Advances in pediatric rheumatologic disease have pavedthe way to better outcomes for children. Anchoring an improved standardof care is the patient care team, including the primary carephysician, pediatric rheumatologist and associated rheumatologyhealth care personnel, and patient and family. Improved medicationshave expanded the treatment arsenal to include disease-modifyingantirheumatic drugs and biologic agents. The medical regimen can bebolstered with a program of healthy diet and exercise that focuses onsuch low-impact activities as swimming, stretching, and bicycling. Thepatient and family can work together to ensure that the child complieswith the prescribed treatment and also takes care to get adequate,restful sleep; manage stress; and protect bone. (J MusculoskelMed. 2008;25:505-512)
Advances in pediatric rheumatologic disease-from new disease classification and understanding to decreased morbidity and mortality-have been significant over the past 10 years. Accompanying these advances have been declines in joint replacements, hospitalizations, and permanent disability. Now most children with rheumatologic disease attend school regularly and pursue extracurricular activities. Several factors contribute to these advances that probably will lead to continued improvement in the future.
Perhaps a central driver of improvement in the area of pediatric rheumatology has been the implementation of a team approach to patient care.This team includes the patient and his or her family, the pediatric rheumatologist and associated rheumatology personnel, the primary care physician and, when needed, other subspecialists. Depending on the patient, the pediatric rheumatology team also may include a nurse, occupational therapist, physical therapist, dietitian, and psychologist. All of the team members are vital to achieving optimal health for these patients.
In this article, we discuss topics that are germane to all members of the pediatric rheumatologic disease team, especially the primary care physician. We cover advances in the areas of juvenile arthritis, medication monitoring, and evaluation of intercurrent illness. We also offer insights that the primary care physician can use to support and empower the patient to assume some responsibility for his own care in the areas of compliance, sleep, stress management, weight control, and osteoporosis.
The classification of pediatric arthritis has been garnering much attention in the past few years. Considerable discussion and debate have centered around changing the nomenclature for the disorder traditionally referred to as juvenile rheumatoid arthritis (JRA), with subtypes of systemic, polyarticular, and pauciarticular disease. Proposed alternative names include juvenile chronic arthritis (JCA)1 and juvenile idiopathic arthritis (JIA).2 The JCA and JIA systems include additional subtypes of psoriatic arthritis and enthesitis-associated arthritis, which overlap with the spondyloarthropathies. In the old nomenclature, these are separate.
Regardless of the classification system that is used, all the proposed systems contain 3 major patterns of JRA: systemic, polyarticular, and pauciarticular.The goal in renaming these subtypes is to gain consistency for the purposes of research studies conducted in the United States and elsewhere. Nomenclature changes will not affect the approach to diagnosis or management of juvenile arthritis.
Of high interest among pediatric rheumatologists is research aimed at using gene microarrays to improve diagnosis and identify likely responders to treatment options. For example, systemic-onset juvenile arthritis is a disorder in which interleukin (IL)-1 has a prominent role. Gene studies using blood leukocytes and microarray technology have identified 88 genes that are associated with systemic-onset juvenile arthritis, 12 of which appear to be specific for this disorder.3
Improved diagnostic methods may permit earlier diagnosis and more specific management of systemic- onset juvenile arthritis.This is especially important, because subtypes of juvenile arthritis often produce nonspecific symptoms at first. Definitive diagnosis often depends on clinically identifying characteristic features of disease, which may take a long time to emerge.
Those used to control arthritis encompass a wide range, including NSAIDs, disease-modifying antirheumatic drugs (DMARDs), and biologic response modifiers (BRMs). Each medication has unique effects and potential adverse effects that must be considered when individualizing treatment to the patient. Patients and their parents should know about a medication's potential risks and benefits, adverse-effect profile, and monitoring requirements before treatment is started.
NSAIDs have become a focus of concern in the aftermath of reports associating rofecoxib with stroke and cardiovascular disease in adults. To date, the risk of NSAIDs has been low in pediatric patients. The dilemma is that in the absence of a potent NSAID, many patients require the addition of a remittive agent or DMARD, such as methotrexate (MTX), or a BRM to control their disease.
DMARDs often prescribed for persons with arthritis include hydroxychloroquine, sulfasalazine, and MTX. Patients taking DMARDs need to be monitored with a complete blood cell (CBC) count and metabolic profile on a regular basis. The monitoring frequency is specific to each DMARD, but monitoring is typically every 3 to 4 months. Dosing in pediatric patients is based on age and body weight.
BRMs used include etanercept, adalimumab, infliximab, anakinra, and rituximab. Etanercept, adalimumab, and infliximab target tumor necrosis factor α (TNF-α) inhibitors. Anakinra targets IL-1 receptors. Rituximab targets B cells, and dosage, just as in adults, is based on body weight. More BRMs are in development.
This newest class of medications requires some special monitoring. For example, the TNF-α inhibitors may cause reactivation of tuberculosis. The physician considering a TNF-α inhibitor for his patient must therefore perform a tuberculosis screening skin test before starting therapy. If the patient cannot get to a pediatric rheumatology center for this test, the primary care provider may need to assist. All BRMs may affect blood cell counts; patients also are at low risk for sepsis or other serious infection during treatment.
Newer issues with BRMs include concerns about a possible small increase in risk of lymphoid malignancy or demyelinating disease in adults.There are no reports in the adalimumab or JRA literature noting an increase in malignancy or demyelinating disease among patients with juvenile arthritis.4 Rituximab specifically targets B cells and may cause a decrease in immunoglobulin G, thereby requiring temporary immunoglobulin replacement.5
In the past, it often took several months of trial to determine whether a given medication would effectively control the patient's disease. Now a medication's benefit may become evident much sooner. For example, most patients with arthritis receiving MTX plus adalimumab, a BRM, experience significant, rapid improvement in disease activity, achieving an American College of Rheumatology 20 response by the first scheduled visit at week 1.6
Children with rheumatologic disease may present to the primary care physician with fever, pharyngitis, cough, or other symptoms consistent with an intercurrent illness. Patients with fever should be evaluated with a history, physical examination, and laboratory studies, where indicated, to include a CBC count, metabolic profile, lactic dehydrogenase measurement, urinalysis, and cultures. Cultures in a febrile patient would include blood, urine, and possibly other sites, as appropriate.
Any identified illnesses should be managed promptly according to standard of care guidelines. When necessary, the primary care physician should also consult with the pediatric rheumatologist. An otherwise mild intercurrent illness may cause a flare-up of arthritis symptoms. A flare-up that is severe or that persists for more than 2 to 3 weeks is an indication to notify the pediatric rheumatologist.
An important factor in these diagnostic and therapeutic advances is empowerment of patients and their families. This empowerment process begins with efforts to improve the child's compliance with taking medications, which is difficult in chronic disease.
Early strategies for increasing compliance revolved around educating the patient and family about the disease and its management. Although this is helpful, the results of compliance studies show that education alone may not be enough to effect a behavior change in patients. 7 Modifications that affect compliance include simplifying the regimen (eg, prescribing a once-daily preparation), taking steps to reduce the adverse effects of medications (eg, taking with food or water, prescribing a medication that causes less gastric irritation), and providing a reinforcement program.7
One of the biggest contributors to well-being and immune system health is high-quality, restorative sleep. Patients who are experiencing problems with disease control, sensitivity to pain, and depression often report such sleeping difficulties as varied sleep times, absence of a bedtime ritual, poor sleep environment (noise, light), dependency on sleep medications, and insufficient time devoted to sleep.
Studies in swing-shift workers confirm that it takes 2 to 3 weeks for the immune system to adapt to each change in sleep time.8,9 Sleeping with the light on significantly decreases production of growth hormone, diminishing healing ability. Sleep deprivation increases sensitivity to pain and decreases coping skills.
Parents can reverse these effects in their children with counseling on proper sleep. This includes basic sleep learning and sleep hygiene: physical activity to encourage sleepiness; a set bedtime; a bedtime ritual (brushing teeth, story time); a quiet, dark room; and relaxation. Counseling and relaxation exercises may be helpful for some patients. All members of the team can support the patient and family in making these changes.
This adversely effects the immune system in many ways.10,11 Patients with a new diagnosis may hear stories from well-meaning friends and relatives of dramatic disease flare-ups or severe disease in persons they know.The most obvious clinical effects of stress are associated with a major event, such as a death or divorce in the family.
Depression stresses the immune system and causes rheumatologic disease to flare up.12,13 Many patients with well-controlled disease experience reactive or endogenous depression in response to stress, requiring intensive treatment or even hospitalization to regain control of their rheumatologic disease. Milder chronic stress also may make it difficult to control rheumatologic disease.
The more potentially serious a disease flare-up may be, the more crucial stress management becomes. Counseling and stress management techniques, such as use of relaxation tapes, music, tai chi, and sports, may be helpful. Stress management is a life skill for these children that will help them control their disease proactively.
Part of the movement toward empowering children with rheumatologic disease and their families is a general philosophy of using a healthier lifestyle to improve immune function.14,15 In the past, the primary dietary focus for patients with such chronic rheumatologic diseases as systemic arthritis and polyarthritis was increasing calorie consumption. This has changed as medications have improved and the numbers of patients with insufficient caloric intake have declined.
At the same time, the trend toward childhood obesity, particularly morbid obesity, is becoming a more important issue for children with rheumatologic disease. Increased weight, particularly without adequate muscle mass to support it, stresses the joints significantly. Many obese patients have elevated blood glucose levels, which adversely affects immune function. Adipose tissue itself increases background inflammation in patients who have rheumatologic disease.16,17
Obesity often is a family problem. Accordingly, weight management efforts should involve, and be supported by, all members of the family, as well as their health care team. Dietary modification in the child with rheumatologic disease must prioritize nutrition and intake that is timed with medications.
The choice of the weight management plan chosen must be individualized, but some carbohydrate restriction should be considered in consultation with a dietitian.This recommendation is based on observations from many studies correlating weight gain with excess carbohydrate consumption and weight loss with carbohydrate restriction.18
Supplementation with omega 3 fatty acids is still considered beneficial for persons with arthritis. However, adding these supplements to a high-carbohydrate, high–saturated fat diet may make the benefits of omega 3 fatty acids difficult to realize. The diet for arthritis patients should likely contain beneficial fats and omega 3 fatty acids.19,20
Weight management programs that include exercise help burn calories and may be more successful than programs that do not include regular physical activity. Activities may need to be modified according to the child's comfort and abilities. However, we find swimming, stretching, bicycling, and other low-impact activities to be well tolerated. We counsel our patients to avoid high-impact activities, as well as weight training.
Vitamin D deficiency and osteoporosis were once considered rare in children. However, juvenile osteoporosis-even to the point of fracture-is being reported in otherwise healthy children.21
Reports of low vitamin D levels in adults with rheumatologic disease are prompting physicians to order baseline evaluation of 25 OH vitamin D (25[OH]D3) levels as part of the routine workup of patients with immune problems or rheumatologic disease. Some studies have reported that more than 20% of these patients will be found to be lacking vitamin D.22 Vitamin D deficiency, as evidenced by a 25(OH)D3 level lower than 30 ng/mL, is being seen in many more children besides those with fractures.23 In patients with juvenile osteoporosis, vitamin D deficiency may cause pain in the lower back, hips, and feet, as well as problems with immune system function.
Vitamin D deficiency may be increasing because children are drinking less milk, avoiding sun exposure, using more potent sunscreens, and staying indoors more. Vitamin D deficiency also may reflect poor oral absorption of vitamin D2. This has prompted a shift from vitamin D2 supplementation to vitamin D3 supplementation of cow milk and some soy milk products.
We recommend that patients with low levels of 25(OH)D3 supplement their diet with products containing vitamin D3, or cholecalciferol. Some of these products have fish oil as the source; patients sensitive to fish oil may need an alternative product.The recommended daily allowance for vitamin D has been increased from 400 to 800 U/d. The alternative vitamin D source comes from the body's production of vitamin D from cholesterol when exposed to sunlight.
Persons with rheumatologic diseases also need adequate calcium. Absorption and deposition of calcium may be altered by high consumption of carbonated beverages and decreased consumption of foods containing magnesium. Some of the richest food sources of magnesium include spinach, nuts, and whole grains.
Calcium deposition and bone remodeling also may be affected by decreasing physical activity in children. In pediatric patients with rheumatologic disease, a reduction in weight-bearing activity may be required while their disease is active. Partial weight-bearing activities, such as swimming, bicycling, low-impact aerobics, and stretching, are beneficial for these children.
Support from the entire pediatric rheumatologic disease team is needed to optimally control disease and safely monitor children during periods of remission and flare-up. The team approach also effectively supports patient empowerment efforts in areas of compliance, sleep, stress management, nutrition, and bone health.