Classification of juvenile idiopathic arthritis

INTRODUCTION — Juvenile arthritis is a heterogeneous group of inflammatory disorders. The classification categories created for juvenile idiopathic arthritis (JIA) are primarily intended for research use and are not intended for use as diagnostic criteria [1].

This topic reviews the classification categories for JIA. The individual disease categories are discussed in greater detail separately.

OVERVIEW — In general, criteria for the classification of the idiopathic arthritides of childhood are intended to subdivide childhood-onset arthritides in a manner that allows for better understanding of their pathogenesis and treatment responses [2,3].

Juvenile arthritis classification criteria have been developed to measure the incidence of juvenile arthritis, understand its etiology, identify appropriate groups of patients for research, and group patients who may have similar responses to treatment and/or prognoses.

It has become increasingly clear that many forms of JIA have a distinct etiology, pathogenesis, and natural history, which has led to refinements in classification criteria over time [4-6].

Many nomenclature systems include further "descriptors" within each category that are expected to result in additional subclassifications over time [7,8]. While the initial purpose of these categories was to stratify patients enrolled in studies into homogeneous groups, this terminology is now also frequently used in clinical care to facilitate description of disease phenotype.

TERMINOLOGY — The classification and terminology of juvenile arthritis have evolved over time along with understanding of the disease. The older terms "juvenile rheumatoid arthritis" (JRA, used commonly in the United States) and "juvenile chronic arthritis" (JCA, preferred in Europe) were replaced by the term "juvenile idiopathic arthritis" (JIA) at meetings of the International League of Associations for Rheumatology (ILAR) in the late 1990s. JIA now incorporates all of what was called JRA in the past and also includes all other forms of "idiopathic" arthritis in childhood.

JIA CLASSIFICATION CATEGORIES — The International League of Associations for Rheumatology (ILAR) criteria for classification of the idiopathic arthritides of childhood are intended to define the separate childhood-onset arthritides in a manner that allows better evaluation of etiologic mechanisms and newer therapies [2,3]. Despite limitations, these criteria are widely used in research in clinical care.

Several reports have reinforced the idea that many of the children classified as having JIA in fact have early manifestations of what are recognized to be distinct diseases in adults (eg, systemic JIA and adult-onset Still's disease, polyarthritis [rheumatoid factor (RF) positive/RF-negative]/extended oligoarthritis and rheumatoid arthritis, and persistent oligoarthritis/enthesitis related arthritis and spondyloarthritis) [9,10].

Per the ILAR criteria, JIA is a diagnosis of exclusion [11]. Disease onset is before 16 years of age, manifestations persist for at least six weeks, and the etiology is unknown. JIA is further categorized as follows:

●Systemic arthritis

●Polyarthritis, RF positive or negative

●Oligoarthritis, persistent or extended

●Enthesitis related arthritis

●Psoriatic arthritis

●Undifferentiated arthritis

Systemic arthritis — Systemic arthritis (systemic JIA) defines the category of patients that were previously labeled adult-onset Still's disease.

Systemic arthritis is characterized by arthritis in one or more joints and fever of at least two weeks duration that is quotidian for at least three days. In addition, children must have one or more of the following findings: evanescent, erythematous rash; hepatomegaly or splenomegaly; lymph node enlargement; or serositis.

This category is considered an autoinflammatory condition unrelated to other forms of childhood arthritis and requiring different therapy [6]. Children with clearly identifiable syndromes associated with fever and arthritis, such as polyarteritis nodosa, are grouped separately. (See "Vasculitis in children: Incidence and classification" and "Systemic juvenile idiopathic arthritis: Clinical manifestations and diagnosis" and "Systemic juvenile idiopathic arthritis: Treatment" and "Systemic juvenile idiopathic arthritis: Course, prognosis, and complications".)

Polyarthritis, rheumatoid factor positive or negative — The category of polyarthritis (polyarticular JIA) is defined by the presence of arthritis in five or more joints. This group is further divided according to the presence or absence of RF. (See "Polyarticular juvenile idiopathic arthritis: Clinical manifestations, diagnosis, and complications" and "Polyarticular juvenile idiopathic arthritis: Treatment".)

According to the criteria as published, children should have at least two positive immunoglobulin M (IgM) RF tests at least three months apart, although, in practice, this test is often only obtained at baseline.

Children with a first-degree relative with psoriasis, systemic arthritis, or features of enthesitis related arthritis are excluded from the category of polyarthritis.

Oligoarthritis, persistent or extended — Oligoarthritis (oligoarticular JIA) defines the subset of patients that were previously labeled as pauciarticular JRA (see "Oligoarticular juvenile idiopathic arthritis"). These patients have less than five joints involved at diagnosis and are further categorized as follows:

●Persistent oligoarthritis refers to children with one to four joints affected during the first six months of disease who do not develop arthritis in five or more joints during their disease course.

●Extended oligoarthritis refers to children with less than five joints affected during the first six months of disease who subsequently experience involvement of more than four joints.

Children with a positive RF, a first-degree relative with psoriasis, features of enthesitis related arthritis, or systemic arthritis are excluded from these categories.

Enthesitis related arthritis — The category of enthesitis related arthritis is applied to children with both arthritis and enthesitis, arthritis alone, or enthesitis alone and two or more of the following:

●Sacroiliac joint tenderness or lumbosacral inflammatory pain

●Positive human leukocyte antigen (HLA)-B27

●First-degree relative with acute anterior uveitis, ankylosing spondylitis, inflammatory bowel disease with sacroiliitis, or reactive arthritis

●Acute anterior uveitis

●Onset of arthritis in males >6 years of age

Children are excluded from this category if they have a first-degree relative with psoriasis, positive RF, or systemic arthritis.

This category includes some children previously diagnosed with spondyloarthropathies (see "Spondyloarthritis in children"), as well as some children likely to develop psoriatic arthritis (see "Psoriatic juvenile idiopathic arthritis: Pathogenesis, clinical manifestations, and diagnosis") who lack sufficient criteria at the time of diagnosis. In fact, classification of spondyloarthropathies in the adult literature is advancing rapidly with the clear recognition that these diseases are unrelated to other forms of arthritis [4].

Psoriatic arthritis — Psoriatic arthritis is defined as children with psoriasis and arthritis or children with arthritis and two of the following [12] (see "Psoriatic juvenile idiopathic arthritis: Pathogenesis, clinical manifestations, and diagnosis" and "Psoriatic juvenile idiopathic arthritis: Management and prognosis"):

●Psoriasis in a first-degree relative

●Dactylitis

●Appropriate fingernail abnormalities (eg, pitting or onycholysis)

Children are excluded from this category if they have features of enthesitis related arthritis, systemic arthritis, or positive RF.

Undifferentiated arthritis — Children are categorized as undifferentiated if they do not meet criteria for one of the categories above due to incomplete features or the presence of exclusions. Children are also considered undifferentiated if they meet criteria for more than one category.

APPLICABILITY OF THE ILAR CRITERIA — To determine the usefulness of the International League of Associations for Rheumatology (ILAR) classification criteria, 194 children with arthritis of more than six months' duration were assessed [13]. Eighty percent of the children could be categorized. Among the difficult-to-classify children, approximately one-half did not satisfy criteria for any specific category, although the remainder met criteria for more than one category. As an example, eight children could be categorized as having both enthesitis related arthritis and rheumatoid factor (RF) negative polyarthritis.

ONGOING RESEARCH INTO JIA CLASSIFICATION — The classification of juvenile arthritis is an area of active research and is continuing to evolve along with improved understanding of the biologic heterogeneity of the disease. Alternative classification systems have been suggested based upon evolving understanding of disease phenotypes, cytokine profiles, and genetics [14]. These various classification systems require additional biologic and prospective validation to determine their utility.

Many patients in the pediatric JIA categories share similar genetics to adult patients with arthritis and therefore represent a spectrum of arthritis, rather than separate entities. An overview of these genetic similarities proposed four primary categories based upon these patterns [15]:

●Seropositive (rheumatoid factor [RF] positive) arthritis

●Seronegative (RF-negative) arthritis

●Spondyloarthritis

●Systemic arthritis

A consensus conference led by the Pediatric Rheumatology International Trials Organization (PRINTO) proposed a revision to the existing categories based upon Delphi and nominal group methodologies [16]. The categories resulting from this project include:

●Systemic JIA

●RF-positive JIA

●Early-onset antinuclear antibody (ANA) positive JIA

●Enthesitis/spondylitis-related JIA

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Juvenile idiopathic arthritis".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Juvenile idiopathic arthritis (The Basics)")

SUMMARY

●Overview – The classification of juvenile idiopathic arthritis (JIA) remains a challenging area given the heterogeneity of the disease. Classification criteria are intended for use in the research setting, and not as diagnostic criteria to be used at the bedside, but may still have utility in helping providers communicate about disease features, treatment options, and prognosis. (See 'Introduction' above and 'Overview' above.)

●ILAR classification categories for JIA – The International League of Associations for Rheumatology (ILAR) state that JIA is a diagnosis of exclusion. Disease onset is before 16 years of age, manifestations persist for at least six weeks, and the etiology is unknown. (See 'JIA classification categories' above.)

JIA is further categorized as follows:

•Systemic arthritis

•Polyarthritis, rheumatoid factor (RF) positive or negative

•Oligoarthritis, persistent or extended

•Enthesitis related arthritis

•Psoriatic arthritis

•Undifferentiated arthritis

●Future classification schemes – The ILAR criteria are considered the standard, and any proposed new systems still require further validation. With improving genetic and pathophysiologic understanding of arthritis, it is hoped that future classification schemes will define homogeneous collections of children with biologically distinct illnesses. (See 'JIA classification categories' above and 'Ongoing research into JIA classification' above.)

ACKNOWLEDGMENT — The editorial staff at UpToDate acknowledge Thomas JA Lehman, MD and Sarah Ringold, MD, MS, who contributed to earlier versions of this topic review.