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Polyarticular Juvenile Idiopathic Arthritis

Polyarticular Juvenile Rheumatoid Arthritis

Polyarticular juvenile idiopathic arthritis is a multi-etiological condition characterized by arthritis, affecting more than four joints within six months after the condition’s first appearance. It forms a part of the group of conditions named juvenile idiopathic arthritis open link but patients with the polyarticular variant are subject to different diagnostic and therapeutic approaches compared to those with fewer joints involved.

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Presentation

By definition, polyarticular JIA affects at least four joints during the first six months of the beginning of the disease. While polyarticular JIA rarely begins before the first year of life, it typically starts anytime before the age of 16 years. Arthritis must persist for at least 6 weeks in order to make the diagnosis of polyarticular JIA.

The beginning is usually indolent. Morning stiffness or stiffness after prolonged periods of inactivity as well as arthralgia during the day could be the first symptoms. Due to pain, children usually stop using their joints in a normal way and muscle contractures may appear. A decrease in school attendance or deferring participation in sports-related activities may be a clue to the disease severity.

Symmetrical small joint involvement, as well as rheumatoid nodules, may be observed in rheumatoid factor- positive patients. Involvement of the cervical spine may lead to C2,C3 subluxations or fusion of the posterior ligaments of the spine. Arthritis of the temporal-mandibular joint may manifest as micrognathia, decreased mouth aperture or lateral deviation of the jaw.

Possible complications due to polyarticular JIA include high-level subluxation, accelerated bone age with increased epiphyseal size and narrowing of the joint spaces. The involvement of the cervical spine may lead to difficult intubation during anesthesia due to the resulting limited cervical extension.

Pain
  • Disease activity, current treatment, disease duration, functional ability, pain and fatigue were assessed. Structured interviews were applied to explore participation in PA and PE, and PA facilitators and barriers.[ncbi.nlm.nih.gov]
  • CLINICAL CASE: This is the case of RF-negative polyarticular juvenile idiopathic arthritis that was reported with six-week history of neck pain, torticollis and left knee effusion. The case was sent to the radiology department from primary care.[ncbi.nlm.nih.gov]
  • Polyarticular JIA (Poly-JIA) is a severe subtype that can cause joint damage, poor growth and development, limited mobility, and pain.[chop.edu]
  • Upon initiation of treatment with Humira, the most common adverse reactions that occurred were injection site pain and injection site reaction (19 percent and 16 percent, respectively).[fiercebiotech.com]
Difficulty Walking
  • Limited mobility can be a problem for school attendance; it may cause difficulty walking, fatigue, pain or stiffness.[printo.it]
Coarctation of the Aorta
  • We present the case of a 5-year-old boy with double outlet right ventricle, ventricular septal defect, coarctation of the aorta and MONA.[ncbi.nlm.nih.gov]
Coronary Artery Disease
  • METHODS: Based on the National Cholesterol Education Program, fasting lipoprotein levels and risk levels for coronary artery disease were determined in 28 patients with polyarticular juvenile idiopathic arthritis.[ncbi.nlm.nih.gov]
Arthritis
  • Abstract Recent advances in biologic therapy have enabled reduction of the progression of destructive arthritis in rheumatoid arthritis. Once destroyed, however, the affected bones and cartilage are not fully repaired.[ncbi.nlm.nih.gov]
  • RESULTS: Dyslipoproteinemia was identified in 20 of the 28 (71%) patients with polyarticular juvenile idiopathic arthritis.[ncbi.nlm.nih.gov]
  • Polyarticular juvenile idiopathic arthritis is a multi-etiological condition characterized by arthritis, affecting more than four joints within six months after the condition’s first appearance.[symptoma.com]
  • To conclude, in polyarticular seronegative JIA, infliximab showed a transient beneficial effect which was more pronounced on uveitis than arthritis.[ncbi.nlm.nih.gov]
  • It also highlights the possible role of cervical spine imaging in all children with juvenile idiopathic arthritis. The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.[ncbi.nlm.nih.gov]
Joint Swelling
  • She was diagnosed with RF-positive polyarticular JIA based on positive RF and multiple joint swelling and tenderness 3 years ago. She was admitted in our hospital with myalgia for 2 days and a high fever for half a day.[ncbi.nlm.nih.gov]
  • A diagnosis can be insidious because children may not complain of pain and joint swelling may not be so obvious.[news-medical.net]
  • Inflammatory • Juvenile idiopathic arthritis Onset before 16 years of age, joint swelling for more than 6 weeks, possible systemic symptoms.[healio.com]
  • Notably, her arthritis showed dramatic improvement during the varicella infection and her joint swelling diminished with the onset of the varicella lesions, allowing her to walk for the first time since the onset of arthritis.[academic.oup.com]
  • Typical symptoms include stiffness when awakening, limping, and joint swelling. Any joint can be affected and inflammation may limit the mobility of the affected joints.[fiercebiotech.com]
Morning Stiffness
  • Morning stiffness or stiffness after prolonged periods of inactivity as well as arthralgia during the day could be the first symptoms. Due to pain, children usually stop using their joints in a normal way and muscle contractures may appear.[symptoma.com]
  • Symptoms include painful, swollen and tender joints, limping, morning stiffness, decreased activity and the reluctance to use an arm or leg. Early diagnosis and appropriate management of JIA are important in managing this chronic disease.[news.abbvie.com]
  • One characteristic common to all six forms of JIA is that of "morning stiffness" that improves during the day as more movement is done.[medicinenet.com]
  • Children with polyarticular JIA often present with pronounced morning stiffness and fatigue. Constitutional symptoms may also be present.[healio.com]
  • stiffness and joint pain joint stiffness and pain can also be noted with prolonged periods of inactivity ( e.g., sitting) visual changes can be suggestive of a uveitis Physical exam joint involvement swelling limited range of motion tenderness to palpation[medbullets.com]
Arthralgia
  • Morning stiffness or stiffness after prolonged periods of inactivity as well as arthralgia during the day could be the first symptoms. Due to pain, children usually stop using their joints in a normal way and muscle contractures may appear.[symptoma.com]
  • In the placebo-controlled clinical trials in plaque psoriasis, the incidence of arthralgia was 3 percent in Humira-treated patients versus 1 percent in controls.[fiercebiotech.com]
  • Physical Exam Arthritis must be present, not just arthralgias: In addition to swelling, warmth, and tenderness, there may be restricted range of motion in the affected joints and soft tissue contractures.[unboundmedicine.com]
  • Can be preceded by arthralgias and sometimes arthritis develops weeks to months following disease onset. Wrists, knees, and ankles are most commonly involved on initial presentation.[pathophys.org]
Joint Deformity
  • Complications Joint deformities: Knee flexure contractures. Involved joints mature faster than unaffected joints. This can lead to limb length discrepancy. Accelerated bone age with narrowed joint spaces.[patient.info]

Workup

There is no particular diagnostic test able to detect polyarticular JIA. Laboratory tests are used to support rather than confirm the diagnosis.

As the main clinical manifestations of polyarticular JIA are due to joint inflammation, inflammatory markers such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are routinely analyzed along with complete and differential blood counts in order to monitor the degree of inflammation.

Various imaging techniques are used in order to evaluate the joints, conventional radiography being the most accessible and easy to perform. Ultrasonography can demonstrate the presence of intra-articular fluid even before its clinical manifestations appear. The role of both standard and functional magnetic resonance imaging increases as these techniques allow for detection of joint erosions, reduced joint space or cartilage and ligament damage, all signs of progressive joint inflammation [31] [32] [33].

Rheumatoid factor test has prognostic value [34]. However, at least two rheumatoid factor tests performed three months apart during the first six months of the disease, are necessary for adequate interpretation.

As the presence of anti-nuclear antibodies (ANA) is associated with a higher risk for developing asymptomatic uveitis, ANA must be analyzed in every patient with oligo- or polyarticular involvement [35] [36]. Anti-cyclic citrullinated peptide (anti-CCP) antibodies are a marker of severity of the disease. They are not, however, measured usually [37].

Scintigraphy with technetium-99m could be performed in order to detect early stages of the disease [38].

Joint Space Narrowing
  • Classically, radiographs of affected joints in children with JIA can demonstrate soft tissue swelling, joint space narrowing, erosion, subluxation, ankylosis, calcification, and osteoporosis (see Figure 3 ).[healio.com]
Elevated Sedimentation Rate
  • Many patients with JIA, especially the polyarticular and systemic types, have elevated sedimentation rates and anemia. Antinuclear antibody is a useful test in classifying patients with JIA and determining the risk of uveitis.[unboundmedicine.com]

Treatment

Treatment guidelines for polyarticular JIA have not been yet established. The therapy, therefore, varies worldwide from region to region depending on the different availability of drugs.

Several groups of medicaments are used in the management of polyarticular JIA, including non-steroid anti-inflammatory drugs, intravenous and intraarticular steroids, non-biologic and biologic disease modifying agents.

Approximately 30% of the patients respond well to treatment with nonsteroidal anti-inflammatory drugs. The rest are subject to more intense therapy with other classes of anti-rheumatoid medicaments.

First-line medicaments for patients with multiple joint involvements (more than 4 joints) include intra-articular or intravenous steroids in combination with methotrexate.

Patients with poor response to methotrexate at doses 15mg/m2 subcutaneously for at least three months are candidates for therapy with TNF-alfa inhibitor. If no satisfactory results are obtained, another anti-TNF-alfa may be prescribed. If the lack of improvement persists, rituximab is then recommended for RF+ patients, while tocilizumab or abatacept is recommended for RF- patients.

The involvement of the axial skeleton is an indication for immediate treatment with TNF-alfa inhibitor.

Other biological agents used in polyarticular JIA include intravenous immunoglobulin and interleukin-1 (IL-1) inhibitors. However, intravenous immunoglobulin showed no long-term benefits in clinical studies [39].

Treatment must be accompanied by appropriate physical therapy.

Prognosis

Polyarticular JIA is a chronic disease. With the advent of new treatment approaches introduced in the last 20 years, the prognosis has improved remarkably. Although some patients may experience lifelong problems, the early use of the new intra-articular steroids, methotrexate, and biological drugs now allows the majority of patients to lead a fully normal life. However, continuous remission is rarely achieved.

Positive RF (rheumatoid factor) antibodies, positive anti-CCP antibodies (cyclic citrullinated peptide antibody), hip or cervical spine arthritis, erosions or joint space reduction on conventional radiographs are poor prognostic markers [28] [29] [30].

Etiology

Polyarticular juvenile idiopathic arthritis has a genetic etiology with multiple genes (such as IL2RA/CD25 and VTCN1) involved. Certain HLA-alleles (eg HLA-DRB1) have been associated with the disease [4] [5]. Polymorphisms in class-II HLA genes may also play a significant role in this disease [6] [7] [8] [9] [10].

However, the exact cause of the disease remains uncertain. Several viral microorganisms (e.g. influenza A virus and Epstein-Barr virus) are likely to be involved in the polyarticular JIA pathogenesis.

Some risk factors, particularly smoking, are also suggested to play a role in this condition. Tobacco smoke has been proven to suppress the immune system, influencing both cell and humoral immunity [11] [12]. Maternal smoking in pregnant women is also associated with an increased risk of PJIA.

Other pregnancy-related factors, such as vitamins and mineral uptake, alcohol abuse and use of antibiotics have been studied but statistically, significant results confirming their role have not been obtained [13] [14].

Stress and psychosocial problems also participate into the disease initiation and progression [15].

Epidemiology

Polyarticular juvenile idiopathic arthritis represents between 15% and 25% of JIA but is the predominant form of arthritis in childhood in several regions of the world including India, Czech Republic, Africa, and Kuwait [16] [17] [18] [19] [20] [21].

Polyarticular JIA begins at a young age with two peaks of the age of onset- the first one between the ages of 2 and 5 years and the second one between 10 and 14 years. Females are two to four times more likely to develop the disease.

Vast differences amongst different races have been observed- the prevalence in Asian populations is lower than in Europeans [22] [23] [24] [25]. Different distribution of polyarticular arthritis has also been observed in different regions within the same country- eg the frequency in Southern India is higher than in Northern India [26].

Approximately 15% of the patients are rheumatoid factor (RF)-positive. RF- positive polyarticular JIA tends to affect older children and correlates with a more serious prognosis.

Sex distribution
Age distribution

Pathophysiology

Both humoral and cell-mediated immunity are involved in the pathophysiologic mechanisms of polyarticular JIA. It is considered that the T-lymphocytes, particularly a disruption in the interaction between type 1 and type 2 T-helpers is responsible for the changes seen in JIA. T-lymphocytes produce a number of pro-inflammatory cytokines such as interleukins 1 and 6 (Il-1 and IL-6) and tumor necrosis factor-alfa (TNF- α), which actively participate in the joint destruction.

The central role of TNF in the process of joint damage has been demonstrated in research where elevated levels of TNF in both serum, synovial fluid (and synovial tissue) were found [27].

Prevention

As the etiology of polyarticular JIA remains unclear, no specific recommendations in terms of primary prevention are established.

Summary

Polyarticular juvenile idiopathic arthritis (formerly named polyarticular-onset juvenile rheumatoid arthritis) is one of the six subtypes of juvenile idiopathic arthritis (JIA) characterized by the involvement of at least four joints during the first six months after the condition’s onset. 20-30% of the patients with JIA appertain to this subgroup. Furthermore, patients with polyarticular juvenile idiopathic arthritis can be divided into rheumatoid factor positive RF(+) or rheumatoid factor negative RF (-) [1].

The aim of the therapy is to restrain the inflammation of the joints and its eventual consequences (such as joint damage) and to minimize the treatment’s side effects [2]. First- choice medicaments are non-steroidal anti-inflammatory drugs (NSAIDs) and nonbiologic disease-modifying antirheumatic drugs (DMARDs). Other agents used in the management of polyarticular juvenile idiopathic arthritis are biological disease-modifying antirheumatic drugs such as anti-tumor necrosis factor-alpha (anti-TNF-alpha) agents.

Diagnosis of polyarticular JIA may be hard to establish as the condition has an often initial indolent course, especially in children under the age of 10 years where less than 2 joints may be affected [3]. An intercurrent infection may trigger a sudden increase in symptoms and result in the involvement of more than four joints. According to research, approximately 50% of patients with oligoarticular symptoms subsequently progress to polyarticular involvement.

The most common joints affected are the knees, ankles, and wrists, with symmetric involvement that is the key feature of this disease. This disease may also have a waxing-and-waning quality to it, with relapses being quite common.

Patient Information

There are six subtypes of juvenile idiopathic arthritis (JIA). Patients with polyarticular JIA represent around 40% of all patients with JIA. Polyarticular JIA is a condition in which four or more joints are inflamed for reasons still unknown. Patients with inflammatory arthritis may be rheumatoid factor positive or negative. Rheumatoid factor positive patients with polyarticular JIA tend to have a more serious prognosis. The age of onset is anytime before 16 years. Approximately 50% of the cases with RF+ polyarticular JIA end up with serious physical disabilities.

This condition is seen four to five times more in girls than boys. The involvement of the joints is usually symmetrical and small joints (fingers, wrists) are the target of the disease. However, weight-bearing joints such as knees, hips, and ankles may also be damaged.

Diagnosis is made through blood tests measuring the inflammatory markers as well as conventional radiographic techniques.

This disease should be treated aggressively and early in its course. Several options for therapy exist for this disease. The most common drugs used are the non-steroidal anti-inflammatory drugs, with a response rate of 30 %. Other drugs that may be prescribed include intravenous and local steroids, methotrexate or biologic agents like TNF-alfa inhibitors. Treatment should be accompanied by appropriate levels of physical activity.

References

Article

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Last updated: 2018-06-21 17:02