Oligoarticular juvenile idiopathic arthritis

INTRODUCTION — 

Oligoarticular juvenile idiopathic arthritis (JIA) is the most common type of JIA and is defined by the involvement of ≤4 peripheral joints during the first six months of disease. This subgroup is further divided into persistent oligoarticular JIA, in which arthritis remains limited to four or fewer uniquely affected joints, and extended oligoarticular JIA, in which arthritis spreads to more than four joints over time [1]. Historically, oligoarticular JIA was called pauciarthritis or pauciarticular-onset juvenile rheumatoid arthritis (JRA). (See "Classification of juvenile idiopathic arthritis".)

This topic reviews the clinical presentation, diagnosis, differential diagnosis, treatment, and prognosis of oligoarticular JIA. The classification, epidemiology, pathogenesis, and complications of JIA are discussed in detail separately:

●(See "Classification of juvenile idiopathic arthritis".)

●(See "Juvenile idiopathic arthritis: Epidemiology and immunopathogenesis".)

●(See "Juvenile idiopathic arthritis: Immunizations and complications".)

Other forms of JIA, including polyarticular JIA, psoriatic JIA, spondyloarthritis (enthesitis related JIA), and systemic JIA, are also discussed separately:

●(See "Polyarticular juvenile idiopathic arthritis: Clinical manifestations, diagnosis, and complications".)

●(See "Polyarticular juvenile idiopathic arthritis: Treatment and prognosis".)

●(See "Psoriatic juvenile idiopathic arthritis: Epidemiology, clinical manifestations, and diagnosis".)

●(See "Psoriatic juvenile idiopathic arthritis: Management and prognosis".)

●(See "Spondyloarthritis in children".)

●(See "Systemic juvenile idiopathic arthritis: Clinical manifestations and diagnosis".)

●(See "Systemic juvenile idiopathic arthritis: Treatment and prognosis".)

EPIDEMIOLOGY — 

Oligoarticular juvenile idiopathic arthritis (JIA) is the most common type of JIA, constituting approximately 40 to 50 percent of cases [2]. It affects female patients more often than male patients, as does polyarticular JIA. The peak incidence of oligoarticular JIA is in the second and third years of life. It is less common over five years of age and rarely begins after age 10 years. Key demographic and clinical features that differentiate oligoarticular, polyarticular, and systemic JIA are summarized in the table (table 1). More information on the classification, epidemiology, and pathogenesis of JIA is provided separately. (See "Classification of juvenile idiopathic arthritis" and "Juvenile idiopathic arthritis: Epidemiology and immunopathogenesis".)

CLINICAL PRESENTATION — 

Oligoarticular juvenile idiopathic arthritis (JIA) often affects knees and ankles and sometimes affects wrists and elbows. Hip involvement is possible but rare and should prompt consideration of alternative diagnoses that can affect the hip, including various forms of spondyloarthritis (SpA; eg, psoriatic JIA [psJIA], enthesitis related JIA [ERA]), infection, neoplasms (eg, osteoid osteoma), Legg-Calve-Perthes disease (ie, avascular necrosis of the hip), transient synovitis in young children, and slipped capital femoral epiphysis in older children (see "Approach to hip pain in childhood"). Patients can develop involvement of the temporomandibular joint (TMJ). (See "Juvenile idiopathic arthritis: Immunizations and complications", section on 'Temporomandibular joint arthritis'.)

While involved joints are typically swollen and tender and are usually warm, erythema is characteristically absent. In addition, it may be difficult to appreciate a limited range of motion in affected joints unless they are compared with the opposite site, since young children normally have a much greater range of motion than adults.

Despite the inflammation, many patients with oligoarticular JIA do not complain of pain and instead come to medical attention for a visibly swollen joint or a change in their mobility, such as limping [3]. Often, the caregiver notices that the child "walks funny" in the morning and then seems fine after a little while, which likely reflects the "morning stiffness" described by older patients. It is unusual for the caregiver to be able to specify exactly when the illness started.

Some patients who present with oligoarticular JIA may have comorbid iridocyclitis/uveitis that is frequently asymptomatic, underscoring the importance of routine screening (see "Juvenile idiopathic arthritis: Immunizations and complications", section on 'Complications'). Other than uveitis, there should not be any systemic complications of oligoarticular JIA. Features that suggest other types of JIA rather than oligoarticular JIA include constitutional symptoms (eg, fever, rash); development of axial arthritis, dactylitis, or psoriasis affecting the skin and/or nails; and a personal or family history of conditions related to SpA (eg, ankylosing spondylitis [AS], psoriasis, inflammatory bowel disease [IBD]). (See 'Differential diagnosis' below.)

LABORATORY FINDINGS — 

There are no diagnostic laboratory tests that are specific for diagnosing oligoarticular juvenile idiopathic arthritis (JIA). However, several abnormalities may be seen, including the following:

●Elevated inflammatory markers – The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are generally normal or mildly elevated. Having an elevated ESR (>40 mm/hour) and/or CRP (>0.8 mg/dL) at presentation is associated with an increased risk of progression to extended oligoarticular JIA or polyarticular JIA [4,5]. (See 'Course and prognosis' below.)

●Anemia – Patients may develop mild anemia (hemoglobin <11.0 g/dL) which, like elevated inflammatory markers, is associated with an increased risk of arthritis progressing to affect more joints [4,5]. (See 'Course and prognosis' below.)

●Positive antinuclear antibodies (ANAs) – ANAs are frequently present and are associated with an increased risk of iridocyclitis/uveitis (see "Juvenile idiopathic arthritis: Immunizations and complications", section on 'Chronic anterior uveitis'). However, more specific types of ANAs that are measured by the extractable nuclear antigen (ENA) panel (eg, anti-Ro/SSA, anti-La/SSB, anti-Smith [Sm], anti-ribonucleoprotein [RNP]) are typically absent. The presence of these other autoantibodies should prompt consideration of alternative underlying causes of inflammatory arthritis. (See 'Differential diagnosis' below.)

Autoantibodies associated with rheumatoid arthritis (RA; ie, rheumatoid factor [RF] and anti-cyclic citrullinated peptide [CCP]) are typically absent. The presence of a positive human leukocyte antigen B27 (HLA-B27) should prompt consideration of spondyloarthritis (SpA), especially in children >6 years old. (See 'Differential diagnosis' below.)

EVALUATION AND DIAGNOSIS

When to suspect — The diagnosis of oligoarticular juvenile idiopathic arthritis (JIA) should be suspected in a young child (typically ≤10 years old) who presents with arthritis affecting ≤4 joints, especially when it involves a knee and/or ankle and begins without a history of antecedent injury or illness. Patients may come to clinical attention due to impaired mobility (eg, limping) rather than vocalizing pain. The typical patient presenting with oligoarticular JIA is a female toddler who is limping without complaint.

Approach to evaluation — Children suspected of having oligoarticular JIA need a thorough history and physical examination, as well as selected laboratory testing to evaluate for poor prognostic factors and alternative diagnoses. Imaging is not routinely required.

History and physical examination — We obtain a detailed history focused on potential functional limitations caused by arthritis, such as difficulty meeting gross or fine motor milestones and reluctance to do certain activities (eg, getting out of bed, climbing stairs, running, jumping). We also ask about personal or family history of conditions that would suggest alternative diagnoses (eg, ankylosing spondylitis [AS], psoriasis, inflammatory bowel disease [IBD]).

We perform a comprehensive musculoskeletal examination looking for evidence of arthritis and subsequent complications (eg, joint contractures, decreased oral aperture, jaw asymmetry, muscle atrophy, leg length discrepancy). Given that children normally have an increased range of motion in joints compared with adults, it is important to examine pairs of joints to evaluate for relative symmetry. Often patients with suspected oligoarticular JIA are young toddlers who are not vocalizing pain and who may have difficulty tolerating the joint examination. In such cases, it may be especially informative to observe the patient navigating the examination room (eg, getting up onto the examination table, what positions are naturally comfortable to sit in) and to watch as they walk or run with their caregiver. We also look for evidence of psoriasis in the skin and nails, which would suggest psoriatic JIA [psJIA] as an alternative diagnosis; findings of psoriasis can be subtle, especially in young children. (See "Psoriatic juvenile idiopathic arthritis: Epidemiology, clinical manifestations, and diagnosis", section on 'Skin and nail disease'.)

The evaluation of the child with a limp, joint pain, and/or joint swelling is reviewed in detail separately. (See "Evaluation of limp in children" and "Evaluation of the child with joint pain and/or swelling".)

Laboratory testing — Although laboratory findings in oligoarticular JIA are nonspecific, we routinely send the following tests to evaluate for alternative diagnoses, look for poor prognostic factors, and obtain a baseline prior to potentially starting systemic therapies:

●Complete blood count (CBC)

●Inflammatory markers (ie, erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP])

●Selected autoantibodies including antinuclear antibody (ANA), rheumatoid factor (RF), and cyclic citrullinated peptides (CCP)

●Baseline kidney and liver function (ie, serum blood urea nitrogen [BUN] and creatinine, aspartate aminotransferase [AST], and alanine aminotransferase [ALT]) 

●Lactate dehydrogenase (LDH)

●For children who are >6 years old, human leukocyte antigen B27 (HLA-B27)

●For those living in an endemic area, Lyme testing (see "Diagnosis of Lyme disease", section on 'Serologic tests')

The typical laboratory findings in oligoarticular JIA are outlined above. (See 'Laboratory findings' above.)

Additional diagnostic testing in selected cases — Imaging is not routinely required to diagnose patients with oligoarticular JIA, as affected joints can usually be adequately evaluated through physical examination. However, imaging may be helpful when is unclear if a particular joint is affected and involvement of that joint would change the differential diagnosis or treatment (eg, ultrasound to evaluate for possible hip arthritis or MRI to evaluate for temporomandibular joint [TMJ] arthritis or tenosynovial giant cell tumor [TGCT]). Additionally, baseline radiographs of selected joints may be indicated if there is suspicion of damage (eg, erosion, loss of joint space) from longstanding disease.

Similarly, arthrocentesis and analysis of synovial fluid are rarely required for patients with suspected oligoarticular JIA unless there is a high suspicion for certain alternative diagnoses (eg, septic arthritis, leukemic arthritis, TGCT, or, rarely, gout). In addition, if we are performing an intraarticular (IA) glucocorticoid injection, then we often concurrently send synovial fluid for analysis with a cell count with differential, Gram stain, and culture. (See "Joint aspiration or injection in children: Indications, technique, and complications", section on 'Indications for joint aspiration'.)

Establishing the diagnosis — Oligoarticular JIA is a clinical diagnosis that is made in children <16 years of age based on the presence of arthritis affecting ≤4 joints for at least six weeks in the absence of factors that suggest another specific cause of the symptoms (eg, other subtypes of JIA, systemic autoimmune diseases, infection) [1]. (See "Classification of juvenile idiopathic arthritis", section on 'Oligoarthritis, persistent or extended'.)

Role of classification criteria — While the International League of Associations for Rheumatology (ILAR) classification criteria for JIA were developed to facilitate research, they are also used clinically. Occasionally, patients who are initially classified as having oligoarticular JIA may develop features over time that prompt a reclassification of their JIA subtype, such as involvement of >4 peripheral joints during the first six months of disease, development of axial arthritis, or evolution of comorbid psoriasis or inflammatory bowel disease (IBD). As an example, a patient with isolated knee involvement at presentation who later develops hip and spine involvement would typically be reclassified as having enthesitis related arthritis (ERA). However, with the exception of systemic JIA, the initial management of peripheral arthritis in JIA is similar regardless of the subtype [6]. (See "Classification of juvenile idiopathic arthritis", section on 'Revised ILAR JIA classification criteria'.)

DIFFERENTIAL DIAGNOSIS — 

It is important to recognize that patients may have oligoarthritis (ie, inflammatory arthritis in ≤4 joints) from causes other than oligoarticular juvenile idiopathic arthritis (JIA). The differential diagnosis of oligoarticular JIA principally includes the other nonsystemic subtypes of JIA, tenosynovial giant cell tumor (TGCT), Lyme disease, malignancy, and other infectious and inflammatory disorders:

●Polyarticular JIA – It can be challenging to differentiate patients with oligoarticular and polyarticular JIA at presentation, since the latter may present similarly in children less than 10 years of age with one or two affected joints. However, patients with polyarticular JIA are distinguished by developing arthritis in >4 joints during the first six months after disease onset. Joint involvement is frequently symmetric, in contrast to the often asymmetric arthritis in oligoarticular JIA. Laboratory findings in polyarticular and oligoarticular JIA can be similar, including a positive antinuclear antibody (ANA), elevated inflammatory markers (ie, erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP]), and anemia; patients with polyarticular JIA can also develop hypergammaglobulinemia. (See "Polyarticular juvenile idiopathic arthritis: Clinical manifestations, diagnosis, and complications".)

●Spondyloarthritis – Spondyloarthritis (SpA) is an umbrella term for arthritis (peripheral and/or axial) and varying degrees of enthesitis (ie, inflammation where the tendons attach to the bone). According to the International League of Associations for Rheumatology (ILAR) classification criteria for JIA, children with SpA are classified as having enthesitis related arthritis (ERA), psoriatic JIA (psJIA), or undifferentiated arthritis [1]. Arthritis related to inflammatory bowel disease (IBD) is also a type of SpA. (See "Classification of juvenile idiopathic arthritis".)

•ERA – The peripheral arthritis related to ERA is similar to that seen in oligoarticular JIA, with asymmetrical arthritis primarily affecting large joints in the lower extremities. However, ERA can be distinguished by the cooccurrence of enthesitis and often axial arthritis. It should also be suspected in the setting of a family history of conditions related to SpA (eg, acute anterior uveitis, ankylosing spondylitis [AS], IBD). (See "Spondyloarthritis in children".)

•psJIA – Patients with psJIA often present with an oligoarthritis that affects a knee and/or ankle, as is seen in oligoarticular JIA, and may not have psoriasis. Dactylitis (ie, a swollen finger or toe, sometimes referred to as a sausage digit) can be seen in both JIA subtypes but is more typical of psJIA. Other features that help distinguish psJIA from oligoarticular JIA include the development of enthesitis, axial arthritis, and/or psoriasis affecting the skin or nails. (See "Clinical manifestations and diagnosis of psoriatic arthritis".)

•IBD-related arthritis – A diagnosis of IBD-related arthritis should be suspected in children with oligoarticular arthritis in the setting of significantly elevated inflammatory markers, anemia, hypoalbuminemia, history of loose stools/diarrhea, poor weight gain, poor linear growth, and/or a family history of IBD. One-third of children with IBD develop arthritis, and the arthritis may precede the onset of gastrointestinal symptoms by months to years. (See "Clinical presentation and diagnosis of inflammatory bowel disease in children", section on 'Extraintestinal manifestations' and "Clinical manifestations and diagnosis of arthritis associated with inflammatory bowel disease and other gastrointestinal diseases".)

●Tenosynovial giant cell tumor – Episodic swelling of a single joint should raise suspicion for TGCT, formerly known as pigmented villonodular synovitis, where synovial inflammation and overgrowth cause joint pain and swelling [7]. TGCT typically affects large joints and is more common in males than females. The synovial fluid is often bloody. This condition can be distinguished from inflammatory arthritis on magnetic resonance imaging (MRI). (See "Treatment for tenosynovial giant cell tumor and other benign neoplasms affecting soft tissue and bone".)

●Lyme arthritis – Oligoarticular arthritis is one of the most common late manifestations of Lyme disease, a tickborne illness. While Lyme arthritis can affect almost any joint, it preferentially affects large joints. The classic presentation is monoarticular arthritis of the knee with a very large effusion that is not as painful as would be expected. The diagnosis of Lyme arthritis is based on serologic testing. (See "Lyme disease: Clinical manifestations in children", section on 'Arthritis' and "Musculoskeletal manifestations of Lyme disease", section on 'Diagnosis of Lyme arthritis'.)

●Other infectious and inflammatory disorders – Children with various types of infectious and inflammatory disorders, including septic arthritis, osteomyelitis, and plant thorn synovitis, are sometimes mistakenly diagnosed with oligoarticular JIA. Features that suggest an infectious etiology of joint pain or arthritis rather than oligoarticular JIA include moderate to severe pain, erythema of the overlying skin, and fever. While most patients with infectious arthritis present acutely with significant pain, those with atypical pathogens (eg, mycobacteria, fungi) can present subacutely and indolently. Inflammatory markers are often elevated and are typically higher than levels seen with oligoarticular JIA. (See "Bacterial arthritis: Clinical features and diagnosis in infants and children" and "Hematogenous osteomyelitis in children: Clinical features and complications".)

●Malignancy – Malignancy is an infrequent but important cause of monoarticular pain and, less commonly, arthritis in children [8]. As examples, both acute lymphocytic leukemia (ALL) and neuroblastoma may present with joint pain in the same age group as oligoarticular JIA. In general, children with an underlying malignancy appear sicker and experience more severe periarticular pain, rather than the milder articular pain as is seen in oligoarticular JIA. In addition, malignancy should be suspected in the presence of night sweats, monoarticular hip involvement, and certain laboratory abnormalities (eg, cytopenias, elevated lactate dehydrogenase [LDH] and/or uric acid, markedly elevated inflammatory markers) [8,9]. In such cases, further diagnostic testing is required since no single laboratory test can differentiate malignancy from JIA, with the exception of neoplastic cells in a peripheral smear. Radiologic evaluation may reveal bony metastases in neuroblastoma or metaphyseal rarefaction ("leukemic lines") in ALL. (See "Overview of the clinical presentation and diagnosis of acute lymphoblastic leukemia/lymphoma in children" and "Clinical presentation, diagnosis, and staging evaluation of neuroblastoma".)

PRETREATMENT CONSIDERATIONS — 

Some patients with oligoarticular juvenile idiopathic arthritis (JIA) are treated with a disease-modifying antirheumatic drug (DMARD) that suppresses the immune system to some degree, making them more vulnerable to infection and potentially dampening their response to preventive vaccinations. In such cases, we consider whether patients are due for any routine preventive vaccinations prior to starting therapy. This is especially important for patients with oligoarticular JIA who are often younger and may be due for live vaccinations (eg, measles, mumps, and rubella [MMR]), which are contraindicated while taking systemic immunosuppression. The approach to immunizations in patients with JIA is discussed in detail elsewhere. (See "Juvenile idiopathic arthritis: Immunizations and complications", section on 'Immunizations'.)

In addition, we screen for tuberculosis prior to starting patients on biologic DMARDs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs). (See "Tuberculosis infection (latent tuberculosis) in children", section on 'TBI testing'.)

TREATMENT

Overview of our approach — The treatment of oligoarticular juvenile idiopathic arthritis (JIA) depends primarily on the number and type of joints involved and whether there are factors associated with a poorer prognosis. Our approach is outlined in the algorithm and described in detail below (algorithm 1).

The presence of any of the following are considered risk factors for poorer prognosis [10]:

●Arthritis affecting an ankle, wrist, hip, cervical vertebrae, temporomandibular joint (TMJ), and/or sacroiliac (SI) joint

●Symmetrical arthritis

●Marked or prolonged elevation of erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP; eg, ESR >40 mm/hour and/or CRP >0.8 mg/dL)

●Evidence of prolonged disease activity at diagnosis (eg, joint damage on physical examination [eg, joint contracture] or imaging)

For the initial treatment of patients who do not have any of the above risk factors, we typically use intraarticular (IA) glucocorticoid injection(s) and a short-term course of a nonsteroidal antiinflammatory drug (NSAID). However, if patients do have one or more risk factors for a poor prognosis, then we also add methotrexate as a conventional synthetic disease-modifying antirheumatic drug (csDMARD) (see 'Methotrexate for patients with poor prognostic factors' below). Similarly, patients who have persistent disease despite IA glucocorticoids and NSAIDs and those who eventually develop extended oligoarticular JIA are typically started on methotrexate. When patients fail to respond to methotrexate, we either add or switch to a biologic DMARD (bDMARD) or targeted synthetic DMARD (tsDMARD). (See 'Refractory disease' below.)

Data comparing different regimens for the initial therapy of oligoarticular JIA are very limited. An open-label trial examined the incremental value of adding oral methotrexate to IA glucocorticoid injections in 207 patients with oligoarticular JIA who either had ≥2 swollen joints or one swollen joint (shoulder, elbow, wrist, ankle, or knee) if they had received IA glucocorticoids in the prior 12 months [11]. The disease duration was variable, with a mean of 7 months (range 2 to 22). Over the following 16 months, there was a significantly longer time to flare in patients randomly assigned to IA glucocorticoids plus methotrexate compared with those assigned to IA glucocorticoids alone (10 versus 6 months, respectively). However, the two treatment groups had similar rates of inactive disease at 12 months, progression of arthritis to involve new joints, and development of new-onset uveitis.

While the benefit of adding methotrexate appears to be modest based on these limited data, we do favor the early initiation of methotrexate for patients who have risk factors for progressive disease. By contrast, patients without such risk factors may not need to be exposed to the risk of adverse effects from systemic immunosuppressive therapies, since a sizeable proportion of patients with oligoarticular JIA experience prolonged remission with IA glucocorticoids alone. Our approach to initial treatment is generally consistent with that outlined in the 2021 American College of Rheumatology (ACR) JIA treatment guidelines [10].

Initial treatment

Intraarticular glucocorticoids and NSAIDs for most patients — For most patients with oligoarticular JIA who do not have poor prognostic risk factors, we suggest giving IA glucocorticoid injection(s) in all affected joints and a short-term course of an NSAID as needed for pain, rather than giving a DMARD with or without IA glucocorticoids and NSAIDs.

If the diagnostic evaluation is not complete, arthritis has been present for less than six weeks, and/or the caregiver is very hesitant about intervention, then a short-term course of NSAID monotherapy for symptomatic relief may be used as an alternative. However, if joint swelling persists, we treat with IA glucocorticoids and/or other DMARDs [10].

More information on the dosing and supportive evidence for these therapies is provided below:

●IA glucocorticoids – The dose of IA glucocorticoid depends upon both the size of the child and the size of the affected joint. IA injection typically provides relief of symptoms within days and lasts for at least four months, but this varies based on the type of long-acting glucocorticoid used. The dosing, administration, and complications of IA glucocorticoids are described in detail elsewhere. (See "Joint aspiration or injection in children: Indications, technique, and complications".)

Multiple observational studies support the use of IA glucocorticoids for children with various types of JIA [12,13]. As an example, a study evaluated the outcomes of IA glucocorticoid injections in 71 children with various forms of arthritis [12]. The 43 patients with oligoarticular JIA received a total of 141 IA glucocorticoid injections; 82 percent of injected joints experienced a sustained remission of at least six months and 74 percent of patients were able to discontinue oral therapies. In addition, among the whole study group, there was correction of joint contractures in 55 joints, complete remission in all 11 patients with Baker's cysts and all 12 with tenosynovitis, and no infections or other serious complications. Another study of 440 children with JIA who received ≥1 IA glucocorticoid injection(s) found that the percentage of patients in remission decreased over time and was lower when patients required more joint injections [13]. Specifically, for patients who received one, two, or three or more IA injections, the probability of staying in remission after one year was 70, 45, and 44 percent respectively, while after three years the probability decreased to 37, 22, and 19 percent, respectively. For the 318 patients with oligoarticular JIA, the percentage of patients in remission decreased from 67 after one year to 37 percent after three years. The strongest predictors of arthritis flare among all patients were having an elevated CRP, a negative antinuclear antibody (ANA), and arthritis affecting the ankle.

●NSAIDs – Several NSAIDs have been approved for use in children with JIA, including nonselective NSAIDs (eg, naproxen, ibuprofen) and more cyclooxygenase 2 (COX-2) selective ones (eg, celecoxib, meloxicam). Many other NSAIDs are routinely used by pediatric rheumatologists but have not been specifically approved for use in children. We prescribe NSAIDs at typical antiinflammatory doses (eg, naproxen 10 to 15 mg/kg/day [maximum daily dose 1000 mg], divided in two doses). More information on the dosing, contraindications to, and adverse effects of NSAIDs is provided separately:

•(See "NSAIDs (including aspirin): Pharmacology and mechanism of action".)

•(See "Nonselective NSAIDs: Overview of adverse effects".)

•(See "Overview of COX-2 selective NSAIDs".)

The efficacy of NSAIDs for treating JIA is discussed in detail elsewhere. (See "Spondyloarthritis in children", section on 'NSAIDs for most patients'.)

Methotrexate for patients with poor prognostic factors — For patients with poor prognostic risk factors for disease progression (eg, arthritis affecting an ankle, wrist, hip, cervical vertebrae, TMJ, and/or SI joint; symmetrical arthritis, elevated ESR or CRP, evidence of prolonged disease activity at diagnosis), we add methotrexate to IA glucocorticoids, rather than using IA glucocorticoids alone. For patients who have contraindications to or intolerance of methotrexate, alternative csDMARDs that may be substituted include leflunomide and sulfasalazine. A short course of an NSAID can be added as needed for pain.

Our rationale for taking a more aggressive initial approach to management in patients with poor prognostic factors is provided above (see 'Overview of our approach' above). While there are very little data directly comparing csDMARDs in patients with JIA, we favor using methotrexate given the relatively greater body of supportive evidence. Likewise, we favor methotrexate over bDMARDs and tsDMARDs for this patient group since there are more longitudinal safety data. The dosing and supportive evidence for these therapies is as follows:

●Methotrexate – For patients with JIA, methotrexate is dosed at 10 to 15 mg/m² (alternatively 15 mg/dose) and may be given orally or subcutaneously, although tolerance of doses >10 mg/m² is often better with injections [14]. The dose may be increased to 20 to 30 mg/m² (alternatively 1 mg/kg; maximum 25 mg). Folic acid is given daily to prevent adverse effects, which can be especially prominent in children and are discussed in detail elsewhere. (See "Major adverse effects of low-dose methotrexate".)

Studies describing the efficacy of methotrexate in patients with JIA are presented separately. (See "Polyarticular juvenile idiopathic arthritis: Treatment and prognosis", section on 'Methotrexate'.)

●Other csDMARDs – The dosing of and supportive evidence for leflunomide and sulfasalazine in JIA are discussed in detail elsewhere:

•(See "Polyarticular juvenile idiopathic arthritis: Treatment and prognosis", section on 'Sulfasalazine'.)

•(See "Polyarticular juvenile idiopathic arthritis: Treatment and prognosis", section on 'Leflunomide'.)

Refractory disease — Oligoarticular JIA typically affects younger children who are at important stages of bone growth and development. It is therefore imperative to carefully monitor the response to therapy and escalate as needed to achieve complete remission. (See 'Monitoring' below.)

●Persistent disease activity despite initial therapy – For patients with persistent disease activity despite initial therapy, we escalate treatment as follows:

•Initial treatment with IA glucocorticoids – If patients do not respond completely within two to three weeks to the initial IA glucocorticoid injection(s) with or without NSAIDs, we suggest starting methotrexate for most patients rather than an alternative DMARD. We also start methotrexate for patients who develop extended oligoarticular JIA (ie, arthritis in >4 joints during the first six months of disease). Patients with a contraindication to or intolerance of methotrexate may use alternative csDMARDs. An alternative approach in patients who have not developed risk factors for progressive disease is to administer a second injection ≥4 weeks after the first. This approach may be preferable when the patient and/or caregivers have concerns about starting systemic therapy. NSAIDs can be used concurrently until disease activity and/or pain subsides. (See 'Methotrexate for patients with poor prognostic factors' above.)

Data are very limited to support specific treatment strategies in patients with oligoarticular JIA who do not respond to initial therapy with IA glucocorticoids. Regarding patients with extended oligoarticular JIA, one trial randomly assigned 43 such patients to receive methotrexate or placebo; the improvements in ESR and the provider and parent/caregiver global assessment were greater in the group receiving methotrexate compared with the group receiving placebo [15].

•Initial treatment with a csDMARD – For patients with persistent disease activity despite ≥3 months of a csDMARD with or without IA glucocorticoids, we suggest adding or switching to a bDMARD or tsDMARD rather than switching to an alternative csDMARD or combining csDMARDs. We stop the csDMARD if it has not provided any benefit or has caused significant adverse effects; otherwise, we generally combine the existing csDMARD with the new DMARD.

Our preference for escalating to a bDMARD rather than changing or adding csDMARDs is based on the more rapid onset of action of bDMARDs and the desire to quickly control ongoing arthritis in children with ongoing skeletal development. When choosing a bDMARD, there are no comparative effectiveness studies in patients with oligoarticular JIA who have not responded to a csDMARD; thus, we pick a bDMARD based on provider and family preferences, as well as the presence of certain disease complications (eg, uveitis) [10]. Options include tumor necrosis factor (TNF) inhibitors, which are most commonly used, as well as abatacept and interleukin 6 (IL-6) inhibitors (ie, tocilizumab). While Janus kinase (JAK) inhibitors are another option, they are only approved for patients who fail TNF inhibitors, and there are limited safety data in children [10]. The approval of specific bDMARDs for subtypes of JIA varies by country. Additionally, in the United States, insurance coverage of specific bDMARDs may dictate initial therapy choices. More information on the dosing, monitoring, and efficacy of bDMARDs is provided separately. (See "Polyarticular juvenile idiopathic arthritis: Treatment and prognosis", section on 'Biologic agents'.)

●Refractory disease – Definitions of refractory disease in JIA vary. We generally consider patients to be refractory if they have active disease despite a four-month trial of a bDMARD with or without a csDMARD, IA glucocorticoids, and/or NSAIDs. In such cases, we switch to an alternative bDMARD or tsDMARD. Depending on the initial agent and the patient's response, we use shared decision-making to either try a similar agent (eg, an alternative TNF or JAK inhibitor) or switch to a drug with a different mechanism of action (eg, changing from a TNF inhibitor to an IL-6 inhibitor or tsDMARD).

Our approach to escalating therapy is generally consistent with that outlined in the 2021 American College of Rheumatology (ACR) JIA treatment guidelines [10].

Recurrent disease — Patients can experience recurrent disease where the arthritis returns after a period of remission. We usually restart the same regimen that previously induced remission, with certain caveats depending on the initial therapy that was used:

●Recurrence of transient swelling responsive initially to NSAID monotherapy – For such patients, we typically administer IA glucocorticoids with or without an NSAID as needed for pain (see 'Intraarticular glucocorticoids and NSAIDs for most patients' above). However, if patients have developed risk factors for progressive disease or progress to having extended oligoarticular JIA, then we also start methotrexate. (See 'Methotrexate for patients with poor prognostic factors' above.)

●Recurrence after IA glucocorticoids – For such patients who have subsequently developed risk factors for progressive disease or extended oligoarticular JIA, we use a combination of methotrexate, IA glucocorticoids, and as-needed NSAIDs (see 'Intraarticular glucocorticoids and NSAIDs for most patients' above and 'Methotrexate for patients with poor prognostic factors' above). Otherwise, another option in patients without these factors is to give repeated IA glucocorticoid injection(s) with or without NSAIDs. Repeat IA injections may be preferable for patients who experienced a prolonged period of remission (eg, >4 months) after their initial injection and those who have monoarthritis. The exact number of IA injections that should prompt escalation to systemic therapy varies based on the type of glucocorticoid used, the joint injected, and patient, family, and provider preferences; however, we generally add a DMARD for patients who require more than two or three injections of triamcinolone acetonide in a single joint.

●Recurrence after a DMARD – For such patients, we typically restart their prior therapy. If they do not respond, then we escalate along the same pathway used to treat persistent initial disease. (See 'Methotrexate for patients with poor prognostic factors' above and 'Refractory disease' above.)

Duration of therapy — For patients who are taking systemic immunosuppression, the approach to tapering varies based on many factors including the type and number of agents being used; provider, patient, and family/caregiver preferences; and the presence of adverse drug effects. In general, we wait until patients have been in remission for at least 6 to 12 months before attempting a taper. The approach to tapering therapy in oligoarticular JIA is similar to that used in polyarticular JIA, which is discussed in detail separately. (See "Polyarticular juvenile idiopathic arthritis: Treatment and prognosis", section on 'Duration of therapy'.)

MONITORING

Disease activity and complications — Monitoring for ongoing disease activity in oligoarticular juvenile idiopathic arthritis (JIA) is primarily clinical, based on a combination of history and physical examination. As is the case with the initial presentation, patients with active arthritis may not vocalize discomfort, underscoring the importance of assessing other factors such as the patients' level of physical activity and attainment of developmental gross and fine motor milestones. We also watch carefully for evidence of asymmetry on examination that suggests certain complications (eg, joint contractures, temporomandibular joint [TMJ] arthritis, leg-length discrepancies) and ensure that the patient is screened appropriately for comorbid uveitis. (See "Juvenile idiopathic arthritis: Immunizations and complications", section on 'Clinical presentation and routine monitoring'.)

Children with oligoarticular JIA who have unexplained anemia or elevated inflammatory markers (ie, erythrocyte sedimentation rate [ESR] or C-reactive protein [CRP]) are more likely to have recurrent disease and ultimately evolve into extended oligoarticular JIA with widespread joint involvement [4,5]. We pay particular attention this subgroup of patients since their course, prognosis, and optimal therapy appear to differ from typical oligoarticular JIA. In patients who initially had evidence of systemic inflammation on laboratory testing (eg, elevated ESR or CRP, anemia), we periodically trend these measures and ensure that they normalize with therapy. (See 'Course and prognosis' below and 'Overview of our approach' above.)

Immunosuppressive therapy — We monitor patients taking systemic immunosuppression for the development of drug-related adverse effects based on their reported symptoms and laboratory findings. The frequency and type of laboratory monitoring depend on the agents being used, as summarized in the table (table 2) and described in detail in the respective drug topics.

COURSE AND PROGNOSIS — 

Patients who ultimately develop arthritis in >4 joints after the first six months of disease are classified as having extended oligoarticular juvenile idiopathic arthritis (JIA); otherwise, patients have persistent oligoarticular JIA [1]. Twenty-five to 35 percent of children go on to have extended oligoarticular disease [16-18]. The presence of anemia, an elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP), ankle or wrist involvement, or two or more involved joints at presentation is associated with an increased risk of progression to extended oligoarticular or polyarticular JIA [4,5,19].

While most patients improve after a few months of treatment, some have ongoing disease activity, and approximately one-fifth of children who initially do well eventually develop disease recurrence. In one cohort study, six months after the diagnosis of oligoarticular JIA, 70, 65, and 50 percent of children achieved an American College of Rheumatology (ACR) Pediatric 30, 50, or 70 response, respectively [20]. In this same cohort, 86 percent of patients attained inactive disease within two years, and 58 percent achieved remission within five years [16].

Patients with persistent oligoarticular JIA have a better chance of achieving remission compared with patients who develop extended oligoarticular JIA. In a longitudinal study with follow-up a median of 98 months after diagnosis, remission was achieved by 69 percent of children with persistent oligoarthritis (66 and 3 percent off and on medication, respectively), compared with only 37 percent of those with extended oligoarthritis (21 and 16 percent on and off medication, respectively) [17].

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: Uveitis" and "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 AND RECOMMENDATIONS

●Epidemiology – Oligoarticular juvenile idiopathic arthritis (JIA) is defined by the involvement of ≤4 peripheral joints during the first six months of disease. Is the most common JIA subtype, constituting approximately 40 to 50 percent of cases, with a peak incidence in the second and third years of life. (See 'Epidemiology' above.)

●Clinical presentation – Patients with oligoarticular JIA develop arthritis in ≤4 peripheral joints, often in the knees and ankles and sometimes the wrists and elbows. Hips are rarely the first involved joint. Many patients present with limping rather than complaints of pain. Systemic manifestations other than uveitis are characteristically absent. (See 'Clinical presentation' above.)

●Evaluation and diagnosis

•When to suspect – The diagnosis of oligoarticular JIA should be suspected in a young child (typically ≤10 years old) who presents with arthritis affecting ≤4 joints, especially when it involves a knee and/or ankle and begins without a history of antecedent injury or illness. (See 'When to suspect' above.)

•Approach to evaluation – In addition to a thorough history and physical examination, we obtain selected laboratory testing to evaluate for poor prognostic factors and alternative diagnoses. Imaging, arthrocentesis, and synovial fluid analysis may be indicated, depending upon the presentation and differential diagnoses. (See 'Approach to evaluation' above.)

•Establishing the diagnosis – Oligoarticular JIA is a clinical diagnosis made in children <16 years of age based on the presence of arthritis affecting ≤4 joints for at least six weeks in the absence of factors that suggest another specific cause of the symptoms. (See 'Establishing the diagnosis' above.)

●Differential diagnosis – The differential diagnosis of oligoarticular JIA principally includes the other nonsystemic subtypes of JIA, tenosynovial giant cell tumor (TGCT), Lyme disease, malignancy, and other infectious and inflammatory disorders. (See 'Differential diagnosis' above.)

●Treatment – The treatment of oligoarticular JIA depends primarily on the number and type of joints involved and whether there are factors associated with a poorer prognosis (eg, arthritis affecting an ankle, wrist, hip, cervical vertebrae, temporomandibular joint [TMJ], and/or sacroiliac [SI] joint; symmetrical arthritis, elevated erythrocyte sedimentation rate [ESR] or C-reactive protein [CRP], evidence of prolonged disease activity at diagnosis) (algorithm 1). (See 'Overview of our approach' above.)

•Initial treatment

-Intraarticular (IA) glucocorticoids for most patients – For most patients with oligoarticular JIA who do not have poor prognostic risk factors, we suggest giving IA glucocorticoid injection(s) in all affected joints, rather than giving a disease-modifying antirheumatic drug (DMARD) with or without IA glucocorticoids (Grade 2C). We add a short-term course of a nonsteroidal antiinflammatory drug (NSAID) as needed for pain. (See 'Intraarticular glucocorticoids and NSAIDs for most patients' above.)

-Methotrexate for patients with poor prognostic factors – For patients with poor prognostic risk factors for disease progression, we add methotrexate to IA glucocorticoid injection(s), rather than using IA glucocorticoids (Grade 2C). (See 'Methotrexate for patients with poor prognostic factors' above.)

•Refractory disease – For patients with persistent disease activity despite initial therapy, we escalate treatment depending on the initial therapy used (see 'Refractory disease' above):

-Initial treatment with IA glucocorticoids – For patients who do not completely respond within two to three weeks to initial IA glucocorticoids, we suggest adding methotrexate rather than an alternative DMARD (Grade 2C). An alternative approach is giving a second injection ≥4 weeks after the first.

-Initial treatment with a csDMARD – For patients with persistent disease activity despite ≥3 months of a conventional synthetic DMARD (csDMARD) with or without IA glucocorticoids, we suggest adding or switching to a biologic or targeted synthetic DMARD (tsDMARD; eg, tumor necrosis factor [TNF] inhibitors, interleukin 6 [IL-6] inhibitors, abatacept, Janus kinase [JAK] inhibitor) rather than switching to an alternative csDMARD or combining csDMARDs (Grade 2C). We stop the csDMARD if it has not provided any benefit or has caused significant adverse effects; otherwise, we generally combine the existing csDMARD with the new DMARD.

•Recurrent disease – If patients experience recurrent disease, we usually restart the same regimen that previously induced remission. We generally add a DMARD for patients who require more than two or three injections of glucocorticoid in a single joint. (See 'Recurrent disease' above.)

●Course and prognosis – Approximately one-fifth of children who initially do well eventually develop disease recurrence, and some develop chronic destructive arthritis. Twenty-five to 35 percent of patients ultimately develop extended oligoarticular JIA (ie, arthritis in >4 joints after the first six months of disease); the remainder has persistent oligoarticular JIA. (See 'Course and prognosis' above.)

ACKNOWLEDGMENT — 

The UpToDate editorial staff acknowledges Thomas JA Lehman, MD, who contributed to earlier versions of this topic review.