Sharon Worcester

Patients presenting with hyperuricemia or gout should be evaluated for metabolic syndrome, and any recommendations regarding dietary changes and medical treatment for gout should take into consideration the potential benefits of urate reduction, according to Dr. N. Lawrence Edwards.

Both hyperuricemia and gout are independent risk factors for metabolic syndrome and its individual components, said Dr. Edwards, professor of medicine at the University of Florida, Gainesville.

In a 2007 study looking at the prevalence of metabolic syndrome in nearly 8,700 patients with hyperuricemia from the NHANES (National Health and Nutrition Examination Survey) III database, the prevalence of metabolic syndrome increased in tandem with increasing levels of serum urate, and the increase persisted across subgroups stratified by age, sex, alcohol intake, body mass index, hypertension, and diabetes (Am. J. Med. 2007;120:442-7).

The investigators found that the prevalence of metabolic syndrome (defined using both original and revised National Cholesterol Education Program Adult Treatment Panel III criteria) was 19% in those with uric acid levels less than 6 mg/dL, 36% in those with 8.0-8.9 mg/dL, 62% for 9.0-9.9 mg/dL, and 71% for levels of 10 mg/dL or greater.

Physicians should recognize that metabolic syndrome occurs frequently in patients with hyperuricemia, and should be treated to prevent serious complications, they concluded.

In a related study, the prevalence of metabolic syndrome in patients with doctor-diagnosed gout from the same NHANES population was high (nearly 63%), compared with 25% in those without a gout diagnosis. The prevalence was even higher (83%) among those with a more stringently defined gout diagnosis (specifically, those on urate-lowering therapy), Dr. Edwards noted (Arthritis Rheum. 2007;57:109-15).

As with hyperuricemia, the investigators concluded that the prevalence of metabolic syndrome is high in individuals with gout, and that, given the serious complications that can be associated with metabolic syndrome, the condition should be recognized and taken into account when clinicians plan the long-term treatment of patients with gout.

The findings of these two studies support a pathogenic overlap between metabolic syndrome and gout, and underscore the importance of evaluating gout patients for the syndrome, Dr. Edwards said.

“You see a lot of patients coming in, and they haven't had fasting glucoses performed, blood pressures may be a little out of control, and weight is certainly out of control,” he noted.

“We need to look at these patients much more seriously than if they only have gout; they need a full-court press on all of their metabolic problems and not just their uric acid.”

Dietary recommendations that consist of the standard advice to avoid foods high in purines are not sufficient. Patients will often cut out meat and shellfish, but replace those with foods high in carbohydrates and fat, which can increase insulin resistance. Therefore, it is important to advise patients to reduce intake of high-purine foods, but also to avoid high-fat foods and the wrong kinds of carbohydrates.

About 40% of their diet should be complex carbohydrates, no more than 30% should be proteins, and no more than 30% should be mono- or polyunsaturated fats, he said.

As for medical treatment considerations, it is important to keep in mind the mechanisms of hyperuricemia as it relates to insulin resistance, he added.

In patients who are hypertriglyceridemic, for example, niacin is a commonly used drug.

However, niacin can elevate uric acid levels “by quite a margin” of 1.5-2.5 mg/dL. Conversely, fenofibrate can also be used to treat hypertriglyceridemia, and can lower the levels by a similar margin.

“So just making that switch might make a pretty substantial difference,” Dr. Edwards said.

In patients who are being treated for hypertension, keep in mind that hydrochlorothiazide is associated with elevated uric acid levels, and consider switching to the angiotensin receptor blocker losartan in those in whom hydrochlorathiazide is used solely for hypertension control and not for fluid control, as losartan has uric acid lowering effects, he said.

Dr. Edwards had no disclosures relevant to his presentation.

Patients presenting with hyperuricemia or gout should be evaluated for metabolic syndrome, and any recommendations regarding dietary changes and medical treatment for gout should take into consideration the potential benefits of urate reduction, according to Dr. N. Lawrence Edwards.

Both hyperuricemia and gout are independent risk factors for metabolic syndrome and its individual components, said Dr. Edwards, professor of medicine at the University of Florida, Gainesville.

In a 2007 study looking at the prevalence of metabolic syndrome in nearly 8,700 patients with hyperuricemia from the NHANES (National Health and Nutrition Examination Survey) III database, the prevalence of metabolic syndrome increased in tandem with increasing levels of serum urate, and the increase persisted across subgroups stratified by age, sex, alcohol intake, body mass index, hypertension, and diabetes (Am. J. Med. 2007;120:442-7).

The investigators found that the prevalence of metabolic syndrome (defined using both original and revised National Cholesterol Education Program Adult Treatment Panel III criteria) was 19% in those with uric acid levels less than 6 mg/dL, 36% in those with 8.0-8.9 mg/dL, 62% for 9.0-9.9 mg/dL, and 71% for levels of 10 mg/dL or greater.

Physicians should recognize that metabolic syndrome occurs frequently in patients with hyperuricemia, and should be treated to prevent serious complications, they concluded.

In a related study, the prevalence of metabolic syndrome in patients with doctor-diagnosed gout from the same NHANES population was high (nearly 63%), compared with 25% in those without a gout diagnosis. The prevalence was even higher (83%) among those with a more stringently defined gout diagnosis (specifically, those on urate-lowering therapy), Dr. Edwards noted (Arthritis Rheum. 2007;57:109-15).

As with hyperuricemia, the investigators concluded that the prevalence of metabolic syndrome is high in individuals with gout, and that, given the serious complications that can be associated with metabolic syndrome, the condition should be recognized and taken into account when clinicians plan the long-term treatment of patients with gout.

The findings of these two studies support a pathogenic overlap between metabolic syndrome and gout, and underscore the importance of evaluating gout patients for the syndrome, Dr. Edwards said.

“You see a lot of patients coming in, and they haven't had fasting glucoses performed, blood pressures may be a little out of control, and weight is certainly out of control,” he noted.

“We need to look at these patients much more seriously than if they only have gout; they need a full-court press on all of their metabolic problems and not just their uric acid.”

Dietary recommendations that consist of the standard advice to avoid foods high in purines are not sufficient. Patients will often cut out meat and shellfish, but replace those with foods high in carbohydrates and fat, which can increase insulin resistance. Therefore, it is important to advise patients to reduce intake of high-purine foods, but also to avoid high-fat foods and the wrong kinds of carbohydrates.

About 40% of their diet should be complex carbohydrates, no more than 30% should be proteins, and no more than 30% should be mono- or polyunsaturated fats, he said.

As for medical treatment considerations, it is important to keep in mind the mechanisms of hyperuricemia as it relates to insulin resistance, he added.

In patients who are hypertriglyceridemic, for example, niacin is a commonly used drug.

However, niacin can elevate uric acid levels “by quite a margin” of 1.5-2.5 mg/dL. Conversely, fenofibrate can also be used to treat hypertriglyceridemia, and can lower the levels by a similar margin.

“So just making that switch might make a pretty substantial difference,” Dr. Edwards said.

In patients who are being treated for hypertension, keep in mind that hydrochlorothiazide is associated with elevated uric acid levels, and consider switching to the angiotensin receptor blocker losartan in those in whom hydrochlorathiazide is used solely for hypertension control and not for fluid control, as losartan has uric acid lowering effects, he said.

Dr. Edwards had no disclosures relevant to his presentation.

Patients presenting with hyperuricemia or gout should be evaluated for metabolic syndrome, and any recommendations regarding dietary changes and medical treatment for gout should take into consideration the potential benefits of urate reduction, according to Dr. N. Lawrence Edwards.

Both hyperuricemia and gout are independent risk factors for metabolic syndrome and its individual components, said Dr. Edwards, professor of medicine at the University of Florida, Gainesville.

In a 2007 study looking at the prevalence of metabolic syndrome in nearly 8,700 patients with hyperuricemia from the NHANES (National Health and Nutrition Examination Survey) III database, the prevalence of metabolic syndrome increased in tandem with increasing levels of serum urate, and the increase persisted across subgroups stratified by age, sex, alcohol intake, body mass index, hypertension, and diabetes (Am. J. Med. 2007;120:442-7).

The investigators found that the prevalence of metabolic syndrome (defined using both original and revised National Cholesterol Education Program Adult Treatment Panel III criteria) was 19% in those with uric acid levels less than 6 mg/dL, 36% in those with 8.0-8.9 mg/dL, 62% for 9.0-9.9 mg/dL, and 71% for levels of 10 mg/dL or greater.

Physicians should recognize that metabolic syndrome occurs frequently in patients with hyperuricemia, and should be treated to prevent serious complications, they concluded.

In a related study, the prevalence of metabolic syndrome in patients with doctor-diagnosed gout from the same NHANES population was high (nearly 63%), compared with 25% in those without a gout diagnosis. The prevalence was even higher (83%) among those with a more stringently defined gout diagnosis (specifically, those on urate-lowering therapy), Dr. Edwards noted (Arthritis Rheum. 2007;57:109-15).

As with hyperuricemia, the investigators concluded that the prevalence of metabolic syndrome is high in individuals with gout, and that, given the serious complications that can be associated with metabolic syndrome, the condition should be recognized and taken into account when clinicians plan the long-term treatment of patients with gout.

The findings of these two studies support a pathogenic overlap between metabolic syndrome and gout, and underscore the importance of evaluating gout patients for the syndrome, Dr. Edwards said.

“You see a lot of patients coming in, and they haven't had fasting glucoses performed, blood pressures may be a little out of control, and weight is certainly out of control,” he noted.

“We need to look at these patients much more seriously than if they only have gout; they need a full-court press on all of their metabolic problems and not just their uric acid.”

Dietary recommendations that consist of the standard advice to avoid foods high in purines are not sufficient. Patients will often cut out meat and shellfish, but replace those with foods high in carbohydrates and fat, which can increase insulin resistance. Therefore, it is important to advise patients to reduce intake of high-purine foods, but also to avoid high-fat foods and the wrong kinds of carbohydrates.

About 40% of their diet should be complex carbohydrates, no more than 30% should be proteins, and no more than 30% should be mono- or polyunsaturated fats, he said.

As for medical treatment considerations, it is important to keep in mind the mechanisms of hyperuricemia as it relates to insulin resistance, he added.

In patients who are hypertriglyceridemic, for example, niacin is a commonly used drug.

However, niacin can elevate uric acid levels “by quite a margin” of 1.5-2.5 mg/dL. Conversely, fenofibrate can also be used to treat hypertriglyceridemia, and can lower the levels by a similar margin.

“So just making that switch might make a pretty substantial difference,” Dr. Edwards said.

In patients who are being treated for hypertension, keep in mind that hydrochlorothiazide is associated with elevated uric acid levels, and consider switching to the angiotensin receptor blocker losartan in those in whom hydrochlorathiazide is used solely for hypertension control and not for fluid control, as losartan has uric acid lowering effects, he said.

Dr. Edwards had no disclosures relevant to his presentation.

The jury is still out on just how cardiovascular risk should be screened for and managed in rheumatoid arthritis patients, but it is clear that the risk is increased and must be addressed.

In one study, silent myocardial infarction was shown to occur more often in RA patients than controls, and sudden death was also more likely in the RA patients (Arthritis Rheum. 2005;52:402-11). In another study, survival among patients with acute cardiac syndrome was substantially reduced in patients with RA versus those without (Ann. Rheum. Dis. 2006; 65:348-53).

The European League Against Rheumatism has proposed that conventional cardiovascular risk models be multiplied by 1.5 when assessing risk in RA patients (Ann. Rheum. Dis. 2010;69:325-31). This approach is not well validated, and Dr. Joan Bathon, director of the division of rheumatology at Columbia University, New York, said she is not sure it is being widely used at this point.

The proposal illustrates the importance of focusing on cardiovascular risk in RA patients, and it suggests that considering RA as a risk factor equivalent to diabetes mellitus – at least for decision making regarding low-density lipoprotein goals – is a reasonable strategy, Dr. Bathon said at the annual congress of clinical rheumatology.

She also said a potential screening strategy involves yearly cardiovascular risk assessments. The benefits of using imaging and biomarkers for screening are unclear, and no guidelines are currently in place, but some data suggest that the use of carotid ultrasound scans to look for plaques and to assess intima-media thickness, and the calculation of a coronary artery calcium score calculated on computed tomography findings may be useful in patients over age 40 years.

As for potential management strategies, aspirin therapy might be beneficial, but it should be considered in the context of other medications the patient is taking. Statins are also a potential management tool, but questions remain about whether all RA patients should be treated regardless of LDL level, she said.

Definite treatment strategies for RA patients include weight management for overweight patients, which will help reduce inflammation, and exercise for all RA patients, because good quality muscle building will help restore insulin sensitivity and reduce fat deposits that are the most inflammatory. Tight blood pressure control and tight RA control are also imperative, she said.

Dr. Bathon had no relevant disclosures.

The jury is still out on just how cardiovascular risk should be screened for and managed in rheumatoid arthritis patients, but it is clear that the risk is increased and must be addressed.

In one study, silent myocardial infarction was shown to occur more often in RA patients than controls, and sudden death was also more likely in the RA patients (Arthritis Rheum. 2005;52:402-11). In another study, survival among patients with acute cardiac syndrome was substantially reduced in patients with RA versus those without (Ann. Rheum. Dis. 2006; 65:348-53).

The European League Against Rheumatism has proposed that conventional cardiovascular risk models be multiplied by 1.5 when assessing risk in RA patients (Ann. Rheum. Dis. 2010;69:325-31). This approach is not well validated, and Dr. Joan Bathon, director of the division of rheumatology at Columbia University, New York, said she is not sure it is being widely used at this point.

The proposal illustrates the importance of focusing on cardiovascular risk in RA patients, and it suggests that considering RA as a risk factor equivalent to diabetes mellitus – at least for decision making regarding low-density lipoprotein goals – is a reasonable strategy, Dr. Bathon said at the annual congress of clinical rheumatology.

She also said a potential screening strategy involves yearly cardiovascular risk assessments. The benefits of using imaging and biomarkers for screening are unclear, and no guidelines are currently in place, but some data suggest that the use of carotid ultrasound scans to look for plaques and to assess intima-media thickness, and the calculation of a coronary artery calcium score calculated on computed tomography findings may be useful in patients over age 40 years.

As for potential management strategies, aspirin therapy might be beneficial, but it should be considered in the context of other medications the patient is taking. Statins are also a potential management tool, but questions remain about whether all RA patients should be treated regardless of LDL level, she said.

Definite treatment strategies for RA patients include weight management for overweight patients, which will help reduce inflammation, and exercise for all RA patients, because good quality muscle building will help restore insulin sensitivity and reduce fat deposits that are the most inflammatory. Tight blood pressure control and tight RA control are also imperative, she said.

Dr. Bathon had no relevant disclosures.

The jury is still out on just how cardiovascular risk should be screened for and managed in rheumatoid arthritis patients, but it is clear that the risk is increased and must be addressed.

In one study, silent myocardial infarction was shown to occur more often in RA patients than controls, and sudden death was also more likely in the RA patients (Arthritis Rheum. 2005;52:402-11). In another study, survival among patients with acute cardiac syndrome was substantially reduced in patients with RA versus those without (Ann. Rheum. Dis. 2006; 65:348-53).

The European League Against Rheumatism has proposed that conventional cardiovascular risk models be multiplied by 1.5 when assessing risk in RA patients (Ann. Rheum. Dis. 2010;69:325-31). This approach is not well validated, and Dr. Joan Bathon, director of the division of rheumatology at Columbia University, New York, said she is not sure it is being widely used at this point.

The proposal illustrates the importance of focusing on cardiovascular risk in RA patients, and it suggests that considering RA as a risk factor equivalent to diabetes mellitus – at least for decision making regarding low-density lipoprotein goals – is a reasonable strategy, Dr. Bathon said at the annual congress of clinical rheumatology.

She also said a potential screening strategy involves yearly cardiovascular risk assessments. The benefits of using imaging and biomarkers for screening are unclear, and no guidelines are currently in place, but some data suggest that the use of carotid ultrasound scans to look for plaques and to assess intima-media thickness, and the calculation of a coronary artery calcium score calculated on computed tomography findings may be useful in patients over age 40 years.

As for potential management strategies, aspirin therapy might be beneficial, but it should be considered in the context of other medications the patient is taking. Statins are also a potential management tool, but questions remain about whether all RA patients should be treated regardless of LDL level, she said.

Definite treatment strategies for RA patients include weight management for overweight patients, which will help reduce inflammation, and exercise for all RA patients, because good quality muscle building will help restore insulin sensitivity and reduce fat deposits that are the most inflammatory. Tight blood pressure control and tight RA control are also imperative, she said.

Dr. Bathon had no relevant disclosures.

The burden of pain among older patients is great, and its consequences can be "serious and significant," according to Dr. Perry G. Fine.

The prevalence of pain ranges from 25% to 50% in the older population and increases with age, he said.

In fact, among older nursing home residents, the prevalence is estimated at 45%-80%. In one study, 20% of individuals aged 65 and older admitted to having a day-long bout of pain in the past month, and about 60% said they had experienced pain for a year or more, said Dr. Fine, professor of anesthesiology at the University of Utah, Salt Lake City.

The sources of pain in these patients are many and varied, and the consequences can include mood disorders, sleep disturbances, decreased socialization, increased health care utilization and costs, limitations in activities of daily living, comorbidities, and polypharmacy, all of which can lead to diminished function and quality of life.

Further complicating the problem is the fact that studies have repeatedly shown that pain in older adults is frequently undertreated, Dr. Fine said.

This may be the result of one or more of the numerous identified barriers to the management of pain in older patients, including language and cultural barriers, fear of judgment, fear of addiction, cognitive impairment, sensory impairment, and adverse effects such as fear of falling, constipation, sedation, and drug-drug interactions. Barriers for clinicians can include the lack of objective measures of pain and pain response, concerns regarding addiction and/or drug seeking, fear of causing harm from medication-related adverse effects, lack of time in the office setting, and lack of pain management training, according to findings from two studies on the topic (Clin. J. Pain. 2007;23[suppl. 1]:S1-43; J. Adv. Nurs. 2009;65:2-10).

Following a list of 10 "universal precautions" in pain management can help with overcoming some of these barriers, Dr. Fine said (Pain. Med. 2005;6:107-12). These include the following:

• Making a diagnosis with appropriate differential diagnoses.

• Performing psychological assessments, including evaluation for risk of addictive disorders.

• Obtaining informed consent.

• Developing treatment agreements.

• Performing pain and function assessments.

• Using pain medication – and particularly opioids – on a trial basis.

• Reassessing pain, function, and behavior.

• Regularly reassessing the "Four As" (analgesia, activities of daily living, adverse events, and aberrant drug-taking behaviors).

• Periodically reviewing diagnosis and comorbidities.

• Documenting thoroughly.

Also, keep in mind that aging results in a number of physiological changes that will influence both pharmacokinetics and pharmacodynamics, including changes in body composition; decreases in gastrointestinal motility, hepatic metabolism, renal clearance, and protein binding; and increased central nervous system sensitivity to noxious stimuli and medication effects, Dr. Fine said (Neurobiol. Aging 2010;31:494-503; Clin. J. Pain. 2004;20:220-6).

While speaking at the Congress of Clinical Rheumatology, Dr. Fine listed the following general principles to follow when it comes to pharmacotherapy in light of these changes and the needs of older adults:

• Titrate according to individual circumstances.

• Anticipate and monitor for adverse effects, prevent them when possible, and treat them when necessary.

• Practice synergy by combining lower doses of drugs that mediate analgesia via different mechanisms.

• Know and understand the distinctions among tolerance, dependence, addiction, and pseudoaddiction.

In those with cognitive impairment, in whom pain assessment can be particularly challenging, consider alternatives to standard numeric rating scales for pain assessment. Patients who have difficulty reporting pain based on these types of scales may do better with the Iowa Pain Thermometer, which allows a patient to rate pain using increments on a picture of a thermometer (Pain Med. 2007;8:585-600) or with the Brief Pain Inventory. Reports from caregivers may also be useful, Dr. Fine said.

Dr. Fine reported having no conflicts of interest that were relevant to his presentation.

The burden of pain among older patients is great, and its consequences can be "serious and significant," according to Dr. Perry G. Fine.

The prevalence of pain ranges from 25% to 50% in the older population and increases with age, he said.

In fact, among older nursing home residents, the prevalence is estimated at 45%-80%. In one study, 20% of individuals aged 65 and older admitted to having a day-long bout of pain in the past month, and about 60% said they had experienced pain for a year or more, said Dr. Fine, professor of anesthesiology at the University of Utah, Salt Lake City.

The sources of pain in these patients are many and varied, and the consequences can include mood disorders, sleep disturbances, decreased socialization, increased health care utilization and costs, limitations in activities of daily living, comorbidities, and polypharmacy, all of which can lead to diminished function and quality of life.

Further complicating the problem is the fact that studies have repeatedly shown that pain in older adults is frequently undertreated, Dr. Fine said.

This may be the result of one or more of the numerous identified barriers to the management of pain in older patients, including language and cultural barriers, fear of judgment, fear of addiction, cognitive impairment, sensory impairment, and adverse effects such as fear of falling, constipation, sedation, and drug-drug interactions. Barriers for clinicians can include the lack of objective measures of pain and pain response, concerns regarding addiction and/or drug seeking, fear of causing harm from medication-related adverse effects, lack of time in the office setting, and lack of pain management training, according to findings from two studies on the topic (Clin. J. Pain. 2007;23[suppl. 1]:S1-43; J. Adv. Nurs. 2009;65:2-10).

Following a list of 10 "universal precautions" in pain management can help with overcoming some of these barriers, Dr. Fine said (Pain. Med. 2005;6:107-12). These include the following:

• Making a diagnosis with appropriate differential diagnoses.

• Performing psychological assessments, including evaluation for risk of addictive disorders.

• Obtaining informed consent.

• Developing treatment agreements.

• Performing pain and function assessments.

• Using pain medication – and particularly opioids – on a trial basis.

• Reassessing pain, function, and behavior.

• Regularly reassessing the "Four As" (analgesia, activities of daily living, adverse events, and aberrant drug-taking behaviors).

• Periodically reviewing diagnosis and comorbidities.

• Documenting thoroughly.

Also, keep in mind that aging results in a number of physiological changes that will influence both pharmacokinetics and pharmacodynamics, including changes in body composition; decreases in gastrointestinal motility, hepatic metabolism, renal clearance, and protein binding; and increased central nervous system sensitivity to noxious stimuli and medication effects, Dr. Fine said (Neurobiol. Aging 2010;31:494-503; Clin. J. Pain. 2004;20:220-6).

While speaking at the Congress of Clinical Rheumatology, Dr. Fine listed the following general principles to follow when it comes to pharmacotherapy in light of these changes and the needs of older adults:

• Titrate according to individual circumstances.

• Anticipate and monitor for adverse effects, prevent them when possible, and treat them when necessary.

• Practice synergy by combining lower doses of drugs that mediate analgesia via different mechanisms.

• Know and understand the distinctions among tolerance, dependence, addiction, and pseudoaddiction.

In those with cognitive impairment, in whom pain assessment can be particularly challenging, consider alternatives to standard numeric rating scales for pain assessment. Patients who have difficulty reporting pain based on these types of scales may do better with the Iowa Pain Thermometer, which allows a patient to rate pain using increments on a picture of a thermometer (Pain Med. 2007;8:585-600) or with the Brief Pain Inventory. Reports from caregivers may also be useful, Dr. Fine said.

Dr. Fine reported having no conflicts of interest that were relevant to his presentation.

The burden of pain among older patients is great, and its consequences can be "serious and significant," according to Dr. Perry G. Fine.

The prevalence of pain ranges from 25% to 50% in the older population and increases with age, he said.

In fact, among older nursing home residents, the prevalence is estimated at 45%-80%. In one study, 20% of individuals aged 65 and older admitted to having a day-long bout of pain in the past month, and about 60% said they had experienced pain for a year or more, said Dr. Fine, professor of anesthesiology at the University of Utah, Salt Lake City.

The sources of pain in these patients are many and varied, and the consequences can include mood disorders, sleep disturbances, decreased socialization, increased health care utilization and costs, limitations in activities of daily living, comorbidities, and polypharmacy, all of which can lead to diminished function and quality of life.

Further complicating the problem is the fact that studies have repeatedly shown that pain in older adults is frequently undertreated, Dr. Fine said.

This may be the result of one or more of the numerous identified barriers to the management of pain in older patients, including language and cultural barriers, fear of judgment, fear of addiction, cognitive impairment, sensory impairment, and adverse effects such as fear of falling, constipation, sedation, and drug-drug interactions. Barriers for clinicians can include the lack of objective measures of pain and pain response, concerns regarding addiction and/or drug seeking, fear of causing harm from medication-related adverse effects, lack of time in the office setting, and lack of pain management training, according to findings from two studies on the topic (Clin. J. Pain. 2007;23[suppl. 1]:S1-43; J. Adv. Nurs. 2009;65:2-10).

Following a list of 10 "universal precautions" in pain management can help with overcoming some of these barriers, Dr. Fine said (Pain. Med. 2005;6:107-12). These include the following:

• Making a diagnosis with appropriate differential diagnoses.

• Performing psychological assessments, including evaluation for risk of addictive disorders.

• Obtaining informed consent.

• Developing treatment agreements.

• Performing pain and function assessments.

• Using pain medication – and particularly opioids – on a trial basis.

• Reassessing pain, function, and behavior.

• Regularly reassessing the "Four As" (analgesia, activities of daily living, adverse events, and aberrant drug-taking behaviors).

• Periodically reviewing diagnosis and comorbidities.

• Documenting thoroughly.

Also, keep in mind that aging results in a number of physiological changes that will influence both pharmacokinetics and pharmacodynamics, including changes in body composition; decreases in gastrointestinal motility, hepatic metabolism, renal clearance, and protein binding; and increased central nervous system sensitivity to noxious stimuli and medication effects, Dr. Fine said (Neurobiol. Aging 2010;31:494-503; Clin. J. Pain. 2004;20:220-6).

While speaking at the Congress of Clinical Rheumatology, Dr. Fine listed the following general principles to follow when it comes to pharmacotherapy in light of these changes and the needs of older adults:

• Titrate according to individual circumstances.

• Anticipate and monitor for adverse effects, prevent them when possible, and treat them when necessary.

• Practice synergy by combining lower doses of drugs that mediate analgesia via different mechanisms.

• Know and understand the distinctions among tolerance, dependence, addiction, and pseudoaddiction.

In those with cognitive impairment, in whom pain assessment can be particularly challenging, consider alternatives to standard numeric rating scales for pain assessment. Patients who have difficulty reporting pain based on these types of scales may do better with the Iowa Pain Thermometer, which allows a patient to rate pain using increments on a picture of a thermometer (Pain Med. 2007;8:585-600) or with the Brief Pain Inventory. Reports from caregivers may also be useful, Dr. Fine said.

Dr. Fine reported having no conflicts of interest that were relevant to his presentation.

BOCA RATON, FLA. – Pediatric melanoma can be difficult to predict, as the known risk factors in adults typically don't apply in children, but one exception is in the setting of giant congenital melanocytic nevi.

Giant congenital melanocytic nevi (CMN) are rare, occurring in fewer than 1 in 100,000 live births, but the estimated incidence of soft tissue melanoma in association with such nevi, based on a number of retrospective studies, is about 4%, said Dr. Seth J. Orlow at the annual meeting of the Florida Society of Dermatology and Dermatologic Surgery.

Interestingly, the risk of melanoma of the central nervous system or other internal site is slightly higher at about 5% (J. Am. Acad. Dermatol. 1979;1:123-300) , said Dr. Orlow, chair of dermatology and a professor of pediatric dermatology at New York University.

The risk of melanoma in association with giant CMN across the lifetime is up to 10%. The risk appears based on findings from several prospective trials that half of that risk is concentrated in the first 5 years of life, he said.

The greatest risk, in his experience, is in children with giant CMN involving the scalp or posterior axial location, and in particular in those with satellite congenital nevi.

"The child who is born with multiple small congenital nevi – in fact, even if they don't have a giant congenital nevus with multiple small congenital nevi – has a risk factor," he said. Giant CMN by itself doesn't seem to be much of an issue, he noted.

To date there have been no reports of melanoma developing within a satellite nevus, despite some of these patients having up to 100 congenital nevi for years, he said.

When melanomas do arise in patients with giant CMN, they can be very difficult to recognize early, he added. In addition to those that arise in the central nervous system, some develop in the dermis or below, and in some cases no primary site can be found.

The risk of melanoma in children who have medium-sized CMN is much lower than with giant CMN and is estimated at less than 0.1% over the lifetime, he noted.

In one study of 227 patients with medium CMN followed for nearly 7 years, no melanomas developed (J. Am. Acad. Dermatol. 1998;39:428-33). Findings from another study involving information from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program database showed that the risk is about 1 in 10,000 patients before puberty, and 1 in 4,000 patients over the lifetime (Pediatr. Dermatol. 1994;11:204-8).

Thus it appears that most of the medium CMN occur after puberty, and they tend to arise at the dermal-epidermal junction, Dr. Orlow said.

The risk with small CMN can't be quantified, but is "much, much, much lower," he said.

Dr. Orlow had no disclosures relevant to his presentation.

BOCA RATON, FLA. – Pediatric melanoma can be difficult to predict, as the known risk factors in adults typically don't apply in children, but one exception is in the setting of giant congenital melanocytic nevi.

Giant congenital melanocytic nevi (CMN) are rare, occurring in fewer than 1 in 100,000 live births, but the estimated incidence of soft tissue melanoma in association with such nevi, based on a number of retrospective studies, is about 4%, said Dr. Seth J. Orlow at the annual meeting of the Florida Society of Dermatology and Dermatologic Surgery.

Interestingly, the risk of melanoma of the central nervous system or other internal site is slightly higher at about 5% (J. Am. Acad. Dermatol. 1979;1:123-300) , said Dr. Orlow, chair of dermatology and a professor of pediatric dermatology at New York University.

The risk of melanoma in association with giant CMN across the lifetime is up to 10%. The risk appears based on findings from several prospective trials that half of that risk is concentrated in the first 5 years of life, he said.

The greatest risk, in his experience, is in children with giant CMN involving the scalp or posterior axial location, and in particular in those with satellite congenital nevi.

"The child who is born with multiple small congenital nevi – in fact, even if they don't have a giant congenital nevus with multiple small congenital nevi – has a risk factor," he said. Giant CMN by itself doesn't seem to be much of an issue, he noted.

To date there have been no reports of melanoma developing within a satellite nevus, despite some of these patients having up to 100 congenital nevi for years, he said.

When melanomas do arise in patients with giant CMN, they can be very difficult to recognize early, he added. In addition to those that arise in the central nervous system, some develop in the dermis or below, and in some cases no primary site can be found.

The risk of melanoma in children who have medium-sized CMN is much lower than with giant CMN and is estimated at less than 0.1% over the lifetime, he noted.

In one study of 227 patients with medium CMN followed for nearly 7 years, no melanomas developed (J. Am. Acad. Dermatol. 1998;39:428-33). Findings from another study involving information from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program database showed that the risk is about 1 in 10,000 patients before puberty, and 1 in 4,000 patients over the lifetime (Pediatr. Dermatol. 1994;11:204-8).

Thus it appears that most of the medium CMN occur after puberty, and they tend to arise at the dermal-epidermal junction, Dr. Orlow said.

The risk with small CMN can't be quantified, but is "much, much, much lower," he said.

Dr. Orlow had no disclosures relevant to his presentation.

BOCA RATON, FLA. – Pediatric melanoma can be difficult to predict, as the known risk factors in adults typically don't apply in children, but one exception is in the setting of giant congenital melanocytic nevi.

Giant congenital melanocytic nevi (CMN) are rare, occurring in fewer than 1 in 100,000 live births, but the estimated incidence of soft tissue melanoma in association with such nevi, based on a number of retrospective studies, is about 4%, said Dr. Seth J. Orlow at the annual meeting of the Florida Society of Dermatology and Dermatologic Surgery.

Interestingly, the risk of melanoma of the central nervous system or other internal site is slightly higher at about 5% (J. Am. Acad. Dermatol. 1979;1:123-300) , said Dr. Orlow, chair of dermatology and a professor of pediatric dermatology at New York University.

The risk of melanoma in association with giant CMN across the lifetime is up to 10%. The risk appears based on findings from several prospective trials that half of that risk is concentrated in the first 5 years of life, he said.

The greatest risk, in his experience, is in children with giant CMN involving the scalp or posterior axial location, and in particular in those with satellite congenital nevi.

"The child who is born with multiple small congenital nevi – in fact, even if they don't have a giant congenital nevus with multiple small congenital nevi – has a risk factor," he said. Giant CMN by itself doesn't seem to be much of an issue, he noted.

To date there have been no reports of melanoma developing within a satellite nevus, despite some of these patients having up to 100 congenital nevi for years, he said.

When melanomas do arise in patients with giant CMN, they can be very difficult to recognize early, he added. In addition to those that arise in the central nervous system, some develop in the dermis or below, and in some cases no primary site can be found.

The risk of melanoma in children who have medium-sized CMN is much lower than with giant CMN and is estimated at less than 0.1% over the lifetime, he noted.

In one study of 227 patients with medium CMN followed for nearly 7 years, no melanomas developed (J. Am. Acad. Dermatol. 1998;39:428-33). Findings from another study involving information from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program database showed that the risk is about 1 in 10,000 patients before puberty, and 1 in 4,000 patients over the lifetime (Pediatr. Dermatol. 1994;11:204-8).

Thus it appears that most of the medium CMN occur after puberty, and they tend to arise at the dermal-epidermal junction, Dr. Orlow said.

The risk with small CMN can't be quantified, but is "much, much, much lower," he said.

Dr. Orlow had no disclosures relevant to his presentation.

BOCA RATON, FLA. – Pigmented Spitz nevi, and even atypical Spitzoid melanocytic tumors, are unlikely to be melanoma in children.

"Boy, does this create controversy," noted Dr. Seth J. Orlow at the meeting of the Florida Society of Dermatology and Dermatologic Surgery.

Pigmented Spitz nevi and atypical Spitzoid melanocytic tumors (ASMT) can appear suddenly and grow rapidly in children. Part of the problem is that these lesions have been shown to be associated with microscopic foci in draining lymph nodes in children who have been subjected to sentinel lymph node biopsy.

In some cases, this has been used as a basis for a diagnosis of melanoma.

"It turns logic upside down, but it's no proof of anything – only that the child has Spitz nevus," said Dr. Orlow, chair of dermatology and the Samuel Weinberg professor of pediatric dermatology at New York University.

Spitz nevi are common, and typically appear as pink-red papules on the face that are less than 1 cm in diameter. However, they can also develop as pigmented lesions, particularly on the limbs.

Although a pigmented lesion in a child is likely a Spitz nevus, the dermatoscope is particularly helpful for confirming the diagnosis, as Spitz nevi have a very characteristic starburst or peripheral globule appearance.

"This is one of those examples where having a dermatoscope really changes things I do," Dr. Orlow said, explaining that although he tends to assume that a pigmented lesion in a child is a Spitz nevus, seeing the typical pattern that is diagnostic of a Spitz nevus is reassuring for both him and the patient’s parents.

Even with ASMT (a subset of Spitzlike growths with features such as mitoses that are associated with melanoma), the risk of melanoma is minimal, he noted.

Although interobserver agreement on diagnosis and prognosis is poor with these lesions, data show that the prognosis is favorable in patients both with and without positive lymph nodes. In one recent study of 11 children with ASMT and positive lymph nodes, all remained disease free at an average of 47 months’ follow-up. By comparison, two of five children younger than age 18 years with histologically unambiguous melanoma and positive sentinel lymph nodes died from metastatic melanoma (Am. J. Surg. Pathol. 2009;33:1386-95).

This finding is not surprising, because these are not melanomas, Dr. Orlow said.

What are pediatric dermatologists' attitudes about Spitz nevi and ASMTs?

Findings from a recent Web-based survey of 350 pediatric dermatologists conducted by Dr. Orlow and his associates showed that academic pediatric dermatologists are most comfortable following Spitz nevi clinically, and are more likely to do so than are those in private practice. It also showed that both never seeing an unambiguous melanoma in a child and believing that Spitz nevi are not precursors to melanoma are – not unexpectedly – predictors of following patients clinically, Dr. Orlow said.

Also, clinicians observe both involution and evolution of Spitz nevi to more banal nevus subtypes as evidence of their benign nature, he said.

Of all those surveyed, only two (who were in private practice) had reported that a death resulting from melanoma had occurred in a patient of theirs.

"Not a single pediatric dermatologist at any academic medical center had ever seen a death from an atypical Spitz nevus in their entire career" he concluded.

Dr. Orlow had no disclosures relevant to his presentation.

BOCA RATON, FLA. – Pigmented Spitz nevi, and even atypical Spitzoid melanocytic tumors, are unlikely to be melanoma in children.

"Boy, does this create controversy," noted Dr. Seth J. Orlow at the meeting of the Florida Society of Dermatology and Dermatologic Surgery.

Pigmented Spitz nevi and atypical Spitzoid melanocytic tumors (ASMT) can appear suddenly and grow rapidly in children. Part of the problem is that these lesions have been shown to be associated with microscopic foci in draining lymph nodes in children who have been subjected to sentinel lymph node biopsy.

In some cases, this has been used as a basis for a diagnosis of melanoma.

"It turns logic upside down, but it's no proof of anything – only that the child has Spitz nevus," said Dr. Orlow, chair of dermatology and the Samuel Weinberg professor of pediatric dermatology at New York University.

Spitz nevi are common, and typically appear as pink-red papules on the face that are less than 1 cm in diameter. However, they can also develop as pigmented lesions, particularly on the limbs.

Although a pigmented lesion in a child is likely a Spitz nevus, the dermatoscope is particularly helpful for confirming the diagnosis, as Spitz nevi have a very characteristic starburst or peripheral globule appearance.

"This is one of those examples where having a dermatoscope really changes things I do," Dr. Orlow said, explaining that although he tends to assume that a pigmented lesion in a child is a Spitz nevus, seeing the typical pattern that is diagnostic of a Spitz nevus is reassuring for both him and the patient’s parents.

Even with ASMT (a subset of Spitzlike growths with features such as mitoses that are associated with melanoma), the risk of melanoma is minimal, he noted.

Although interobserver agreement on diagnosis and prognosis is poor with these lesions, data show that the prognosis is favorable in patients both with and without positive lymph nodes. In one recent study of 11 children with ASMT and positive lymph nodes, all remained disease free at an average of 47 months’ follow-up. By comparison, two of five children younger than age 18 years with histologically unambiguous melanoma and positive sentinel lymph nodes died from metastatic melanoma (Am. J. Surg. Pathol. 2009;33:1386-95).

This finding is not surprising, because these are not melanomas, Dr. Orlow said.

What are pediatric dermatologists' attitudes about Spitz nevi and ASMTs?

Findings from a recent Web-based survey of 350 pediatric dermatologists conducted by Dr. Orlow and his associates showed that academic pediatric dermatologists are most comfortable following Spitz nevi clinically, and are more likely to do so than are those in private practice. It also showed that both never seeing an unambiguous melanoma in a child and believing that Spitz nevi are not precursors to melanoma are – not unexpectedly – predictors of following patients clinically, Dr. Orlow said.

Also, clinicians observe both involution and evolution of Spitz nevi to more banal nevus subtypes as evidence of their benign nature, he said.

Of all those surveyed, only two (who were in private practice) had reported that a death resulting from melanoma had occurred in a patient of theirs.

"Not a single pediatric dermatologist at any academic medical center had ever seen a death from an atypical Spitz nevus in their entire career" he concluded.

Dr. Orlow had no disclosures relevant to his presentation.

BOCA RATON, FLA. – Pigmented Spitz nevi, and even atypical Spitzoid melanocytic tumors, are unlikely to be melanoma in children.

"Boy, does this create controversy," noted Dr. Seth J. Orlow at the meeting of the Florida Society of Dermatology and Dermatologic Surgery.

Pigmented Spitz nevi and atypical Spitzoid melanocytic tumors (ASMT) can appear suddenly and grow rapidly in children. Part of the problem is that these lesions have been shown to be associated with microscopic foci in draining lymph nodes in children who have been subjected to sentinel lymph node biopsy.

In some cases, this has been used as a basis for a diagnosis of melanoma.

"It turns logic upside down, but it's no proof of anything – only that the child has Spitz nevus," said Dr. Orlow, chair of dermatology and the Samuel Weinberg professor of pediatric dermatology at New York University.

Spitz nevi are common, and typically appear as pink-red papules on the face that are less than 1 cm in diameter. However, they can also develop as pigmented lesions, particularly on the limbs.

Although a pigmented lesion in a child is likely a Spitz nevus, the dermatoscope is particularly helpful for confirming the diagnosis, as Spitz nevi have a very characteristic starburst or peripheral globule appearance.

"This is one of those examples where having a dermatoscope really changes things I do," Dr. Orlow said, explaining that although he tends to assume that a pigmented lesion in a child is a Spitz nevus, seeing the typical pattern that is diagnostic of a Spitz nevus is reassuring for both him and the patient’s parents.

Even with ASMT (a subset of Spitzlike growths with features such as mitoses that are associated with melanoma), the risk of melanoma is minimal, he noted.

Although interobserver agreement on diagnosis and prognosis is poor with these lesions, data show that the prognosis is favorable in patients both with and without positive lymph nodes. In one recent study of 11 children with ASMT and positive lymph nodes, all remained disease free at an average of 47 months’ follow-up. By comparison, two of five children younger than age 18 years with histologically unambiguous melanoma and positive sentinel lymph nodes died from metastatic melanoma (Am. J. Surg. Pathol. 2009;33:1386-95).

This finding is not surprising, because these are not melanomas, Dr. Orlow said.

What are pediatric dermatologists' attitudes about Spitz nevi and ASMTs?

Findings from a recent Web-based survey of 350 pediatric dermatologists conducted by Dr. Orlow and his associates showed that academic pediatric dermatologists are most comfortable following Spitz nevi clinically, and are more likely to do so than are those in private practice. It also showed that both never seeing an unambiguous melanoma in a child and believing that Spitz nevi are not precursors to melanoma are – not unexpectedly – predictors of following patients clinically, Dr. Orlow said.

Also, clinicians observe both involution and evolution of Spitz nevi to more banal nevus subtypes as evidence of their benign nature, he said.

Of all those surveyed, only two (who were in private practice) had reported that a death resulting from melanoma had occurred in a patient of theirs.

"Not a single pediatric dermatologist at any academic medical center had ever seen a death from an atypical Spitz nevus in their entire career" he concluded.

Dr. Orlow had no disclosures relevant to his presentation.

BOCA RATON, FLA. – The risk factors for melanoma are well established in adults, as is the well-known ABCD method for self-evaluation for the disease, but assessing risk and recognizing melanoma in children are far less clear cut.

The typical risk factors, such as a history of changing moles, white race, and sun sensitivity, don't seem to apply in children to the degree they do in adults, and although the ABCDs (asymmetry, border irregularity, color variations, diameter over 6 mm) have withstood the test of time in adults, for whom they were developed, they don’t necessarily apply in children, Dr. Seth J. Orlow said at the meeting of the Florida Society of Dermatology and Dermatologic Surgery.

The relatively recent addition of an E to the ABCD method adds an element that is applicable to assessment of suspected melanoma in children, noted Dr. Orlow, chair of dermatology and the Samuel Weinberg professor of pediatric dermatology at New York University.

The E stands for evolving, and it refers to any unexpected change in a mole. It is the word "unexpected" that is important when it comes to moles in children, because in many cases – such as with Spitz nevi – some change is normal, he noted.

Adding to the challenge of predicting and diagnosing melanoma in children is the fact that the disease is very rare in this population, he said.

Based on information from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) Program database from 1973 to 2001, only 95 of 140,206 cases of melanoma were in children under age 10 years. Compared with older children with melanoma, those in this age group who had melanoma were more likely to be nonwhite; have metastatic disease; show nodular histology; have primary tumors on the head, face, and neck; and have a history of other cancer (J. Clin. Oncol. 2005;23:4735-41).

Among the melanoma patients younger than 10 years old, survival was about 90%, which was comparable to that in individuals aged 10-19 years and 20-24 years. Among those under age 20, survival was 100% if the melanoma was in situ, and 96%, 77%, and 57% if it was localized, regional, or distant, respectively.

Dr. Orlow noted that findings from other series over the years have also underscored the rarity of pediatric melanomas: Children's Hospital of Boston reported only 23 cases over 36 years, a Montreal hospital reported only 13 cases over 22 years, and Istituto Nazionale Tumor reported only 33 cases over 25 years. Many of the cases included nodular or amelanotic disease, reinforcing other data suggesting that children tend to have a different presentation than adults. For example, studies have shown that about 20% of melanomas are nodular in adults, compared with 30%-40% in children, and about 10%-20% of melanomas in adults are amelanotic, compared with about 30% in children.

Dr. Orlow noted that his own experience over 21 years underscores the rarity and differences of melanoma in children, compared with adults.

He has encountered only five authentic cases (excluding giant congenital melanocytic nevi), including one that he said "made the most sense" because it involved a 12-year-old boy from Chernobyl, the site of a 1986 large-scale explosion at a nuclear power plant in Ukraine. Radiation levels at that site remain high to this day. The child had a lesion on his lower back and innumerable dysplastic nevi. The boy's mother also had a history of melanoma as a child.

The other cases included one involving a 12-year old Ashkenazic Jewish girl with a less than 1-mm-thick lesion on her shoulder, one involving a 14-year-old Peruvian Indian girl with deeply pigmented skin and a 1-mm-thick lesion on her fingertip, one involving a 15-year old Ashkenazic/Sephardic boy with xeroderma pigmentosum C and two melanomas in situ, and one involving a 16-year-old Jamaican girl with very deeply pigmented skin who had an 8-mm-deep lesion on her posterior thigh and who died of her disease within 3 months.

"I think this list is typical in that it shows you that these are not people you would necessarily predict to have a problem," he said.

Children seem to differ from adults not only in terms of who gets melanoma, but also in terms of how they develop the disease.

Molecular alterations appear to differ in children, Dr. Orlow noted. While BRAF/NRAS pathway genetic mutations are present in 50%-70% of adults with superficial spreading melanomas, and mutations in the c-KIT gene are present in acral lentiginous and mucosal melanomas in adults, in children melanomas appear to have an increased incidence of deletion of c-KIT as well as mutations in the CDKN2A gene, according to one study (J. Invest. Dermatol. 2009;129:1759-68).

The workup and treatment of children with pediatric melanoma are well established. The prognostic value of sentinel lymph node biopsy – which is well established in adults – is also believed to apply in children. There is no evidence regarding lymph node dissection in either adults or children, although it is used frequently. Risks of lymph node dissection include infection and lymphedema, he noted.

As for treatment, adjuvant therapy includes high-dose interferon-alpha, which is approved for use in adults but not children. It has been used in several case series in children. Risks include fever, malaise, neutropenia, and abnormal liver function tests.

While there remains a great deal to learn about melanoma in children, there are several fallacies about the disease that dermatologists should know. The top five falacies, according to Dr. Orlow, are:

• Any new mole that appears suddenly in a child, or a mole that has grown over the past 6 months, should prompt concern about melanoma just as it does in adults. Reality: The appearance of new nevi in children is normal, and it is also normal for nevi to grow and evolve until they reach their zenith.

• Nevi on the scalp are particularly worrisome and should be removed because they are difficult to follow. Reality: The scalp is a common site for nevi to arise in white children. Such nevi will often have a targetlike appearance or resemble a fried egg. Many resolve by adulthood.

• All atypical/dysplastic nevi must be removed. Reality: Even in patients with the highest risk, such as those with familial atypical mole melanoma syndrome, more than 50% of melanomas will not have any evidence of a preexisting nevus.

• If melanocytic cells are found in a sentinel lymph node biopsy, it must be melanoma. Reality: Such cells can be found in the lymph nodes of children with Spitz nevi, atypical spitzoid melanocytic tumors, and blue nevi.

• We can prevent most prepubertal melanomas by applying our experience with melanoma and melanoma risk in adults. Reality: Such melanomas are unusual both clinically and with respect to the patients in whom they arise.

Dr. Orlow had no disclosures relevant to his presentation.

BOCA RATON, FLA. – The risk factors for melanoma are well established in adults, as is the well-known ABCD method for self-evaluation for the disease, but assessing risk and recognizing melanoma in children are far less clear cut.

The typical risk factors, such as a history of changing moles, white race, and sun sensitivity, don't seem to apply in children to the degree they do in adults, and although the ABCDs (asymmetry, border irregularity, color variations, diameter over 6 mm) have withstood the test of time in adults, for whom they were developed, they don’t necessarily apply in children, Dr. Seth J. Orlow said at the meeting of the Florida Society of Dermatology and Dermatologic Surgery.

The relatively recent addition of an E to the ABCD method adds an element that is applicable to assessment of suspected melanoma in children, noted Dr. Orlow, chair of dermatology and the Samuel Weinberg professor of pediatric dermatology at New York University.

The E stands for evolving, and it refers to any unexpected change in a mole. It is the word "unexpected" that is important when it comes to moles in children, because in many cases – such as with Spitz nevi – some change is normal, he noted.

Adding to the challenge of predicting and diagnosing melanoma in children is the fact that the disease is very rare in this population, he said.

Based on information from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) Program database from 1973 to 2001, only 95 of 140,206 cases of melanoma were in children under age 10 years. Compared with older children with melanoma, those in this age group who had melanoma were more likely to be nonwhite; have metastatic disease; show nodular histology; have primary tumors on the head, face, and neck; and have a history of other cancer (J. Clin. Oncol. 2005;23:4735-41).

Among the melanoma patients younger than 10 years old, survival was about 90%, which was comparable to that in individuals aged 10-19 years and 20-24 years. Among those under age 20, survival was 100% if the melanoma was in situ, and 96%, 77%, and 57% if it was localized, regional, or distant, respectively.

Dr. Orlow noted that findings from other series over the years have also underscored the rarity of pediatric melanomas: Children's Hospital of Boston reported only 23 cases over 36 years, a Montreal hospital reported only 13 cases over 22 years, and Istituto Nazionale Tumor reported only 33 cases over 25 years. Many of the cases included nodular or amelanotic disease, reinforcing other data suggesting that children tend to have a different presentation than adults. For example, studies have shown that about 20% of melanomas are nodular in adults, compared with 30%-40% in children, and about 10%-20% of melanomas in adults are amelanotic, compared with about 30% in children.

Dr. Orlow noted that his own experience over 21 years underscores the rarity and differences of melanoma in children, compared with adults.

He has encountered only five authentic cases (excluding giant congenital melanocytic nevi), including one that he said "made the most sense" because it involved a 12-year-old boy from Chernobyl, the site of a 1986 large-scale explosion at a nuclear power plant in Ukraine. Radiation levels at that site remain high to this day. The child had a lesion on his lower back and innumerable dysplastic nevi. The boy's mother also had a history of melanoma as a child.

The other cases included one involving a 12-year old Ashkenazic Jewish girl with a less than 1-mm-thick lesion on her shoulder, one involving a 14-year-old Peruvian Indian girl with deeply pigmented skin and a 1-mm-thick lesion on her fingertip, one involving a 15-year old Ashkenazic/Sephardic boy with xeroderma pigmentosum C and two melanomas in situ, and one involving a 16-year-old Jamaican girl with very deeply pigmented skin who had an 8-mm-deep lesion on her posterior thigh and who died of her disease within 3 months.

"I think this list is typical in that it shows you that these are not people you would necessarily predict to have a problem," he said.

Children seem to differ from adults not only in terms of who gets melanoma, but also in terms of how they develop the disease.

Molecular alterations appear to differ in children, Dr. Orlow noted. While BRAF/NRAS pathway genetic mutations are present in 50%-70% of adults with superficial spreading melanomas, and mutations in the c-KIT gene are present in acral lentiginous and mucosal melanomas in adults, in children melanomas appear to have an increased incidence of deletion of c-KIT as well as mutations in the CDKN2A gene, according to one study (J. Invest. Dermatol. 2009;129:1759-68).

The workup and treatment of children with pediatric melanoma are well established. The prognostic value of sentinel lymph node biopsy – which is well established in adults – is also believed to apply in children. There is no evidence regarding lymph node dissection in either adults or children, although it is used frequently. Risks of lymph node dissection include infection and lymphedema, he noted.

As for treatment, adjuvant therapy includes high-dose interferon-alpha, which is approved for use in adults but not children. It has been used in several case series in children. Risks include fever, malaise, neutropenia, and abnormal liver function tests.

While there remains a great deal to learn about melanoma in children, there are several fallacies about the disease that dermatologists should know. The top five falacies, according to Dr. Orlow, are:

• Any new mole that appears suddenly in a child, or a mole that has grown over the past 6 months, should prompt concern about melanoma just as it does in adults. Reality: The appearance of new nevi in children is normal, and it is also normal for nevi to grow and evolve until they reach their zenith.

• Nevi on the scalp are particularly worrisome and should be removed because they are difficult to follow. Reality: The scalp is a common site for nevi to arise in white children. Such nevi will often have a targetlike appearance or resemble a fried egg. Many resolve by adulthood.

• All atypical/dysplastic nevi must be removed. Reality: Even in patients with the highest risk, such as those with familial atypical mole melanoma syndrome, more than 50% of melanomas will not have any evidence of a preexisting nevus.

• If melanocytic cells are found in a sentinel lymph node biopsy, it must be melanoma. Reality: Such cells can be found in the lymph nodes of children with Spitz nevi, atypical spitzoid melanocytic tumors, and blue nevi.

• We can prevent most prepubertal melanomas by applying our experience with melanoma and melanoma risk in adults. Reality: Such melanomas are unusual both clinically and with respect to the patients in whom they arise.

Dr. Orlow had no disclosures relevant to his presentation.

BOCA RATON, FLA. – The risk factors for melanoma are well established in adults, as is the well-known ABCD method for self-evaluation for the disease, but assessing risk and recognizing melanoma in children are far less clear cut.

The typical risk factors, such as a history of changing moles, white race, and sun sensitivity, don't seem to apply in children to the degree they do in adults, and although the ABCDs (asymmetry, border irregularity, color variations, diameter over 6 mm) have withstood the test of time in adults, for whom they were developed, they don’t necessarily apply in children, Dr. Seth J. Orlow said at the meeting of the Florida Society of Dermatology and Dermatologic Surgery.

The relatively recent addition of an E to the ABCD method adds an element that is applicable to assessment of suspected melanoma in children, noted Dr. Orlow, chair of dermatology and the Samuel Weinberg professor of pediatric dermatology at New York University.

The E stands for evolving, and it refers to any unexpected change in a mole. It is the word "unexpected" that is important when it comes to moles in children, because in many cases – such as with Spitz nevi – some change is normal, he noted.

Adding to the challenge of predicting and diagnosing melanoma in children is the fact that the disease is very rare in this population, he said.

Based on information from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) Program database from 1973 to 2001, only 95 of 140,206 cases of melanoma were in children under age 10 years. Compared with older children with melanoma, those in this age group who had melanoma were more likely to be nonwhite; have metastatic disease; show nodular histology; have primary tumors on the head, face, and neck; and have a history of other cancer (J. Clin. Oncol. 2005;23:4735-41).

Among the melanoma patients younger than 10 years old, survival was about 90%, which was comparable to that in individuals aged 10-19 years and 20-24 years. Among those under age 20, survival was 100% if the melanoma was in situ, and 96%, 77%, and 57% if it was localized, regional, or distant, respectively.

Dr. Orlow noted that findings from other series over the years have also underscored the rarity of pediatric melanomas: Children's Hospital of Boston reported only 23 cases over 36 years, a Montreal hospital reported only 13 cases over 22 years, and Istituto Nazionale Tumor reported only 33 cases over 25 years. Many of the cases included nodular or amelanotic disease, reinforcing other data suggesting that children tend to have a different presentation than adults. For example, studies have shown that about 20% of melanomas are nodular in adults, compared with 30%-40% in children, and about 10%-20% of melanomas in adults are amelanotic, compared with about 30% in children.

Dr. Orlow noted that his own experience over 21 years underscores the rarity and differences of melanoma in children, compared with adults.

He has encountered only five authentic cases (excluding giant congenital melanocytic nevi), including one that he said "made the most sense" because it involved a 12-year-old boy from Chernobyl, the site of a 1986 large-scale explosion at a nuclear power plant in Ukraine. Radiation levels at that site remain high to this day. The child had a lesion on his lower back and innumerable dysplastic nevi. The boy's mother also had a history of melanoma as a child.

The other cases included one involving a 12-year old Ashkenazic Jewish girl with a less than 1-mm-thick lesion on her shoulder, one involving a 14-year-old Peruvian Indian girl with deeply pigmented skin and a 1-mm-thick lesion on her fingertip, one involving a 15-year old Ashkenazic/Sephardic boy with xeroderma pigmentosum C and two melanomas in situ, and one involving a 16-year-old Jamaican girl with very deeply pigmented skin who had an 8-mm-deep lesion on her posterior thigh and who died of her disease within 3 months.

"I think this list is typical in that it shows you that these are not people you would necessarily predict to have a problem," he said.

Children seem to differ from adults not only in terms of who gets melanoma, but also in terms of how they develop the disease.

Molecular alterations appear to differ in children, Dr. Orlow noted. While BRAF/NRAS pathway genetic mutations are present in 50%-70% of adults with superficial spreading melanomas, and mutations in the c-KIT gene are present in acral lentiginous and mucosal melanomas in adults, in children melanomas appear to have an increased incidence of deletion of c-KIT as well as mutations in the CDKN2A gene, according to one study (J. Invest. Dermatol. 2009;129:1759-68).

The workup and treatment of children with pediatric melanoma are well established. The prognostic value of sentinel lymph node biopsy – which is well established in adults – is also believed to apply in children. There is no evidence regarding lymph node dissection in either adults or children, although it is used frequently. Risks of lymph node dissection include infection and lymphedema, he noted.

As for treatment, adjuvant therapy includes high-dose interferon-alpha, which is approved for use in adults but not children. It has been used in several case series in children. Risks include fever, malaise, neutropenia, and abnormal liver function tests.

While there remains a great deal to learn about melanoma in children, there are several fallacies about the disease that dermatologists should know. The top five falacies, according to Dr. Orlow, are:

• Any new mole that appears suddenly in a child, or a mole that has grown over the past 6 months, should prompt concern about melanoma just as it does in adults. Reality: The appearance of new nevi in children is normal, and it is also normal for nevi to grow and evolve until they reach their zenith.

• Nevi on the scalp are particularly worrisome and should be removed because they are difficult to follow. Reality: The scalp is a common site for nevi to arise in white children. Such nevi will often have a targetlike appearance or resemble a fried egg. Many resolve by adulthood.

• All atypical/dysplastic nevi must be removed. Reality: Even in patients with the highest risk, such as those with familial atypical mole melanoma syndrome, more than 50% of melanomas will not have any evidence of a preexisting nevus.

• If melanocytic cells are found in a sentinel lymph node biopsy, it must be melanoma. Reality: Such cells can be found in the lymph nodes of children with Spitz nevi, atypical spitzoid melanocytic tumors, and blue nevi.

• We can prevent most prepubertal melanomas by applying our experience with melanoma and melanoma risk in adults. Reality: Such melanomas are unusual both clinically and with respect to the patients in whom they arise.

Dr. Orlow had no disclosures relevant to his presentation.

The jury is still out on just how cardiovascular risk should be screened and managed in rheumatoid arthritis patients, but it is clear that the risk is increased and must be addressed.

Patients with RA are known to have a lower probability of survival than do controls, and a major cause of excess death is from cardiovascular disease. In one study, silent myocardial infarction was shown to occur more often in RA patients than controls, and sudden death was also more likely in the RA patients (Arthritis Rheum. 2005;52:402-11). In another study, survival among patients with acute cardiac syndrome was substantially reduced in RA vs. non-RA patients (Ann. Rheum. Dis. 2006;65:348-53).

In fact, RA is now considered by some experts to be equivalent to diabetes mellitus in terms of the extent to which it confers cardiovascular risk, according to Dr. Joan Bathon, director of the division of rheumatology at Columbia University, New York.

The European League Against Rheumatism (EULAR) has proposed that conventional cardiovascular risk models be multiplied by 1.5 when risk is assessed in RA patients, said Dr. Bathon (Ann. Rheum. Dis. 2010;69:325-31).

This approach is not well validated and may not be widely used at this point, according to Dr. Bathon. But the proposal illustrates the importance of focusing on cardiovascular risk in RA patients. Furthermore, it suggests that considering RA as a risk factor equivalent to diabetes mellitus – at least for making decisions about LDL cholesterol goals – is a reasonable strategy, she said.

She also said that a potential screening strategy involves yearly cardiovascular risk screening. The benefits of using imaging and biomarkers for screening are unclear, and no guidelines are currently in place. Some data suggest that the use of carotid ultrasound scans to look for plaques and to assess intima-media thickness – and the calculation of a coronary artery calcium score using CT – may be useful in patients older than 40 years.

As for potential management strategies, aspirin therapy might be useful but should be considered in the context of other medications the patient is taking.

Statins are also a potential management tool, but questions remain about whether all RA patients should be treated regardless of LDL cholesterol level, Dr. Bathon said.

Definite treatment strategies for RA patients include weight management for overweight patients – which will help reduce inflammation – as well as exercise for all RA patients, because good quality muscle building will help restore insulin sensitivity and reduce fat depots that are the most inflammatory. Tight blood pressure control and tight RA control are also imperative, Dr. Bathon said.

She noted that conventional cardiovascular risk factors do not fully explain the excess risk in RA patients, and that inflammation probably plays an important role.

"We also have to think about ourselves," she said, referring to whether rheumatologists are aggressive enough in their management of cardiovascular risk in RA patients.

There is some question as to whether the increased risk in RA patients, compared with controls, is a result of less-aggressive treatment, she said.

Dr. Bathon had no disclosures relevant to her presentation.

The jury is still out on just how cardiovascular risk should be screened and managed in rheumatoid arthritis patients, but it is clear that the risk is increased and must be addressed.

Patients with RA are known to have a lower probability of survival than do controls, and a major cause of excess death is from cardiovascular disease. In one study, silent myocardial infarction was shown to occur more often in RA patients than controls, and sudden death was also more likely in the RA patients (Arthritis Rheum. 2005;52:402-11). In another study, survival among patients with acute cardiac syndrome was substantially reduced in RA vs. non-RA patients (Ann. Rheum. Dis. 2006;65:348-53).

In fact, RA is now considered by some experts to be equivalent to diabetes mellitus in terms of the extent to which it confers cardiovascular risk, according to Dr. Joan Bathon, director of the division of rheumatology at Columbia University, New York.

The European League Against Rheumatism (EULAR) has proposed that conventional cardiovascular risk models be multiplied by 1.5 when risk is assessed in RA patients, said Dr. Bathon (Ann. Rheum. Dis. 2010;69:325-31).

This approach is not well validated and may not be widely used at this point, according to Dr. Bathon. But the proposal illustrates the importance of focusing on cardiovascular risk in RA patients. Furthermore, it suggests that considering RA as a risk factor equivalent to diabetes mellitus – at least for making decisions about LDL cholesterol goals – is a reasonable strategy, she said.

She also said that a potential screening strategy involves yearly cardiovascular risk screening. The benefits of using imaging and biomarkers for screening are unclear, and no guidelines are currently in place. Some data suggest that the use of carotid ultrasound scans to look for plaques and to assess intima-media thickness – and the calculation of a coronary artery calcium score using CT – may be useful in patients older than 40 years.

As for potential management strategies, aspirin therapy might be useful but should be considered in the context of other medications the patient is taking.

Statins are also a potential management tool, but questions remain about whether all RA patients should be treated regardless of LDL cholesterol level, Dr. Bathon said.

Definite treatment strategies for RA patients include weight management for overweight patients – which will help reduce inflammation – as well as exercise for all RA patients, because good quality muscle building will help restore insulin sensitivity and reduce fat depots that are the most inflammatory. Tight blood pressure control and tight RA control are also imperative, Dr. Bathon said.

She noted that conventional cardiovascular risk factors do not fully explain the excess risk in RA patients, and that inflammation probably plays an important role.

"We also have to think about ourselves," she said, referring to whether rheumatologists are aggressive enough in their management of cardiovascular risk in RA patients.

There is some question as to whether the increased risk in RA patients, compared with controls, is a result of less-aggressive treatment, she said.

Dr. Bathon had no disclosures relevant to her presentation.

The jury is still out on just how cardiovascular risk should be screened and managed in rheumatoid arthritis patients, but it is clear that the risk is increased and must be addressed.

Patients with RA are known to have a lower probability of survival than do controls, and a major cause of excess death is from cardiovascular disease. In one study, silent myocardial infarction was shown to occur more often in RA patients than controls, and sudden death was also more likely in the RA patients (Arthritis Rheum. 2005;52:402-11). In another study, survival among patients with acute cardiac syndrome was substantially reduced in RA vs. non-RA patients (Ann. Rheum. Dis. 2006;65:348-53).

In fact, RA is now considered by some experts to be equivalent to diabetes mellitus in terms of the extent to which it confers cardiovascular risk, according to Dr. Joan Bathon, director of the division of rheumatology at Columbia University, New York.

The European League Against Rheumatism (EULAR) has proposed that conventional cardiovascular risk models be multiplied by 1.5 when risk is assessed in RA patients, said Dr. Bathon (Ann. Rheum. Dis. 2010;69:325-31).

This approach is not well validated and may not be widely used at this point, according to Dr. Bathon. But the proposal illustrates the importance of focusing on cardiovascular risk in RA patients. Furthermore, it suggests that considering RA as a risk factor equivalent to diabetes mellitus – at least for making decisions about LDL cholesterol goals – is a reasonable strategy, she said.

She also said that a potential screening strategy involves yearly cardiovascular risk screening. The benefits of using imaging and biomarkers for screening are unclear, and no guidelines are currently in place. Some data suggest that the use of carotid ultrasound scans to look for plaques and to assess intima-media thickness – and the calculation of a coronary artery calcium score using CT – may be useful in patients older than 40 years.

As for potential management strategies, aspirin therapy might be useful but should be considered in the context of other medications the patient is taking.

Statins are also a potential management tool, but questions remain about whether all RA patients should be treated regardless of LDL cholesterol level, Dr. Bathon said.

Definite treatment strategies for RA patients include weight management for overweight patients – which will help reduce inflammation – as well as exercise for all RA patients, because good quality muscle building will help restore insulin sensitivity and reduce fat depots that are the most inflammatory. Tight blood pressure control and tight RA control are also imperative, Dr. Bathon said.

She noted that conventional cardiovascular risk factors do not fully explain the excess risk in RA patients, and that inflammation probably plays an important role.

"We also have to think about ourselves," she said, referring to whether rheumatologists are aggressive enough in their management of cardiovascular risk in RA patients.

There is some question as to whether the increased risk in RA patients, compared with controls, is a result of less-aggressive treatment, she said.

Dr. Bathon had no disclosures relevant to her presentation.

Patients presenting with hyperuricemia or gout should be evaluated for metabolic syndrome, and any recommendations regarding dietary changes and medical treatment for gout should take into consideration the potential benefits of urate reduction, according to Dr. N. Lawrence Edwards.

Both hyperuricemia and gout are independent risk factors for metabolic syndrome and its individual components, said Dr. Edwards, professor of medicine at the University of Florida, Gainesville.

In a 2007 study looking at the prevalence of metabolic syndrome in nearly 8,700 patients with hyperuricemia from the NHANES (National Health and Nutrition Examination Survey) III database, the prevalence of metabolic syndrome increased in tandem with increasing levels of serum urate, and the increase persisted across subgroups stratified by age, sex, alcohol intake, body mass index, hypertension, and diabetes (Am. J. Med. 2007;120:442-7).

The investigators found that the prevalence of metabolic syndrome (defined using both original and revised National Cholesterol Education Program Adult Treatment Panel III criteria) was 19% in those with uric acid levels less than 6 mg/dL, 36% in those with 8.0-8.9 mg/dL, 62% for 9.0-9.9 mg/dL, and 71% for levels of 10 mg/dL or greater.

Physicians should recognize that metabolic syndrome occurs frequently in patients with hyperuricemia, and should be treated to prevent serious complications, they concluded.

In a related study, the prevalence of metabolic syndrome in patients with doctor-diagnosed gout from the same NHANES population was high (nearly 63%) when compared with 25% in those without a gout diagnosis. The prevalence was even higher (83%) among those with a more stringently defined gout diagnosis (specifically, those on urate-lower therapy), Dr. Edwards noted (Arthritis Rheum. 2007;57:109-15).

As with hyperuricemia, the investigators concluded that the prevalence of metabolic syndrome is high in individuals with gout, and that, given the serious complications that can be associated with metabolic syndrome, the condition should be recognized and taken into account when clinicians plan the long-term treatment of patients with gout.

Evaluating Gout Patients for Metabolic Syndrome

The findings of these two studies support a pathogenic overlap between metabolic syndrome and gout, and underscore the importance of evaluating gout patients for the syndrome, Dr. Edwards said.

"You see a lot of patients coming in, and they haven’t had fasting glucoses performed, blood pressures may be a little out of control, and weight is certainly out of control," he noted. "We need to look at these patients much more seriously than if they only have gout; they need a full-court press on all of their metabolic problems and not just their uric acid."

Dietary recommendations that consist of the standard advice to avoid foods high in purines are not sufficient. Patients will often cut out meat and shellfish but replace those with foods high in carbohydrates and fat, which can increase insulin resistance. Therefore, it is important to advise patients to reduce intake of high-purine foods and also to avoid high-fat foods and the wrong kinds of carbohydrates.

About 40% of their diet should be complex carbohydrates, no more than 30% should be proteins, and no more than 30% should be mono- or polyunsaturated fats, he said.

As for medical treatment considerations, it is important to keep in mind the mechanisms of hyperuricemia as it relates to insulin resistance, he added.

In patients who are hypertriglyceridemic, for example, niacin is a commonly used drug. However, niacin can elevate uric acid levels "by quite a margin" of 1.5-2.5 mg/dL. Conversely, fenofibrate can also be used to treat hypertriglyceridemia, and can lower the levels by a similar margin.

"So just making that switch might make a pretty substantial difference," Dr. Edwards said.

In patients who are being treated for hypertension, keep in mind that hydroclorothiazide is associated with elevated uric acid levels and consider switching to the angiotensin receptor blocker losartan in those in whom hydrochlorothiazide is used solely for hypertension control and not for fluid control, as losartan has uric acid lowering effects, he said.

Dr. Edwards had no disclosures relevant to his presentation.

Patients presenting with hyperuricemia or gout should be evaluated for metabolic syndrome, and any recommendations regarding dietary changes and medical treatment for gout should take into consideration the potential benefits of urate reduction, according to Dr. N. Lawrence Edwards.

Both hyperuricemia and gout are independent risk factors for metabolic syndrome and its individual components, said Dr. Edwards, professor of medicine at the University of Florida, Gainesville.

In a 2007 study looking at the prevalence of metabolic syndrome in nearly 8,700 patients with hyperuricemia from the NHANES (National Health and Nutrition Examination Survey) III database, the prevalence of metabolic syndrome increased in tandem with increasing levels of serum urate, and the increase persisted across subgroups stratified by age, sex, alcohol intake, body mass index, hypertension, and diabetes (Am. J. Med. 2007;120:442-7).

The investigators found that the prevalence of metabolic syndrome (defined using both original and revised National Cholesterol Education Program Adult Treatment Panel III criteria) was 19% in those with uric acid levels less than 6 mg/dL, 36% in those with 8.0-8.9 mg/dL, 62% for 9.0-9.9 mg/dL, and 71% for levels of 10 mg/dL or greater.

Physicians should recognize that metabolic syndrome occurs frequently in patients with hyperuricemia, and should be treated to prevent serious complications, they concluded.

In a related study, the prevalence of metabolic syndrome in patients with doctor-diagnosed gout from the same NHANES population was high (nearly 63%) when compared with 25% in those without a gout diagnosis. The prevalence was even higher (83%) among those with a more stringently defined gout diagnosis (specifically, those on urate-lower therapy), Dr. Edwards noted (Arthritis Rheum. 2007;57:109-15).

As with hyperuricemia, the investigators concluded that the prevalence of metabolic syndrome is high in individuals with gout, and that, given the serious complications that can be associated with metabolic syndrome, the condition should be recognized and taken into account when clinicians plan the long-term treatment of patients with gout.

Evaluating Gout Patients for Metabolic Syndrome

The findings of these two studies support a pathogenic overlap between metabolic syndrome and gout, and underscore the importance of evaluating gout patients for the syndrome, Dr. Edwards said.

"You see a lot of patients coming in, and they haven’t had fasting glucoses performed, blood pressures may be a little out of control, and weight is certainly out of control," he noted. "We need to look at these patients much more seriously than if they only have gout; they need a full-court press on all of their metabolic problems and not just their uric acid."

Dietary recommendations that consist of the standard advice to avoid foods high in purines are not sufficient. Patients will often cut out meat and shellfish but replace those with foods high in carbohydrates and fat, which can increase insulin resistance. Therefore, it is important to advise patients to reduce intake of high-purine foods and also to avoid high-fat foods and the wrong kinds of carbohydrates.

About 40% of their diet should be complex carbohydrates, no more than 30% should be proteins, and no more than 30% should be mono- or polyunsaturated fats, he said.

As for medical treatment considerations, it is important to keep in mind the mechanisms of hyperuricemia as it relates to insulin resistance, he added.

In patients who are hypertriglyceridemic, for example, niacin is a commonly used drug. However, niacin can elevate uric acid levels "by quite a margin" of 1.5-2.5 mg/dL. Conversely, fenofibrate can also be used to treat hypertriglyceridemia, and can lower the levels by a similar margin.

"So just making that switch might make a pretty substantial difference," Dr. Edwards said.

In patients who are being treated for hypertension, keep in mind that hydroclorothiazide is associated with elevated uric acid levels and consider switching to the angiotensin receptor blocker losartan in those in whom hydrochlorothiazide is used solely for hypertension control and not for fluid control, as losartan has uric acid lowering effects, he said.

Dr. Edwards had no disclosures relevant to his presentation.

Patients presenting with hyperuricemia or gout should be evaluated for metabolic syndrome, and any recommendations regarding dietary changes and medical treatment for gout should take into consideration the potential benefits of urate reduction, according to Dr. N. Lawrence Edwards.

Both hyperuricemia and gout are independent risk factors for metabolic syndrome and its individual components, said Dr. Edwards, professor of medicine at the University of Florida, Gainesville.

In a 2007 study looking at the prevalence of metabolic syndrome in nearly 8,700 patients with hyperuricemia from the NHANES (National Health and Nutrition Examination Survey) III database, the prevalence of metabolic syndrome increased in tandem with increasing levels of serum urate, and the increase persisted across subgroups stratified by age, sex, alcohol intake, body mass index, hypertension, and diabetes (Am. J. Med. 2007;120:442-7).

The investigators found that the prevalence of metabolic syndrome (defined using both original and revised National Cholesterol Education Program Adult Treatment Panel III criteria) was 19% in those with uric acid levels less than 6 mg/dL, 36% in those with 8.0-8.9 mg/dL, 62% for 9.0-9.9 mg/dL, and 71% for levels of 10 mg/dL or greater.

Physicians should recognize that metabolic syndrome occurs frequently in patients with hyperuricemia, and should be treated to prevent serious complications, they concluded.

In a related study, the prevalence of metabolic syndrome in patients with doctor-diagnosed gout from the same NHANES population was high (nearly 63%) when compared with 25% in those without a gout diagnosis. The prevalence was even higher (83%) among those with a more stringently defined gout diagnosis (specifically, those on urate-lower therapy), Dr. Edwards noted (Arthritis Rheum. 2007;57:109-15).

As with hyperuricemia, the investigators concluded that the prevalence of metabolic syndrome is high in individuals with gout, and that, given the serious complications that can be associated with metabolic syndrome, the condition should be recognized and taken into account when clinicians plan the long-term treatment of patients with gout.

Evaluating Gout Patients for Metabolic Syndrome

The findings of these two studies support a pathogenic overlap between metabolic syndrome and gout, and underscore the importance of evaluating gout patients for the syndrome, Dr. Edwards said.

"You see a lot of patients coming in, and they haven’t had fasting glucoses performed, blood pressures may be a little out of control, and weight is certainly out of control," he noted. "We need to look at these patients much more seriously than if they only have gout; they need a full-court press on all of their metabolic problems and not just their uric acid."

Dietary recommendations that consist of the standard advice to avoid foods high in purines are not sufficient. Patients will often cut out meat and shellfish but replace those with foods high in carbohydrates and fat, which can increase insulin resistance. Therefore, it is important to advise patients to reduce intake of high-purine foods and also to avoid high-fat foods and the wrong kinds of carbohydrates.

About 40% of their diet should be complex carbohydrates, no more than 30% should be proteins, and no more than 30% should be mono- or polyunsaturated fats, he said.

As for medical treatment considerations, it is important to keep in mind the mechanisms of hyperuricemia as it relates to insulin resistance, he added.

In patients who are hypertriglyceridemic, for example, niacin is a commonly used drug. However, niacin can elevate uric acid levels "by quite a margin" of 1.5-2.5 mg/dL. Conversely, fenofibrate can also be used to treat hypertriglyceridemia, and can lower the levels by a similar margin.

"So just making that switch might make a pretty substantial difference," Dr. Edwards said.

In patients who are being treated for hypertension, keep in mind that hydroclorothiazide is associated with elevated uric acid levels and consider switching to the angiotensin receptor blocker losartan in those in whom hydrochlorothiazide is used solely for hypertension control and not for fluid control, as losartan has uric acid lowering effects, he said.

Dr. Edwards had no disclosures relevant to his presentation.

PARIS – A panel of blood-based biomarkers for neocortical amyloid burden – a known predictor of progression to Alzheimer’s disease – shows promise as an effective and economical screening test for early identification of individuals at risk for the disease, according to findings from an Australian study highlighted at an international conference on Alzheimer’s disease.

Currently, neocortical amyloid burden is assessable only by expensive positron emission tomography, which requires radiotracers such as Pittsburgh Compound B (PiB) that are not widely available, or by invasive cerebrospinal fluid evaluation, Samantha Burnham, Ph.D., reported at an international conference on Alzheimer’s disease.

After analyzing 273 samples from patients with baseline blood and PiB-PET measurements from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study, the researchers developed a model using 9 blood-based markers (including A beta 1-42, ApoE, and cortisol) to estimate the amount of deposited amyloid in the brain.

That panel of markers had 83% sensitivity and 85% specificity for identifying the level of amyloid deemed to indicate risk of Alzheimer’s, said Dr. Burnham of the Commonwealth Scientific and Industrial Research Organization (CSIRO), Perth, Australia.

Predictions using the panel were also made in 817 nonimaged AIBL study participants. When those participants were grouped according to clinical diagnosis, the percentages of high neocortical amyloid burden were consistent with prior findings in the literature, with 34% of healthy controls, 87% of mild cognitively impaired individuals, and 100% of Alzheimer’s disease patients having a high burden, Dr. Burnham said.

In addition, the panel of markers was assessed in 74 subjects from the Alzheimer’s Disease Neuroimaging Initiative for validation. In that validation study, measurements for two of the markers from the panel were unavailable, and the sensitivity and specificity were slightly lower, at 76%.

Furthermore, when the samples from the AIBL study were reassessed without the two missing markers, the sensitivity and specificity dropped to a level comparable to that seen in the validation study (74%), suggesting that the accuracy in the validation study might have been even greater if all nine markers were available, she noted.

Because neocortical amyloid burden predicts progression to Alzheimer’s disease, and given that the model used in the study accurately predicts neocortical amyloid burden, Dr. Burnham said, it appears likely that the findings will lead to development of a useful, affordable screening test for the early identification of individuals at risk for developing Alzheimer’s disease.

While it is impossible to provide a timeline for development of such a test, as further validation is needed, she added, these findings are indeed a "first stepping stone toward early diagnosis.

"This is a good start toward having a blood-based diagnosis," Dr. Burnham said.

The conference was sponsored by the Alzheimer’s Association. Dr. Burnham had no disclosures relevant to her presentation.

PARIS – A panel of blood-based biomarkers for neocortical amyloid burden – a known predictor of progression to Alzheimer’s disease – shows promise as an effective and economical screening test for early identification of individuals at risk for the disease, according to findings from an Australian study highlighted at an international conference on Alzheimer’s disease.

Currently, neocortical amyloid burden is assessable only by expensive positron emission tomography, which requires radiotracers such as Pittsburgh Compound B (PiB) that are not widely available, or by invasive cerebrospinal fluid evaluation, Samantha Burnham, Ph.D., reported at an international conference on Alzheimer’s disease.

After analyzing 273 samples from patients with baseline blood and PiB-PET measurements from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study, the researchers developed a model using 9 blood-based markers (including A beta 1-42, ApoE, and cortisol) to estimate the amount of deposited amyloid in the brain.

That panel of markers had 83% sensitivity and 85% specificity for identifying the level of amyloid deemed to indicate risk of Alzheimer’s, said Dr. Burnham of the Commonwealth Scientific and Industrial Research Organization (CSIRO), Perth, Australia.

Predictions using the panel were also made in 817 nonimaged AIBL study participants. When those participants were grouped according to clinical diagnosis, the percentages of high neocortical amyloid burden were consistent with prior findings in the literature, with 34% of healthy controls, 87% of mild cognitively impaired individuals, and 100% of Alzheimer’s disease patients having a high burden, Dr. Burnham said.

In addition, the panel of markers was assessed in 74 subjects from the Alzheimer’s Disease Neuroimaging Initiative for validation. In that validation study, measurements for two of the markers from the panel were unavailable, and the sensitivity and specificity were slightly lower, at 76%.

Furthermore, when the samples from the AIBL study were reassessed without the two missing markers, the sensitivity and specificity dropped to a level comparable to that seen in the validation study (74%), suggesting that the accuracy in the validation study might have been even greater if all nine markers were available, she noted.

Because neocortical amyloid burden predicts progression to Alzheimer’s disease, and given that the model used in the study accurately predicts neocortical amyloid burden, Dr. Burnham said, it appears likely that the findings will lead to development of a useful, affordable screening test for the early identification of individuals at risk for developing Alzheimer’s disease.

While it is impossible to provide a timeline for development of such a test, as further validation is needed, she added, these findings are indeed a "first stepping stone toward early diagnosis.

"This is a good start toward having a blood-based diagnosis," Dr. Burnham said.

The conference was sponsored by the Alzheimer’s Association. Dr. Burnham had no disclosures relevant to her presentation.

PARIS – A panel of blood-based biomarkers for neocortical amyloid burden – a known predictor of progression to Alzheimer’s disease – shows promise as an effective and economical screening test for early identification of individuals at risk for the disease, according to findings from an Australian study highlighted at an international conference on Alzheimer’s disease.

Currently, neocortical amyloid burden is assessable only by expensive positron emission tomography, which requires radiotracers such as Pittsburgh Compound B (PiB) that are not widely available, or by invasive cerebrospinal fluid evaluation, Samantha Burnham, Ph.D., reported at an international conference on Alzheimer’s disease.

After analyzing 273 samples from patients with baseline blood and PiB-PET measurements from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study, the researchers developed a model using 9 blood-based markers (including A beta 1-42, ApoE, and cortisol) to estimate the amount of deposited amyloid in the brain.

That panel of markers had 83% sensitivity and 85% specificity for identifying the level of amyloid deemed to indicate risk of Alzheimer’s, said Dr. Burnham of the Commonwealth Scientific and Industrial Research Organization (CSIRO), Perth, Australia.

Predictions using the panel were also made in 817 nonimaged AIBL study participants. When those participants were grouped according to clinical diagnosis, the percentages of high neocortical amyloid burden were consistent with prior findings in the literature, with 34% of healthy controls, 87% of mild cognitively impaired individuals, and 100% of Alzheimer’s disease patients having a high burden, Dr. Burnham said.

In addition, the panel of markers was assessed in 74 subjects from the Alzheimer’s Disease Neuroimaging Initiative for validation. In that validation study, measurements for two of the markers from the panel were unavailable, and the sensitivity and specificity were slightly lower, at 76%.

Furthermore, when the samples from the AIBL study were reassessed without the two missing markers, the sensitivity and specificity dropped to a level comparable to that seen in the validation study (74%), suggesting that the accuracy in the validation study might have been even greater if all nine markers were available, she noted.

Because neocortical amyloid burden predicts progression to Alzheimer’s disease, and given that the model used in the study accurately predicts neocortical amyloid burden, Dr. Burnham said, it appears likely that the findings will lead to development of a useful, affordable screening test for the early identification of individuals at risk for developing Alzheimer’s disease.

While it is impossible to provide a timeline for development of such a test, as further validation is needed, she added, these findings are indeed a "first stepping stone toward early diagnosis.

"This is a good start toward having a blood-based diagnosis," Dr. Burnham said.

The conference was sponsored by the Alzheimer’s Association. Dr. Burnham had no disclosures relevant to her presentation.

PARIS – A 25% reduction in seven potentially modifiable lifestyle-based risk factors for Alzheimer’s disease could lower the prevalence of Alzheimer’s cases by 3 million worldwide, according to the findings of a study presented July 19 at the International Conference on Alzheimer’s Disease.

Just a 10% reduction in the factors could lower the prevalence of cases by 1 million, Deborah Barnes, Ph.D., reported at the conference, sponsored by the Alzheimer’s Association.

She and her colleagues calculated population attributable risks using data from recent systematic reviews and meta-analyses, and found that worldwide, low educational attainment was associated with the highest proportion (19%) of potentially attributable cases of Alzheimer’s disease, followed by smoking (14%), physical inactivity (13%), depression (11%), midlife hypertension (5%), midlife obesity (2%), and diabetes (2%).

Among subjects in the United States, where the prevalence of some risk factors such as educational attainment differ from the worldwide prevalence, thus affecting the population attributable risks, physical inactivity had the highest associated proportion of potentially attributable cases of Alzheimer’s disease (21%), followed by depression (15%), smoking (11%), midlife hypertension (8%), midlife obesity (7%), low educational attainment (7%), and diabetes (3%).The findings were published simultaneously in the Lancet Neurology (Lancet Neurol. 2011 July 19 [doi:10.1016/S1474-4422(11)70072-2]).

The mathematical modeling used by Dr. Barnes and her colleagues for this study indicates that when combined, these seven risk factors contribute to more than half of the nearly 36 million cases of Alzheimer’s disease worldwide and nearly 60% of the 6 million cases in the United States. The investigators selected the seven factors because they have the most consistent evidence for an association with Alzheimer’s disease, Dr. Barnes said during a press briefing.

This is particularly important given that the prevalence of Alzheimer’s disease is expected to almost triple to 106 million by 2050. The current absence of effective disease-modifying treatment, and an increasing awareness that symptoms develop over many years, has contributed to the interest in identifying effective prevention strategies, said Dr. Barnes of the department of psychiatry at the University of California, San Francisco.

"There are no cures or treatments that modify the course of disease right now, so we’re really focusing on identifying strategies for prevention," she said.

Many potentially modifiable risk factors have been identified, but it remains unclear which factors should be targeted. Therefore, Dr. Barnes and her associates set out to estimate what the impact of risk factor reduction strategies would be on Alzheimer’s disease prevalence.

She cautioned that their findings were derived by making an important, but unproven, assumption that a causal relationship exists between the risk factors and Alzheimer’s disease, and that modifying the risk factors will lower the risk of developing Alzheimer’s disease.

But the factors are promising nonetheless, she said. "I think the findings are exciting, because they suggest that public health interventions to increase education and physical activity and reduce smoking rates and depression could potentially have a really dramatic impact on Alzheimer’s disease prevalence over time, so I feel like it gives us a little bit of hope about things we might be able to do now to try to prevent the epidemic we see coming our way," she said.

The next step is to conduct randomized controlled intervention trials to test the impact of prevention strategies, she said, also adding that campaigns to promote risk factor modification among the public should be considered.

Dr. Ronald Petersen, who moderated the press briefing, agreed the findings provide hope in the fight against Alzheimer’s disease.

A theme that has been emerging, and which is underscored by these findings is that "the development of cognitive impairment, and Alzheimer’s disease in particular, need not be a passive process," said Dr. Petersen, professor of neurology and director of the Alzheimer’s Disease Research Center at the Mayo Medical School, Rochester, Minn.

"I think what we’re realizing is that we can do something about this. We may not be able to prevent [Alzheimer’s disease], or stop it in its tracks by lifestyle modification, but I think there are significant inroads that can be made into this disease," he said.

Dr. Barnes had no relevant disclosures. Dr. Petersen disclosed that he chairs data safety monitoring committees for Pfizer and Janssen Alzheimer Immunotherapy, and serves as a consultant for Elan and GE Healthcare.

PARIS – A 25% reduction in seven potentially modifiable lifestyle-based risk factors for Alzheimer’s disease could lower the prevalence of Alzheimer’s cases by 3 million worldwide, according to the findings of a study presented July 19 at the International Conference on Alzheimer’s Disease.

Just a 10% reduction in the factors could lower the prevalence of cases by 1 million, Deborah Barnes, Ph.D., reported at the conference, sponsored by the Alzheimer’s Association.

She and her colleagues calculated population attributable risks using data from recent systematic reviews and meta-analyses, and found that worldwide, low educational attainment was associated with the highest proportion (19%) of potentially attributable cases of Alzheimer’s disease, followed by smoking (14%), physical inactivity (13%), depression (11%), midlife hypertension (5%), midlife obesity (2%), and diabetes (2%).

Among subjects in the United States, where the prevalence of some risk factors such as educational attainment differ from the worldwide prevalence, thus affecting the population attributable risks, physical inactivity had the highest associated proportion of potentially attributable cases of Alzheimer’s disease (21%), followed by depression (15%), smoking (11%), midlife hypertension (8%), midlife obesity (7%), low educational attainment (7%), and diabetes (3%).The findings were published simultaneously in the Lancet Neurology (Lancet Neurol. 2011 July 19 [doi:10.1016/S1474-4422(11)70072-2]).

The mathematical modeling used by Dr. Barnes and her colleagues for this study indicates that when combined, these seven risk factors contribute to more than half of the nearly 36 million cases of Alzheimer’s disease worldwide and nearly 60% of the 6 million cases in the United States. The investigators selected the seven factors because they have the most consistent evidence for an association with Alzheimer’s disease, Dr. Barnes said during a press briefing.

This is particularly important given that the prevalence of Alzheimer’s disease is expected to almost triple to 106 million by 2050. The current absence of effective disease-modifying treatment, and an increasing awareness that symptoms develop over many years, has contributed to the interest in identifying effective prevention strategies, said Dr. Barnes of the department of psychiatry at the University of California, San Francisco.

"There are no cures or treatments that modify the course of disease right now, so we’re really focusing on identifying strategies for prevention," she said.

Many potentially modifiable risk factors have been identified, but it remains unclear which factors should be targeted. Therefore, Dr. Barnes and her associates set out to estimate what the impact of risk factor reduction strategies would be on Alzheimer’s disease prevalence.

She cautioned that their findings were derived by making an important, but unproven, assumption that a causal relationship exists between the risk factors and Alzheimer’s disease, and that modifying the risk factors will lower the risk of developing Alzheimer’s disease.

But the factors are promising nonetheless, she said. "I think the findings are exciting, because they suggest that public health interventions to increase education and physical activity and reduce smoking rates and depression could potentially have a really dramatic impact on Alzheimer’s disease prevalence over time, so I feel like it gives us a little bit of hope about things we might be able to do now to try to prevent the epidemic we see coming our way," she said.

The next step is to conduct randomized controlled intervention trials to test the impact of prevention strategies, she said, also adding that campaigns to promote risk factor modification among the public should be considered.

Dr. Ronald Petersen, who moderated the press briefing, agreed the findings provide hope in the fight against Alzheimer’s disease.

A theme that has been emerging, and which is underscored by these findings is that "the development of cognitive impairment, and Alzheimer’s disease in particular, need not be a passive process," said Dr. Petersen, professor of neurology and director of the Alzheimer’s Disease Research Center at the Mayo Medical School, Rochester, Minn.

"I think what we’re realizing is that we can do something about this. We may not be able to prevent [Alzheimer’s disease], or stop it in its tracks by lifestyle modification, but I think there are significant inroads that can be made into this disease," he said.

Dr. Barnes had no relevant disclosures. Dr. Petersen disclosed that he chairs data safety monitoring committees for Pfizer and Janssen Alzheimer Immunotherapy, and serves as a consultant for Elan and GE Healthcare.

PARIS – A 25% reduction in seven potentially modifiable lifestyle-based risk factors for Alzheimer’s disease could lower the prevalence of Alzheimer’s cases by 3 million worldwide, according to the findings of a study presented July 19 at the International Conference on Alzheimer’s Disease.

Just a 10% reduction in the factors could lower the prevalence of cases by 1 million, Deborah Barnes, Ph.D., reported at the conference, sponsored by the Alzheimer’s Association.

She and her colleagues calculated population attributable risks using data from recent systematic reviews and meta-analyses, and found that worldwide, low educational attainment was associated with the highest proportion (19%) of potentially attributable cases of Alzheimer’s disease, followed by smoking (14%), physical inactivity (13%), depression (11%), midlife hypertension (5%), midlife obesity (2%), and diabetes (2%).

Among subjects in the United States, where the prevalence of some risk factors such as educational attainment differ from the worldwide prevalence, thus affecting the population attributable risks, physical inactivity had the highest associated proportion of potentially attributable cases of Alzheimer’s disease (21%), followed by depression (15%), smoking (11%), midlife hypertension (8%), midlife obesity (7%), low educational attainment (7%), and diabetes (3%).The findings were published simultaneously in the Lancet Neurology (Lancet Neurol. 2011 July 19 [doi:10.1016/S1474-4422(11)70072-2]).

The mathematical modeling used by Dr. Barnes and her colleagues for this study indicates that when combined, these seven risk factors contribute to more than half of the nearly 36 million cases of Alzheimer’s disease worldwide and nearly 60% of the 6 million cases in the United States. The investigators selected the seven factors because they have the most consistent evidence for an association with Alzheimer’s disease, Dr. Barnes said during a press briefing.

This is particularly important given that the prevalence of Alzheimer’s disease is expected to almost triple to 106 million by 2050. The current absence of effective disease-modifying treatment, and an increasing awareness that symptoms develop over many years, has contributed to the interest in identifying effective prevention strategies, said Dr. Barnes of the department of psychiatry at the University of California, San Francisco.

"There are no cures or treatments that modify the course of disease right now, so we’re really focusing on identifying strategies for prevention," she said.

Many potentially modifiable risk factors have been identified, but it remains unclear which factors should be targeted. Therefore, Dr. Barnes and her associates set out to estimate what the impact of risk factor reduction strategies would be on Alzheimer’s disease prevalence.

She cautioned that their findings were derived by making an important, but unproven, assumption that a causal relationship exists between the risk factors and Alzheimer’s disease, and that modifying the risk factors will lower the risk of developing Alzheimer’s disease.

But the factors are promising nonetheless, she said. "I think the findings are exciting, because they suggest that public health interventions to increase education and physical activity and reduce smoking rates and depression could potentially have a really dramatic impact on Alzheimer’s disease prevalence over time, so I feel like it gives us a little bit of hope about things we might be able to do now to try to prevent the epidemic we see coming our way," she said.

The next step is to conduct randomized controlled intervention trials to test the impact of prevention strategies, she said, also adding that campaigns to promote risk factor modification among the public should be considered.

Dr. Ronald Petersen, who moderated the press briefing, agreed the findings provide hope in the fight against Alzheimer’s disease.

A theme that has been emerging, and which is underscored by these findings is that "the development of cognitive impairment, and Alzheimer’s disease in particular, need not be a passive process," said Dr. Petersen, professor of neurology and director of the Alzheimer’s Disease Research Center at the Mayo Medical School, Rochester, Minn.

"I think what we’re realizing is that we can do something about this. We may not be able to prevent [Alzheimer’s disease], or stop it in its tracks by lifestyle modification, but I think there are significant inroads that can be made into this disease," he said.

Dr. Barnes had no relevant disclosures. Dr. Petersen disclosed that he chairs data safety monitoring committees for Pfizer and Janssen Alzheimer Immunotherapy, and serves as a consultant for Elan and GE Healthcare.