criteria by the use of imaging techniques.

 

Inclusion criteria for the patients to be collected prospectively

The patients to be included in the prospective data collection must fit the following inclusion criteria:

1. A diagnosis of JIA according to the ILAR criteria by the treating physician.


2. The availability to provide an evaluation within 6 months after the onset of JIA. The onset evaluation can also be completed retrospectively (based on reliable family history or prior attending physician’s reports), but only if joint assessment data can be provided.


3. A clinical evaluation 3 months apart and then at least annually up to year 5.

This project is funded by the Italian Ministry of Health (project RF-2016-02364008).

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