Differences
This shows you the differences between two versions of the page.
| Both sides previous revision Previous revision Next revision | Previous revision | ||
|
group_2_presentation_2_-_juvenile_arthritis [2017/03/03 20:00] ramachg |
group_2_presentation_2_-_juvenile_arthritis [2018/01/25 15:18] (current) |
||
|---|---|---|---|
| Line 16: | Line 16: | ||
| Systemic juvenile idiopathic arthritis causes inflammation in one or more joints, and its symptoms include high daily fevers that can last up to two weeks either preceding or accompanying the arthritis. A skin rash or enlargement of lymph nodes, liver or spleen are symptoms that differentiate this type of juvenile arthritis from other types (Genetics Home Reference, 2015). | Systemic juvenile idiopathic arthritis causes inflammation in one or more joints, and its symptoms include high daily fevers that can last up to two weeks either preceding or accompanying the arthritis. A skin rash or enlargement of lymph nodes, liver or spleen are symptoms that differentiate this type of juvenile arthritis from other types (Genetics Home Reference, 2015). | ||
| + | |||
| + | <box 50% round right |>{{:piechartjia2.png|{{:piechartjia.png|}}</box|Figure 2. This image shows the percentage at which each subtype of JIA is prevalent. Retrieved from: https://warmsocks.files.wordpress.com/2012/08/jiabreakdown.png> | ||
| ==== Oligoarticular JIA ==== | ==== Oligoarticular JIA ==== | ||
| Line 41: | Line 43: | ||
| Undifferentiated arthritis is given to patients who have symptoms that are not explained by the descriptions of any of the above forms of JIA or who have fit the criteria for more than one of the given descriptions of JIA (Genetics Home Reference, 2015). | Undifferentiated arthritis is given to patients who have symptoms that are not explained by the descriptions of any of the above forms of JIA or who have fit the criteria for more than one of the given descriptions of JIA (Genetics Home Reference, 2015). | ||
| - | <box 50% round right |>{{:piechartjia2.png|{{:piechartjia.png|}}</box|Figure 2. This image shows the percentage at which each subtype of JIA is prevalent. Retrieved from: https://warmsocks.files.wordpress.com/2012/08/jiabreakdown.png> | ||
| ===== Symptoms & Diagnosis ===== | ===== Symptoms & Diagnosis ===== | ||
| Line 65: | Line 66: | ||
| ==== Subcutaneous Nodules ==== | ==== Subcutaneous Nodules ==== | ||
| - | Nodules have been observed in approximately 10% of children who have been diagnosed with JRA and can appear subcutaneously. Characteristics of nodules include varying in sizes (from a few millimeters to several centimetres in diameter) nontender, no attachment to overlying skin and therefore move freely under the skin. Many times, they are found over the extensor tendon sheath of the hands, specifically over the metacarpophalangeal, proximal interphalangeal and distal interphalangeal joints. They are also found near the olecranon process of the elbow, over the anterior tibial surfaces and around the wrists and when fever is prevalent in the patient, nodules are found along the tendons of the erector spinae group and over the aponeurosis of the scalp (Miller, 1994). | + | Nodules have been observed in approximately 10% of children who have been diagnosed with JIA and can appear subcutaneously. Characteristics of nodules include varying in sizes (from a few millimeters to several centimetres in diameter) nontender, no attachment to overlying skin and therefore move freely under the skin. Many times, they are found over the extensor tendon sheath of the hands, specifically over the metacarpophalangeal, proximal interphalangeal and distal interphalangeal joints. They are also found near the olecranon process of the elbow, over the anterior tibial surfaces and around the wrists and when fever is prevalent in the patient, nodules are found along the tendons of the erector spinae group and over the aponeurosis of the scalp (Miller, 1994). |
| ==== Uveitis Eye condition ==== | ==== Uveitis Eye condition ==== | ||
| Line 84: | Line 85: | ||
| ===== Causes and Risk Factors ===== | ===== Causes and Risk Factors ===== | ||
| - | It has been determined that most cases of JRA are sporadic, meaning that they occur in patients who don’t necessarily have a history of the disorder in their family (Genetics Home Reference, 2015). With that being said, there are many causes that occur prior to the diagnosis of JRA that have been mentioned to potentially lead to or affect the prevalence of JRA. Infectious agents, immunologic abnormalities of the host, physical trauma to joints, psychological trauma to the child, and allergy or reactions to drugs, foods, or toxins can all potentially lead to an individual to JRA (Schaller, 1997). Keeping in mind that there is no clear evidence that proves these are leadings causes of JRA (Schaller, 1997). JRA is not considered to be a familial disease, except in the place in which there is an onset of pauciarticular arthritis (Schaller, 1997). Also, there has been no evidence showing that JRA is transmissible. Various kinds of JRA have been shown to differ in sex, age, types of complications and prognosis, however, epidemiologic studies have not be able to clarify these observations (Schaller, 1997). A small percentage of cases of JRA have shown to have run in the family, however the inheritance pattern of the conditions is unclear (Genetics Home Reference, 2015). | + | It has been determined that most cases of JIA are sporadic, meaning that they occur in patients who don’t necessarily have a history of the disorder in their family (Genetics Home Reference, 2015). With that being said, there are many causes that occur prior to the diagnosis of JIA that have been mentioned to potentially lead to or affect the prevalence of JIA. Infectious agents, immunologic abnormalities of the host, physical trauma to joints, psychological trauma to the child, and allergy or reactions to drugs, foods, or toxins can all potentially lead to an individual to JIA (Schaller, 1997). Keeping in mind that there is no clear evidence that proves these are leadings causes of JIA (Schaller, 1997). JIA is not considered to be a familial disease, except in the place in which there is an onset of pauciarticular arthritis (Schaller, 1997). Also, there has been no evidence showing that JIA is transmissible. Various kinds of JIA have been shown to differ in sex, age, types of complications and prognosis, however, epidemiologic studies have not be able to clarify these observations (Schaller, 1997). A small percentage of cases of JIA have shown to have run in the family, however the inheritance pattern of the conditions is unclear (Genetics Home Reference, 2015). |
| - | Maternal smoking has also been observed to potentially cause or play a role in the onset of JRA through various ways (Symmons, 2005). Firstly, a mother who smokes while pregnant can induce some permanent immunological abnormality in the child which can later lead to arthritis (Symmons, 2005). Smoking while pregnant could also cause a low birth weight which could in turn lead to an increase in the susceptibility to infection and later, JRA (Symmons, 2005). Lastly, the continual smoking, even after a baby is born may lead to a contaminated environment which could ultimately lead to the onset of JRA later on during the early years of that child’s life (Symmons, 2005). | + | Maternal smoking has also been observed to potentially cause or play a role in the onset of JIA through various ways (Symmons, 2005). Firstly, a mother who smokes while pregnant can induce some permanent immunological abnormality in the child which can later lead to arthritis (Symmons, 2005). Smoking while pregnant could also cause a low birth weight which could in turn lead to an increase in the susceptibility to infection and later, JIA (Symmons, 2005). Lastly, the continual smoking, even after a baby is born may lead to a contaminated environment which could ultimately lead to the onset of JIA later on during the early years of that child’s life (Symmons, 2005). |
| {{:causes_and_risk.png|{{:weight_status_category.png|}} | {{:causes_and_risk.png|{{:weight_status_category.png|}} | ||
| Line 94: | Line 95: | ||
| ===== Epidemiology ===== | ===== Epidemiology ===== | ||
| - | |||
| - | The incidence of JIA in North America and Europe is 4 - 16 affected children out of a sub-population of 10000 children. 1 in 1000, or approximately 294000 children in the United States, are affected by the most common type of JIA in the United States, which is oligoarticular JIA. For reasons that continue to be studied, females seem to be affected with JIA more frequently than males. In the case of enthesitis-related JIA, males are affected more often than females. Furthermore, the incidence of JIA varies between different populations and ethnic groups (Genetics Home Reference, 2015). | ||
| <sup>[1]</sup> | <sup>[1]</sup> | ||
| - | <box 70% round right |>{{:prev.png|{{:epi_world_map.png|}}</box| | + | <box 60% round right |>{{:prev.png|{{:epi_world_map.png|}}</box| |
| Figure 4.This image is showing the prevalence of the common forms of arthritis in the United States. Retrieved from: https://rheumatoidarthritis.net/wp-content/uploads/2013/07/prevalence_arthritis.png> | Figure 4.This image is showing the prevalence of the common forms of arthritis in the United States. Retrieved from: https://rheumatoidarthritis.net/wp-content/uploads/2013/07/prevalence_arthritis.png> | ||
| - | In a study done by Saurenmann et al, questionnaires pertaining to ethnicity were distributed to patients with JRA and then followed up at the Hospital for Sick Children in Toronto. When the data was collected, the relative risk of developing JRA was calculated and the results were compared with data from the age matched general population in the Toronto region. The frequency at which JRA has been perceived shows that European descendants had about 69.7% of their patients diagnosed with JRA, which patients in the Toronto region has about 54.7%. Statistically lower percentages were shown to patients who were of the black, Asian, or Indian subcontinental origin. Kids from the European origin had a higher relative rate for developing any of the subtypes of juvenile arthritis, except oligoarthritis or psoriatic. Patients of the Asian origin showed to have a greater chance of being diagnosed with enthesitis-related JIA while those of black or Native North American origin were more likely to develop polyarticular rheumatoid positive JIA (Saurenmann, 2007). | + | The incidence of JIA in North America and Europe is 4 - 16 affected children out of a sub-population of 10000 children. 1 in 1000, or approximately 294000 children in the United States, are affected by the most common type of JIA in the United States, which is oligoarticular JIA. For reasons that continue to be studied, females seem to be affected with JIA more frequently than males. In the case of enthesitis-related JIA, males are affected more often than females. Furthermore, the incidence of JIA varies between different populations and ethnic groups (Genetics Home Reference, 2015). |
| + | |||
| + | In a study done by Saurenmann et al, questionnaires pertaining to ethnicity were distributed to patients with JIA and then followed up at the Hospital for Sick Children in Toronto. When the data was collected, the relative risk of developing JIA was calculated and the results were compared with data from the age matched general population in the Toronto region. The frequency at which JIA has been perceived shows that European descendants had about 69.7% of their patients diagnosed with JIA, which patients in the Toronto region has about 54.7%. Statistically lower percentages were shown to patients who were of the black, Asian, or Indian subcontinental origin. Kids from the European origin had a higher relative rate for developing any of the subtypes of juvenile arthritis, except oligoarthritis or psoriatic. Patients of the Asian origin showed to have a greater chance of being diagnosed with enthesitis-related JIA while those of black or Native North American origin were more likely to develop polyarticular rheumatoid positive JIA (Saurenmann, 2007). | ||
| ===== Pathophysiology ===== | ===== Pathophysiology ===== | ||
| Line 176: | Line 177: | ||
| ACPAs are important for the diagnosis of JIA. These are the patient’s own antibodies which have been modified by citrullination, a process where proteins’ arginine residues are converted to citrulline post-translationally by the enzyme peptidyl arginine deiminase (PAD) (Figure 7). Once modified, the body recognizes its own antigens to be foreign, causing an immune response (Demoruelle & Deane, 2011). | ACPAs are important for the diagnosis of JIA. These are the patient’s own antibodies which have been modified by citrullination, a process where proteins’ arginine residues are converted to citrulline post-translationally by the enzyme peptidyl arginine deiminase (PAD) (Figure 7). Once modified, the body recognizes its own antigens to be foreign, causing an immune response (Demoruelle & Deane, 2011). | ||
| - | <box 60% round right |>{{:autom1a.png|}}</box|Figure 7: The Process of Citrullination. Retrived from: https://www.hopkinsarthritis.org/wp-content/uploads/2012/08/round4-slide-12.jpg.> | + | <box 50% round right |>{{:autom1a.png|}}</box|Figure 7: The Process of Citrullination. Retrived from: https://www.hopkinsarthritis.org/wp-content/uploads/2012/08/round4-slide-12.jpg.> |
| **Rheumatoid Factor (RF)** | **Rheumatoid Factor (RF)** | ||
| Line 189: | Line 190: | ||
| Cytokines are protein messengers that transmit signals from one cell to another by binding to specific receptors on the surface of cells. Both pro- and anti-inflammatory cytokines, chemokines, and mitogenic factors are produced, but proinflammatory mediators predominate during the active phase of disease.Tumor necrosis factor alpha (TNFα), IL-1, IL-6 and IL-17 are of key importance in the pathogenesis of inflammation in RA. IL-1 and TNFα are also key players in the regulation of mediators of connective tissue damage by synoviocytes, including matrix metalloproteinases (MMPs) and prostaglandins (Nath Maini, 2010). | Cytokines are protein messengers that transmit signals from one cell to another by binding to specific receptors on the surface of cells. Both pro- and anti-inflammatory cytokines, chemokines, and mitogenic factors are produced, but proinflammatory mediators predominate during the active phase of disease.Tumor necrosis factor alpha (TNFα), IL-1, IL-6 and IL-17 are of key importance in the pathogenesis of inflammation in RA. IL-1 and TNFα are also key players in the regulation of mediators of connective tissue damage by synoviocytes, including matrix metalloproteinases (MMPs) and prostaglandins (Nath Maini, 2010). | ||
| + | |||
| + | <box 60% round right |>{{:p4.png|}}</box|Figure 8: Summary of the pathogenic pathways in JIA. Retrived from: https://www.researchgate.net/profile/Abdullah_Nahian/publication/263585727/figure/fig1/AS:202832654409738@1425370481906/Figure-illustrates-the-pathogenic-pathways-of-rheumatoid-arthritis-following-31-38.png> | ||
| ACPAs may also bind to citrullinated proteins directly in the synovial membrane. Immune complexes between citrullinated proteins ,such as fibrinogen, and ACPA-igG can drive inflammation (including the production of IL-6 and tumor necrosis factor) by engaging both toll-like receptor (TLR4) and Fc receptors (Nath Maini, 2010). | ACPAs may also bind to citrullinated proteins directly in the synovial membrane. Immune complexes between citrullinated proteins ,such as fibrinogen, and ACPA-igG can drive inflammation (including the production of IL-6 and tumor necrosis factor) by engaging both toll-like receptor (TLR4) and Fc receptors (Nath Maini, 2010). | ||
| Line 195: | Line 198: | ||
| Both ACPA- and RF-dependent events could contribute to the initiation and propagation of chronic synovial inflammation, and further synergize with T cell activation and enhance the local production of autoantibodies (McInnes & Schett, 2011). | Both ACPA- and RF-dependent events could contribute to the initiation and propagation of chronic synovial inflammation, and further synergize with T cell activation and enhance the local production of autoantibodies (McInnes & Schett, 2011). | ||
| - | |||
| - | |||
| - | <box 60% round right |>{{:p4.png|}}</box|Figure 8: Summary of the pathogenic pathways in JIA. Retrived from: https://www.researchgate.net/profile/Abdullah_Nahian/publication/263585727/figure/fig1/AS:202832654409738@1425370481906/Figure-illustrates-the-pathogenic-pathways-of-rheumatoid-arthritis-following-31-38.png> | ||
| ===Bone Destruction=== | ===Bone Destruction=== | ||
| Line 241: | Line 241: | ||
| === Disease-modifying anti-rheumatic drugs (DMARDs) === | === Disease-modifying anti-rheumatic drugs (DMARDs) === | ||
| + | |||
| + | <box 45% round right |>{{:graph2345.png|}}</box|Figure 9 shows a graph of the percentage of patients that improved over the study span of six months. Retrieved from (Giannini et al., 1990).> | ||
| DMARDs are usually used as a second option if NSAIDs do not work. They are “slow acting” drugs that can take weeks to six months to work (Brescia, 2016). They act to treat JIA by slowing or stopping the immune system from causing the inflammation that destroys the joints (Juvenile Idiopathic Arthritis, 2017). Since, it is the inflammation is what slowly destroys joint tissue over the years. Some common non-biologic DMARDs include methotrexate, leflunomide, and sulfasalazine (Harris et al., 2014). The most common non-biologic DMARD administered to children with JIA is methotrexate. Methotrexate is a folic acid analogue and it competitively inhibits with dihydrofolate reductase to interfere with purine biosynthesis and DNA production (Harris et al., 2014). Although the mechanism of action for methotrexate is not known, it is suggested that the extracellular adenosine release and its interaction with specific cell surface receptors may be related to the anti-inflammatory effects (Ramanan et al., 2003). | DMARDs are usually used as a second option if NSAIDs do not work. They are “slow acting” drugs that can take weeks to six months to work (Brescia, 2016). They act to treat JIA by slowing or stopping the immune system from causing the inflammation that destroys the joints (Juvenile Idiopathic Arthritis, 2017). Since, it is the inflammation is what slowly destroys joint tissue over the years. Some common non-biologic DMARDs include methotrexate, leflunomide, and sulfasalazine (Harris et al., 2014). The most common non-biologic DMARD administered to children with JIA is methotrexate. Methotrexate is a folic acid analogue and it competitively inhibits with dihydrofolate reductase to interfere with purine biosynthesis and DNA production (Harris et al., 2014). Although the mechanism of action for methotrexate is not known, it is suggested that the extracellular adenosine release and its interaction with specific cell surface receptors may be related to the anti-inflammatory effects (Ramanan et al., 2003). | ||
| - | A study by Giannini et al. 1990 formed the basis for current use of methotrexate in JIA. They conducted a six-month randomized, double blind controlled multicenter study of 127 children with resistant juvenile rheumatoid arthritis. The results indicated that 63% of the group treated with 10 mg/m2, of MTX, improved compared with only 32% of those treated with 5mg/m2, and 36% of the placebo group (Giannini et al., 1990). Figure 13 shows a comparison of the three treatment category outcomes over a period of six months. | + | A study by Giannini et al. 1990 formed the basis for current use of methotrexate in JIA. They conducted a six-month randomized, double blind controlled multicenter study of 127 children with resistant juvenile rheumatoid arthritis. The results indicated that 63% of the group treated with 10 mg/m2, of MTX, improved compared with only 32% of those treated with 5mg/m2, and 36% of the placebo group (Giannini et al., 1990). Figure 9 shows a comparison of the three treatment category outcomes over a period of six months. |
| - | + | ||
| - | <box 35% round right |>{{:graph234.png|{{:orlistat.jpg|}}</box|Figure 13 shows a graph of the percentage of patients that improved over the study span of six months. Retrieved from (Giannini et al., 1990).> | + | |
| Line 256: | Line 256: | ||
| === Corticosteroid Injections === | === Corticosteroid Injections === | ||
| - | In the circumstance that a child does not show significant signs of recovery with the usage of other drug treatments, corticosteroids can be injected into the inflammatory joints. This method is effective as it minimizes the side effects by directly targeting the affected areas. This induces an immediate response within the course of a week. The three corticosteroids that are commonly used include Aristospan, Kenalog and Depo-Medrol. Please refer to Figure 14 to understand the process of injecting corticosteroids into the affected joints (AboutKidsHealth, 2017). | + | In the circumstance that a child does not show significant signs of recovery with the usage of other drug treatments, corticosteroids can be injected into the inflammatory joints. This method is effective as it minimizes the side effects by directly targeting the affected areas. This induces an immediate response within the course of a week. The three corticosteroids that are commonly used include Aristospan, Kenalog and Depo-Medrol. Please refer to Figure 10 to understand the process of injecting corticosteroids into the affected joints (AboutKidsHealth, 2017). |
| + | {{:surg1.png|}} | ||
| - | <box 30% round right |>{{:surg.png|{{:surgical_procedures.png|}}</box|Figure 14. This figure depicts the process of injecting corticosteroids into affected joints in individuals with juvenile idiopathic arthritis. (Retrieved from http://www.aboutkidshealth.ca/En/ResourceCentres/JuvenileIdiopathicArthritis/TreatmentofJIA/MedicationsforJIA/Pages/CorticosteroidJointInjections.aspx> | + | Figure 10. This figure depicts the process of injecting corticosteroids into affected joints in individuals with juvenile idiopathic arthritis. (Retrieved from http://www.aboutkidshealth.ca/En/ResourceCentres/JuvenileIdiopathicArthritis/TreatmentofJIA/MedicationsforJIA/Pages/CorticosteroidJointInjections.aspx> |
| ==== Surgical Treatment ==== | ==== Surgical Treatment ==== | ||
| - | Children must be of at least 6 years of age to be considered for surgery. Even when children are older than 6, surgery is usually very rare because there is a very low risk of a child developing joint damage that’s substantial enough to require some type of surgical intervention. Of the surgical interventions one that seem to be common for children is the soft tissue release of contractures. A contracture is a joint abnormally bent by shortened soft tissues in and around the joint. It involves cutting the excess tissue attached to the abnormally bent joint, and as the tissues are released the joint is able to return more to its normal position (Juvenile Idiopathic Arthritis, 2017). The goal of soft tissue releasing is to (1) return the joint to a closer to normal position, and (2) increase range of motion. After soft tissue release surgery casts are usually worn for several weeks, followed by physiotherapy. Total joint replacement or arthroplasty is another form of surgery and it is practiced as a last resort for damaged joints. The image on the __ (right/left) (Fig 15) shows a patient’s knee after total knee replacement (Abdel & Figgie 2014). Total joint replacement is usually delayed until the child’s bones have stopped growing. This type of surgery can relieve pain and restore joint function but joints will not be restored to normal position. Other surgical methods include osteotomy, epiphysiodesis, synovectomy, and arthrodesis. Osteotomy is when a piece of a bone is removed to allow for better movement. Epiphysiodesis is carried out if there is specifically excessive growth, and the portion that is overgrown is removed. Synovectomy is rarely used in JIA cases, but it is the removal of the synovium to reduce inflammation. Lastly, arthrodesis is also rarely used, as it requires the fusing of two bones in the diseased joint to prevent joint movement. | + | Children must be of at least 6 years of age to be considered for surgery. Even when children are older than 6, surgery is usually very rare because there is a very low risk of a child developing joint damage that’s substantial enough to require some type of surgical intervention. Of the surgical interventions one that seem to be common for children is the soft tissue release of contractures. A contracture is a joint abnormally bent by shortened soft tissues in and around the joint. It involves cutting the excess tissue attached to the abnormally bent joint, and as the tissues are released the joint is able to return more to its normal position (Juvenile Idiopathic Arthritis, 2017). The goal of soft tissue releasing is to (1) return the joint to a closer to normal position, and (2) increase range of motion. After soft tissue release surgery casts are usually worn for several weeks, followed by physiotherapy. Total joint replacement or arthroplasty is another form of surgery and it is practiced as a last resort for damaged joints. Figure 11 shows a patient’s knee after total knee replacement (Abdel & Figgie 2014). Total joint replacement is usually delayed until the child’s bones have stopped growing. This type of surgery can relieve pain and restore joint function but joints will not be restored to normal position. Other surgical methods include osteotomy, epiphysiodesis, synovectomy, and arthrodesis. Osteotomy is when a piece of a bone is removed to allow for better movement. Epiphysiodesis is carried out if there is specifically excessive growth, and the portion that is overgrown is removed. Synovectomy is rarely used in JIA cases, but it is the removal of the synovium to reduce inflammation. Lastly, arthrodesis is also rarely used, as it requires the fusing of two bones in the diseased joint to prevent joint movement. |
| - | + | ||
| - | {{:bone.png|{{:screen_shot_2017-03-03_at_6.37.40_pm.png|{{:flowchart_final.png|}} | + | |
| + | {{:bone1.png|}} | ||
| - | Figure 15. This image shows the view before and after total knee replacement. Retrieved from (Abdel & Figgie, 2014). | + | Figure 11. This image shows the view before and after total knee replacement. Retrieved from (Abdel & Figgie, 2014). |
| ==== Direction for Future Treatments ==== | ==== Direction for Future Treatments ==== | ||
