Childhood arthritis (pediatric rheumatic disease) is an umbrella term used to describe any rheumatic disease or chronic arthritis-related condition which affects individuals under the age of 16. There are several subtypes that differentiate themselves via prognosis, complications, and treatments. Most types are autoimmune disorders, where an individual's immune system may attack its own healthy tissues and cells.
Diagnosis of juvenile idiopathic arthritis is typically considered for children that are below the age of 16 years old and currently experiencing arthritis for at least six weeks with no other evident alternative causes for the symptoms. In 1997 the International League of Associations for Rheumatology (ILAR) presented a classification of juvenile idiopathic arthritis. This was later revised in 2001. In this classification juvenile idiopathic arthritis is the umbrella term and comprises seven categories: systemic arthritis, oligoarthritis, polyarthritis (reumatic factor negative), polyarthritis (reumatic factor positive), psoriatic arthritis, enthesitis related arthritis and undifferntiatied arthritis.
Juvenile arthritis may last for a few months, years, or becomes a lifelong disease that requires treatment as the child becomes an adult. Common complications that can arise include leg-length discrepancy, joint contracture, growth retardation, low bone mineral density, and macrophage activation syndrome.
Some causes or potential risk factors denoting a higher chance of developing childhood arthritis have been identified. However, similar to other autoimmune diseases, the exact cause or mechanism for development is still largely unknown and additional associations are continuously being researched and discovered.
Signs and symptoms Several types of childhood arthritis exist, including juvenile idiopathic arthritis, juvenile myositis, juvenile lupus, juvenile scleroderma, vasculitis, and fibromyalgia.
The most common type, juvenile idiopathic arthritis (previously known as juvenile rheumatoid arthritis or juvenile chronic arthritis) can be divided into six main forms. The classification is based upon symptoms, number of joints involved and the presence of certain antibodies in the blood. However, some subtypes have overlapping clinical presentation in addition as the child grow older symptoms may change over time. The six subforms of juvenile idiopathic arthritis include: Polyarticular arthritis is the first type of arthritis, which affects about 30–40% of children with arthritis and is more common in girls than boys. This subtype begins later in childhood and could be subdivided into two types: Rheumatoid Factor (RF) negative and RF positive depending on the presence of the RF antibody. Typically five or more joints are affected during the first six months (usually smaller joints such as the hands and feet but many also affect the hips, neck, shoulders and jaw). Oligoarticular (aka pauciarticular) arthritis can be early or late onset and is the second type of arthritis, affecting about 50% of children with juvenile arthritis. It typically affects fewer than four joints, usually the large joints such as knees, ankles, or wrists, during first six months of the disease with the knee being the most frequently affected joint. This type affects fewer than four joints (usually the large joints such as knees, ankles or wrists) and may cause eye inflammation in girls with positive anti-nuclear antibodies. Girls younger than eight are more likely to develop this type of arthritis. This is a mildest form of juvenile arthritis and is considered to be persistent if the individual experience symptoms for more than 6 months, and if five or more joints become affected. Systemic disease is the least common form, with 10–20% of children (boys and girls equally) being affected with limited movement, swelling and pain in at least one joint. A common symptom of this type is a high, spiking fever of or higher, lasting for weeks or months, and a rash of pale red spots on the chest, thighs or other parts of the body may be visible. Enthesitis-Related Arthritis: children impacted by this subtype has arthritis as well as inflammation caused by tendons and ligaments that have inserted themselves into the none. The most commonly impacted area of the body with this subtype include the hips, knees, and feet. Psoriatic Arthritis: children that is impacted by this type of arthritis has arthritis in addition to psoriasis. The child will experience symptoms such as red, scaly skin patches, as well as inflammation in their toes, fingers, or along the ridges of their fingernails. Undifferentiated arthritis: children that is impacted by this has two or more of the symptoms from any of the arthritis subtypes described above, or the child has symptoms that does not match any.
Cause The cause of this complex disorder is typically idiopathic which can include multiple genes that affects the humoral and cell-mediated immunity in addition to environmental factors. However, Dietary habits and emotional state seem to have no effect on the disease. In most cases, juvenile arthritis is caused by the body attacking its own healthy cells and tissues, i.e. autoimmunity, causing the joint to become inflamed and stiff. Once the joint has become inflamed and stiff, damage is done to the joint and the growth of the joint may by changed or impaired. The underlying cause in the malfunction of the autoimmune system is unknown, however it is common to see an imbalance or abnormality in regulatory T cell levels in a majority of juvenile arthritis cases. Researchers have found that there is an elevation of cytokines like IL-1 and IL-18 in individuals with systemic juvenile idiopathic arthritis. In juvenile idiopathic arthritis (JIA) individuals, it is theorized that a possible environmental trigger for this condition is an infection due to the discovery of elevated heat shock proteins in JIA patients.
Genetic factors play a significant role in the predisposition to juvenile arthritis. Specific genetic markers, such as HLA (human leukocyte antigen) genes, have been associated with an increased risk of developing the disease. The HLA-DRB1 gene, for example, is linked to rheumatoid arthritis in adults and similar associations have been observed in juvenile arthritis, suggesting a genetic overlap between these conditions. Additionally, variations in genes related to the immune system, such as those involved in the production of cytokines and other inflammatory mediators, may contribute to the susceptibility and severity of the disease.
Environmental factors, while not directly causing juvenile arthritis, can influence its onset and progression. Infections are considered a potential trigger, as certain viral or bacterial infections may activate the immune system in a way that leads to autoimmune reactions in genetically predisposed individuals.Environmental pollutants and toxins have also been suggested to play a role in exacerbating the condition, although more research is needed to establish a clear connection.
Recent studies have also highlighted the potential influence of the gut microbiome on the development and course of juvenile arthritis. The balance of beneficial and harmful bacteria in the gut can affect immune responses and inflammation. Dysbiosis, or an imbalance in the gut microbiota, has been observed in individuals with juvenile arthritis, indicating that gut health may be a contributing factor to the disease. Interventions aimed at restoring a healthy gut microbiome are being explored as potential therapeutic strategies.
Understanding the multifactorial causes of juvenile arthritis is crucial for developing targeted treatments and preventive measures. Ongoing research continues to investigate the complex interactions between genetic predispositions, environmental exposures, and immune system dysfunctions to provide a clearer picture of the disease's etiology.
Diagnosis Early diagnosis and treatment by a pediatric rheumatologist or a rheumatologist can help manage inflammation, relieve pain, and prevent joint damage. However, it is difficult for doctors to diagnose the disease because there is not a single test that doctors can use to diagnose this disease. Physical exams, laboratory tests (blood and urine), and various forms of imaging like X-rays, ultrasound, CT scan, and MRIs may be some of the tests conducted by a doctor. Doctors may perform some of the following tests to diagnose the condition
ANA (Antinuclear Antibody) Test: ANA are antibodies that are commonly found in individuals who have autoimmune disease which can be helpful for doctors to diagnose juvenile arthritis since it is an autoimmune disease. Joint Aspiration Rheumatoid Factor (RF) Test: RF is another type of antibody, but it is more specific than ANA in that it is usually found in individuals with rheumatoid arthritis as well as other rheumatoid disease. The presence of RF in a child's blood test can be indicative for RF-positive polyarticular arthritis These tests are helpful in determining the type of juvenile idiopathic arthritis that an individual have, in addition the results are also helpful in identifying the complications that the individual could be at risk for.
Furthermore, in order to adequately diagnose the patient for juvenile idiopathic arthritis, a complete patient history with the symptoms and illness as a whole must be taken, consisting of the age of onset, duration, specific joints affected, symptoms, and physical and musculoskeletal examinations as well. Laboratory tests must be taken as well, including the complete blood count, erythrocyte sedimentation rate, C-reactive protein test, as well as the ANA and RF tests as mentioned above. Radiography is also recommended, but this is usually only beneficial in later stages of the disease, since it does not catch early stages of juvenile idiopathic arthritis. Overall, however, MRI's are considered to be the number one choice in terms of observing all the affected joints with adequate contrast observed in the imaging, especially due to its sensitivity.
Treatment Clinical guidelines provide treatment recommendations dependent on the clinical characteristics. The treatment of most types of juvenile arthritis include medications, physical therapy, splints and in severe cases surgery. The type and intensity of the treatment is largely based upon the subtype and severity of damage of the disease. Guideline-informed pharmacological include intraarticular glucocorticoids, scheduled non-steroidal anti-inflammatory drugs, disease-modifying anti-rheumatic drugs, and interleukin inhibitors, depending on macrophage involvement and if symptoms are localized or systemic.
Intraarticular glucocorticoid injections show clinical benefit in patients with juvenile temporomandibular joint arthritis, polyarticular juvenile arthritis, oligoarticular juvenile arthritis, systemic juvenile arthritis, as well as enthesitis-related arthritis. Specifically, triamcinolone hexacetonide has displayed evidence of the longest duration of resolution in symptoms in all aforementioned juvenile arthritic subtypes. Scheduled dosing of NSAIDs may reduce joint pain and encourage mobility. However, their use is contested among experts, as they provide pain relief without addressing the underlying pathophysiology of the disease. Disease modifying anti-rheumatic drugs, also known as DMARDs, may be orally administered (such as methotrexate) or injected (such as etanercept or tocilizumab). They are often used in autoimmune disorders and have proven clinical efficacy in most subtypes of juvenile arthritis. Due to notable side effects (and in the case of injected DMARDs, cost), DMARDs are often given if intraarticular glucocorticoids are deemed insufficient in controlling the patients’ symptoms.