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Childhood arthritis

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Childhood arthritis
Other namesJuvenile arthritis, Pediatric rheumatic disease
SpecialtyRheumatology

Childhood arthritis (juvenile arthritis or 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.[1][2]

Juvenile arthritis may last for a few months, years, or becomes a lifelong disease that requires treatment as the child becomes an adult.[3] Common complications that can arise include leg-length discrepancy, joint contracture, growth retardation, low bone mineral density, and macrophage activation syndrome.[4]

Some causes or potential risk factors denoting a higher chance of developing childhood arthritis have been identified.[5] 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.[6]

Signs and symptoms

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Several types of childhood arthritis exist, including juvenile idiopathic arthritis, juvenile myositis, juvenile lupus, juvenile scleroderma, vasculitis, and fibromyalgia.[7]

The clinical manifestation of this group of disorders is chronic joint inflammation that results in pain, swelling, warm and stiffness of the joints that persistent for a long period of time.[8] General signs of childhood arthritis disorders include:

  • Joints: Swollen, stiff, red, warm, and/or painful joints.[7] Depending on the severity of the disease, joints may grow too quickly or too slowly which results in one leg/arm to be disproportional to the other.[8]
  • Eyes: Painful/dry eyes, sensitivity to light and/or difficulty seeing caused by uveitis[7] If this is left untreated, the uveitis can lead to cataracts, glaucoma, and/or vision loss.[8]
  • Skin: Scaly red rash (psoriatic), light spotted pink rash (systemic), butterfly shaped rash across the bridge of the nose and cheeks (lupus) or thick, hardened patches of skin (scleroderma)[7]
  • Organs: Digestive tract (diarrhea and bloating), lungs (shortness of breath) and heart[7]
  • Other: Fatigue, appetite loss, and/or high, spiking fever[7]

The most common type of childhood arthritis, juvenile idiopathic arthritis [JIA] (previously known as juvenile rheumatoid arthritis (JRA) or juvenile chronic arthritis (JCA))[9] 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.[1][10] 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:

  1. 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.[1][10][11][12] 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).[1][11]
  2. 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.[1][10][11] 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 (ANA).[1][10] Girls younger than eight are more likely to develop this type of arthritis.[9]</ref>[10] This is a mildest form of juvenile arthritis and is consider to be persistent if the individual experience symptoms for more than 6 months, and if five or more joints become affected.[8]
  3. 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.[1][11] A common symptom of this type is a high, spiking fever of 103 °F (39.4 °C) 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.[1]
  4. 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. [13]
  5. 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. [13]
  6. 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. [13]

Cause

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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.[4] However, Dietary habits and emotional state seem to have no effect on the disease.[9][3]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.[14][10] Once the joint has become inflammed and stiff, damage is done to the joint and the growth of the joint may by changed or impaired.[10] 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.[4] Researchers have found that there is an elevation of cytokines like IL-1 and IL-18 in individuals with systemic juvenile idiopathic arthritis.[15] 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. [15]

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.[1]

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.[2]

Diagnosis

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Early diagnosis and treatment by a pediatric rheumatologist or a rheumatologist can help manage inflammation, relieve pain, and prevent joint damage.[1][10] However, it is difficult for doctors to diagnose the disease[16][9] because there is not a single test that doctors can use to diagnose this disease.[3] Physical exams,[3] 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.[17][1][10] Doctors may perform some of the following tests to diagnose the condition[16]

  • ANA (Antinuclear Antibody) Test[18]: 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[19]
  • Rheumatoid Factor (RF) Test[20]: 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

Treatment

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Clinical guidelines provide treatment recommendations dependent on the clinical characteristics.[21] The treatment of most types of juvenile arthritis include medications, physical therapy, splints and in severe cases surgery.[10] The type and intensity of the treatment is largely based upon the subtype and severity of damage of the disease.[4] 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.[21] These treatments are focused on reducing swelling, relieving pain and maintaining full movement of joints.[1]

In rare or more serious cases, surgery may be required as a treatment for juvenile arthritis. Most common causes of those needing surgery are the ineffectiveness of medication to slow the rate of damage or the initial diagnosis of the disease came after a large amount of damage has already been sustained. The most common surgeries for juvenile arthritis include epiphysiodesis, arthrodesis, synovectomy, osteotomy, or arthroplasty.[22]

Children are also encouraged to be involved in extra-curricular activities, such as physical activity when possible, and to live a "normal" life.[1][12] The goal of physical activity is to expand the child's range of motion without imposing too much stress on their joints. [4]Consistent exercise can reduce both pain and immobility while also improving life quality.[23] Exercise helps to improve symptoms that one with childhood arthritis might be experiencing, by significantly improving the extent to which the body's joints can move and be flexible.[2]

With the duration of the disease being finite, treatment will most likely last as long as the disease persists. In most children, the disease goes into spontaneous remission after a few years. Periodic remissions and exacerbations are characteristics of this disease which often requires frequent therapy changes. Although complete treatment withdrawal is possible after the disease is considered to be "quiet" for 6-12 months or longer, regular physician follow up is still recommended.[24]

Additionally, emerging research is focusing on the role of the gut microbiome and its potential impact on juvenile arthritis. Studies suggest that certain probiotics and dietary interventions may help in modulating immune responses and reducing inflammation. Complementary therapies, such as acupuncture and massage, are also being explored for their potential benefits in alleviating symptoms and improving quality of life. Psychological support for both the child and their family is crucial, as living with a chronic condition can be challenging. Support groups and counseling can provide emotional relief and coping strategies. Advances in genetic research may also pave the way for more personalized treatment plans in the future, tailoring therapies to the individual’s genetic makeup for more effective management of the disease.[3]

Prognosis

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Depending on the severity and the type of juvenile arthritis in addition to treatment time, the prognosis could vary for each individual.

Epidemiology

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Globally, about 3 million children and young adults are impacted by this disease.[25] In the US it affects about 250,000-294,000 children making it one of the most common groups of childhood diseases.[10] However, due to not having consistent guidelines or criteria for diagnosis, this number is an estimation based on smaller population groups.[26] It is likely that a child with juvenile arthritis has a family member with chronic inflammatory arthritis or other autoimmune disorders such as type I diabetes, inflammatory bowel disease, psoriasis, and other conditions.[8] This is also more common in girls compared to boys.[25] The subtype that is most common is the oligoarticular arthritis.

Risk Factors

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The exact causes or risks leading to a higher chance of developing childhood arthritis are under research but, at this moment, still largely unknown. Currently, the most likely associations of possible development of childhood arthritis are genetic and environmental factors.[27]

Genetic factors are in two main categories: having some variation in the genes that code for our immune system, such as the HLA complex, or having a direct parent who also has the disease. Various mutations have been associated with a higher chance of developing childhood arthritis, however the exact increase of risk is unknown. The HLA complex proteins also represent a large family of genes, therefore variations tend to occur in these regions. Which specific genes and mutations lead to increased risk of childhood arthritis are still currently being pursued.[5] Those with parents who have the disease, or who are known to have these mutations, have been shown to have a significantly higher risk of developing the disease as well.[27]

Psychosocial Impact

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Childhood arthritis not only affects the physical health of children but also has significant psychosocial implications. The chronic nature of the disease, frequent medical appointments, and physical limitations can lead to emotional and social challenges. Children with arthritis may experience feelings of isolation, frustration, and anxiety, which can affect their overall quality of life and development.[4]

One major psychosocial impact is the potential for academic challenges. Frequent absences from school due to medical appointments or flare-ups can lead to gaps in learning and difficulties in keeping up with peers. This can result in a need for educational accommodations, such as individualized education plans (IEPs) or 504 plans, to support the child’s learning needs and ensure they have equal access to education.

Social relationships can also be affected. Children with arthritis might find it difficult to participate in physical activities or social events, leading to feelings of exclusion or differentness from their peers. This can impact their self-esteem and social skills. Support groups and peer networks can provide valuable social support, helping children to connect with others who understand their experiences and fostering a sense of community.[5]

Psychological support is crucial for managing these psychosocial challenges. Counseling and therapy can help children and their families cope with the emotional aspects of the disease. Cognitive-behavioral therapy (CBT) has been shown to be effective in helping children manage pain and anxiety associated with arthritis. In addition, family therapy can be beneficial in addressing the impacts on family dynamics and helping parents and siblings understand and support the affected child.[6]

Overall, a comprehensive approach to treating childhood arthritis should include attention to the psychosocial aspects of the disease. Integrating psychological and social support with medical treatment can help improve the overall well-being and quality of life for children with arthritis.[7]

References

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  1. ^ a b c d e f g h i j k l "Juvenile Arthritis Facts". Arthritis Foundation. 2012. Archived from the original on 7 March 2012. Retrieved 22 March 2012.
  2. ^ a b Garrick N (2017-04-07). "Juvenile Arthritis". National Institute of Arthritis and Musculoskeletal and Skin Diseases. Retrieved 2024-07-25.
  3. ^ a b c d NIAMS Science Communications and Outreach Branch (2017-04-07). "Juvenile Idiopathic Arthritis (JIA)". National Institute of Arthritis and Musculoskeletal and Skin Diseases. Retrieved 2024-07-23.
  4. ^ a b c d e Thatayatikom A, Modica R, De Leucio A (2024). "Juvenile Idiopathic Arthritis". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID 32119492. Retrieved 2024-07-26.
  5. ^ a b "Juvenile Rheumatoid Arthritis". John Hopkins Medicine.
  6. ^ Horton DB, Shenoi S (2019-11-06). "Review of environmental factors and juvenile idiopathic arthritis". Open Access Rheumatology : Research and Reviews. 11: 253–267. doi:10.2147/OARRR.S165916. ISSN 1179-156X. PMC 6842741. PMID 31807094.
  7. ^ a b c d e f "Juvenile Arthritis". Arthritis Foundation. Retrieved 2020-10-26.
  8. ^ a b c d e Branch NS (2017-04-07). "Juvenile Idiopathic Arthritis (JIA)". National Institute of Arthritis and Musculoskeletal and Skin Diseases. Retrieved 2024-07-29.
  9. ^ a b c d "Juvenile Arthritis". American College of Rheumatology. Retrieved 2022-11-18.
  10. ^ a b c d e f g h i j k "Orthoinfo". American Academy of Orthopaedic Surgeons. 2012. Retrieved 21 March 2012.
  11. ^ a b c d "Arthritis". U.S. Centers for Disease Control and Prevention. 2011. Retrieved 20 March 2012.
  12. ^ a b "Practice Management". American College of Rheumatology. 2011. Retrieved 20 March 2012.
  13. ^ a b c "Juvenile Idiopathic Arthritis". Yale Medicine. Retrieved 2024-07-30.
  14. ^ "Autoimmune Diseases". MedlinePlus. U.S. National Library of Medicine. Retrieved 2020-10-29.
  15. ^ a b "Overview of Juvenile Idiopathic Arthritis". openorthopaedicsjournal.com. Retrieved 2024-07-29.
  16. ^ a b "Juvenile Arthritis". MedlinePlus. U.S. National Library of Medicine. Retrieved 2022-11-18.
  17. ^ Bennett J, Hollingsworth K, Foster H, McErlane F (2018-04-01). "298 Magnetic resonance imaging and the assessment of disease activity in juvenile idiopathic arthritis". Rheumatology. 57 (suppl_3). doi:10.1093/rheumatology/key075.522. ISSN 1462-0324.
  18. ^ "ANA (Antinuclear Antibody) Test". MedlinePlus. U.S. National Library of Medicine. Retrieved 2022-11-18.
  19. ^ "Joint Aspiration (Arthrocentesis) (for Parents)". Nemours KidsHealth. Retrieved 2022-11-18.
  20. ^ "Rheumatoid Factor (RF) Test". MedlinePlus. U.S. National Library of Medicine. Retrieved 2022-11-18.
  21. ^ a b Onel KB, Horton DB, Lovell DJ, Shenoi S, Cuello CA, Angeles-Han ST, et al. (April 2022) [2022-03-01]. "2021 American College of Rheumatology Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Oligoarthritis, Temporomandibular Joint Arthritis, and Systemic Juvenile Idiopathic Arthritis". Arthritis & Rheumatology. 74 (4): 553–569. doi:10.1002/art.42037. PMC 10161784. PMID 35233993.
  22. ^ "Surgeries for Juvenile Idiopathic Arthritis | Arthritis Foundationk". www.arthritis.org. Retrieved 2024-07-29.
  23. ^ Nijhof LN, Nap-van der Vlist MM, van de Putte EM, van Royen-Kerkhof A, Nijhof SL (November 2018). "Non-pharmacological options for managing chronic musculoskeletal pain in children with pediatric rheumatic disease: a systematic review". Rheumatology International. 38 (11): 2015–2025. doi:10.1007/s00296-018-4136-8. PMC 6208689. PMID 30155667.
  24. ^ "Paediatric Rheumatic Diseases". www.printo.it. Retrieved 2024-07-30.
  25. ^ a b Al-Mayouf SM, Al Mutairi M, Bouayed K, Habjoka S, Hadef D, Lotfy HM, et al. (2021-12-02). "Epidemiology and demographics of juvenile idiopathic arthritis in Africa and Middle East". Pediatric Rheumatology Online Journal. 19 (1): 166. doi:10.1186/s12969-021-00650-x. ISSN 1546-0096. PMC 8638433. PMID 34857004.
  26. ^ Grom AA (20 March 2024). Klein-Gitelman M, Case SM (eds.). "Juvenile idiopathic arthritis: Epidemiology and immunopathogenesis". UpToDate. Waltham, MA. Retrieved 2024-07-26.
  27. ^ a b "Risk Factors of Juvenile Arthritis". Juvenile Arthritis News. Retrieved 2024-07-30.
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