Juvenile Idiopathic Arthritis
OLIGOARTICULAR, POLYARTICULAR, AND SYSTEMIC CATEGORIES
Carol A. Wallace, David A. Cabral, and Robert P. Sundel
Arthritis is a clinical finding of persistent joint swelling or painful restriction of joint movement. Arthralgia is pain in a joint, with or without inflammation. Thus, a patient with arthralgia will not necessarily have arthritis, nor does a patient with arthritis always have arthralgia. There are many causes of arthritis and arthralgia in childhood, and this section will be limited to the chronic arthritides of childhood that have no known cause.
Terminology for this category of disease is problematic: In ongoing attempts to rationalize the nomenclature, at least three different classification schemes have been used during the past 20 years (see eTable 201.1 ). Without a clear-cut understanding of the pathogenesis or biologic variability of arthritis in children, however, these systems have often served more to confuse than to elucidate. Idiopathic arthritis lasting for at least 6 weeks; with onset before age 16; and not the result of infections, neoplasms, orthopedic disorders, chronic inflammatory or autoimmune conditions, or metabolic inherited and endocrine diseases, will be referred to as juvenile idiopathic arthritis (JIA) in this section. This term is increasingly used internationally to describe this group of conditions. Details of the definitions and subcategories within this system are shown in Table 201-1. The Juvenile Rheumatoid Arthritis system still used by most care-givers in the United States is shown in Table 201-2. Further background regarding these classification systems is provided on the DVD.
COMPARING SYSTEMS OF NOMENCLATURE AND CLASSIFICATION
Diagnosis, stratification, and study of arthritis in children are all dependent on a consistent and agreed on system for classifying and naming disease subsets. In the absence of a clear understanding of the etiology and pathogenesis of arthritis, however, criteria must be based on demographic, clinical, and laboratory factors, and consequently they are bound to be imperfect. Over time, the features that are thought to distinguish apparently discrete types of arthritis have changed, and so classification systems have changed as well. The most recent modification of the classification criteria for childhood arthritis was published by the International League of Associations for Rheumatology (ILAR) in 2001. Although childhood arthritis in the United States generally continues to be known as juvenile rheumatoid arthritis, after a previous classification system, the ILAR criteria have gained widespread acceptance in most other countries and in most medical journals. Thus, in order to allow clinicians from around the world to communicate using common terminology, this edition of Pediatrics utilizes the ILAR classification of juvenile idiopathic arthritis (JIA).
Criteria to classify chronic arthritis in childhood as JIA were first proposed by the Pediatric standing committee of ILAR in 1993 and subsequently revised in 2001. Arthritis of childhood had previously been characterized on different sides of the Atlantic in the 1970s by a committee of the American College of Rheumatology (ACR), and by the European League against Rheumatism (EULAR). They respectively coined the terms juvenile rheumatoid arthritis (JRA) and juvenile chronic arthritis (JCA) but confusingly, within the EULAR classification one of the categories of arthritis describing patients with rheumatoid factor positive disease was also called JRA. The systems of nomenclature of the ACR, EULAR, and ILAR are compared in Table 201-1. These classifications share some common features: They all refer to patients whose disease onset was before age 16; they require a minimum period of duration of arthritis–6 weeks for ACR and ILAR, and 6 months for EULAR; they all use terms to describe the pattern of disease during the first 6 months from onset—oligoarticular (or pauciarticular) arthritis occurring in 4 or fewer joints and polyarticular, defining arthritis occurring in 5 or more joints. Systemic in all schemes refers to arthritis in association with characteristic fever and other extra-articular features, including rash, lymphadenopathy, hepatosplenomegaly, or serositis. The presence of rheumatoid factor has also been recognized as a defining feature for subclassification, and in the EULAR system, patients with rheumatoid factor are described as having JRA, whereas in the ILAR system a subclass of JIA is described as rheumatoid factor positive polyarthritis.
A major deficiency of the ACR, EULAR, and current ILAR classification systems is in how they deal with childhood spondyloarthropathies. They are respectively not included, incompletely included, or inadequately described in the context of adult disease. These deficiencies are further discussed in the section on enthesitis-related arthritis and the spondyloarthropathies (Chapter 229).
PRINCIPLES AND UNIQUE FEATURES OF THE ILAR (JIA) SYSTEM
The philosophy of the ILAR system of classification was to describe categories and subcategories of JIA that apart from the presence of arthritis are clinically distinct, with the assumption that the homogeneity of each subgroup reflects an underlying biological or pathophysiological homogeneity. Thus, the results of research into the causes of arthritis, assessments of disease outcomes, and evaluation of new drugs and treatment strategies are intended to be not only clinically useful, but also biologically relevant. To achieve this, the ILAR classification system is unique because categories of JIA are defined by specific inclusion criteria as well as by exclusion criteria. These are designed so that patients who fulfill criteria for more than one category of arthritis will be relegated to the undifferentiated JIA category. For example, a patient whose disease is characterized by enthesitis, and who also has a persistently positive rheumatoid factor, would fit within the category of undifferentiated JIA. Although it is acknowledged that this principle of mutual exclusivity will result in many patients being included in the undifferentiated category, it is hoped that those patients within each category (or subcategory) will have as homogeneous a disease as possible. In practice, this is useful if the categories truly represent biologically discrete conditions, but it is not clear that this is the case.1 Unfortunately, those patients remaining within the undifferentiated category have a condition that is difficult to explain to families, and are usually excluded from clinical trials. Nonetheless, the ILAR system has gained a great deal of international acceptance to replace the two previous parallel systems, although its scientific merits and consistency have not been confirmed. The ILAR system is complicated to use and is decidedly imperfect, but it appears to be the preferred system for most of the world, giving it a cache lacking in the previous systems.
JIA is arthritis of unknown etiology that begins before the 16th birthday and persists for at least 6 weeks; other known conditions including infections, neoplasms, orthopedic disorders, chronic inflammatory or autoimmune conditions, or metabolic inherited and endocrine diseases.
Arthritis in one or more joints with or preceded by fever of at least 2 weeks’ duration that is documented to be daily (“quotidian”) for at least 3 days, and accompanied by one or more of the following:
1. Evanescent (nonfixed) erythematous rash
2. Generalized lymph node enlargement
3. Hepatomegaly and/or splenomegaly
Arthritis affecting one to 4 joints during the first 6 months of disease. Two subcategories are recognized:
1. Persistent oligoarthritis: Affecting not more than 4 joints throughout the disease course
2. Extended oligoarthritis: Affecting a total of more than 4 joints after the first 6 months of disease
Polyarthritis (Rheumatoid Factor Negative)
Arthritis affecting 5 or more joints during the first 6 months of disease; a test for RF is negative.
Exclusions: a, b, c, d, e.
Polyarthritis (Rheumatoid Factor Positive)
Arthritis affecting 5 or more joints during the first 6 months of disease; 2 or more tests for RF at least 3 months apart during the first 6 months of disease are positive.
Arthritis and psoriasis, or arthritis and at least 2 of the following:
2. Nail pitting or onycholysis
3. Psoriasis in a first-degree relative
Exclusions: b, c, d, e.
Enthesitis Related Arthritis
Arthritis and enthesitis, or arthritis or enthesitis with at least 2 of the following:
1. The presence of or a history of sacroiliac joint tenderness and/or inflammatory lumbosacral pain
2. The presence of HLA-B27 antigen
3. Onset of arthritis in a male over 6 years of age
4. Acute (symptomatic) anterior uveitis
5. History of ankylosing spondylitis, enthesitis related arthritis, sacroiliitis with inflammatory bowel disease, Reiter’s syndrome, or acute anterior uveitis in a first-degree relative
Arthritis that fulfills criteria in no category or in 2 or more of the above categories.
Exclusions: a) Psoriasis or a history of psoriasis in the patient or first-degree relative. b) Arthritis in an HLA-B27 positive male beginning after the 6th birthday. c) Ankylosing spondylitis, enthesitis related arthritis, sacroiliitis with inflammatory bowel disease, Reiter’s syndrome, or acute anterior uveitis, or a history of one of these disorders in a first-degree relative. d) The presence of IgM rheumatoid factor on at least 2 occasions at least 3 months apart. e) The presence of systemic JIA in the patient.
Definitions of Terms: Dactylitis: Swelling of one or more digits, usually in an asymmetric distribution, which extends beyond the joint margin. Enthesitis: Tenderness at the insertion of a tendon, ligament, joint capsule, or fascia to bone. Inflammatory lumbosacral pain: Lumbosacral spinal pain at rest with morning stiffness that improves on movement. Nail pitting: A minimum of 2 pits on one or more nails at any time. Positive test for rheumatoid factor (RF): At least 2 positive results (as routinely defined in an accredited laboratory), at least 3 months apart, during the first 6 months of disease. Quotidian fever: Fever that rises to ≥ 39°C once a day and returns to ≤ 37°C between fever peaks. Serositis: Pericarditis and/or pleuritis and/or peritonitis. Sacroiliac joint arthritis: Presence of tenderness on direct compression over the sacroiliac joints. Spondyloarthropathy: Inflammation of entheses and joints of the lumbosacral spine. Uveitis: Chronic anterior uveitis as diagnosed by an ophthalmologist.