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

  The extreme left end of the line represents 'no pain' and the extreme right end represents 'very extreme pain'. A higher score indicates more pain. [clinicaltrials.gov]

  […] retrain your pain system. [msk.org.au]

  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]

  Pain is an important symptom. Morning stiffness that improves later in the day is a common feature (this implies inflammatory-type joint pain versus mechanical-type joint pain). [en.wikipedia.org]

• Difficulty Walking

  Foot pain and difficulty walking. More common in polyarthritis and enthesitis-related arthritis. Skin. Symptoms can range from a faint salmon colored rash (SJIA) to a red, scaly rash (psoriatic arthritis). Lungs. [arthritis.org]

  Limited mobility can be a problem for school attendance; it may cause difficulty walking, fatigue, pain or stiffness. [printo.it]

• Underweight

  Being underweight or overweight can be a problem in JIA. Pain specialist Pain Specialists are doctors who can provide medication and other strategies to reduce pain. [rch.org.au]

• Overeating

  In the CHERISH study, infections were the most common adverse events (AEs) and serious adverse events (SAEs) over 40 weeks. [raredr.com]

  Of the 22 patients with oligo/polyarticular JIA in clinical remission, 13 patients with low S100A12 and VEGF concentrations could discontinue treatment without relapse over 2 years. [ncbi.nlm.nih.gov]

  Oligo- or polyarticular arthritis, disease onset over 6 years of age, disease duration over 4 years. Oligo- or polyarticular arthritis, disease onset under 6 years, but disease duration now over 7 years. Every 12 months Table 4. [healio.com]

  Only over time will your child’s doctor have a better sense of the challenges she faces. [kidsgetarthritistoo.org]

• Dental Caries

  These can include an increasing incidence of dental caries, stomatitis with the use of methotrexate, oral candidiasis with the use of immunosuppressive medication and temporal mandibular joint (TMJ) arthritis. [ntvt.nl]

• Subcutaneous Nodule

  Results: One child had subcutaneous nodules; one (of 11) was rheumatoid factor positive; six were ANA positive. Median age at diagnosis was 10.7 years (2.5 to 15.9). [ard.bmj.com]

  The presence of autoantibodies, subcutaneous nodules, secondary Sjögren syndrome, and hypothyroidism, was determined in 20 adult patients with polyarticular JIA and in 50 patients with RA (paired for gender and duration of the disease), as well as the [scielo.br]

  Subcutaneous nodule formation and elevated serum rheumatoid factor levels are common. Patients typically complain of joint stiffness in the morning rather than after activities. Women are affected three times more often than men. [medical-dictionary.thefreedictionary.com]

  Subcutaneous nodules, cervical spine fusion, chronic uveitis, and destructive hip disease occur RF+ PoJIA. [2] Rheumatoid factor negative (RF-) - patient tests negative on all tests for the RF. [4] Morning stiffness, fatigue and possibly a low grade fever [physio-pedia.com]

  Patients with Farber disease typically have subcutaneous nodules and a hoarse or weak voice due to growth of nodules on the larynx. [en.wikipedia.org]

• Arthritis

  CONCLUSIONS: The transcriptome of FLS from extended-to-be juvenile idiopathic arthritis is distinct from persistent course before a clinical distinction can be made. [ncbi.nlm.nih.gov]

  Idiopathic Arthritis (PJIA) Therapeutics Clinical Trials, Global, Key Sponsors, 2018* 27 Polyarticular Juvenile Idiopathic Arthritis (PJIA) Therapeutics Clinical Trials, Global, Top Companies by Phase, 2018* 28 Polyarticular Juvenile Idiopathic Arthritis [gii.co.jp]

  Oen KG, Cheang M (1996) Epidemiology of chronic arthritis in childhood. Semin Arthritis Rheum 26(3):575–591 CrossRef PubMed Google Scholar 5. [link.springer.com]

• 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]

  Extended; affecting no more than 4 joints in the first 6 months of disease, then affecting 5 or more joints thereafter. Painless joint swelling, gait disturbance. Most common in white girls 2–4 years of age. [healio.com]

  Systemic onset JIA may cause inflammation of the internal organs as well as the joints, though joint swelling may not appear until months or even years after the fevers began. [rheumatology.org]

  A diagnosis can be insidious because children may not complain of pain and joint swelling may not be so obvious. [news-medical.net]

  Signs and symptoms of juvenile idiopathic arthritis may include: Joint swelling, with pain and stiffness. This may be more pronounced in the morning or after a nap. Commonly it affects the knees and the joints in the hands and feet. [attra.registry.cz]

• Morning Stiffness

  Symptoms of joint pain and tenderness are worse in the morning in association with the previously described morning stiffness (see systemic onset JIA). [medicinenet.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]

  Systemic (20%) systemic symptoms (rash, fever, multiple joint involvement) anemia, high WBC, elevated ESR, CRP, platelets hepatosplenomegaly, lymphadenopathy, pericarditis M=F, age 5-10y includes Stills disease poorest prognosis Presentation Symptoms morning [orthobullets.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]

  The affected joints are often stiff in the mornings or after longer periods of inactivity (e.g., sitting). Mobility improves with movement and is less impaired later in the day! [amboss.com]

• Joint Deformity

  Systemic glucocorticoid therapy (oral, IV) Supportive therapy Physiotherapy: to prevent joint deformities Surgery, splints, and/or orthotics: to correct limb length discrepancy and/or joint deformities References:[1][15][16] Complications Joint destruction [amboss.com]

  Surgery choices When surgery to correct joint deformity is needed, the more common procedures include: Soft tissue releases of contractures. This involves cutting the muscles attached to an abnormally bent joint. Total joint replacement. [uofmhealth.org]

  Accelerated bone age with narrowed joint spaces. Swan-neck and/or boutonnière deformities, and joint subluxation. Cervical spine involvement in RF positive polyarticular JIA. [patient.info]

  […] following naps Commonly in, but not limited to knees, hands and feet Loss of joint function (reduced range of motion/ROM) [2] Limp, due to pain in lower extremities Joint deformities, abnormal growth (i.e. leg length discrepancies) Eye irritations/inflammation [physio-pedia.com]

  […] polyarthritis 10% RF positive: Rheumatoid nodules Joint deformities (e.g. [pathophys.org]

• Ankylosis

  Cervical spine radiographs may demonstrate: atlantoaxial subluxation odontoid erosions ankylosis, especially of the facet joints Hepatosplenomegaly may be seen on abdominal radiographs, and pericardial or pleural effusions may be seen on chest radiographs [radiopaedia.org]

  […] least one of the following forms: (1) distal interphalangeal (DIP) involvement; (2) polyarticular arthritis (absence of rheumatoid nodules and presence of psoriasis); (3) arthritis mutilans; (4) asymmetric psoriatic arthritis; or (5) spondylitis- like ankylosis [mymemory.translated.net]

  In addition to the clinical findings in deformed joints, joint space narrowing, joint surface erosion, subcortical cysts, ankylosis and fusion formation have been defined by radiological findings. [elynsgroup.com]

  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]

  The view of the left wrist shows boney ankylosis involving the lateral 4 carpal bones with sparing of the pisiform. Erosions are present in the distal radius and ulna. [emedicine.medscape.com]

• Suggestibility

  These gene expression data suggest that FLS already reflect a polyarticular behavior early in disease course, suggesting that extended-to-be may be "latent polyarticular" at onset. [ncbi.nlm.nih.gov]

  In an acute polyarthritis in the absence of features suggestive of SOJIA, elevated transaminases are suggestive of a viral associated arthritis or SLE. These are normal in polyarticular and oligoarticular JIA. [rheumatologyadvisor.com]

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

  DMARD, disease modifying antirheumatic drug JSN, joint space narrowing RCL, relative carpal length juvenile rheumatoid arthritis radiographic progression Statistics from Altmetric.com DMARD, disease modifying antirheumatic drug JSN, joint space narrowing [ard.bmj.com]

  Once infection occurs, cartilage is destroyed and the joint space narrows. Patients at greatest risk are those with pre-existing arthritis, joint trauma, or immune deficiencies and those who use intravenous drugs. [medical-dictionary.thefreedictionary.com]

  In addition to the clinical findings in deformed joints, joint space narrowing, joint surface erosion, subcortical cysts, ankylosis and fusion formation have been defined by radiological findings. [elynsgroup.com]

  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]

  Basic radiographic changes in JIA include the following: Soft tissue swelling Osteopenia or osteoporosis Joint-space narrowing Bony erosions Intra-articular bony ankylosis Periosteitis Growth disturbances Epiphyseal compression fracture Joint subluxation [emedicine.medscape.com]

• Thrombocytosis

  Thrombocytosis is usually seen in patients with the systemic onset and polyarticular group [7]. Thrombocytosis was detected in 73.5% of our patients. This ratio is consistent with data in the literature [30,31]. [elynsgroup.com]

  CBC: Anemia, thrombocytosis, and/or leukocytosis are seen in the case of systemic JIA. [amboss.com]

  Anemia was found in 49 (59.7%), high ESR in 45 (54.8%), and leukocytosis and thrombocytosis in 33 (40.2%). [hindawi.com]

• Synovial Cyst

  […] common synovial cysts [1,3]. [oatext.com]

  […] radiographic absorptiometry (DRA) Arthrocentesis and synovial biopsy Pericardiocentesis See Workup for more detail. [emedicine.medscape.com]

• Leukocytosis

  Leukocytosis is often observed in systemic-onset of JIA. In literature, leukocytosis rate in systemic JIA is reported as 80% [30]. The leukocytosis rate was detected 8.2% in our patients. [elynsgroup.com]

  CBC: Anemia, thrombocytosis, and/or leukocytosis are seen in the case of systemic JIA. [amboss.com]

  Anemia was found in 49 (59.7%), high ESR in 45 (54.8%), and leukocytosis and thrombocytosis in 33 (40.2%). [hindawi.com]

  Manifestations include daily spiking (quotidian) fevers of >102°F; an evanescent, salmon-pink rash; arthritis; generalizedlymphadenopathy; serositis; hepato- or splenomegaly; weight loss; myalgias; neutrophilic leukocytosis; anemia; increased ESR (often [rheumaknowledgy.com]

  Many also have additional features, such as generalized enlargement of the lymph nodes (lymphadenopathy); enlargement of the liver and spleen (hepatosplenomegaly), increased levels of circulating white blood cells (leukocytosis), reduced levels of the [rarediseases.org]

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.

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].

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].

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.

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].

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

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.

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.

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