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group_2_presentation_2_-_juvenile_arthritis [2017/03/03 17:51]
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group_2_presentation_2_-_juvenile_arthritis [2018/01/25 15:18] (current)
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 ====== Juvenile Idiopathic Arthritis ====== ====== Juvenile Idiopathic Arthritis ======
  
- ​Juvenile idiopathic arthritis (JIA), also known as juvenile rheumatoid arthritis (JRA) is a chronic form of arthritis that can be seen in children between the ages of 1-16 (Shiel, n.a). This disease refers to a group of conditions that pertain to joint inflammation (Genetics Home Reference, 2015). According to The Genetics Home Reference, “It is classified as an autoimmune disorder which means that the immune system malfunctions and attacks the body’s organs and tissues, in this case joints ​(Genetics Home Reference, 2015).” Through much research, it has been determined that there are seven types of JIA which are classified in accordance to their signs and symptoms, number of affected joints, results from medical tests and familial history ​(Genetics Home Reference, 2015). All seven types of JIA are chronic, thus individuals must develop coping methods that are long lasting and effective. The prevalence of the seven types of JIA are shown in Figure 2.  ​+ ​Juvenile idiopathic arthritis (JIA), also known as juvenile rheumatoid arthritis (JRA) is a chronic form of arthritis that can be seen in children between the ages of 1-16 (Shiel, n.a). This disease refers to a group of conditions that pertain to joint inflammation (Figure 1). According to The Genetics Home Reference, “It is classified as an autoimmune disorder which means that the immune system malfunctions and attacks the body’s organs and tissues, in this case joints.” Through much research, it has been determined that there are seven types of JIA which are classified in accordance to their signs and symptoms, number of affected joints, results from medical tests and familial history. All seven types of JIA are chronic, thus individuals must develop coping methods that are long lasting and effective. The prevalence of the seven types of JIA are shown in Figure 2  ​(Genetics Home Reference, 2015).  ​
 <style float-right>​ <style float-right>​
 </​style>​ </​style>​
  
-<box 75% round right |>​{{:​obesity_chart.jpg}}</​box|Figure 1: Individual becoming obese over time from https://www.stayhealthy.com/​Template/​en_us/​BinaryResource/​Theme/​Default/content/images/obesity_chart.jpg ​+<box 75% round right |>{{:​jiaintro.png|{{:​obesity_chart.jpg}}</​box|Figure 1.This image illustrates a comparison between a normal joint, osteoarthritis and rheumatoid arthritis. Retrieved ​from: http://www.onhealth.com/​content/​1/rheumatoid_arthritis_ra
  
 ===== Subtypes ===== ===== Subtypes =====
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 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 ====
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 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). ​
- 
-===== Epidemiology ===== 
- 
-There are two broad categories for genetic susceptibility genes: human leucocyte antigen (HLA) genes and non HLA-related genes. As a polygenic disease, JIA is mostly affected at the HLA region, while the non-HLA loci exhibit moderate or weak genetic influence ​ on susceptibility (Prahalad and Glass, 2008). JIA is influenced by both HLA class I and HLA class II alleles, which contain certain peptides leading to the activation of certain autoreactive T cells (Wedderburn et al., 2001). Several genetic studies have shown the contribution of polymorphisms in the major histocompatibility complex (MHC). The MHC region is on chromosome 6 and is packed with more than 200 genes, many of which are essential to the immune system. Since MHC class II genes play a great role as a genetic risk factor for JIA, CD4+ T cells play a crucial role in disease development. Associations between HLA polymorphisms and JIA subtypes have been reported in multiple populations (Figure 8) (Prahalad and Glass, 2008). ​ 
- 
- 
-<​sup>​[1]</​sup>​ 
-<box 70% round right |>​{{:​epi_world_map.png|}}</​box| 
-Figure 2: Age-standardized prevalence of obesity in women over 18 years of age (BMI greater than 30kg/m^2, 2014) from http://​cdn.zmescience.com/​wp-content/​uploads/​2015/​01/​WomenObese.jpg>​ 
- 
-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 (Saurenmann,​ 2007). 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 (Saurenmann,​ 2007). ​ 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% (Saurenmann,​ 2007). Statistically lower percentages were shown to patients who were of the black, Asian, or Indian subcontinental origin (Saurenmann,​ 2007). Kids from the European origin had a higher relative rate for developing any of the subtypes of juvenile arthritis, except oligoarthritis or psoriatic (Saurenmann,​ 2007). 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).  ​ 
  
  
 ===== Symptoms & Diagnosis ===== ===== Symptoms & Diagnosis =====
- 
-<box 50% round right |>​{{:​bmi_classification_final.png}}</​box|Figure 3: WHO standardized BMI categories in adults (Seidell & Halberstadt,​ 2015)> ​ 
  
 JIA is diagnosed once symptoms are persistent for at least six weeks since the diagnosis (Shiel, n.a). Common symptoms of JIA include swelling, redness, and warmth of joints, however, many researchers and scientists attempt to formulate a criteria for the precise diagnosis of JIA (Nelson & Kilegman, 2016). The proposed criteria includes six requirements. Firstly, polyarticular or monoarticular arthritis must be present for at least six weeks or in the presence of the following: Iritis, rash, flexion contractures,​ ankyloses, muscle wasting, anemia, white blood cell count of 20000, cervical spine pain (Grossman & Mukhopadhyay,​ 1975). The second criteria is expressed as polyarticular or monoarticular arthritis for 6 weeks or less having the following characteristics:​ nonmigratory for at least 1 week, no symptomatic response to therapeutic blood levels of salicylate (20 mg/100 ml or above) preponderance of small joint involvement,​ involvement of the temporomandibular joints, morning stiffness (Grossman & Mukhopadhyay,​ 1975). Next, polyarticular or monoarticular arthritis for 6 weeks or less accompanied by pericarditis in the absence of endocarditis (Grossman & Mukhopadhyay,​ 1975). Fourth would be classified as constitutional symptoms known as any combination of fever, weakness, or weight loss (Grossman & Mukhopadhyay,​ 1975). The fifth criteria mention the elevated erythrocyte sedimentation rate. Lastly the exclusion of all other diagnoses such as rheumatic fever, systemic lupus erythematosus,​ periarteritis nodosa, dermatomyositis,​ scleroderma,​ tuberculosis synovitis, leukemia, lymphoma, septic arthritis, osteomyelitis,​ sickle cell anemia and serum sickness (Grossman & Mukhopadhyay,​ 1975). This set of criteria was put together to ensure that the diagnosis of JIA was accurate and any symptoms shown couldn’t be associated with any other chronic disease. There are many symptoms that occur for JIA to be an option for diagnosis. JIA is diagnosed once symptoms are persistent for at least six weeks since the diagnosis (Shiel, n.a). Common symptoms of JIA include swelling, redness, and warmth of joints, however, many researchers and scientists attempt to formulate a criteria for the precise diagnosis of JIA (Nelson & Kilegman, 2016). The proposed criteria includes six requirements. Firstly, polyarticular or monoarticular arthritis must be present for at least six weeks or in the presence of the following: Iritis, rash, flexion contractures,​ ankyloses, muscle wasting, anemia, white blood cell count of 20000, cervical spine pain (Grossman & Mukhopadhyay,​ 1975). The second criteria is expressed as polyarticular or monoarticular arthritis for 6 weeks or less having the following characteristics:​ nonmigratory for at least 1 week, no symptomatic response to therapeutic blood levels of salicylate (20 mg/100 ml or above) preponderance of small joint involvement,​ involvement of the temporomandibular joints, morning stiffness (Grossman & Mukhopadhyay,​ 1975). Next, polyarticular or monoarticular arthritis for 6 weeks or less accompanied by pericarditis in the absence of endocarditis (Grossman & Mukhopadhyay,​ 1975). Fourth would be classified as constitutional symptoms known as any combination of fever, weakness, or weight loss (Grossman & Mukhopadhyay,​ 1975). The fifth criteria mention the elevated erythrocyte sedimentation rate. Lastly the exclusion of all other diagnoses such as rheumatic fever, systemic lupus erythematosus,​ periarteritis nodosa, dermatomyositis,​ scleroderma,​ tuberculosis synovitis, leukemia, lymphoma, septic arthritis, osteomyelitis,​ sickle cell anemia and serum sickness (Grossman & Mukhopadhyay,​ 1975). This set of criteria was put together to ensure that the diagnosis of JIA was accurate and any symptoms shown couldn’t be associated with any other chronic disease. There are many symptoms that occur for JIA to be an option for diagnosis.
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 ==== Flares ==== ==== Flares ====
  
-Flares are known as a classification of symptoms referring to joint pain and inflammation and can last from time periods ranging from weeks to months ​(Shiel, n.a). JIA patients tend to have periods of remission, where these symptoms aren’t as prevalent as they would have been in the past (Shiel, n.a). Following this grace period where pain is minimal, these symptoms can reappear and this is known as a relapse ​(Shiel, n.a). This notion of relapsing and remission varies from patient to patient and can also be a known trend with other symptoms as well (Shiel, n.a). +Flares are known as a classification of symptoms referring to joint pain and inflammation and can last from time periods ranging from weeks to months. JIA patients tend to have periods of remission, where these symptoms aren’t as prevalent as they would have been in the past. Following this grace period where pain is minimal, these symptoms can reappear and this is known as a relapse. This notion of relapsing and remission varies from patient to patient and can also be a known trend with other symptoms as well (Shiel, n.a). 
  
 ==== Fever ==== ==== Fever ====
  
-Fever is a common symptom for JIA and can be classified to many degrees. A fever in an individual who may have JIA can be recognized in three different states. “Intermittent fever with a daily single high spike of temperature to 104-105 ​~ F, then returning down to a normal temperature. A remittent fever with a persistent elevation of 100-101 ​~ F with occasional, somewhat irregular increases in temperature to 103-104 ​~ F (Grossman & Mukhopadhyay,​ 1975). Lastly, low grade fever with periodic elevation of temperature to 100-101 ​~ F, the elevations frequently occurring in the late afternoon or evening, the morning temperature being normal (Grossman & Mukhopadhyay,​ 1975).”+A fever is a common symptom for JIA and can be classified ​according ​to various ​degrees ​of a spectrum. A fever in an individual who may have JIA can be recognized in three different states. “Intermittent fever with a daily single high spike of temperature to 104-105 ​fahrenheit ​, then returning down to a normal temperature. A remittent fever with a persistent elevation of 100-101 ​fahrenheit ​with occasional, somewhat irregular increases in temperature to 103-104 ​ ​fahrenheit. Lastly, low grade fever with periodic elevation of temperature to 100-101 ​fahrenheit, the elevations frequently occurring in the late afternoon or evening, the morning temperature being normal (Grossman & Mukhopadhyay,​ 1975).”
  
 ==== Morning Stiffness ==== ==== Morning Stiffness ====
  
-Morning stiffness is a symptom that helps with the diagnosis of JIA. It constitutes as difficulty in moving muscles after a period of rest or inactivity ​(Miller, 1994). Individuals feel this pain in the morning after waking up from a night’s sleep and is not a result of pain (Miller, 1994). With activity and movement throughout the day it tends to disappear ​(Miller, 1994). It can vary in the time that it lasts from a few minutes to many hours (Miller, 1994). The degree to which morning stiffness occurs can also vary. It can be so sever that the child cannot move without help from another person ​(Miller, 1994). In these circumstances,​ the combination of a warm bath and an increase in activity will aid with the relief of the stiffness ​(Miller, 1994). Other times in the day where morning stiffness is prevalent is after a nap or sitting down for a prolonged period, however, this is usually not as sever as the morning occurrence ​(Miller, 1994).  Morning stiffness is an important differential characteristic between JIA and rheumatic fever or septic arthritis and if it is noted to be happening, physicians and other medical assistance should take a further look into it (Miller, 1994).+Morning stiffness is a symptom that helps with the diagnosis of JIA. It constitutes as difficulty in moving muscles after a period of rest or inactivity. Individuals feel this pain in the morning after waking up from a night’s sleep and is not a result of pain. With activity and movement throughout the day it tends to disappear. It can vary in the time that it lasts from a few minutes to many hours. The degree to which morning stiffness occurs can also vary. It can be so sever that the child cannot move without help from another person. In these circumstances,​ the combination of a warm bath and an increase in activity will aid with the relief of the stiffness. Other times in the day where morning stiffness is prevalent is after a nap or sitting down for a prolonged period, however, this is usually not as sever as the morning occurrence. ​ Morning stiffness is an important differential characteristic between JIA and rheumatic fever or septic arthritis and if it is noted to be happening, physicians and other medical assistance should take a further look into it (Miller, 1994).
  
 ==== Rheumatoid Rash ==== ==== Rheumatoid Rash ====
  
-This symptom is extremely helpful when diagnosing JIA, especially in the acute onset of disease ​ ​(Miller,​ 1994). According to Miller, “The characteristic rheumatoid rash is an erythematous,​ salmon-pink,​ evanescent, usually circumscribed macular (although occasionally maculopapular) eruption involving the trunk, neck, velar aspect to the arms, inner aspect of the thighs, buttocks and face. It may last for only a few minutes, a few hours or several years (Miller, 1994).” Again, the degree to which the rash may last varies, lasting from only a few minutes to many hours and appears strongly during times of high fever or during warm baths (Miller, 1994). Many times, the rash experienced in patients who have JIA can be mistaken for erythema annulare or marginatum, however, erythema annulare or marginatum does not spread to the face region which is prevalent in the rheumatoid rash of JIA (Miller, 1994). ​+This symptom is extremely helpful when diagnosing JIA, especially in the acute onset of disease. According to Miller, “The characteristic rheumatoid rash is an erythematous,​ salmon-pink,​ evanescent, usually circumscribed macular (although occasionally maculopapular) eruption involving the trunk, neck, velar aspect to the arms, inner aspect of the thighs, buttocks and face. It may last for only a few minutes, a few hours or several years.” Again, the degree to which the rash may last varies, lasting from only a few minutes to many hours and appears strongly during times of high fever or during warm baths. Many times, the rash experienced in patients who have JIA can be mistaken for erythema annulare or marginatum, however, erythema annulare or marginatum does not spread to the face region which is prevalent in the rheumatoid rash of JIA (Miller, 1994). ​
  
 ==== Subcutaneous Nodules ==== ==== Subcutaneous Nodules ====
  
-Nodules have been observed in approximately 10% of children who have been diagnosed with JRA and can appear subcutaneously ​(Miller, 1994). 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 (Miller, 1994). Many times, they are found over the extensor tendon sheath of the hands, specifically over the metacarpophalangeal,​ proximal interphalangeal and distal interphalangeal joints ​(Miller, 1994). 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 ====
  
-Juvenile rheumatoid arthritis can also lead to an eye condition called uveitis, also named iridocyclitis or iritis ​(Goldstein et al, 2013). This may or may not lead to any symptoms arising, however, some symptoms of this condition are red eyes, eye pain, vision changes and sensitivity to light (Goldstein et al, 2013). Uveitis is known as the swelling and irritation of the uvea, which is the middle layer of the eye (Goldstein et al, 2013). ​+Juvenile rheumatoid arthritis can also lead to an eye condition called uveitis, also named iridocyclitis or iritis). This may or may not lead to any symptoms arising, however, some symptoms of this condition are red eyes, eye pain, vision changes and sensitivity to light. Uveitis is known as the swelling and irritation of the uvea, which is the middle layer of the eye (Goldstein et al, 2013). ​
  
 ==== Blood Tests for JIA ==== ==== Blood Tests for JIA ====
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 Complete Blood Count (CBC) measures three types of cells that are found in the blood; red cells (carry oxygen), white blood cells (fight infection) and platelets (cause blood clots) (Arthritis Foundation, 2016). This test is useful when discovering more about the condition, for example, kids with low red blood cell counts are usually ones who are suffering from JIA (Arthritis Foundation, 2016). ​ Complete Blood Count (CBC) measures three types of cells that are found in the blood; red cells (carry oxygen), white blood cells (fight infection) and platelets (cause blood clots) (Arthritis Foundation, 2016). This test is useful when discovering more about the condition, for example, kids with low red blood cell counts are usually ones who are suffering from JIA (Arthritis Foundation, 2016). ​
  
-{{:​bmi_formula.png|}} 
  
-Figure 4: BMI Calculation Equation  +===== Causes and Risk Factors =====
-from http://​www.heartnewslinks.com/​editors-blog/​body-mass-index-bmi-bad+
  
 +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).
  
-{{:​weight_status_category.png|}}+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|}}
  
-Figure 5: BMI-for-Age Percentile Ranges for Children ​ 
-from https://​www.cdc.gov/​healthyweight/​assessing/​bmi/​childrens_bmi/​about_childrens_bmi.html> ​ 
  
 +Figure 3.This image is illustrating where rheumatoid arthritis is present on a hand. Retrieved from: https://​www.epainassist.com/​images/​Juvenile-Arthritis.jpg
  
-===== Causes and Risk Factors ​=====+===== Epidemiology ​=====
  
-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 transmissibleVarious 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).+<​sup>​[1]</​sup>​ 
 +<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 StatesRetrieved from: https://​rheumatoidarthritis.net/​wp-content/​uploads/​2013/​07/​prevalence_arthritis.png>
  
-Maternal smoking has also been observed to potentially cause or play a role in the onset of JRA through various ways (Symmons, 2005)Firstlya mother who smokes while pregnant can induce some permanent immunological abnormality ​in the child which can later lead to arthritis (Symmons2005). ​ Smoking while pregnant could also cause a low birth weight which could in turn lead to an increase ​in the susceptibility to infection and laterJRA (Symmons, 2005)Lastlythe 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 (Symmons2005). +The incidence of JIA in North America and Europe ​ is 4 - 16 affected children out of a sub-population of 10000 children1 in 1000or approximately 294000 children ​in the United Statesare affected by the most common type of JIA in the United Stateswhich is oligoarticular JIAFor reasons that continue to be studiedfemales 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 Reference2015).
  
 +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 =====
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 JIA is believed to be a complex genetic trait. A complex genetic trait is defined as phenotypes not exhibiting classic mendelian inheritance patterns and therefore, cannot be attributed to variants in a single gene locus. Thus, JIA is a disease which is believed to be determined by a number of genetic and environmental factors (Glass and Giannini, 1999). ​ JIA is believed to be a complex genetic trait. A complex genetic trait is defined as phenotypes not exhibiting classic mendelian inheritance patterns and therefore, cannot be attributed to variants in a single gene locus. Thus, JIA is a disease which is believed to be determined by a number of genetic and environmental factors (Glass and Giannini, 1999). ​
-  
-<box 35% round left |>​{{:​adipose_finalllll.png|}}</​box|Figure 7:This figure is a visual depiction of the secretory pathway and function of adipokines in conditions where excessive adipocyte buildup occurs from http://​www.the-scientist.com/​images/​December2012/​Obese_Infograph.jpg>​ 
  
  
 ==== HLA and non-HLA Polymorphisms ​ ==== ==== HLA and non-HLA Polymorphisms ​ ====
  
-There are two broad categories for genetic susceptibility genes: human leucocyte antigen (HLA) genes and non HLA-related genes. As a polygenic disease, JIA is mostly affected at the HLA region, while the non-HLA loci exhibit moderate or weak genetic influence ​ on susceptibility (Prahalad and Glass, 2008). JIA is influenced by both HLA class I and HLA class II alleles, which contain certain peptides leading to the activation of certain autoreactive T cells (Wedderburn et al., 2001). Several genetic studies have shown the contribution of polymorphisms in the major histocompatibility complex (MHC). The MHC region is on chromosome 6 and is packed with more than 200 genes, many of which are essential to the immune system. Since MHC class II genes play a great role as a genetic risk factor for JIA, CD4+ T cells play a crucial role in disease development. Associations between HLA polymorphisms and JIA subtypes have been reported in multiple populations. (Table ​X) (Prahalad and Glass, 2008). ​+There are two broad categories for genetic susceptibility genes: human leucocyte antigen (HLA) genes and non HLA-related genes. As a polygenic disease, JIA is mostly affected at the HLA region, while the non-HLA loci exhibit moderate or weak genetic influence ​ on susceptibility (Prahalad and Glass, 2008). JIA is influenced by both HLA class I and HLA class II alleles, which contain certain peptides leading to the activation of certain autoreactive T cells (Wedderburn et al., 2001). Several genetic studies have shown the contribution of polymorphisms in the major histocompatibility complex (MHC). The MHC region is on chromosome 6 and is packed with more than 200 genes, many of which are essential to the immune system. Since MHC class II genes play a great role as a genetic risk factor for JIA, CD4+ T cells play a crucial role in disease development. Associations between HLA polymorphisms and JIA subtypes have been reported in multiple populations. (Table ​4) (Prahalad and Glass, 2008). ​ 
 + 
 +{{:​p1b.png|}} 
 + 
 +Figure 4 shows several associations between JIA subtypes and different HLA alleles. Retrieved from (Prahalad and Glass, 2008)  
 + 
 +In addition to associations between numerous HLA variants and JIA, non-HLA polymorphisms have also shown to be linked to JIA. For example, genes such as PTPN22, tumor necrosis factor (TNF) alpha (TNFA), MIF, WISP3 and SLC11A6 have been associated with JIA  (Figure 5) (Prahalad, 2004; Rosen et al., 2003).  ​
  
-In addition to associations between numerous HLA variants and JIA, non-HLA polymorphisms have also shown to be linked to JIAFor example, genes such as PTPN22, tumor necrosis factor (TNF) alpha (TNFA), MIF, WISP3 and SLC11A6 have been associated with JIA  (Figure 9) (Prahalad, 2004; Rosen et al., 2003).  ​+{{:p2b.png|}}
  
 +Figure 5 shows non-HLA genetic genes associated with JIA that have been independently confirmed. Retrieved from (Prahalad and Glass, 2008)
  
 ==== Twin Studies ​ ==== ==== Twin Studies ​ ====
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 ==== Genetic Variables Underlying Autoimmunity ​ ==== ==== Genetic Variables Underlying Autoimmunity ​ ====
  
-Several studies have shown that clinically distinct autoimmune phenotypes cluster in individuals and families. The data supports the hypothesis that common genetic factors might predispose to clinically distinct autoimmune phenotypes. There are genetic variants which influence susceptibility to multiple clinically distinct autoimmune disorders (Figure ​10) (Prahalad and Glass, 2008). ​+Several studies have shown that clinically distinct autoimmune phenotypes cluster in individuals and families. The data supports the hypothesis that common genetic factors might predispose to clinically distinct autoimmune phenotypes. There are genetic variants which influence susceptibility to multiple clinically distinct autoimmune disorders (Figure ​6) (Prahalad and Glass, 2008). ​
  
 +{{:​p3.png|}}
  
-<box 45% round right|>​{{:​intake_final.png|}}</​box|Figure 8: Human hormones ​and food intake from http://​blog.naturessunshine.com/​wp-content/​uploads/​2015/​12/​Control_Food_Intake.jpg>​+Figure 6 shows different examples of genes associated with multiple autoimmune diseasesRetrieved from (Prahalad ​and Glass, 2008)
  
 ==== Environmental Factors ​ ==== ==== Environmental Factors ​ ====
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 **Antibodies to Citrullinated Protein Antigens (ACPA)** **Antibodies to Citrullinated Protein Antigens (ACPA)**
  
-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 ​11). 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 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 191: 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).
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 The literature suggests that osteoclasts and osteoclast precursors might be the major cell types that express citrullinated antigens on their surface in the normal non-inflamed bone and joint compartment,​ making precursor cells prime targets for circulating ACPAs. This feature is associated with the role of PADs but the exact role of PADs and citrullination in osteoclast differentiation is unknown (Malmström,​ Catrina & Klareskog, 2016). ​ The literature suggests that osteoclasts and osteoclast precursors might be the major cell types that express citrullinated antigens on their surface in the normal non-inflamed bone and joint compartment,​ making precursor cells prime targets for circulating ACPAs. This feature is associated with the role of PADs but the exact role of PADs and citrullination in osteoclast differentiation is unknown (Malmström,​ Catrina & Klareskog, 2016). ​
  
-{{:​genetics.gif}} 
- 
- 
-Figure 9: Human obesity gene map, updated in 2005.  
-From http://​onlinelibrary.wiley.com.libaccess.lib.mcmaster.ca/​doi/​10.1038/​oby.2006.71/​full 
- 
-==== start ==== 
  
 ===== Treatments ===== ===== Treatments =====
  
-**Goals of Weight Loss and Management ** +It is important to understand that treatment options ​for individuals with juvenile idiopathic arthritis focus primarily on managing ​the progression ​of the diseaseWhile pharmacologic treatments do not cure the diseasespecific types of physical therapy, drug therapy ​and surgical procedures aim to sustain the child’s physical and psychological integrity ​and minimizing side effectsIn effect, ​combination ​of the following types of intervention are most beneficialhowever the process of recovery varies with the individual’s risk for disease progression (Ravelli & Martini2007)
- +
-When undergoing weight loss therapy, practice guidelines issued by the National Heart, Lung and Blood Institute and the North American Association ​for the Study of Obesity recommend an initial weight loss goal of approximately 10% from baseline over a period of 6 months of therapy <​sup>​[25]</​sup>​. +
- +
-A weight loss of 10% has the potential to improve glycemic controlblood pressure control ​and lipid levels, especially in individuals with Type 2 diabetes or hypertension. Additionally,​ it might help to reduce symptoms from comorbidities,​ such as gastroesophageal reflux ​and osteoarthritisIf weight loss is maintained over long period ​of timeadverse clinical outcomes, such as myocardial infarction, stroke and cardiovascular-related deathscan be reduced <​sup>​[26]</​sup>​ +
- +
- +
-**Intervention**+
  
-For the optimal weight loss and health benefits, it is important to adopt lifestyle modifications,​ such as dietary therapy, physical activity and cognitive behaviour therapy. Typically, health care practitioners recommend their patients to pursue the lifestyle modifications for 6 months. Thereafter, clinicians assess whether they have reached the weight loss goal of 10% from baseline estimates. If patients have attained a satisfactory progression upon evaluation, it is recommended that they maintain their lifestyle modifications for sustainable weight loss results. Regular monitoring is a crucial aspect of ensuring a healthy lifestyle, as the influences of side effects must also be considered. In the case that patients have not attained their recommended weight after 6 months, health care practitioners typically recommend pharmacotherapy and/ or bariatric surgery to achieve their weight loss goal. The most conclusive results are seen when either pharmacotherapy or bariatric surgery are used in conjunction with lifestyle modifications <​sup>​[25]</​sup>​. ​ 
  
-**Diet**+====Physical Therapy====
  
-<box 25% round right |>​{{:​meal.png|}}<​/box|Figure 10: Illustration of the ideal food plate including all food groups from http://​www.arthritis.org/​images/​slideshows/​ra-diet/​ra-diet-13-fill-your-plate.jpg  +===Heat/Cold===
-+
-The first component of lifestyle modifications to treating obesity is undergoing dietary therapy (Figure 10). When assessing diet management in obese patients, weight reduction is highly dependent upon energy intake in comparison to energy expenditure <​sup>​[27]</​sup>​. ​+
  
-According to a study conducted by Poirier and Despres (2001), it has been concluded that approximately 1 pound of mass can be lost within a week without any changes being made to the level of physical activity <​sup>​[27]</​sup>​There are various types of diets that an individual can choose ​to pursue. Each type of diet is subjective to the patienttherefore ​it can produce differing resultsThree diets that are typically suggested to obese patients are the low carbohydrate dietthe low-fat diet and the high protein diet+Physical treatments are often combined with other forms of treatment ​to ensure maximal efforts ​of juvenile idiopathic arthritis managementThe application ​of heat to affected areas is soothingas it increases blood flow and alleviates muscle or joint stiffnessApplying a cold pack or a compress numbs nerve endings associated with swollen jointswhich reduces inflammation ​and swelling (AboutKidsHealth,​ 2017)
  
-The low carbohydrate diet is consists of a reduced carbohydrate consumption <​sup>​[28]<​/sup>. Long-term studies ​ have shown that low carbohydrate diets produce significant results at the 3 and 6 month points. However, results become insignificant at about a year onwards <​sup>​[29]</​sup>​. When examining the weight reduction that high protein diets produced, the results were indifferent <​sup>​[29]</​sup>​. Patients were losing a significant amount of weight up until about a year and then the results started to decrease <​sup>​[29]</​sup>​. Studies about the low-fat diet have shown that  patients saw a significant weight reduction for about three years and then results were insignificant <​sup>​[30]</​sup>​. ​+===Exercise/Stretches===
  
-Although all three of these diets show promising resultsthe low carbohydrate ​and high protein diets show short term effectswhile the low fat diet seems to display long term fat reductionIn conclusion, it is important ​to note that many individuals ​are susceptible to regaining their weight, thus a sustainable lifestyle is integral. Managing weight loss through dietary means can be difficult, however it can be made easier when incorporating ​physical activity ​into the daily routine.+Prior to exercisingstretching or massaging tender areas allows for muscles to loosen ​and minimizes additional stress on affected areas. An important aspect regarding exercise for young children with arthritis is that it is done at a moderate intensity on a regular basis. Building muscle strengthens the support for affected jointsand regular exercise maintains a child’s body mass so that the child does not need to endure additional weightIt is important that children ​are not over exhausted by physical activity, as this could increase ​the pain and soreness (AboutKidsHealth,​ 2017)
  
 +===Physiotherapy===
  
-**Weight Loss Programs**+Physiotherapy assists in reducing stiffness, thus enabling a consistent continuous recovery over a long period of time. In addition to heat and ice physiotherapy,​ transcutaneous electrical nerve stimulation is a type of physiotherapy that disrupts pain signals from being transmitted to the brain in a non-invasive manner. A small device containing electrodes is attached to the skin on either side of the painful area. Pain relief tends to increase with prolonged use. (AboutKidsHealth,​ 2017). ​
  
-Due to the vast technological advances of our time, there are many weight loss programs available that are highly accessible. Although there are a wide variety of programs to choose from, it is always encouraged to keep in mind that not every weight loss program will produce the same kinds of results for everyone. It is always important to consult with a family physician when trying to find a weight loss program that will have a positive effect on a personal weight reduction. ​+==== Occupational Therapy====
  
 +An occupational therapist assesses, treats and educates individuals and families affected by JIA. Their training focuses on assessing and treating fine motor skills, hand function and the application of hand splints (AboutKidsHealth,​ 2017). ​
  
-Some examples of weight loss programs that are available for further investigation are listed below: ​+===Assistive Devices=== ​
  
-__The Paleo Diet__: It works to incorporate whole foods, lean protein, veggies, fruits, nuts, and seeds and encourages ​to stay away from foods with sugarsdairy and grains.+Assistive devices provide support in completing many of the daily basic tasks. An individual who may have trouble holding a pencil when writing may use an angled writing surface ​to reduce the stress placed on his/her joints. Something as simple as replacing a notebook with a computer allows the individual ​to record the notes from class and complete a project at their own pace . A splint is another assistive device that can be customized to adhere ​with the mold of a child’s hand. This allows for a greater range of motion and reduced contracturesswelling stress ​and pain. In individuals with knee joint pain, splints can decrease flexion contractures (AboutKidsHealth,​ 2017)
  
-__The Vegan Diet:__ It is an ‘extreme’ vegetarian diet that works to eliminate dairy, eggs, and animal derived products, such as gelatin, honey, whey, and vitamin D3. 
  
-__The Low Carbohydrate Diet:__ It encourages individuals to eat an unlimited amount of protein and fat, while completely eliminating carbohydrates.+==== Drug Therapy ====
  
-__The Ultra Low-Fat Diet:__ It consists of a diet where 10% or less calories come from fat. This diet is almost entirely made up plant based food items, with a very limited intake of animal products.+=== Nonsteroidal anti-inflammatory drugs (NSAIDs) ===
  
-__The Zone Diet:__ This diet encourages participants to balance each meal with one third of protein, and two thirds ​of fruits ​and veggiesA small amount ​of fat that comes from natural ​and healthy sourcessuch as avocadoalmonds, or olive oil can also be consumed.+NSAIDs include common painkillers such as ibuprofen and naproxen. Other commonly used NSAIDs include ketaprofen, diclofenac, and piroxicam (Juvenile Idiopathic Arthritis, 2017). The NSAIDs are not used with the aim of preventing joint damage; they are rather used as a first line of treatment to manage pain and inflammation among children with JIANSAIDs work by interfering with prostaglandin synthesis through inhibition ​of the enzyme cyclooxygenase (COX), thus reducing swelling ​and pain (Kim2010). The most common side effects of NSAIDs are an upset stomach resulting in pain or nausea. Howeversome less common side effects include dizzinessheadaches, bruising ​or rash (Juvenile Idiopathic Arthritis, 2017)
  
-__Intermediate Fasting:__ This diet challenges its participants to fast during portions of the day, while restricting the calorie intake during the times you do choose to eat. This diet is most efficient when you aren’t overeating during the times where the fast has been broken.+=== 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 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 methotrexateleflunomide, 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).
-There are a few options when trying ​to reduce weight lossAll of the diets that are listed above prove to have a positive impact on weight reductionHowever every diet has its consequences. When the body is restricted from having certain kinds of foodsnutrientsminerals ​and vitamins are compromisedFor exampleif an individual were to go on the paleo diet, the restriction ​of whole grains ​and dairy prevents individuals from consuming certain vitamins. A family physician or a dietician would be able to provide ​the most representative diet plan for each individual <​sup>​[31]</​sup>​+
    
 +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.
  
  
 +===Biological Response Modifiers===
  
-**Physical Activity**+Biological medications can be used to treat individuals who are resistant to commonly used antirheumatic drugs. Proinflammatory cytokines involved in the pathogenesis of JIA are the main components of biologic drugs. Etanercept, infliximab, and adalimumab block anti-tumour necrosis factors (TNF-ɑ), thus reducing inflammation. Etanercept is administered through subcutaneous injections, and optimal dosage includes 0.4mg/kg twice a week or 0.8 mg/kg once a week. Infliximab and adalimumab are anti-TNF-α monoclonal antibodies that are administered through IV infusions and subcutaneous injections respectively. A concern with biologic drugs is immunosuppression,​ thus infections at the site of injection and respiratory tract develop. Furthermore,​ the reactivation of hepatitis B and tuberculosis are risks that individuals administered with anti-TNF-α agents endure (Ungar, et al., 2013). ​
  
-The second component of the lifestyle modifications approach to treating obesity is to be physically active. The purpose behind weight loss and management programs is to stop future weight gain, decrease body weight and permanently maintain a lower body weight <​sup>​[32]</​sup>​. Maintaining a physically active lifestyle is known to be key to a long term weight maintenance,​ because it increases the energy expenditure through caloric deficit <​sup>​[33]</​sup>​. When incorporating physical activity into a daily routine with hopes of maintaining the reduction of body weight, it is important to remember that different training modalities such as walking, cycling and swimming can have a different impact on different individuals <​sup>​[34]</​sup>​.  ​ 
  
-When involved in physical activity, many adaptive responses take place, which cause a more efficient system for oxygen transfer to muscle <​sup>​[32]</​sup>​. In addition, reduced adipose tissue mass representing an important mechanical advantage, allows better long-term work <​sup>​[32]</​sup>​. Physical training helps counteract the permissive and affluent environment that predisposes reduced-obese subjects to regain weight <​sup>​[32]</​sup>​. Many studies have recommended thirty to forty-five minutes of moderately intensive physical activity, to be done 3-5 times a week <​sup>​[35]</​sup>​. In particular, public health interventions have promoted walking as a physical activity, since it is safe, accessible and a low intense aerobic exercise that results in high fat loss <​sup>​[32]</​sup>​. Losing weight through physical activity can be very difficult, especially for obese patients and therefore, it is important to set realistic weight loss goals of about 0.5-1 pound per week, with the assistance <​sup>​[32]</​sup>​. Because it may seem like small steps are made in weight reduction while working out, it is important for patients to remain determined and persevere to reach their goals <​sup>​[32]</​sup>​. Keeping a positive attitude during this process can be very difficult and so, it is extremely important for the patient to have one-on-one interaction between the clinician or healthcare professional on a regular basis <​sup>​[32]</​sup>​.+=== 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 10 to understand the process of injecting corticosteroids into the affected joints (AboutKidsHealth,​ 2017). ​
  
-**Cognitive Behaviour Therapy**+{{:​surg1.png|}}
  
-<box 30% round right  |>{{:cbt.png}}</​box|Figure 11: The three main components ​of Cognitive Behaviour Therapy: thought, emotion and behaviour  +Figure 10This 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>
-from http://in8.uk.com/wp-content/uploads/2016/03/CBT-image.png>+
  
-The third component of lifestyle modifications is to undergo cognitive behaviour therapy (CBT) to assess one’s current habits and identify factors, stressors or situations that may trigger one’s overeating habits and contribute to their obesity (Figure 11). With a CBT approach, patients suffering from obesity can get help through counseling, support groups, as well as adopt the family-based approach <​sup>​[25,​26]</​sup>​. ​+==== Surgical Treatment ====
  
-The purpose ​of the CBT treatment ​is not to eliminate ​psychiatric disorder but to change eating ​and exercise behaviours <​sup>​[36]</​sup>​This intervention aims to educate individuals on how to change problematic behavioursFirstlyCBT is based on the cognitive conceptualization ​of the processes that lead to overeatingSpecificallythoughts ​and thinking patterns that are considered central ​to the problemSecondlyCBT is focused on altering ​the cognitive and behavioural mechanisms that maintain ​the problem behaviour. Lastly, ​CBT uses both cognitive and behavioural techniques to maintain healthy mechanisms <​sup>​[37]</​sup>​. The diagram here shows different components that contribute ​to CBT+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 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 motionAfter soft tissue release surgery casts are usually worn for several weeksfollowed 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 positionOther 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 removedSynovectomy is rarely used in JIA casesbut 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.
  
-Counselling is one way a patient can undergo CBT. It can either be delivered on a one-on-one basis, or in a group setting of approximately 10 participants with a trained healthcare professional <​sup>​[38,​39]</​sup>​. A study conducted by Renjilian and colleagues comparing the two treatment modalities concluded that participants who were randomized to receive group-based therapy lost more weight after 26 weekly sessions compared to those who were treated individually. Specifically,​ those receiving group therapy lost about 11 kg after 26 weekly sessions, in comparison to 9 kg for those who were individually treated <​sup>​[40]</​sup>​+{{:bone1.png|}}
  
-In addition to counselling,​ having a support network is important. This is  especially true if the individual is undergoing drastic changesReceiving encouragement ​from family, friends and health care practitioners can be very motivating during challenging times of the weight loss and maintenance programs. Furthermorepatients can also join support groups with other people undergoing weight loss <​sup>​[25]</​sup>​+Figure 11. This image shows the view before and after total knee replacementRetrieved ​from (Abdel & Figgie2014).
  
-Family-based obesity treatment has also been proven to be a very effective and sustainable approach, especially when treating pediatric obesity. The role of this treatment is to target eating and activity change in both child and parent. Programs using this approach teach parents behavioural skills to facilitate child behaviour change and utilize family resources to improve the efficacy of childhood obesity treatments. Simultaneously treating the child and parent helps create positive relationships between them as they both aim to reach their weight loss goal together <​sup>​[41,​42]</​sup>​. ​+==== Direction for Future Treatments ====
  
- +The majority ​of children are treated adequately ​with a combination ​of treatments ​such as NSAIDscorticosteroids ​and DMARDs available todayYet, there are still some children, who are intolerant ​or resistant ​to these therapieshence suffer from joint damageFor children ​who fall under this categoryautologous stem cell transplantation seems to be a potential option ​(Brinkman ​et al., 2007)Autologous stem cell transplantation ​is a procedure where person’s own stem cells to replace damaged cells (Autologous Transplants,n.d.). This method ​of treatment has only been tried on a few as thirty childrenFirstWulffraat et al., reported positive ​results ​of autologous stem cell transplantation ​in four children (Brinkman et al., 2007)
- +
-**Pharmacotherapy** +
- +
-The Canadian Clinical Practice Guidelines on the Management and Prevention ​of Obesity in Adults and Children recommends that in addition to lifestyle modifications such as dietary changes, physical activity and behaviour therapy, overweight ​ individuals ​with BMIs greater than 27 kg/m^2 but with life threatening diseases, or obese individuals with BMIs greater than 30 kg/m^2 can undergo pharmacotherapy <​sup>​[2]</​sup>​.  +
- +
-<box 35% round right |>​{{:​orlistat.jpg|}}</​box|Figure 12: Orlistat, one of the pharmacological ​treatments ​for obesity +
-from https://​www.medexpress.co.uk/​javax.faces.resource/​treatments/​335x335xorlistat-120mg-pills.jpg.xhtml,​qln=img.pagespeed.ic.3lJxOPoYEm.jpg>​ +
- +
-A meta analysis investigated 21 randomized control trials (RCT) that involved a total of 11 533 participants using either one of the two drugs: orlistat or sibutramine,​ or a placebo. These RCTs had a follow-up period of at least 1 year in obese and overweight adults.  +
- +
- +
-Olistat functions ​as a gastrointestinal lipase inhibitor and reduces fat absorption by approximately 30% (Figure 12). Patients can use it for up to two years <​sup>​[43]</​sup>​. On the other handsibutramine functions as a serotonin ​and noradrenaline reuptake inhibitor which induces weight loss through enhanced satiety and increased basal energy expenditureSibutramine is approved for clinical use for up to 1 year <​sup>​[44]</​sup>​.  +
- +
-Pharmacotherapy trials comparing the effect of combined dietary and pharmacotherapy treatment to dietary treatment aloneshowed that patients ​who received treatment underwent a greater weight loss compared to those who only had a reduced-energy diet. This was when orlistat ​or sibutramine was combined with a reduced-energy diet. More specifically,​ the long term weight loss for those receiving combined therapy of dietary and pharmacotherapy was about 6 to 7 kgcompared to about 2 to 3 kg for those who received dietary therapy only <​sup>​[26]</​sup>​ +
- +
- +
- +
- +
-**Maintenance of weight loss** +
- +
-  +
-Studies that assessed orlistat therapy for at least 2 years and up to 5 years showed that weight loss attained by year 1 was better maintained over the subsequent 3 years in patients ​who received ongoing drug therapy. SpecificallyDavidson et al. showed that patients who had ongoing treatment of orlistat for 2 years were associated with less regain of weight loss (32%) compared with diet only therapy (63%) <​sup>​[45]</​sup>​.  +
- +
-In addition, a 2-year study conducted by James et al., showed that 43% of patients who received 6 months of weight loss induction using diet-only therapy, followed by sibutramine-diet therapy had better maintained 80% or more of weight loss, compared to only 16% in the diet-only group who received diet-placebo therapy <​sup>​[46]</​sup>​. This shows that combined therapy is more effective than diet-only group.  +
- +
- +
-**Bariatric Surgery** +
- +
-<box 30% round right |>​{{:​surgical_procedures.png|}}</​box|Figure 13:  Four highly used surgical procedures used to treating obesity from http://​www.cmaj.ca/​content/​suppl/​2007/09/04/176.8.S1.DC1/​obesity-lau-onlineNEW.pdf>​ +
- +
-Bariatric surgery ​is a treatment method that is considered for adult patients who have BMI over 35kg/m^2 with severe comorbid diseases such as life-threatening cardiopulmonary problems, severe sleep apnea, or severe diabetes mellitus, or for those in the severely obese category with a BMI greater than 40 kg/m2. For teenagers, the Canadian Clinical Practice Guidelines on the Management and Prevention of Obesity in Adults and Children recommends that bariatric surgery be limited ​to an appropriately trained and experienced surgical team. After 6 months of using lifestyle modificationshealthcare practitioners assess the health of the patient and evaluate whether a satisfactory progress of weight loss or goal of 10% of body weight has been reachedIn the case that satisfactory progress or goal has not been achieved, physicians will consider the eligibility of patients to undergo bariatric surgeryThis is only considered if other nonsurgical weight loss attempts have failed. The goal of bariatric surgery is to relieve a patient suffering from obesity from his or her morbid body weight, improve their comorbidity and improve their quality of life. There are different surgical procedures (Figure 13). It is important to note that this treatment option requires lifelong medical surveillance <​sup>​[26]</​sup>​.  +
- +
-A study on obese Swedish patients investigated the conventional,​ nonsurgical management with surgery for morbid obesity in 2004 found that surgical management is more efficacious than medical management. Patients who received surgical treatment produced greater weight loss, improved lifestyle and dramatic improvement of comorbid disease. At 10 years of follow-up, the surgical cohort showed that they maintained a weight loss greater than 16.1% of their original body weight. In contrast, those who received the conventional,​ nonsurgical management had a weight gain of 1.6%. This 16.3% weight difference demonstrates the effectiveness and maintenance of surgical procedures <​sup>​[47]</​sup>​.  +
- +
-**Summary of Treatment Options** +
- +
-As seen in figure 14, there are different approaches to treating obesity. First, it is important to set a weight loss goal to reduce body weight by approximately 10% from baseline during the first six months ​of treatment. Healthcare practitioners typically recommend their patients to first undergo lifestyle modifications:​ proper nutrition, physical fitness, and cognitive behaviour therapy. After six months of treatment, healthcare practitioners will assess the patient’s progress and determine whether satisfactory progress or weight loss goal has been reached. In the case that it has been reached, the patient would be closely monitored ​on a regular basis to make sure that their weight is maintainedIn the event that satisfactory progress is not attainedphysicians will assess the patient’s eligibility to either undergo pharmacotherapy or bariatric surgeryPhysicians typically opt for bariatric treatment in the event that nonsurgical treatments have failed. It is important to note that best weight loss and maintenance ​results ​are achieved when pharmacotherapy or bariatric treatment is used in conjunction with lifestyle modifications +
- +
-{{:​flowchart_final.png|}} +
- +
- +
-Figure 14: A holistic approach to treating obesity.+
  
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