Ilar classification

ILAR is the acronym for "International League of Associations for Rheumatology", an international organization dedicated to the research, treatment and education of rheumatic diseases. The ILAR was founded in 1973 and aims to promote the exchange of knowledge and information on rheumatic diseases, to support research in this field and to improve standards for the diagnosis and treatment of rheumatic diseases.

The ILAR classification designates different categories of juvenile idiopathic arthritis. Based on clinical and laboratory parameters, including the total number of joints affected in the first 6 months of the disease, the presence of extra-articular manifestations or rheumatoid factor (RF) and family history of psoriasis or HLA-B27-associated diseases, six defined JIA categories are distinguished, including oligoarthritis with two progression categories, and undifferentiated arthritis. The following exclusion criteria must be taken into account for each of the defined categories:

a) Psoriasis in the patient or a first-degree relative;

b) Arthritis in an HLA-B27-positive boy after the 6th birthday;

c) Ankylosing spondylitis, enthesitis-associated arthritis, sacroiliitis in inflammatory bowel disease, Reiter's syndrome or acute anterior uveitis in a first-degree relative;

d) IgM rheumatoid factor (RF) detection in two examinations at least 3 months apart;

e) signs of systemic arthritis.

see also under Juvenile idiopathic arthritis

1. Systemic juvenile idiopathic arthritis (Still's syndrome) (ICD-10: M08.2-) Definition: Arthritis and fever (intermittent, lasting at least 2 weeks) and at least one other criterion: transient erythematous rash, generalized lymph node enlargement, hepato- and/or splenomegaly, serositis. Exclusion: a, b, c, d
2. Oligoarthritis. Definition: Arthritis of 1-4 joints within the first 6 months of illness. Subcategories: Persistent oligoarthritis (ICD-10: M08.4-): 1-4 affected joints during the course of the disease. Extended oligoarthritis (ICD-10: M08.3-): >4 affected joints after the first 6 months of the disease. Exclusion: a, b, c, d,
3. RF-negative polyarthritis (ICD-10: M08.3-): Definition: Arthritis in >4 joints during the first 6 months of illness and negative test for RF. Exclusion: a, b, c, d, e
4. RF-positive polyarthritis (ICD-10: M08.0-) Definition: Arthritis in >4 joints during the first 6 months of illness and positive test for RF (at least twice every 3 months). Exclusion: a, b, c, e
5. Psoriatic arthritis (ICD-10: L40.5/M09.0-) Definition: Arthritis and psoriasis or arthritis and at least two of the following criteria: dactylitis; nail changes (spotting or onycholysis); psoriasis in a first-degree relative. Exclusion: b, c, d, e
6. Enthesitis-associated arthritis (ICD-10: M08.1-) Definition: Arthritis and enthesitis (i.e. Inflammation at the bony insertion of tendons, ligaments, joint capsules or fascia) or arthritis and at least two of the following criteria: Pressure pain over the sacroiliac joints and/or inflammatory lumbosacral back pain; HLA-B27 detection; young onset >6 years; acute (symptomatic) anterior uveitis; ankylosing spondylitis, enthesitis-associated arthritis, sacroiliitis in inflammatory bowel disease, reactive arthritis (Reiter's syndrome) or acute anterior uveitis in a first-degree relative. Exclusion: a, d, e
7. Undifferentiated arthritis (ICD-10:M08.8-) Definition: Arthritis that cannot be classified in one or more categories.

The ILAR classification has been evaluated in over 15 studies with the inclusion of almost 3500 children; however, the sensitivity and specificity of this classification has not yet been investigated. It has been shown that the ILAR criteria are only suitable to a limited extent in everyday clinical practice: 10-15% of patients are incorrectly categorized (Oen et al. 2010; Sengler et al. 2015), and the required double determination of RF only occurs in practice in a minority of cases (Berntson et al. 2001). Individual criteria have been tested for reliability and precision; for example, clinical examination is less sensitive than sonography or magnetic resonance imaging in detecting peripheral arthritis or inflammatory axial involvement (e.g. sacroiliitis) or in the precise localization of inflammation (Weiss et al. 2016; Colebatch-Bourn et al. 2015).

Like its predecessors, the ILAR classification is based on expert opinion. It does not reflect the underlying disease biology and has relevant shortcomings, e.g. the arbitrary cut-off of four affected joints as a criterion for assignment to oligoarthritis or polyarthritis and the age cut-off at the 16th birthday, which is not based on pathophysiological or epidemiological data. In addition, the ILAR nomenclature is completely different from the arthritis nomenclature used in adult rheumatology, although many childhood-onset arthritides have an adult counterpart (e.g. systemic arthritis in adult-onset Still's disease, RF-positive polyarthritis in seropositive rheumatoid arthritis (RA), or enthesitis-associated arthritis in peripheral or axial spondyloarthritis) (Nigrovic et al. 2018).

The ILAR classification provides more clarity and homogeneity than previous classifications. It delineates immunogenetically and prognostically different forms of juvenile arthritis (Nordal et al. 2011; Nigrovic et al. 2018). However, there are still overlaps between and heterogeneity within the categories of JIA. There is overlap between the RF-negative polyarthritis and oligoarthritis categories, among others; patients with early onset polyarthritis and oligoarthritis share common clinical and genetic features (Hinks et al. 2017). This is supported by a study by Ravelli and colleagues (Ravelli et al. 2011), which showed that ANA-positive patients share common features regardless of the number of affected joints. On the other hand, heterogeneity has been demonstrated within the categories of systemic arthritis (Gattorno et al. 2008), RF-negative polyarthritis (Hollenbach et al. 2010) and psoriatic arthritis (Stoll et al. 2011)

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