Rudolph's Pediatrics, 22nd Ed.

CHAPTER 201. 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.

Table 201-1. ILAR Classification System for Juvenile Idiopathic Arthritis (JIA)

ILAR, International League of Associations for Rheumatology. Data from Petty RE, Southwood TR, Manners P, et al. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol. 2004;31:390-392.

Table 201-2. American Rheumatology Association Diagnostic Criteria for Juvenile Rheumatoid Arthritis

INTERCHANGEABILITY OF TERMINOLOGY

It is tempting to use similarly named subcategories within each of the classification systems interchangeably. Because of the very exclusive ILAR definitions, it is likely that most patients with JIA-oligoarthritis, for example, could also be classified as either oligoarticular JRA or oligoarticular JCA. However, the converse is not true. The categories of oligoarticular JRA or oligoarticular JCA also include patients that might better be described as having the enthesitis-related arthritis, or psoriatic arthritis. In the clinical setting this may not always be critical, but there is a need to be careful in extrapolating the results of clinical or biological studies back to the context of a specific patient. There is a wealth of literature on JRA and JCA that cannot be ignored and that must be applied to patients within the new ILAR classifications. However, going forward, studies will enroll patients according to the ILAR criteria, so eventually the transition in nomenclature must be made.² It is hoped that the next modification in terminology will be based firmly on genetic and pathogenic data, and subsequent changes will not be necessary.

EPIDEMIOLOGY

In the United States, the prevalence of juvenile idiopathic arthritis is 1 in 1000 and the incidence is 1.4 in 10,000. JIA is subdivided into seven categories based on the number of joints involved and other identified features present within the first 6 months of disease onset (rather than on the biology of the disease). Consequently, etiologic and prognostic differences between the oligoarticular, polyarticular, and psoriatic categories are not striking. As fundamental genetic and pathogenic information about these disorders increases, the manner in which we describe, categorize, understand, and treat childhood arthritis will likely undergo dramatic changes.

PATHOPHYSIOLOGY AND GENETICS

A disease of persistent inflammation of the synovium, JIA has long been considered a manifestation of autoimmunity; however, intense investigation has failed to identify autoantibodies or target antigens. The contribution of Human Leukocyte Antigens (HLA) alleles in persistent oligoarticular JIA (DRB1* 1301, 0801) and polyarticular JIA (DPB1* 0301) is emerging as important, possibly through their effect on T-lymphocyte receptor function. Current thinking is leading toward understanding these heretogeneous categories of JIA as autoinflammatory, rather than autoimmune, diseases. It is postulated that persistence of microbial antigens initiates synovial inflammation through the action of antibodies against microbial antigens that cross-react with self (molecular mimicry). Another line of investigation presents evidence that an infection promotes the presentation of self–HLA peptides to T cells.

Evidence for an infectious initiation of synovial inflammation includes the persistent arthritis seen after a variety of infections, including rubella and parvovirus. The clinical features (abrupt onset, high-spiking fever, rash, hepatosplenomegaly, lymphadenopathy, and serositis) and a clustering of cases in the autumn also suggest infection as an inflammatory trigger. Further, polymerase chain reaction has allowed identification of microbes and their antigens in synovial tissue in some arthritides not previously thought to be owing to infection. The immunologic cascade involved in JIA appears to be initiated by presentation of antigens to T lymphocytes by antigen-presenting cells as described in Chapter 198.

The histology of the inflamed synovium in all categories of JIA is identical to that of adult rheumatoid arthritis and is characterized by lymphocytic and plasma cell infiltration and later villous hypertrophy and hyperplasia of the synovial lining. This is accompanied by prominent vascular endothelial cell hyperplasia and angiogenesis resulting in the secretion of large amounts of protein-rich synovial fluid and the migration of neutrophils, lymphocytes, and macrophages into the joint. Synovial fluid white cell counts usually range from 2000 to 30,000/mL. However, even counts exceeding 100,000/mL may be seen in patients with systemic JIA.

An exuberant inflammatory process leads to aggressive expansion of the synovium onto the articular cartilage (pannus formation).

Prolonged synovial inflammation causes irreparable damage to the cartilage, as well as erosion and destruction of subchondral bone. Formation of synovial-lined bony cysts can occur.

CLINICAL PRESENTATIONS

In the absence of laboratory tests specific for the diagnosis of JIA, patient history and physical examination assume critical importance. A cardinal feature of inflammatory synovitis is morning stiffness of at least 30 minutes, with improvement over time or following movement and warming of the joint. Parents and other caregivers may observe changes in walking, running, climbing stairs, or eagerness to play. Children may need help with dressing, eating, bathing, toileting, and other activities that were previously performed independently. Enuresis may recur in a recently toilet-trained child, and developmental milestones may be lost. Children not old enough to describe stiffness or pain may be cranky in the morning or have generally decreased activity.

On physical examination all joints must be thoroughly assessed for swelling, motion, tenderness, pain, and bony enlargement. Muscles should be examined for strength and possible atrophy. In addition, extra-articular signs of juvenile arthritis should be sought, including abnormal pupils, rash, lymphadenopathy, organomegaly, and pericardial and pleural rubs. Occasionally, synovitis may be painless, but the diagnosis requires the physical finding of swelling resulting from inflammation. Indirect evidence of synovitis in those joints where swelling cannot be visualized (ie, spine, hip, and shoulder) is decreased of motion of the joint with associated pain or tenderness. Observing the child moving about in the exam room can be as important as direct examination, which may be difficult in an uncooperative, frightened toddler or infant.

OLIGOARTICULAR CATEGORY

Oligoarticular JIA, defined as synovitis in four or fewer joints over the first 6 months of symptoms, occurs in about 40% of children with JIA. The ratio of males to females is 1:6.5; the usual age of onset is 1 to 3 years. Typically, the arthritis is minimally symptomatic and has an insidious onset. Many of these children will report no pain and come to medical attention after joint swelling is found incidentally. The knee is most frequently involved, followed by the ankle and then the small joints of the hand or the wrist, but almost any joint may be affected. Isolated hip or neck arthritis occurs rarely, although it may also portend evolution into enthesitis-related arthritis, ankylosing spondylitis or psoriatic arthritis. Involvement of only the temporomandibular joints has been described. Children with oligoarticular JIA are systemically well—without fever, rash, lymphadenopathy or organomegaly.

Asymptomatic uveitis (inflammation of the uveal tract—iris, ciliary body, and choroid) develops in approximately 20% of children with oligoarticular JIA, and 80% of these will have a positive antinuclear antibody (ANA) test. Prompt diagnosis and treatment of uveitis is critical to prevent later cataracts and glaucoma, and potential loss of vision. Consequently, ophthalmologic screening by slit-lamp examination every 3 to 4 months is essential for these high-risk children. In fact, persistent or difficult-to-treat uveitis becomes the most prominent chronic feature in a subset of children with JIA. Less frequent screening is adequate in other forms of arthritis that carry a lower risk of uveitis. Guidelines for ophthalmologic screening for children with different JRA subtypes are shown in eTable 201.2.

Over time, about 80% of children with oligoarthritis will continue to have episodes of arthritis with 4 or fewer joints involved (persistent oligoarthritis), whereas 20% will have extension of synovitis into additional joints and become the group labeled as extended oligoarthritis.

Seventy percent of children with oligoarticular JIA are ANA-positive, usually in low titer (≤1:320). Mild elevation of erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) and mild thrombocytosis with a slight decrease in hemoglobin may be found, but these tests are usually normal, as are other laboratory tests. The rheumatoid factor test is rarely positive, but if it is, it often portends conversion to a polyarticular course. Fever, rash, night pain, weight loss, thrombocytopenia, or leukopenia are not seen in this disease, and should prompt further investigations for alternative diagnoses.

POLYARTICULAR JIA

Polyarticular JIA, defined as involvement of at least 5 joints during the first 6 months of illness, is found in about 25% of children with JIA. This group is further split into the categories of RF–and RF+ disease. Those children who are considered to be RF+ must have this test confirmed with repeat testing at least 3 months from the initial test. Females predominate with two peak ages of onset: 1 to 3 years, and again during early adolescence. Both large and small joints may be affected; presentations vary from scattered joint involvement to symmetric synovitis of nearly all joints in the body. Involvement of the cervical spine, hips, shoulders, and temporomandibular joints (TMJ) is common. In most patients, the onset is insidious and accompanied by fatigue. Additionally, some patients have low-grade fever, weight loss, rheumatoid nodules, hepatosplenomegaly, lymphadenopathy, pleuritis, pericarditis and pneumonitis. These patients are more likely to have elevated acute phase reactants, including ESR, CRP and platelet counts, and they will often have mild anemia of chronic disease. White blood cells counts should be normal.

The disease of those children with a positive rheumatoid factor closely resembles adult rheumatoid arthritis, including occasional development of rheumatoid nodules, vasculitis and Felty syndrome (splenomegaly and leukopenia). Antibodies to cyclic citrullinated peptide (anti-CCP) are found in many of the same patients, though they may develop earlier than the rheumatoid factor and may be a more sensitive marker of severe disease.⁴ Other serologic markers are generally negative; about 30% of patients with polyarticular JIA have positive ANA test results. Five percent of patients with polyarticular JIA develop asymptomatic chronic uveitis, but in general children with more than 5 involved joints are at less risk to do so than are children with oligoarticular disease.

SYSTEMIC JIA

Systemic onset juvenile idiopathic arthritis, defined as the occurrence of high-spiking daily fevers and arthritis in one or more joints (often with other systemic findings), affects about 10% of children with JIA. Males and females are affected equally. The age of onset peaks at 5 to 10 years but spans infancy through adulthood. The characteristic finding is daily fever, which, although erratic, usually spikes once or twice a day, rising above 39.3°C (103°F) and then spontaneously falling to or below normal. The peak of the fever curve is often in the evening and may be accompanied by intense arthralgia and myalgia. When the temperature is normal, the child may feel quite well only to appear ill again when the fever spikes. Often the fever and other systemic features will precede the development of arthritis, so in general systemic onset JIA is a diagnosis of exclusion. Such patients must have an extensive evaluation to rule out other sources of fever, especially infections and malignancies.

Patients with systemic JIA may have a wide variety of systemic manifestations. Among these is a macular, evanescent, salmon-colored rash (Fig. 201-1). It typically exhibits discrete borders with or without central clearing, and is often best seen during the fever. The rash may be raised, is usually nonpruritic, and is migratory, appearing anywhere, but most commonly over the trunk, thighs, and axillae. It may be induced by mild trauma (Koebner phenomenon). Other common systemic manifestations include pericarditis, myocarditis, pleuritis, lymphadenopathy, hepatosplenomegaly, abdominal pain, fatigue, anorexia, weight loss, and, rarely, asymptomatic iritis. With time a few or many inflamed joints will appear. These tend to be markedly swollen and more painful than the arthritis of other subgroups. Nighttime pain and awakening are not unusual, but they nonetheless should prompt investigation for underlying malignancy or infection.

The child with typical fever and rash but without arthritis may be treated empirically for probable systemic JIA after other diagnoses are exhaustively excluded. The diagnosis is not firm until synovitis appears, and other potential causes of the child’s symptoms have been duly considered. Many of these children will require bone marrow aspiration and/or lymph node biopsy to exclude malignant diseases. Laboratory abnormalities of systemic JIA are often dramatic, including significant leukocytosis (>40,000), thrombocytosis (>1 million), and elevated inflammatory markers (eg, CRP > 20 mg/dl and ESR > 100 mm/hour). Elevated transaminases, anemia, and low serum albumin levels are found frequently, but urinalysis is normal and rheumatoid factor and DNA are rarely positive. During the acute phase of disease, some children become severely ill with development of leukopenia, thrombocytopenia, profound anemia, and hypofibrinoginemia, and an acute decrease in the sedimentation rate. In addition, D-dimer and ferritin levels may rise dramatically, and prothrombin time and partial thromboplastin time become prolonged, consistent with disseminated intravascular coagulation. This crisis is called macrophage activation syndrome (MAS) and it appears to be related to hereditary lymphohistiocytiosis. As it progresses, serum transaminases may abruptly increase to greater than 1000 U/l, the bone marrow may exhibit hemophagocytosis, and further sequelae of DIC and cytokine storm may develop. With delayed or inappropriate management, MAS carries a 10% to 20% mortality rate, but severe sequellae largely may be avoided with prompt recognition and treatment with pulse IV methylprednisone and further immunosuppression (for example, with IV cyclosporine).

FIGURE 201-1. Salmon-pink rash in systemic onset JIA.

DIAGNOSIS OF JIA

LABORATORY EVALUATION

As described for each category of JIA, there is no test or combination of tests that can differentiate JIA from other diseases. JIA remains a clinical diagnosis dependent on the finding of unexplained synovitis. The major role of laboratory tests is to exclude other potential diagnoses, particularly infection and/or malignancy, and to stratify patients’ risk of disease sequelae.

IMAGING IN JIA

There is no imaging study that can definitively diagnose JIA unless the disease is so advanced that characteristic erosions and joint destruction have occurred. In general, imaging studies demonstrate joint inflammation, but they do not distinguish JIA from infectious or proliferative conditions. Thus, plain radiographs may rule out diseases that mimic JIA, such as leukemia, tumors or chronic recurrent multifocal osteomyelitis. The earliest changes are soft tissue swelling and periarticular osteopenia, though this latter finding is only visible on plain radiographs when 50% of the bone mineral content has been lost because of inflammation. The intense inflammation of the tendon sheath, joint, and tendon attachments can stimulate periosteal new bone formation in the tubular bones of the phalanges, metacarpals, and metatarsals, and occasionally long bones. A characteristic radiographic finding in children with JIA involving a finger is widening of the mid-portion of a phalange from periosteal new bone formation. Plain radiographs are also useful for monitoring chronic joint changes and effectiveness of treatment, but CT and/or MRI evaluations are more sensitive.

DIFFERENTIAL DIAGNOSIS

A thorough and diligent evaluation to exclude other processes such as infection and malignancy must be emphasized. The diagnoses of oligoarticular, polyarticular, or systemic juvenile idiopathic arthritis require swollen joints or evidence of synovitis (see Table 201-1). A well child with joint pain but no swelling may have an orthopedic condition (avascular necrosis, slipped femoral epiphysis, benign joint tumor, Osgood-Schlatter disease), so-called growing pains (benign nocturnal limb pains of childhood), hyper-mobility, or a pain syndrome. An ill child may have infection (of joints, bone or generalized), postinfectious arthritis, a metastatic tumor, leukemia, lymphoma, or multifocal osteomyelitis. Thus, a thorough workup is mandatory.

TREATMENT

Goals of treatment are to minimize symptoms, prevent joint destruction, maintain normal growth and development, and achieve inactive disease. Inactive disease is defined as no joints with active arthritis; no fever, rash, serositis, splenomegaly, or generalized lymphadenopathy attributable to JIA; no uveitis; normal physician global evaluation; and normalization of inflammatory markers such as ESR or CRP. The pillars of treatment are patient/family education, early aggressive medical management, and physical and occupational therapy.⁴

FIGURE 201-2. Algorithm for treatment of oligo and polyarticular juvenile idiopathic arthritis. (TNF, tumor necrosis factor)

EDUCATION

Patient and family education is a critical component of treatment; in order to achieve an optimal outcome, children and their caregivers must be active partners in the treatment plan. Knowledge about the disease, understanding of the goals of treatment, and realistic expectations regarding the medications used are necessary to promote adherence to therapeutic regimens. Patients and families must be provided with careful, detailed explanations about joint functioning, the effects of untreated inflammation on growing joints, the need for early aggressive therapy, the goals of therapy, and potential side effects of treatments. The Arthritis Foundation is an excellent source for additional information and peer support.

MEDICATIONS

The medical treatment of JIA is hampered by incomplete understanding of the etiology of arthritis, and by the nonspecific actions of many key medications. Further, many medications that are effective in adult arthritis have not been approved by the FDA for use in children, generally because of a lack of pivotal studies. Despite this deficiency, with the limited armamentarium of approved medications for JIA, many agents without FDA indications for JIA (eg, leflunomide, infliximab) may still have a place in the treatment of JIA.

Our current understanding of how quickly synovitis can cause joint destruction, coupled with the traditionally poor long-term outcome of JIA, have led to earlier and more aggressive treatment over the past decade (Fig. 201-2). (An algorithm for the treatment of systemic-onset JIA is not presented because the treatment varies considerably depending on individual factors; agents ranging from nonsteroidal anti-inflammatory drugs (NSAIDs) to high-dose methylprednisolone, IV cyclosporine,⁵ and experimental drugs all may be considered in specific cases.) NSAIDs are no longer the mainstay of treatment for arthritis, but they can be useful for mild reduction of pain and as a mild anti-inflammatory agent. Intra-articular injections of triamcinolone hexacetamide, in place of or in addition to systemic therapies, can be particularly effective in quickly suppressing inflammation in a limited number of joints.⁶Depending on the age of the child and the number and location of joints to be injected, brief general anesthesia may be necessary for the injections. Repeat injections (up to 3/joint) can be an important treatment strategy.

For those patients with polyarthritis or persistent or extended oligoarthritis, methotrexate should be started as early as possible.^7,8 Although this drug can be administered orally once weekly (0.3/kg/week), SQ injections of 0.5 to 1.0 mg/kg/week (40 mg maximum) are more effective. Daily folate (1 mg) is usually given for its demonstrated reduction of side effects in adults with rheumatoid arthritis who are treated with methotrexate, though comparable data in children are not available.

Short-term daily oral prednisone (0.5–2 mg/kg/day) and/or weekly IV pulse methylprednisolone (30 mg/kg, 1 gram maximum), followed by low-dose daily prednisone (0.15 mg/kg/day) for several months, may be very helpful in quickly reducing synovitis, joint symptoms and systemic features of disease. Adult data indicate that this treatment strategy may persistently decrease the likelihood of joint damage when begun early in the course of the disease. Although there is concern for potential side effects from the use of corticosteroids, the benefits of better disease control and improved physical activity may be tremendous. Weight gain is temporary, and many patients on 0.15 mg/kg/day or less grow normally and have normal bone density studies.

In tandem with methotrexate, tumor necrosis factor antagonists (etanercept,⁹ infliximab, and adalimumab), anti-IL-1 medications (anakinra, rilonacept), and costimulatory blocking agents (abatacept) have greatly increased the ability to achieve complete disease control in the majority of children with JIA. Other new biologic medications (anti-IL 6 agents, longer-acting anti-TNF preparations, etc) are becoming available, and treatment of JIA is evolving rapidly. Initially, these medications were reserved as “the last treatment”; however, accumulating data suggest that their effectiveness in preventing joint damage is even greater when used early in the disease course, rather than after other treatments have failed.

All of the medications mentioned here (including NSAIDs) have potential side effects and require ongoing laboratory monitoring. Cytopenias and liver function abnormalities are seen most commonly. For patients on methotrexate, complete blood count (CBC), aspartate amino-transterase (AST), blood urea nitrogen (BUN), and creatinine are recommended after one month of treatment and then every 2 to 3 months. For NSAID use, the same monitoring (with a urinalysis) should be done 1 month after starting the medication, and then every 4 months thereafter. Similar monitoring is recommended for most biologic response modifiers.

Clinical follow-up of children with active JIA should occur every 1 to 3 months to allow for thorough evaluations and medication adjustments, with the goal of achieving disease remission. After inactive disease is achieved, medications are kept stable for 6 months to several years before they are gradually tapered and discontinued. Evolving management strategies may be similar to cancer protocols, with induction regimens utilizing many medications together early in the disease course followed by milder maintenance regimens aimed at maintaining remission.

PHYSICAL THERAPY

Physical and occupational therapies are an important component of the treatment for JIA. Therapeutic goals include improving range of motion, strength, and functioning when possible, otherwise at least preventing further deterioration. Because loss of age-appropriate developmental skills can occur, functional skills should to be monitored by a therapist experienced in working with children with arthritis. Frequency of therapy visits varies considerably, but all therapy is based on a daily home program done by the child and parent. An active lifestyle is important for maintaining bone and joint health; low-impact exercises such as swimming are preferable when disease is active.

Nighttime splinting of the wrist, hand, knee, elbow, or ankle may decrease morning stiffness and help to prevent flexion contractures during active disease. Loss of extension can often be improved after corticosteroid injection followed by serial casting of a knee, ankle, wrist, finger, or elbow. Ice, heat, ultrasound, or a combination of these modalities may help restore motion and decrease pain due to muscle spasm. When a leg-length difference is present, a shoe lift for the short limb will help to prevent contralateral knee or hip flexion contractures. Children with arthritis of the tarsal and metatarsal joints may ambulate more easily with shoe splints (soft orthotics).

School can present a particular challenge for children with arthritis. Morning stiffness may make a timely arrival difficult, and stiffness from prolonged sitting may make moving between classes problematic. Daytime stiffness can be ameliorated by allowing the child to get up and move about the classroom, and some children may need extra time to pass from class to class. Upper-extremity involvement may make writing, drawing, working on the blackboard, and participating in class difficult. An extra set of books at home greatly lessens the load that needs to be carried to and from home. Physical education and sports can be a challenge when arthritis is active; most children do well when allowed to participate as much as they are able. Exercise and nonimpact sports will not damage joints or worsen arthritis if bony destruction is not present. Rarely, a child may need a shortened school day, but home tutoring is almost never indicated.

OUTCOME

The outcome of juvenile rheumatoid arthritis is variable for all categories. Some patients may experience a single episode of disease lasting 6 to 12 months, whereas others are afflicted with continuous chronic inflammation, progressive joint destruction, and chronic disability. Children do not outgrow JIA nor does puberty predictably alter its course. Outcome can be measured by functional ability, persistence of synovitis, or radiographic findings. One recent investigation described the entire course of each of 437 patients followed 4 to 22 years with respect to time spent with active or inactive disease, and on or off medications. This investigation revealed that although the majority of patients with oligoarticular JIA spent nearly 60% of their disease course with inactive disease, 64% of patients with RF–polyarticular JIA and 84% of children with RF+ polyarticular JIA spent 60% or more of the time with active disease.¹⁰ Although overall, 44% of patients achieved clinical remission off medications, only 18% remained in that state for more than 2 years and only 4% for 5 years. Thus, many patients begin their adult life with ongoing joint inflammation, and they remain at risk for all of the potential complications that this can cause.

Radiographic changes are yet another measure of arthritis severity and outcome. All patients with JIA are at risk for joint damage—it is common and can occur early in disease. Twenty-eight percent of pauciarticular-onset patients develop radiologic evidence of joint damage at a median time of 5 years, whereas half of those with polyarticular- and systemic-onset JIA develop joint damage within 2 years of onset of disease.

Despite these challenges, mortality from JIA in North America is very rare, largely confined to children with systemic-onset disease. It is calculated at 0.29% of all patients with JIA; although a low number, this rate greatly exceeds overall mortality rates for American children.¹¹