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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/JRA are chronic, thus individuals must develop coping methods that are long lasting and effective. | + | 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). |
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| - | <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 ==== | ||
| - | Oligoarticular juvenile idiopathic arthritis refers primarily to the inflammation of joints. Th is form of arthritis is prevalent in four or fewer joints in the first six months from when the disease was diagnosed. Depending on the onset of the condition, this form of arthritis can be divided into two subtypes. If the arthritis has not spread to more than four joints after six months, it is considered to be persistent oligoarthritis. If more than four joints are affected, it is classified as extended oligoarthritis (Genetics Home Reference, 2015). | + | Oligoarticular juvenile idiopathic arthritis refers primarily to the inflammation of joints. This form of arthritis is prevalent in four or fewer joints in the first six months from when the disease was diagnosed. Depending on the onset of the condition, this form of arthritis can be divided into two subtypes. If the arthritis has not spread to more than four joints after six months, it is considered to be persistent oligoarthritis. If more than four joints are affected, it is classified as extended oligoarthritis (Genetics Home Reference, 2015). |
| ==== Rheumatoid Factor Positive Polyarticular JIA ==== | ==== Rheumatoid Factor Positive Polyarticular JIA ==== | ||
| When inflammation is present in five or more joints within the first six months of the disease, it is considered rheumatoid factor positive polyarticular JIA. Patients with this condition have a positive blood test for proteins called rheumatoid factors. A rheumatoid factor is the amount of protein found in the blood that may attack healthy tissues in the human body. This type of JIA displays symptoms similar to the predominant types of arthritis in adults (Genetics Home Reference, 2015). | When inflammation is present in five or more joints within the first six months of the disease, it is considered rheumatoid factor positive polyarticular JIA. Patients with this condition have a positive blood test for proteins called rheumatoid factors. A rheumatoid factor is the amount of protein found in the blood that may attack healthy tissues in the human body. This type of JIA displays symptoms similar to the predominant types of arthritis in adults (Genetics Home Reference, 2015). | ||
| - | |||
| ==== Rheumatoid Factor Negative Polyarticular JIA ==== | ==== Rheumatoid Factor Negative Polyarticular JIA ==== | ||
| - | This type of arthritis is similar to the rheumatoid factor positive polyarticular juvenile idiopathic arthritis as it also affects five or more joints. As evident in its name, this type of JIA tests negative for the rheumatoid factor in the blood (Genetics Home Reference, 2015). | + | This type of arthritis is similar to the rheumatoid factor positive polyarticular JIA as it also affects five or more joints. As evident in its name, it tests negative for the rheumatoid factor in the blood (Genetics Home Reference, 2015). |
| ==== Psoriatic JIA ==== | ==== Psoriatic JIA ==== | ||
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| ==== Undifferentiated Arthritis ==== | ==== Undifferentiated Arthritis ==== | ||
| - | This classification of 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 ===== | ||
| - | The incidence of JRA in North America and Europe is researched to be 4 to 16 in 10,000 children (Genetics Home Reference, 2015). One in 1,000, or approximately 294,000, children in the United States are affected and the most common type of JRA in the United States is oligoarticular juvenile idiopathic arthritis (Genetics Home Reference, 2015). Females (for an unknown reasons) seem to be affected with JRA somewhat more frequently than males (Genetics Home Reference, 2015). However, in enthesitis-related JRA males are affected more often than females (Genetics Home Reference, 2015). The incidence of JRA varies from different populations and ethnic groups (Genetics Home Reference, 2015). | + | ===== Symptoms & Diagnosis ===== |
| - | <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> | + | |
| - | This is particularly true for women, who have consistently shown a higher increase in obesity compared to men. This trend is observed in developing and developed countries alike.The rate of increase of obesity appears to have been greatest between 1992 and 2002, but has slowed down over the last decade, particularly in developed countries. | + | 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. |
| - | At all ages, prevalence is higher in developed countries (Figure 2). In these countries, men over the age of 15 exhibit higher rates of overweight and obesity than women. In developing countries, women have higher rates than men above age 25. Overweight and obesity peak in developed country men around age 55 years, with 1 in 4 obese. For developed country women, the peak age is closer to 60 years with 31.3% obese.<sup>[1]</sup> | + | ==== Flares ==== |
| - | In 2008, the highest rates of obesity in women were observed, in descending order of severity, in Southern Africa, North Africa and the Middle East, Central Latin America, North America (US and Canada) and Southern Latin America. In men, the top 5 regions were North America (US and Canada), Southern Latin America, Australasia, Central Europe and Central Latin America. Many of these regions consist of low or middle income countries.<sup>[2]</sup> | + | 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). |
| - | The epidemiology of obesity used to be difficult to study because many countries had their own criteria for the classification of obesity. During the 1990s, however, the BMI became a universally accepted measure of body fat, and identical cutoff points are generally recommended. <sup>[2]</sup> | + | ==== Fever ==== |
| - | + | ||
| - | ===== Diagnosis ===== | + | 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).” |
| - | <box 50% round right |>{{:bmi_classification_final.png}}</box|Figure 3: WHO standardized BMI categories in adults (Seidell & Halberstadt, 2015)> | + | ==== Morning Stiffness ==== |
| - | Body Mass Index (BMI) is an index of weight-for-height that is commonly used to classify weight in adults (Figure 3).The BMI was created to estimate the individual’s level of body fat and therefore assesses an individual’s risk of disease. | + | 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). |
| - | BMI is measured standardly as weight in kilograms divided by the square of the height in meters (Figure 4). The values of the BMI are age and sex dependent as body composition varies between sexes and at different ages. The values are then assessed by looking at a BMI table or chart.<sup>[3]</sup> | + | ==== Rheumatoid Rash ==== |
| + | 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 ==== | ||
| - | {{:bmi_formula.png|}} | + | 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). |
| - | Figure 4: BMI Calculation Equation | + | ==== Uveitis Eye condition ==== |
| - | from http://www.heartnewslinks.com/editors-blog/body-mass-index-bmi-bad | + | |
| + | 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). | ||
| - | ==== BMI in children ==== | + | ==== Blood Tests for JIA ==== |
| - | Obesity is defined differently for children and teens compared to adults due to the fact that they are still growing (Figure 5). BMIs for this cohort compare their height and weight against growth charts that take age and sex into account, since males and females in this cohort usually mature at different rates. | + | Rheumatoid factor (RF) is a protein that is produced in the blood in some forms of arthritis (SickKids, 2012). This is more common in adults with rheumatoid arthritis, however, it is found in 5% of children with JIR (SickKids, 2012). The RF test is a test that is used to detect and measure levels of a specific antibody directed against the blood component immunoglobulin (Arthritis Foundation, 2016). |
| - | Their BMI is referred to as BMI-for-age percentile, meaning the child’s BMI is compared with other children of the same sex and age who participated in national surveys that were conducted from 1963-65 to 1988-94.<sup>[4]</sup> | + | Liver function test (LFT) is a test that determines if the liver is healthy and working normally (Arthritis Foundation, 2016). There are many medications that are used to treat arthritis such as, methotrexate that are metabolized in the liver (Arthritis Foundation, 2016). These medications may play a role in overburdening the liver and therefore doctors may order an LFT in order to determine the medication that is causing the damage (Arthritis Foundation, 2016). |
| + | Antinuclear antibody (ANA) is a test used to look at autoantibodies in the blood (SickKids, 2012). Autoantibodies are proteins in the immune system and is also a good indicator to whether children and teenagers with JIA have an increased risk of eye disease (SickKids, 2012). | ||
| - | {{:weight_status_category.png|}} | + | 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). |
| - | Figure 5: BMI-for-Age Percentile Ranges for Children | + | ===== Causes and Risk Factors ===== |
| - | from https://www.cdc.gov/healthyweight/assessing/bmi/childrens_bmi/about_childrens_bmi.html> | + | |
| + | 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 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). | ||
| - | ==== BMI Limitations ==== | + | {{:causes_and_risk.png|{{:weight_status_category.png|}} |
| - | === Variance in Asian Populations === | + | Figure 3.This image is illustrating where rheumatoid arthritis is present on a hand. Retrieved from: https://www.epainassist.com/images/Juvenile-Arthritis.jpg |
| - | There were some debates on whether there is a need for developing different BMI cut-offs for different ethnic groups due to increasing evidence that the associations between BMI, percentage of body fat, and body fat distribution differ across populations and therefore, the health risks increase below the cut-off point of 25 kg/m^2 that defines overweight in the current WHO classification. The WHO Expert Consultation study concluded that the proportion of Asian people with a high risk of type 2 diabetes and cardiovascular disease is substantial at BMI's lower than the existing WHO cut-off point for overweight, but the cut-off point for observed risk varies in different Asian populations and for high risk. Therefore they concluded that the current WHO BMI cut-off points should be retained as the international classification.<sup>[2]</sup> | + | ===== Epidemiology ===== |
| - | However, overtime, the BMI (weight/height) became a universally accepted measure of the degree of overweight, and now, identical cutoffs are recommended.<sup>[2]</sup> | + | <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 States. Retrieved from: https://rheumatoidarthritis.net/wp-content/uploads/2013/07/prevalence_arthritis.png> | ||
| - | === BMI in Athletes === | + | 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). |
| - | Although the BMI is a good gauge of an individual’s level of fat it is problematic in the case of individuals with higher bone and/or muscle mass. Athletes and individuals with jobs that require physical fitness are often wrongly categorized as overweight due to the their muscle mass.<sup>[5]</sup> | + | 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). |
| - | ===== Causes and Risk Factors ===== | + | ===== Pathophysiology ===== |
| - | Obesity does not always have a particular cause and effect. There are a plethora of factors that can be associated with obesity and impact the way an individual’s body reacts. The following are: | + | ==== Genetic Susceptibility ==== |
| + | 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). | ||
| - | **Energy is Unbalanced** | ||
| - | An absence of energy balance is often considered to be the major cause of obesity. Energy balance means that the energy going in, in the terms of calories, equals the individual’s energy out, such as energy that the body uses for things like breathing, digesting, and being physically active. To maintain a healthy weight, the energy needs to be roughly balanced over time <sup>[6]</sup>. | + | ==== HLA and non-HLA Polymorphisms ==== |
| - | **Lack of Active Lifestyle** | + | 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). |
| - | Generally, developed nations’ citizens are not very physically active. Individuals rely on cars instead of walking, encounter fewer physical tasks at work, or remain at home because of modern technology and conveniences. People who are inactive are more likely to gain weight because they do not burn the calories that they take in from food and drinks. An inactive lifestyle also raises the risk for heart disease, high blood pressure, diabetes, and other diseases <sup>[7]</sup>. | + | {{:p1b.png|}} |
| - | **Environment** | + | Figure 4 shows several associations between JIA subtypes and different HLA alleles. Retrieved from (Prahalad and Glass, 2008) |
| - | Sometimes the environment inhibits healthy lifestyle habits and encourages obesity. Some reasons include: lack of neighbourhood sidewalks and safe places for recreation, work schedules are time consuming, oversized food portions, lack of access to healthy foods, and food advertising focused on high-calorie, high-fat snacks and sugary drinks <sup>[8]</sup>. | + | 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). |
| - | <box 45% round right |>{{:obesity_factors.png|}}</box|Figure 6: Factors Associated with Obesity> | + | {{:p2b.png|}} |
| - | **Genes and Family History** | + | Figure 5 shows non-HLA genetic genes associated with JIA that have been independently confirmed. Retrieved from (Prahalad and Glass, 2008) |
| - | Obesity tends to run in families. The chances of being overweight or obese are greater if 1 or both of the individual’s parents are overweight or obese. Genes also may influence the amount and location of excess fat one stores in their body. Since families usually share food and physical activity habits, there is a link between genes and the environment <sup>[9]</sup>. | + | ==== Twin Studies ==== |
| - | **Health Conditions** | + | Family studies have provided strong evidence for genetic factors contributing to the susceptibility to JIA. For instance, twin and affected sibling pair (ASP) studies have supported the role for genetic susceptibility to JIA. Specifically, they have shown that monozygotic twin concordance rates for JIA vary between 25 to 40%, a stark contrast to the population prevalence of 1 in 1000 of having the disease (Ansell et al., 1969; Baum and Fink, 1968; Savolainen et al., 2000). |
| - | Hormone problems may also cause an individual to become overweight and obese. This includes illnesses such: | + | In the largest twin study from the JIA ASP registry conducted by Prahalad and colleagues in 2000, 14 pairs of twins concordant for JIA registered in the National Institute for Arthritis and Musculoskeletal and Skin Diseases were analyzed. Of these 14 pairs of monozygotic twins, 12 were concordant for presence or absence of anti-nuclear antibodies. Prahalad and colleagues found that the first twins to develop JIA did so with an average of 5.5 months before the second twins. This was statistically significant and different compared to the 104 non-twin affected siblings pairs in the registry, who showed a 37 month difference in age at onset between the first and second sibling (Prahalad et al., 2000). Together, these studies solidify evidence for genetic factors in the susceptibility to JIA. |
| - | __Hypothyroidism:__ A condition in which the thyroid gland does not make enough thyroid hormone. The lack of thyroid hormone slows down the metabolism and causes weight gain <sup>[10]</sup>. | ||
| - | __Cushing's syndrome:__ A condition affecting the body's adrenal glands. The glands make too much of the hormone cortisol which alters nutrient intake. Cushing's syndrome also can develop if a person takes high doses of certain medicines for a long time. Patients have upper-body obesity and fat around the neck with thin extremities <sup>[10]</sup>. | + | ==== Genetic Variables Underlying Autoimmunity ==== |
| - | __Polycystic Ovarian Syndrome (PCOS):__ A condition that affects about 7% of women of childbearing age. These women often are obese, have excess hair growth, and have reproductive issues along with and other health issues. These problems are caused by high levels of hormones called androgens <sup>[10]</sup>. | + | 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). |
| - | **Medicines** | + | {{:p3.png|}} |
| - | Certain medicines may cause gain weight. These medicines include specific corticosteroids, antidepressants, and seizure medicines. These pharmaceuticals can slow the rate at which the body burns calories, increases appetite, or causes the body to retain water <sup>[11]</sup>. | + | Figure 6 shows different examples of genes associated with multiple autoimmune diseases. Retrieved from (Prahalad and Glass, 2008) |
| + | ==== Environmental Factors ==== | ||
| - | **Emotional Factors** | + | The cause of JIA is assumed to be multifactorial, as in the case of most human autoimmune diseases. Unlike JIA, a healthy immune system consists of effector and regulatory mechanisms which are kept in balance. Therefore, the innate and adaptive immune systems closely interact. A genetically susceptible individual might develop a deleterious and uncontrolled response towards a self-antigen on exposure to an unknown environmental trigger. In JIA, it can lead to a self-perpetuating loop of activation of both innate and adaptive immunity, causing tissue damage (Prakhen, Albani, Martini, 2011). |
| - | Some people eat more than usual when they are bored, angry, or stressed. Over time, overeating will lead to weight gain and may cause overweight or obesity <sup>[7]</sup>. | ||
| - | **Smoking** | + | ==== Stress and Physiological Factors==== |
| - | It is not uncommon to see people gain weight when they stop smoking. Nicotine raises the rate at which the body burns calories, therefore less calories are burned when one ceases from smoking <sup>[12]</sup>. | + | The influence of stressful life events and psychological factors before the onset of JIA as a disease trigger has been studied. In a study by Henoch and colleagues which compared 88 children with JIA to 2952 geographically matched controls, results showed that children whose parents were unmarried due to divorce, separation, or death comprised 28.4% of the JIA population, compared to 10.6% in controls (Henoch, Batson, Baum, 1978). |
| - | **Age** | + | Stress was also suggested as a contributing factor to the disease. It is a known stimulator to the sympathetic nervous system (SNS) and thus increases the production of interleukin 6, which is one of the most important inflammatory cytokines in JIA (Roupe et al., 2000). |
| - | As we age, muscle is lost, especially if one is less active. Muscle loss can slow down the rate at which the body burns calories. Midlife weight gain in women is mainly due to aging and lifestyle, but menopause also plays a role. Many women gain about 5 pounds during menopause and have more fat around the waist than before <sup>[13]</sup>. | + | Although psychological factors and stress may play a role for the onset of JIA, more research needs to be conducted since past studies have had several methodological shortcomings (Berkun, Padeh, 2010). |
| - | **Pregnancy** | + | ==== Smoking ==== |
| - | Women gain weight to support their child’s development. After giving birth, some women find it hard to lose the weight. This may lead to overweight or obesity, especially after a few pregnancies <sup>[14]</sup>. | + | Smoking is the strongest known environmental risk factor for developing rheumatoid arthritis (RA) in adults. The risk of RA from smoking has been showed by the number of shared epitope copies, which suggest gene-environment interaction. Specifically, the strongest known genetic risk factor for RA is a specific sequence of amino acids on HLA-DRB1 allele. In addition, the risk of developing RA from gene-environment interactions increases with the intensity of smoking (Liao et al., 2009). |
| + | All this suggests that smoke is a stimulator of the immune system and that the exposure to tobacco products during fetal life may influence the developing immune system of the fetus. This can lead to an increased susceptibility to infectious agents and thereafter, trigger arthritis as well as subsequent autoimmune diseases. Jaakkola and Gissler conducted a study assessing the relation between maternal smoking in pregnancy and the risk of inflammatory polyarthropathies, in particular JIA in the first years of life. 58 841 newborn Finnish children until the age of 7 were analyzed. Findings showed that there was a 2-fold higher rate of polyarthropathies during the first 7 years of life in children of smoking mothers, compared to non-smoking ones. In addition, the maternal smoking effect was found prevalent to girls, who experienced 6-fold greater likelihood for JIA compared to unexposed boys (Jaakkola and Gissler, 2005). | ||
| - | **Lack of Sleep** | + | ==== Infectious Agents and JIA ==== |
| - | Lack of sleep increases the risk of obesity. People who sleep fewer hours also seem to prefer eating foods that are higher in calories and carbohydrates, which can lead to overeating, weight gain, and obesity. Additionally, sleep helps maintain a healthy balance of the hormones that make you feel hungry or full. Sleep also affects how the body reacts to insulin, the hormone that controls your blood glucose level. Lack of sleep results in a higher than normal blood sugar level, which may increase the risk for diabetes <sup>[15]</sup>. | + | Infectious agents are believed to be important environmental factors in the development of autoimmunity. An infectious agent may induce a cross-reactive immune response, thereby leading to inflammation provoked by antigen-presenting cells (APCs). This can lead to increased immunogenicity, priming of T cells and subsequent autoimmunity (Berkun and Padeh, 2009). A study by Carlens and colleagues showed that infections during the first year of life and factors related to size and timing of birth were associated with increased risk of developing JIA (Carlens et al., 2009) . However, more research needs to be conducted to understand the role of environmental factors on JIA. |
| - | ===== Pathophysiology ===== | + | ==== Immunology of JIA ==== |
| - | ==== Adipocyte Development and Metabolism ==== | + | The overarching mechanism in all Juvenile Idiopathic Arthritis (JIA) subsets is the activation of the immune system. Different components are involved in each subtype and additional variation may exist within subtypes (Malmström, Catrina & Klareskog, 2016). Over the years, there has been considerable progress in understanding the immune-inflammatory reaction. |
| - | Obesity can be characterized by the excessive accumulation of adipocyte cells forming deposits of adipose tissue. Individuals with a healthy metabolic activity and a normal BMI undergo the process of lipolysis, which is the breakdown of lipids. Lipolysis is regulated in the process of 𝜷₁ and 𝜷₂ adrenergic receptors (ARs) signalling cyclic adenosine monophosphate (cAMP) dependent protein kinase to initiate the phosphorylation of perilipin and hormone-sensitive lipase. Adipocytes express elevated levels of α₂ adrenergic receptors, which inhibit the expression of cAMP, thus preventing lipolysis. Furthermore, reduced lipolytic regulation is evident in hypertrophic subcutaneous fat cells, as they contain more α₂ ARs in comparison to 𝜷₁ and 𝜷₂ ARs. Defects or polymorphisms in the 𝜷₂ AR gene may also impede in the process of lipid breakdown <sup>[16]</sup>. | + | ===Auto-Immunity=== |
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| - | In events of inadequate caloric intake, adipocytes allow excess energy to be stored as triacylglycerol. Non-esterified fatty acids (NEFAs) are primarily involved in insulin signalling, however they are also released when triacylglycerol stores undergo lipolysis. While triacylglycerol synthesis and lipolysis occur in a balanced manner under normal conditions, NEFAs are increased in obese individuals, thus posing a risk for Type 2 diabetes <sup>[16]</sup>. | + | Much of the scientific community believe the disease is initiated as a result of molecular mimicry between epitopes on antigens present on infectious agents and autoantigens. Molecular mimicry, by epitope spreading, overcomes tolerance mechanisms and results in autoimmunity. Over the years, two major subtypes of JIA have been identified on the basis of the presence or absence of auto-antigens: antibodies to citrullinated protein antigens (ACPAs) and rheumatoid factor (RF) (Malmström, Catrina & Klareskog, 2016). |
| + | Both subsets have different disease courses. The seropositive form usually means severe pathology. The seronegative forms of arthritis are not well understood and appear to be more heterogeneous compared to the seropositive variant (Malmström, Catrina & Klareskog, 2016). | ||
| - | The secretory activity of adipocytes plays a huge role in regards to hormonal and metabolic activity that takes place. Adipose cells are increased in size and number in obese conditions, which initiate an immune response. The fat cells release pro-inflammatory adipokines that recruit macrophages to the site. Following this, Tumour Necrosis Factor- alpha (TNF-α) is released and additional immune cells are brought to the site. This constant state of inflammation causes insulin resistance. This is why diabetes is often comorbid with obesity <sup>[17]</sup>. This sequence of events is depicted in Figure 7. | + | **Antibodies to Citrullinated Protein Antigens (ACPA)** |
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| - | <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> | + | |
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| - | When analyzing other inflammatory factors, it is evident that increased concentrations of the adipokine Interleukin-6 (IL-6) are positively correlated with increased fat mass and BMI. Furthermore, IL-6 is increases post-exercise with increased NEFAs, thus proposing a correlation between the adipokine and lipid mobilization <sup>[16]</sup>.Monophosphate activated protein kinase (AMPK) enables the oxidation of fatty acids during muscle contraction. AMPK is regulated by the hormone adiponectin, which induces insulin-sensitivity. In individuals who are obese, the concentration of adiponectin is reduced, as individuals with symptoms of diabetes are resistant to insulin <sup>[16]</sup>. | + | |
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| - | ==== Hormone Regulation ==== | + | |
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| - | The hormonal regulation of insulin, leptin and ghrelin is affected in obese individuals. Hormonal imbalances cause physiological changes that impede on appetite suppression and insulin sensitivity. Figure 8 shows human hormones and food intake. | + | |
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| - | **Insulin** | + | |
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| - | Insulin is a hormone secreted by the 𝜷 cells in the pancreas <sup>[18]</sup>. | + | |
| - | They regulate glucose levels by storing glucose into muscle, fat, and liver cells. In obese individuals, we see a high incidence of insulin resistance, therefore insulin is unable to regulate glucose levels. Under normal physiological conditions, food is broken down into glucose post-consumption, and the pancreas secretes appropriate levels of insulin to maintain homeostatic levels of plasma glucose. Due to the fact that insulin displays insensitivity in obese individuals, the glucose absorbance is very low. Since the cells do not have energy, appetite-suppression is hindered and overeating occurs. The detrimental effects of this include an excessive blood glucose and insulin release, thus making obese individuals more susceptible to Type 2 diabetes. <sup>[18]</sup>. | + | |
| - | Investigating the molecular mechanism underlying insulin resistance is important towards understanding the relationship between insulin and obesity. There are many mechanisms through which insulin is able to promote the accumulation of fat in adipocytes, such as the early differentiation of preadipocytes to mature adipocytes, the unregulated transportation of glucose, the upregulation of lipogenesis, and the downregulation of lipolysis<sup>[19]</sup>. | + | 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.> | ||
| - | **Leptin** | + | **Rheumatoid Factor (RF)** |
| - | Leptin is an appetite-suppressing peptide hormone that is secreted by adipocytes<sup>[20]</sup>. In obese individuals, there is a greater mass of adipose tissue, which directly correlates with a greater secretion of leptin. Theoretically, when there is more leptin, individuals should consume less, because the hormone is appetite suppressing. However, there is a higher appetite-stimulating effect in obese individuals. This suggests that individuals who are obese display leptin resistance. | + | RF is an autoantibody derived from IgM that targets the Fc portion of IgG, specifically IgG1 to form immune complexes. These complexes are present in the synovial fluid along with IgG-producing B cells. Additionally, it can form complexes with complement proteins further promoting inflammation. Although RF has been associated with the pathogenesis of RA, it is possible for patients to develop arthritis without it (McInnes & Schett, 2011). |
| - | A study conducted by Kazmi et al.(1996) investigated leptin concentrations in a sample of a Rawalpindi population. There were three sampling groups—health obese, overweight and non-obese. According to the results, the mean serum leptin concentration for the obese group was 52.8 ug/mL and 6.3 ug/mL for the non-obese group. The results of this study concluded there is certainly a positive correlation between the Body Mass Index and leptin concentrations in individuals <sup>[21]</sup>. | + | Interestingly, the literature suggests that RA-associated antibodies are present in the blood several years before joint inflammation signs are present. It is possible that anti-citrullination precedes the onset of joint inflammation which may be triggered in the lungs or other mucosal regions (Malmström, Catrina & Klareskog, 2016). |
| - | <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> | + | ===Inflammation=== |
| - | **Ghrelin** | + | JIA is considered a T-cell mediated disease in which CD4+ T cells exacerbate inflammation in rheumatoid joints. Majority of the CD4+ T cells in joints appear to be of the Th1 type, with memory and activation markers. T cells in joints increase in number by recruitment, resistance to apoptosis and accumulation. For this process, cytokines are of importance. |
| - | Ghrelin is an appetite-stimulating hormone secreted primarily by the stomach during times of low caloric intake <sup>[20]</sup>. It signals individuals to increase their food intake and promote fat storage. The concentration of ghrelin is expected to be higher with obesity, because it would account for the increased food intake in cases of obesity. However, experimental evidence shows that Ghrelin concentrations are actually much lower in obese individuals. To investigate the role of ghrelin in obese pathology, Tschop et al. (2001) conducted a study where the plasma ghrelin concentrations of lean and obese individuals were measured. The plasma ghrelin concentrations of obese individuals were much lower than in lean individuals <sup>[22]</sup>. There seemed to be a negative correlation between plasma ghrelin concentrations and fat mass. | + | 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). |
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| - | The body’s instinctive shift for homeostasis could account for the downregulation of plasma ghrelin in obese individuals. Since ghrelin and leptin display antagonistic properties, it would not be possible for there to be high concentrations of both hormones. High leptin concentrations could account for low concentrations of ghrelin <sup>[20]</sup>. The exact mechanism through which this happens is yet to be elucidated by research. | + | |
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| - | ==== Genetic Predisposition ==== | + | |
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| - | When assessing the heritability of obesity, it has a numerical association of 0.7, which is fairly high relative to heritability in schizophrenia (0.81) and autism (0.9). In the case of rare familial obesity, gene defects occur in appetite regulation. Variants in the leptin-melanocortin pathway result in about 5% of morbid human obesity. Common polygenic obesity is characterized by the human obesity gene map. When performing a closer analysis of some of the key factors involved in obesity, Pre-B cell colony enhancing factor (PBEF1), which is secreted by lymphocytes, is expressed by adipocytes. Presently, it is referred to as Visfatin <sup>[23]</sup>. | + | |
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| - | Due to the interconnectedness of genes, it can be difficult to address conflicting effects of similar genetic factors. Ghrelin binds to the growth hormone secretagogue receptor (GHSR), and initially, variants of GHSR were evident in common obesity and rare familial obesity. More recent studies show a negative correlation between GHSR variants and obesity. It is hypothesized that these effects could be due to obestatin, which is a hormone that regulates appetite in the opposite way that ghrelin does <sup>[23]</sup>. | + | |
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| - | Having the ability to detect the genetic basis for obesity provides therapeutic solutions that can combat symptoms of obesity. A variety of biomarkers have been identified as factors involved in obesity. These biomarkers are used to differentiate between types of obesity, provide insight on the associated comorbid diseases, genetic susceptibility and explain the implications of the interaction between two or more factors <sup>[23]</sup>. | + | |
| + | <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> | ||
| - | Areas of research pertaining to molecular genetics are expanding the scope of genetic predispositions involved in obesity. As of October 2005, 244 mutated genes or transgenes causing phenotypic changes in weight and adiposity are identified. The human obesity gene map indicates that 176 human obesity cases can be linked to 11 specific genes, and 50 loci pertaining to human obesity are linked to Mendelian syndromes <sup>[24]</sup> | + | 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). |
| + | Furthermore, these cytokines in combination with the cytokines monocyte colony stimulating factor (M-CSF) and receptor activator of NF-κβ ligand (RANKL), activate osteoclasts leading to bone damage. TNFα regulates production of IL-1 and together these two cytokines induce rheumatoid inflammation and damage (Nath Maini, 2010). | ||
| - | The gene map (Figure 9), includes all obesity-related genes and quantitative trait loci identified from the various lines of evidence reviewed in the paper. It is further explained and categorized into the 5 categories, where information pertaining to the mouse chromosome, mouse gene, human chromosome, human homolog, statistical analyses of variance, gene description, details pertaining to its role in obesity and more is provided. Areas of research pertaining to molecular genetics are expanding the scope of genetic predispositions involved in obesity <sup>[24]</sup>. | + | 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). |
| + | ===Bone Destruction=== | ||
| - | {{:genetics.gif}} | + | Osteoclasts, cells that line the bone and are responsible for the breakdown of bone tissue, have an important role in ACPA-dependent pathology. ACPAs generated from B cells found in the synovial fluid of patients with RA are able to promote osteoclastogenesis and bone resorption. The effects of these antibodies are mediated both by direct recognition and activation of Fc receptors on osteoclasts. Antibodies can exert a specific function on osteoclasts at the earliest stages of disease development and before joint inflammation appears (McInnes & Schett, 2011). |
| + | 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). | ||
| - | 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 | ||
| ===== 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 disease. While pharmacologic treatments do not cure the disease, specific types of physical therapy, drug therapy and surgical procedures aim to sustain the child’s physical and psychological integrity and minimizing side effects. In effect, a combination of the following types of intervention are most beneficial, however the process of recovery varies with the individual’s risk for disease progression (Ravelli & Martini, 2007). |
| - | 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 control, blood 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 osteoarthritis. If weight loss is maintained over a long period of time, adverse clinical outcomes, such as myocardial infarction, stroke and cardiovascular-related deaths, can be reduced <sup>[26]</sup>. | + | ====Physical Therapy==== |
| + | ===Heat/Cold=== | ||
| - | **Intervention** | + | Physical treatments are often combined with other forms of treatment to ensure maximal efforts of juvenile idiopathic arthritis management. The application of heat to affected areas is soothing, as it increases blood flow and alleviates muscle or joint stiffness. Applying a cold pack or a compress numbs nerve endings associated with swollen joints, which reduces inflammation and swelling (AboutKidsHealth, 2017). |
| - | 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>. | + | ===Exercise/Stretches=== |
| - | **Diet** | + | Prior to exercising, stretching 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 joints, and regular exercise maintains a child’s body mass so that the child does not need to endure additional weight. It is important that children are not over exhausted by physical activity, as this could increase the pain and soreness (AboutKidsHealth, 2017). |
| - | <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 | + | ===Physiotherapy=== |
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| - | 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 patient, therefore it can produce differing results. Three diets that are typically suggested to obese patients are the low carbohydrate diet, the low-fat diet and the high protein diet. | + | 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). |
| - | 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>. | + | ==== Occupational Therapy==== |
| - | Although all three of these diets show promising results, the low carbohydrate and high protein diets show short term effects, while the low fat diet seems to display long term fat reduction. In 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. | + | 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). |
| + | ===Assistive Devices=== | ||
| - | **Weight Loss Programs** | + | 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 contractures, swelling stress and pain. In individuals with knee joint pain, splints can decrease flexion contractures (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. | ||
| + | ==== Drug Therapy ==== | ||
| - | Some examples of weight loss programs that are available for further investigation are listed below: | + | === Nonsteroidal anti-inflammatory drugs (NSAIDs) === |
| - | __The Paleo Diet__: It works to incorporate whole foods, lean protein, veggies, fruits, nuts, and seeds and encourages to stay away from foods with sugars, dairy and grains. | + | 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 JIA. NSAIDs work by interfering with prostaglandin synthesis through inhibition of the enzyme cyclooxygenase (COX), thus reducing swelling and pain (Kim, 2010). The most common side effects of NSAIDs are an upset stomach resulting in pain or nausea. However, some less common side effects include dizziness, headaches, bruising or rash (Juvenile Idiopathic Arthritis, 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. | + | === Disease-modifying anti-rheumatic drugs (DMARDs) === |
| - | __The Low Carbohydrate Diet:__ It encourages individuals to eat an unlimited amount of protein and fat, while completely eliminating carbohydrates. | + | <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).> |
| - | __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. | + | 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). |
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| - | __The Zone Diet:__ This diet encourages participants to balance each meal with one third of protein, and two thirds of fruits and veggies. A small amount of fat that comes from natural and healthy sources, such as avocado, almonds, or olive oil can also be consumed. | + | |
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| - | __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. | + | |
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| - | There are a few options when trying to reduce weight loss. All of the diets that are listed above prove to have a positive impact on weight reduction. However every diet has its consequences. When the body is restricted from having certain kinds of foods, nutrients, minerals and vitamins are compromised. For example, if 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). |
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| - | 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>. | + | |
| - | + | ||
| - | + | ||
| - | **Cognitive Behaviour Therapy** | + | |
| - | + | ||
| - | <box 30% round right |>{{:cbt.png}}</box|Figure 11: The three main components of Cognitive Behaviour Therapy: thought, emotion and behaviour | + | |
| - | 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>. | + | |
| - | + | ||
| - | The purpose of the CBT treatment is not to eliminate a psychiatric disorder but to change eating and exercise behaviours <sup>[36]</sup>. This intervention aims to educate individuals on how to change problematic behaviours. Firstly, CBT is based on the cognitive conceptualization of the processes that lead to overeating. Specifically, thoughts and thinking patterns that are considered central to the problem. Secondly, CBT 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. | + | |
| - | + | ||
| - | 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>. | + | |
| - | + | ||
| - | In addition to counselling, having a support network is important. This is especially true if the individual is undergoing drastic changes. Receiving encouragement from family, friends and health care practitioners can be very motivating during challenging times of the weight loss and maintenance programs. Furthermore, patients can also join support groups with other people undergoing weight loss <sup>[25]</sup>. | + | |
| - | + | ||
| - | 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>. | + | |
| - | + | ||
| - | + | ||
| - | + | ||
| - | **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 hand, sibutramine functions as a serotonin and noradrenaline reuptake inhibitor which induces weight loss through enhanced satiety and increased basal energy expenditure. Sibutramine 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 alone, showed 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 kg, compared 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. Specifically, Davidson 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. | ||
| + | === Corticosteroid Injections === | ||
| - | **Bariatric Surgery** | + | 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). |
| - | <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> | + | {{:surg1.png|}} |
| - | Bariatric surgery is a treatment method that is considered for adult patients who have a 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 modifications, healthcare 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 reached. In the case that satisfactory progress or goal has not been achieved, physicians will consider the eligibility of patients to undergo bariatric surgery. This 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>. | + | 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> |
| - | 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>. | + | ==== Surgical Treatment ==== |
| - | **Summary of Treatment Options** | + | 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. |
| - | 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 maintained. In the event that satisfactory progress is not attained, physicians will assess the patient’s eligibility to either undergo pharmacotherapy or bariatric surgery. Physicians 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. | + | {{:bone1.png|}} |
| - | {{:flowchart_final.png|}} | + | Figure 11. This image shows the view before and after total knee replacement. Retrieved from (Abdel & Figgie, 2014). |
| + | ==== Direction for Future Treatments ==== | ||
| - | Figure 14: A holistic approach to treating obesity. | + | The majority of children are treated adequately with a combination of treatments such as NSAIDs, corticosteroids and DMARDs available today. Yet, there are still some children, who are intolerant or resistant to these therapies, hence suffer from joint damage. For children who fall under this category, autologous stem cell transplantation seems to be a potential option (Brinkman et al., 2007). Autologous stem cell transplantation is a procedure where a 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 children. First, Wulffraat et al., reported positive results of autologous stem cell transplantation in four children (Brinkman et al., 2007). |
| ===== References ===== | ===== References ===== | ||
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| - | 1. Ng, M., Fleming, T., Robinson, M., Thomson, B., Graetz, N., & Margono, C. et al. (2014). Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013.The Lancet, 384(9945), 766-781. http://dx.doi.org/10.1016/s0140-6736(14)60460-8 | + | 1. Abdel, M. P., & Figgie, M. P. (2014). Surgical Management of the Juvenile Idiopathic Arthritis |
| + | Patient with Multiple Joint Involvement. Orthopedic Clinics of North America, 45(4), 435-442. doi:10.1016/j.ocl.2014.06.002 | ||
| - | 2. Seidell, J. & Halberstadt, J. (2015). The Global Burden of Obesity and the Challenges of Prevention. Annals Of Nutrition And Metabolism, 66(2), 7-12. http://dx.doi.org/10.1159/000375143 | + | 2. AboutKidsHealth, and About.kidshealth@sickkids.ca. "Blood Tests and JIA." Blood |
| + | Tests and Juvenile Idiopathic Arthritis (JIA) - AboutKidsHealth. AboutKidsHealth, 16 Oct. 2012. Web. 02 Mar. 2017. | ||
| - | 3. WHO: Global Database on Body Mass Index. (2017). Apps.who.int. Retrieved 1 February 2017, from http://apps.who.int/bmi/index.jsp?introPage=intro_3.html | + | 3. AboutKidsHealth -JIA Treatment of JIA. (2017). Retrieved February 20, 2017 from http://www.aboutkidshealth.ca/En/ResourceCentres/JuvenileIdiopathicArthritis/TreatmentofJIA/Pages/default.aspx |
| - | 4. Child & Teen BMI | Healthy Weight | CDC. (2017). Centers for Disease Control and Prevention. Retrieved 1 February 2017, from https://www.cdc.gov/healthyweight/assessing/bmi/childrens_bmi/about_childrens_bmi.html | + | 4. Ansell, B. M., Bywaters, E. G., & Lawrence, J. S. (1969). Familial aggregation and twin studies in Still's disease. Juvenile chronic polyarthritis. Rheumatology, 2, 37. |
| - | 5. Jitnarin, N., Poston, W., Haddock, C., Jahnke, S., & Tuley, B. (2012). Accuracy of body mass index-defined overweight in fire fighters. Occupational Medicine, 63(3), | + | 5. Autologous (Self) Transplants. (n.d.). Retrieved March 03, 2017, from http://www.leukaemia.org.au/treatments/stem-cell-transplants/autologous-self-transplants |
| - | 227-230. http://dx.doi.org/10.1093/occmed/kqs213 | + | |
| - | 6. Spiegelman, B. & Flier, J. (2001). Obesity and the Regulation of Energy Balance. Cell, | + | 6. Baum, J., & Fink, C. (1968). Juvenile rheumatoid arthritis in monozygotic twins: a case report and review of the literature. Arthritis & Rheumatology, 11(1), 33-036. |
| - | 104(4), 531-543. http://dx.doi.org/10.1016/s0092-8674(01)00240-9 | + | |
| - | 7. Pietiläinen, K., Kaprio, J., Borg, P., Plasqui, G., Yki-Järvinen, H., & Kujala, U. et al. (2008). Physical Inactivity and Obesity: A Vicious Circle. Obesity, | + | 7. Berkun, Y., & Padeh, S. (2010). Environmental factors and the geoepidemiology of juvenile idiopathic arthritis. Autoimmunity reviews, 9(5), A319-A324. |
| - | 16(2), 409-414. http://dx.doi.org/10.1038/oby.2007.72 | + | |
| - | 8. Cohen-Cole, E. & Fletcher, J. (2008). Is obesity contagious? Social networks vs environmental factors in the obesity epidemic. Journal Of Health Economics, 27(5), | + | 8. Brescia, A. C. (Ed.). (2016, April). Juvenile Idiopathic Arthritis. Retrieved February 19, 2017, from http://kidshealth.org/en/parents/jra.html# |
| - | 1382-1387. http://dx.doi.org/10.1016/j.jhealeco.2008.04.005 | + | |
| - | 9. Masuo, K. (2000). A family history of obesity, a family history of hypertension and blood pressure levels. American Journal Of Hypertension, 13(6), S164. http://dx.doi.org/10.1016/s0895-7061(00)01125-0 | + | 9. Brinkman, D. M., Kleer, I. M., Cate, R. T., Rossum, M. A., Bekkering, W. P., Fasth, A., . . . Vossen, J. M. (2007). Autologous stem cell transplantation in children with severe progressive systemic or polyarticular juvenile idiopathic arthritis: Long-term followup of a prospective clinical trial. Arthritis & Rheumatism, 56(7), 2410-2421. doi:10.1002/art.22656 |
| - | 10. Weaver, J. (2008). Classical Endocrine Diseases Causing Obesity. Obesity And Metabolism, 212-228. http://dx.doi.org/10.1159/000115367 | + | 10. Carlens, C., Jacobsson, L., Brandt, L., Cnattingius, S., Stephansson, O., & Askling, J. (2009). Perinatal characteristics, early life infections and later risk of rheumatoid arthritis and juvenile idiopathic arthritis. Annals of the Rheumatic Diseases, 68(7), 1159-1164. |
| - | 11. Schwartz, T., Nihalani, N., Jindal, S., Virk, S., & Jones, N. (2004). Psychiatric medication-induced obesity: a review. Obesity Reviews, 5(2), 115-121. http://dx.doi.org/10.1111/j.1467-789x.2004.00139.x | + | 11. Demoruelle, M. & Deane, K. (2011). Antibodies to Citrullinated Protein Antigens (ACPAs): Clinical and Pathophysiologic Significance. Current Rheumatology Reports, 13(5), 421-430. doi:10.1007/s11926-011-0193-7 |
| - | 12. Dare, S., Mackay, D., & Pell, J. (2015). Relationship between Smoking and Obesity: A Cross-Sectional Study of 499,504 Middle-Aged Adults in the UK General Population. PLOS ONE, 10(4), e0123579. http://dx.doi.org/10.1371/journal.pone.0123579 | + | 12. Giannini, E. H., Brewer, E. J., & Kuzmina, N. (1990). Arthritis. Journal of Pediatric Orthopaedics, 10(5), 697. doi:10.1097/01241398-199009000-00034 |
| - | 13. Vermeulen, A. (2005). The epidemic of obesity: Obesity and health of the aging male. The Aging Male, 8(1), 39-41. http://dx.doi.org/10.1080/13685530500049037 | + | 13. Gibson, W. M., Grokoest, A. W., & Larson, C. B. (1962). Juvenile rheumatoid arthritis. Arthritis & Rheumatology, 5(2), 211-217. |
| - | 14. Schumann, N., Brinsden, H., & Lobstein, T. (2014). A review of national health policies and professional guidelines on maternal obesity and weight gain in pregnancy. Clinical | + | 14. Ginn, L. R., Lin, J. P., Plotz, P. H., Bale, S. J., Wilder, R. L., Mbauya, A., & Miller, F. W. (1998). Familial autoimmunity in pedigrees of idiopathic inflammatory myopathy patients suggests common genetic risk factors for many autoimmune diseases. Arthritis & Rheumatology, 41(3), 400-405. |
| - | Obesity, n/a-n/a. http://dx.doi.org/10.1111/cob.12062 | + | |
| - | 15. Why Is Sleep Important? - NHLBI, NIH. (2017). National Heart, Lung and Blood Institute. Retrieved 1 February 2017, from https://www.nhlbi.nih.gov/health/health-topics/topics/sdd/why | + | 15. Glass, D. N., & Giannini, E. H. (1999). Juvenile rheumatoid arthritis as a complex genetic trait. Arthritis & Rheumatism, 42(11), 2261-2268. |
| - | 16. Gurevich-Panigrahi, T., Panigrahi, S., Wiechec, E., & Los, M. (2009). Obesity: pathophysiology and clinical management. Current Medical Chemistry, 16, 506-521. Retrieved from http://liu.diva-portal.org/smash/get/diva2:583167/FULLTEXT01.pdf | + | 16. Goldstein, D. A., Horsley, M., & Ulanski, L. J. (2013). II, Tessler HH. Complications of uveitis and their management. Duane's Ophthalmology. |
| - | 17. Odegaard, J., & Chawla, A. (2012). Adipose tissue metabolism in the obese. TheScientist. Retrieved 18 January 2017, from http://www.the-scientist.com/?articles.view/articleNo/33653/title/adipose-tissue-metabolism-in-the-obese/ | + | 17. Grossman, B. J., & Mukhopadhyay, D. (1975). Juvenile rheumatoid arthritis. Current problems in pediatrics, 5(12), CO11-65. |
| - | 18. Kahn, B. B., & Flier, J. S. (2000). Obesity and insulin resistance. Journal of Clinical Investigation, 106(4), 473–481. | + | 18. Harris, J. G., Kessler, E. A., & Verbsky, J. W. (2013). Update on the Treatment of Juvenile Idiopathic Arthritis. Current Allergy and Asthma Reports, 13(4), 337–346. http://doi.org/10.1007/s11882-013-0351-2 |
| - | 19. Després, J., & Marette, A. (1999). Obesity and Insulin Resistance. Insulin Resistance, 51-81. doi:10.1007/978-1-59259-716-1_4 | + | 19. Henoch, M. J., Batson, J. W., & Baum, J. (1978). Psychosocial factors in juvenile rheumatoid arthritis. Arthritis & Rheumatism, 21(2), 229-233. |
| - | 20. Klok, M. D., Jakobsdottir, S., & Drent, M. L. (2007). The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review. Obesity Reviews, 8(1), 21-34. doi:10.1111/j.1467-789x.2006.00270.x | + | 20. Jaakkola, J. J., & Gissler, M. (2005). Maternal smoking in pregnancy as a determinant of rheumatoid arthritis and other inflammatory polyarthropathies during the first 7 years of life. International journal of epidemiology, 34(3), 664-671. |
| - | 21. Kaszmi, A., Sattar.A., Hashim, R., Khan., S.P.., Younus, M., Khan, F.A. (2013). Serum Leptin values in the healthy obese and non-obese subjects of Rawalpindi. J Pak Med Assoc. 63(2), 245-8 | + | 21. Juvenile idiopathic arthritis - Genetics Home Reference. (2015, February 14). Retrieved February 20, 2017, from https://ghr.nlm.nih.gov/condition/juvenile-idiopathic-arthritis#diagnosis |
| - | 22. Tschop, M., Weyer, C., Tataranni, P. A., Devanarayan, V., Ravussin, E., & Heiman, M. L. (2001). Circulating Ghrelin Levels Are Decreased in Human Obesity. Diabetes, 50(4), 707-709. doi:10.2337/diabetes.50.4.707 | ||
| - | 23. Walley, A.J., Blakemore, A.I.F. & Froguel, P. (2006). Genetics of obesity and the prediction of risk for health. Human Molecular Genetics. Retrieved 27January, 2017, from https://academic.oup.com/hmg/article/15/suppl_2/R124/626082/Genetics-of-obesity-and-the-prediction-of-risk-for | + | 22. Juvenile Idiopathic Arthritis: Soft Tissue Release of Contracture - Topic Overview. (n.d.). Retrieved February 13, 2017, from http://www.webmd.com/rheumatoid-arthritis/tc/juvenile-idiopathic-arthritis-soft-tissue-release-of-contracture-topic |
| - | 24. Rankinen, T., Zuberi, A., Chagnon, Y.C., Weisnagel, S.J., Argyropoulos, G., Walts, B., Perusse, L., & Bouchard, C. (2006). The human obesity gene map: the 2005 update. Obesity, | + | 23. Juvenile Idiopathic Arthritis - Treatment Overview. (n.d.). Retrieved February 13, 2017, from http://www.webmd.com/rheumatoid-arthritis/tc/juvenile-rheumatoid-arthritis-treatment-overview#1 |
| - | 14(4), 529-644. | + | |
| - | 25. Pi-Sunyer, F. X., Becker, D. M., Bouchard, C., Carleton, R. A., Colditz, G. A., Dietz, W. H., ... & Higgins, M. (1998). Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults. American Journal of Clinical Nutrition, 68(4), 899-917. | + | 24. Kim, K. N. (2010). Treatment of juvenile rheumatoid arthritis. Korean Journal of Pediatrics, 53(11), 936–941. http://doi.org/10.3345/kjp.2010.53.11.936 |
| - | 26. Lau, D. C., Douketis, J. D., Morrison, K. M., Hramiak, I. M., Sharma, A. M., Ur, E., & members of the Obesity Canada Clinical Practice Guidelines Expert Panel. (2007). 2006 Canadian clinical practice guidelines on the management and prevention of obesity in adults and children [summary]. Canadian Medical Association Journal, 176(8), S1-S13. | + | 25. Liao, K. P., Alfredsson, L., & Karlson, E. W. (2009). Environmental influences on risk for rheumatoid arthritis. Current opinion in rheumatology, 21(3), 279. |
| - | 27. Poirier, P., & Després, J. P. (2001). Exercise in weight management of obesity. Cardiology clinics,19(3),459-470. | + | 26. Malmström, V., Catrina, A., & Klareskog, L. (2016). The immunopathogenesis of seropositive rheumatoid arthritis: from triggering to targeting. Nature Reviews Immunology, 17(1), 60-75. doi:10.1038/nri.2016.124 |
| - | 28. Hey, H., Petersen, H. D., Andersen, T., & Quaade, F. (1987). Formula diet plus free additional food choice up to 1000 kcal (4.2 MJ) compared with an is energetic conventional diet in the treatment of obesity. A randomised clinical trial. Clinical Nutrition,6(3),195-199. | + | 27. McInnes, I. & Schett, G. (2011). The Pathogenesis of Rheumatoid Arthritis. New England Journal Of Medicine, 365(23), 2205-2219. doi:10.1056/nejmra1004965 |
| - | 29. Lau, D. C., Douketis, J. D., Morrison, K. M., Hramiak, I. M., Sharma, A. M., Ur, E., & members of the Obesity Canada Clinical Practice Guidelines Expert Panel. (2007). 2006 Canadian clinical practice guidelines on the management and prevention of obesity in adults and children [summary]. Canadian Medical Association Journal, 176(8), S1-S13. | + | 28. Miller, M. L. (1994). Juvenile rheumatoid arthritis. Current problems in pediatrics, 24(6), 190-198. |
| - | 30. Toubro, S., & Astrup, A. (1997). Randomised comparison of diets for maintaining obese subjects' weight after major weight loss: ad lib, low fat, high carbohydrate diet fixed energy intake. Bmj,314(707329. | + | 29. Nath Maini, R. (2010). Rheumatoid arthritis. Oxford Textbook Of Medicine, 3579-3602. doi:10.1093/med/9780199204854.003.1905_update_001 |
| - | 31. 9 Popular Weight Loss Diets Reviewed by Science. (2016, October 04). Retrieved January 27, 2017, from https://authoritynutrition.com/9-weight-loss-diets-reviewed/ | + | 30. Nelson, W. E., & Kliegman, R. M. (2016). Nelson Textbook of pediatrics. Philadelphia: Elsevier. |
| - | 32. Poirier, P., & Després, J. P. (2001). Exercise in weight management of obesity. Cardiology clinics, 19(3), 459-470. | + | 31. Prahalad, S. (2004). Genetics of juvenile idiopathic arthritis: an update. Current opinion in rheumatology, 16(5), 588-594. |
| - | 33. Tremblay, A., Nadeau, A., Despres, J. P., St-Jean, L., Theriault, G., & Bouchard, C. (1990). Long-term exercise training with constant energy intake. 2: Effect on glucose metabolism and resting energy expenditure. International journal of obesity, 14(1), 75-84. | + | 32. Prahalad, S., & Glass, D. N. (2008). A comprehensive review of the genetics of juvenile idiopathic arthritis. Pediatric Rheumatology, 6(1), 11. |
| - | 34. Gwinup, G. (1987). Weight loss without dietary restriction: efficacy of different forms of aerobic exercise. The American journal of sports medicine, 15(3), 275-279. | + | 33. Prahalad, S., Ryan, M. H., Shear, E. S., Thompson, S. D., Glass, D. N., & Giannini, E. H. (2000). Twins concordant for juvenile rheumatoid arthritis. Arthritis & Rheumatism, 43(11), 2611-2612. |
| - | 35. Pate, R. R., Pratt, M., Blair, S. N., Haskell, W. L., Macera, C. A., Bouchard, C., ... & Kriska, A. (1995). Physical activity and public health: a recommendation from the Centers for Disease Control and Prevention and the American College of Sports Medicine. Jama, 273(5), 402-407. | + | 34. Prakken, B., Albani, S., & Martini, A. (2011). Juvenile idiopathic arthritis. The Lancet, 377(9783), 2138-2149. |
| - | 36. Nozaki, T., Sawamoto, R., & Sudo, N. (2013). Cognitive behavioral therapy for obesity. Nihon rinsho. Japanese journal of clinical medicine, 71(2), 329-334. | + | 35. Ramanan, A. V. (2003). Use of methotrexate in juvenile idiopathic arthritis. Archives of Disease in Childhood, 88(3), 197-200. doi:10.1136/adc.88.3.197 |
| - | 37. Cooper, Z., Fairburn, C. G., & Hawker, D. M. (2003). Cognitive-behavioral treatment of obesity: A clinician's guide. Guilford Press. | + | 36. Ravelli, A., & Martini, A. (2007). Juvenile idiopathic arthritis. The Lancet, 369(3), 767-778. doi:10.1016/S0140-6736(07)60363-8 |
| - | 38. Diabetes Prevention Program (DPP) Research Group. (2002). The diabetes prevention program (DPP). Diabetes care, 25(12), 2165-2171. | + | 37. Rosen, P., Thompson, S., & Glass, D. (2002). Non-HLA gene polymorphisms in juvenile rheumatoid arthritis. Clinical and experimental rheumatology, 21(5), 650-656. |
| - | 39. Look AHEAD Research Group. (2003). Look AHEAD (Action for Health in Diabetes): design and methods for a clinical trial of weight loss for the prevention of cardiovascular disease in type 2 diabetes. Controlled clinical trials,24(5), 610-628. | + | 38. "Rheumatoid Factor | ANA Test | Lab Tests | Arthritis Today." Rheumatoid Factor | ANA Test | Lab Tests | Arthritis Today. N.p., n.d. Web. 02 Mar. 2017. |
| - | 40. Renjilian, D. A., Perri, M. G., Nezu, A. M., McKelvey, W. F., Shermer, R. L., & Anton, S. D. (2001). Individual versus group therapy for obesity: effects of matching participants to their treatment preferences. Journal of consulting and clinical psychology, 69(4), 717. | + | 39. Saurenmann, R. K., Rose, J. B., Tyrrell, P., Feldman, B. M., Laxer, R. M., Schneider, R., & Silverman, E. D. (2007). Epidemiology of juvenile idiopathic arthritis in a multiethnic cohort: ethnicity as a risk factor. Arthritis & Rheumatism, 56(6), 1974-1984. |
| - | 41. Wrotniak, B. H., Epstein, L. H., Paluch, R. A., & Roemmich, J. N. (2004). Parent weight change as a predictor of child weight change in family-based behavioral obesity treatment. Archives of pediatrics | + | 40. Savolainen, A., Saila, H., Kotaniemi, K., KAIPIAINEN-SEPPAN, O., Leirisalo-Repo, M., & Aho, K. (2000). Magnitude of the genetic component in juvenile idiopathic arthritis. Annals of the rheumatic diseases, 59(12), 1001. |
| - | & adolescent medicine, 158(4), 342-347. | + | |
| - | 42. Epstein, L. H., Roemmich, J. N., Stein, R. I., Paluch, R. A., & Kilanowski, C. K. (2005). The challenge of identifying behavioral alternatives to food: clinic and field studies. Annals of | + | 41. Schaller, J. G. (1997). Juvenile rheumatoid arthritis. Pediatrics in review, 18, 337-350. |
| - | Behavioral Medicine, 30(3),201-209 | + | |
| - | 43. Guerciolini, R. (1997). Mode of action of orlistat. International journal of obesity and related metabolic disorders: journal of the International Association for the Study of Obesity, 21, S12-23. | + | 42. Symmons, D. (2005). Commentary: Juvenile idiopathic arthritis—issues of definition and causation. International journal of epidemiology, 34(3), 671-672. |
| - | 44. Finer, N. (2002). Sibutramine: its mode of action and efficacy. International Journal of Obesity, 26(S4), S29. | + | 43. Ungar, W.J., Costa, V., Burnett, H.F., Feldman, B.F., & Laxer, R.M. (2013). The use of biologic response modifiers in polyarticular-course juvenile idiopathic arthritis: A systematic review. Seminars in Arthritis and Rheumatism, 42(6), 597-618. |
| - | 45. Davidson, M. H., Hauptman, J., DiGirolamo, M., Foreyt, J. P., Halsted, C. H., Heber, D., ... & Heymsfield, S. B. (1999). Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial. Jama, 281(3), 235-242. | + | 44. Van der Voort, C. R., Heijnen, C. J., Wulffraat, N., Kuis, W., & Kavelaars, A. (2000). Stress induces increases in IL-6 production by leucocytes of patients with the chronic inflammatory disease juvenile rheumatoid arthritis: a putative role for α 1-adrenergic receptors. Journal of neuroimmunology, 110(1), 223-229. |
| - | 46. James, W. P. T., Astrup, A., Finer, N., Hilsted, J., Kopelman, P., Rössner, S., ... & STORM Study Group. (2000). Effect of sibutramine on weight maintenance after weight loss: a randomised trial. The Lancet, 356(9248), 2119-2125 | + | 45. Wedderburn, L. R., Patel, A., Varsani, H., & Woo, P. (2001). Divergence in the degree of clonal expansions in inflammatory T cell subpopulations mirrors HLA-associated risk alleles in genetically and clinically distinct subtypes of childhood arthritis. International immunology, 13(12), 1541-1550. |
| - | + | 46. William C. Shiel Jr., MD, FACP, FACR. (n.d.). Rheumatoid Arthritis (RA) Symptoms & Treatment. Retrieved February 20, 2017, from http://www.onhealth.com/content/1/rheumatoid_arthritis_ra | |
| - | 47. Sjöström, L., Lindroos, A. K., Peltonen, M., Torgerson, J., Bouchard, C., Carlsson, B., ... & Sullivan, M. (2004). Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. New England Journal of Medicine, 351(26), 2683-2693. | + | |
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