Click here to read the supplement and earn 1 AMA Category 1 Credit ^TM by learning about these unmet needs, and recent advances and novel strategies for management of depression in BD. 

Educational Objectives

• Discuss the prevalence of bipolar disorder in different psychiatric patients.
• Describe the different symptoms that occur in children, adolescents, and adults.
• Use the evidence base, including FDA approval for different treatments, to inform therapy for bipolar depression.
• Provide details to ensure that physicians consider the potential metabolic profile of antipsychotics when choosing agents.

Click here to read the supplement. 

Click here to read the supplement and earn 1 AMA Category 1 Credit ^TM by learning about these unmet needs, and recent advances and novel strategies for management of depression in BD. 

Educational Objectives

• Discuss the prevalence of bipolar disorder in different psychiatric patients.
• Describe the different symptoms that occur in children, adolescents, and adults.
• Use the evidence base, including FDA approval for different treatments, to inform therapy for bipolar depression.
• Provide details to ensure that physicians consider the potential metabolic profile of antipsychotics when choosing agents.

Click here to read the supplement. 

Click here to read the supplement and earn 1 AMA Category 1 Credit ^TM by learning about these unmet needs, and recent advances and novel strategies for management of depression in BD. 

Educational Objectives

• Discuss the prevalence of bipolar disorder in different psychiatric patients.
• Describe the different symptoms that occur in children, adolescents, and adults.
• Use the evidence base, including FDA approval for different treatments, to inform therapy for bipolar depression.
• Provide details to ensure that physicians consider the potential metabolic profile of antipsychotics when choosing agents.

Click here to read the supplement. 

I return to write the Editor’s comments after missing last month because I joined over 700,000 Americans who, this year, will undergo knee replacement surgery.

This month, we feature a couple articles from the 2019 James W. Freston Conference (an annual AGA event that highlights cutting-edge science). Jim was the 89th AGA President (1995) and this conference is a fitting legacy. This year’s topic was “Food at the intersection of gut health and disease.” As usual, the Freston Conference attracted international experts and interested clinicians who want to understand how current research will alter our clinical care in the near future.

Our front-page articles are fascinating. One highlights new advances in the management of celiac disease. Although the only current treatment that reverses intestinal immunological damage is adoption of a gluten-free diet, there is demand for alternative treatments including medical therapies targeting specific steps in the celiac damage pathway. While none are ready for wide-spread adoption, research will continue. Patient self-management with gluten detection-devices were also discussed.

Advances in the genetics of Crohn’s disease are being published at an accelerating rate. This month we highlight an article about how gene expression analysis can predict response to a Crohn’s flare. Evidence-based therapy for inflammatory bowel disease is complex, so clinicians need to stay current. Each year, the premier IBD educational venue is co-produced by the AGA and the Crohn’s & Colitis Foundation. The 2020 Crohn’s and Colitis Congress will be held in Austin, Texas January 23-25. Learn more at: https://www.crohnscolitiscongress.org.

Finally, I want to highlight an article about the risk of venous thromboembolism (VTE) during and after an IBD flare. This risk is underappreciated by many treating physicians but it is real and can be life-threatening. Gastroenterologists must be knowledgeable about current guidelines for VTE in IBD patients (see Gastroenterology 2014;146:835-48).

John I. Allen, MD, MBA, AGAF
Editor in Chief

I return to write the Editor’s comments after missing last month because I joined over 700,000 Americans who, this year, will undergo knee replacement surgery.

This month, we feature a couple articles from the 2019 James W. Freston Conference (an annual AGA event that highlights cutting-edge science). Jim was the 89th AGA President (1995) and this conference is a fitting legacy. This year’s topic was “Food at the intersection of gut health and disease.” As usual, the Freston Conference attracted international experts and interested clinicians who want to understand how current research will alter our clinical care in the near future.

Our front-page articles are fascinating. One highlights new advances in the management of celiac disease. Although the only current treatment that reverses intestinal immunological damage is adoption of a gluten-free diet, there is demand for alternative treatments including medical therapies targeting specific steps in the celiac damage pathway. While none are ready for wide-spread adoption, research will continue. Patient self-management with gluten detection-devices were also discussed.

Advances in the genetics of Crohn’s disease are being published at an accelerating rate. This month we highlight an article about how gene expression analysis can predict response to a Crohn’s flare. Evidence-based therapy for inflammatory bowel disease is complex, so clinicians need to stay current. Each year, the premier IBD educational venue is co-produced by the AGA and the Crohn’s & Colitis Foundation. The 2020 Crohn’s and Colitis Congress will be held in Austin, Texas January 23-25. Learn more at: https://www.crohnscolitiscongress.org.

Finally, I want to highlight an article about the risk of venous thromboembolism (VTE) during and after an IBD flare. This risk is underappreciated by many treating physicians but it is real and can be life-threatening. Gastroenterologists must be knowledgeable about current guidelines for VTE in IBD patients (see Gastroenterology 2014;146:835-48).

John I. Allen, MD, MBA, AGAF
Editor in Chief

I return to write the Editor’s comments after missing last month because I joined over 700,000 Americans who, this year, will undergo knee replacement surgery.

This month, we feature a couple articles from the 2019 James W. Freston Conference (an annual AGA event that highlights cutting-edge science). Jim was the 89th AGA President (1995) and this conference is a fitting legacy. This year’s topic was “Food at the intersection of gut health and disease.” As usual, the Freston Conference attracted international experts and interested clinicians who want to understand how current research will alter our clinical care in the near future.

Our front-page articles are fascinating. One highlights new advances in the management of celiac disease. Although the only current treatment that reverses intestinal immunological damage is adoption of a gluten-free diet, there is demand for alternative treatments including medical therapies targeting specific steps in the celiac damage pathway. While none are ready for wide-spread adoption, research will continue. Patient self-management with gluten detection-devices were also discussed.

Advances in the genetics of Crohn’s disease are being published at an accelerating rate. This month we highlight an article about how gene expression analysis can predict response to a Crohn’s flare. Evidence-based therapy for inflammatory bowel disease is complex, so clinicians need to stay current. Each year, the premier IBD educational venue is co-produced by the AGA and the Crohn’s & Colitis Foundation. The 2020 Crohn’s and Colitis Congress will be held in Austin, Texas January 23-25. Learn more at: https://www.crohnscolitiscongress.org.

Finally, I want to highlight an article about the risk of venous thromboembolism (VTE) during and after an IBD flare. This risk is underappreciated by many treating physicians but it is real and can be life-threatening. Gastroenterologists must be knowledgeable about current guidelines for VTE in IBD patients (see Gastroenterology 2014;146:835-48).

John I. Allen, MD, MBA, AGAF
Editor in Chief

People who eat red meat or processed meat should continue their current meat consumption, according to recent guidelines from an international panel that were recently published in the Annals of Internal Medicine.

Fuse/Thinkstock

This recommendation was based on the panel having found “low- to very-low-certainty evidence that diets lower in unprocessed red meat may have little or no effect on the risk for major cardiometabolic outcomes and cancer mortality and incidence.” Additionally, meta-analysis results from 23 cohort studies provided low- to very-low-certainty evidence that decreasing unprocessed red meat intake may result in a very small reduction in the risk for major cardiovascular outcomes and type 2 diabetes, with no statistically differences in all-cause mortality and cardiovascular mortality, the guidelines say.

“Our weak recommendation that people continue their current meat consumption highlights both the uncertainty associated with possible harmful effects and the very small magnitude of effect, even if the best estimates represent true causation, which we believe to be implausible,” Bradley C. Johnston, PhD, of the department of community health and epidemiology at Dalhousie University, Halifax, N.S., and colleagues wrote in their paper summarizing the panel’s guidelines.

The evidence Dr. Johnston and colleagues examined were from four systematic reviews analyzing the health effects of red meat and processed meat consumption in randomized trials and meta-analyses of cohort studies as well as one systematic review that identified how people viewed their consumption of meat and values surrounding meat consumption.

In one review of 12 randomized trials examining diets of high and low red meat consumption, a diet consisting of low red meat had little effect on cardiovascular mortality (hazard ratio, 0.98; 95% confidence interval, 0.91-1.06), cardiovascular disease (HR, 0.99; 95% CI, 0.94-1.05), all-cause mortality (0.99; 95% CI, 0.95-1.03) and total cancer mortality (HR, 0.95; 95% CI, 0.89-1.01), including on colorectal cancer or breast cancer (Zeraatkar D et al. Ann Intern Med. 2019 Oct 1. doi: 10.7326/M19-0622). A different review of observational cohort studies with more than 1,000 participants found “very-small or possibly small decreases” in all-cause mortality, incidence, and all-cause mortality of cancer, cardiovascular mortality, nonfatal coronary heart disease and MI, and type 2 diabetes for patients who had a diet low in red meat or processed meat (Vernooij R et al. Ann Intern Med. 2019 Oct 1. doi: 10.7326/M19-1583); a second review by Zeraatkar and colleagues of 55 observational cohort studies with more than 4 million participants found three servings of unprocessed red meat and processed meat per week was associated with a “very small reduction” in risk for MI, stroke, type 2 diabetes, cardiovascular mortality, and all-cause mortality (Zeraatkar D et al. Ann Intern Med. 2019 Oct 1. doi: 10.7326/M19-1326). Another systematic review of 56 observational cohort studies found three servings of unprocessed red meat per week was associated with a slight reduction in overall cancer mortality (Han MA et al. Ann Intern Med. 2019 Oct 1. doi: 10.7326/M19-0699).

The authors also performed a systematic review of participant preferences and values regarding meat consumption. The evidence from 54 qualitative studies showed omnivores preferred eating meat, considered it part of a healthy diet, “lack[ed] the skills needed” to prepare meals without meat, and were mostly unwilling to change their meat consumption (Valli C et al. Ann Intern Med. 2019. doi: 10.7326/M19-1326).

“There was a very small and often trivial absolute risk reduction based on a realistic decrease of three servings of red or processed meat per week,” Dr. Johnston and colleagues wrote in their guidelines. If the very-small exposure effect is true, given peoples’ attachment to their meat-based diet, the associated risk reduction is not likely to provide sufficient motivation to reduce consumption of red meat or processed meat in fully informed individuals, and the weak, rather than strong, recommendation is based on the large variability in peoples’ values and preferences related to meat.”

The authors noted they did not examine factors such as cost, acceptability, feasibility, equity, environmental impact, and views on animal welfare when creating the guidelines. In addition, the low level of evidence from the randomized trials and observational studies means that the potential benefits of reducing red meat or processed meat intake may not outweigh the cultural and personal preferences or quality of life issues that could arise from changing one’s diet.

“This assessment may be excessively pessimistic; indeed, we hope that is the case,” they said. “What is certain is that generating higher-quality evidence regarding the magnitude of any causal effect of meat consumption on health outcomes will test the ingenuity and imagination of health science investigators.”

Dr. El Dib reported receiving funding from the São Paulo Research Foundation, the National Council for Scientific and Technological Development, and the faculty of medicine at Dalhousie University. Dr. de Souza reports relationships with the Canadian Institutes of Health Research/Health Canada, the Canadian Foundation for Dietetic Research and the World Health Organization in the forms of personal fees, grants, and speakers bureau and board of directorship appointments. Dr. Patel reports receiving grants and person fees from the National Institutes of Health, Sanofi, the National Science Foundation, XY.health, doc.ai, Janssen, and the CDC.

SOURCE: Johnston B et al. Ann Intern Med. 2019 Oct 1. doi: 10.7326/M19-1621.

People who eat red meat or processed meat should continue their current meat consumption, according to recent guidelines from an international panel that were recently published in the Annals of Internal Medicine.

Fuse/Thinkstock

This recommendation was based on the panel having found “low- to very-low-certainty evidence that diets lower in unprocessed red meat may have little or no effect on the risk for major cardiometabolic outcomes and cancer mortality and incidence.” Additionally, meta-analysis results from 23 cohort studies provided low- to very-low-certainty evidence that decreasing unprocessed red meat intake may result in a very small reduction in the risk for major cardiovascular outcomes and type 2 diabetes, with no statistically differences in all-cause mortality and cardiovascular mortality, the guidelines say.

“Our weak recommendation that people continue their current meat consumption highlights both the uncertainty associated with possible harmful effects and the very small magnitude of effect, even if the best estimates represent true causation, which we believe to be implausible,” Bradley C. Johnston, PhD, of the department of community health and epidemiology at Dalhousie University, Halifax, N.S., and colleagues wrote in their paper summarizing the panel’s guidelines.

The evidence Dr. Johnston and colleagues examined were from four systematic reviews analyzing the health effects of red meat and processed meat consumption in randomized trials and meta-analyses of cohort studies as well as one systematic review that identified how people viewed their consumption of meat and values surrounding meat consumption.

In one review of 12 randomized trials examining diets of high and low red meat consumption, a diet consisting of low red meat had little effect on cardiovascular mortality (hazard ratio, 0.98; 95% confidence interval, 0.91-1.06), cardiovascular disease (HR, 0.99; 95% CI, 0.94-1.05), all-cause mortality (0.99; 95% CI, 0.95-1.03) and total cancer mortality (HR, 0.95; 95% CI, 0.89-1.01), including on colorectal cancer or breast cancer (Zeraatkar D et al. Ann Intern Med. 2019 Oct 1. doi: 10.7326/M19-0622). A different review of observational cohort studies with more than 1,000 participants found “very-small or possibly small decreases” in all-cause mortality, incidence, and all-cause mortality of cancer, cardiovascular mortality, nonfatal coronary heart disease and MI, and type 2 diabetes for patients who had a diet low in red meat or processed meat (Vernooij R et al. Ann Intern Med. 2019 Oct 1. doi: 10.7326/M19-1583); a second review by Zeraatkar and colleagues of 55 observational cohort studies with more than 4 million participants found three servings of unprocessed red meat and processed meat per week was associated with a “very small reduction” in risk for MI, stroke, type 2 diabetes, cardiovascular mortality, and all-cause mortality (Zeraatkar D et al. Ann Intern Med. 2019 Oct 1. doi: 10.7326/M19-1326). Another systematic review of 56 observational cohort studies found three servings of unprocessed red meat per week was associated with a slight reduction in overall cancer mortality (Han MA et al. Ann Intern Med. 2019 Oct 1. doi: 10.7326/M19-0699).

The authors also performed a systematic review of participant preferences and values regarding meat consumption. The evidence from 54 qualitative studies showed omnivores preferred eating meat, considered it part of a healthy diet, “lack[ed] the skills needed” to prepare meals without meat, and were mostly unwilling to change their meat consumption (Valli C et al. Ann Intern Med. 2019. doi: 10.7326/M19-1326).

“There was a very small and often trivial absolute risk reduction based on a realistic decrease of three servings of red or processed meat per week,” Dr. Johnston and colleagues wrote in their guidelines. If the very-small exposure effect is true, given peoples’ attachment to their meat-based diet, the associated risk reduction is not likely to provide sufficient motivation to reduce consumption of red meat or processed meat in fully informed individuals, and the weak, rather than strong, recommendation is based on the large variability in peoples’ values and preferences related to meat.”

The authors noted they did not examine factors such as cost, acceptability, feasibility, equity, environmental impact, and views on animal welfare when creating the guidelines. In addition, the low level of evidence from the randomized trials and observational studies means that the potential benefits of reducing red meat or processed meat intake may not outweigh the cultural and personal preferences or quality of life issues that could arise from changing one’s diet.

“This assessment may be excessively pessimistic; indeed, we hope that is the case,” they said. “What is certain is that generating higher-quality evidence regarding the magnitude of any causal effect of meat consumption on health outcomes will test the ingenuity and imagination of health science investigators.”

Dr. El Dib reported receiving funding from the São Paulo Research Foundation, the National Council for Scientific and Technological Development, and the faculty of medicine at Dalhousie University. Dr. de Souza reports relationships with the Canadian Institutes of Health Research/Health Canada, the Canadian Foundation for Dietetic Research and the World Health Organization in the forms of personal fees, grants, and speakers bureau and board of directorship appointments. Dr. Patel reports receiving grants and person fees from the National Institutes of Health, Sanofi, the National Science Foundation, XY.health, doc.ai, Janssen, and the CDC.

SOURCE: Johnston B et al. Ann Intern Med. 2019 Oct 1. doi: 10.7326/M19-1621.

People who eat red meat or processed meat should continue their current meat consumption, according to recent guidelines from an international panel that were recently published in the Annals of Internal Medicine.

Fuse/Thinkstock

This recommendation was based on the panel having found “low- to very-low-certainty evidence that diets lower in unprocessed red meat may have little or no effect on the risk for major cardiometabolic outcomes and cancer mortality and incidence.” Additionally, meta-analysis results from 23 cohort studies provided low- to very-low-certainty evidence that decreasing unprocessed red meat intake may result in a very small reduction in the risk for major cardiovascular outcomes and type 2 diabetes, with no statistically differences in all-cause mortality and cardiovascular mortality, the guidelines say.

“Our weak recommendation that people continue their current meat consumption highlights both the uncertainty associated with possible harmful effects and the very small magnitude of effect, even if the best estimates represent true causation, which we believe to be implausible,” Bradley C. Johnston, PhD, of the department of community health and epidemiology at Dalhousie University, Halifax, N.S., and colleagues wrote in their paper summarizing the panel’s guidelines.

The evidence Dr. Johnston and colleagues examined were from four systematic reviews analyzing the health effects of red meat and processed meat consumption in randomized trials and meta-analyses of cohort studies as well as one systematic review that identified how people viewed their consumption of meat and values surrounding meat consumption.

In one review of 12 randomized trials examining diets of high and low red meat consumption, a diet consisting of low red meat had little effect on cardiovascular mortality (hazard ratio, 0.98; 95% confidence interval, 0.91-1.06), cardiovascular disease (HR, 0.99; 95% CI, 0.94-1.05), all-cause mortality (0.99; 95% CI, 0.95-1.03) and total cancer mortality (HR, 0.95; 95% CI, 0.89-1.01), including on colorectal cancer or breast cancer (Zeraatkar D et al. Ann Intern Med. 2019 Oct 1. doi: 10.7326/M19-0622). A different review of observational cohort studies with more than 1,000 participants found “very-small or possibly small decreases” in all-cause mortality, incidence, and all-cause mortality of cancer, cardiovascular mortality, nonfatal coronary heart disease and MI, and type 2 diabetes for patients who had a diet low in red meat or processed meat (Vernooij R et al. Ann Intern Med. 2019 Oct 1. doi: 10.7326/M19-1583); a second review by Zeraatkar and colleagues of 55 observational cohort studies with more than 4 million participants found three servings of unprocessed red meat and processed meat per week was associated with a “very small reduction” in risk for MI, stroke, type 2 diabetes, cardiovascular mortality, and all-cause mortality (Zeraatkar D et al. Ann Intern Med. 2019 Oct 1. doi: 10.7326/M19-1326). Another systematic review of 56 observational cohort studies found three servings of unprocessed red meat per week was associated with a slight reduction in overall cancer mortality (Han MA et al. Ann Intern Med. 2019 Oct 1. doi: 10.7326/M19-0699).

The authors also performed a systematic review of participant preferences and values regarding meat consumption. The evidence from 54 qualitative studies showed omnivores preferred eating meat, considered it part of a healthy diet, “lack[ed] the skills needed” to prepare meals without meat, and were mostly unwilling to change their meat consumption (Valli C et al. Ann Intern Med. 2019. doi: 10.7326/M19-1326).

“There was a very small and often trivial absolute risk reduction based on a realistic decrease of three servings of red or processed meat per week,” Dr. Johnston and colleagues wrote in their guidelines. If the very-small exposure effect is true, given peoples’ attachment to their meat-based diet, the associated risk reduction is not likely to provide sufficient motivation to reduce consumption of red meat or processed meat in fully informed individuals, and the weak, rather than strong, recommendation is based on the large variability in peoples’ values and preferences related to meat.”

The authors noted they did not examine factors such as cost, acceptability, feasibility, equity, environmental impact, and views on animal welfare when creating the guidelines. In addition, the low level of evidence from the randomized trials and observational studies means that the potential benefits of reducing red meat or processed meat intake may not outweigh the cultural and personal preferences or quality of life issues that could arise from changing one’s diet.

“This assessment may be excessively pessimistic; indeed, we hope that is the case,” they said. “What is certain is that generating higher-quality evidence regarding the magnitude of any causal effect of meat consumption on health outcomes will test the ingenuity and imagination of health science investigators.”

Dr. El Dib reported receiving funding from the São Paulo Research Foundation, the National Council for Scientific and Technological Development, and the faculty of medicine at Dalhousie University. Dr. de Souza reports relationships with the Canadian Institutes of Health Research/Health Canada, the Canadian Foundation for Dietetic Research and the World Health Organization in the forms of personal fees, grants, and speakers bureau and board of directorship appointments. Dr. Patel reports receiving grants and person fees from the National Institutes of Health, Sanofi, the National Science Foundation, XY.health, doc.ai, Janssen, and the CDC.

SOURCE: Johnston B et al. Ann Intern Med. 2019 Oct 1. doi: 10.7326/M19-1621.

Stephen R. Lindemann, PhD, assistant professor of food science and nutrition science, Purdue University, shares four talking points to use when your patients ask about prebiotics.

Explaining prebiotics:

• • Prebiotics serve as food for specific microbes in the gut but their health benefits are likely due to broader changes in the function of communities of microbes.
• • Prebiotics can lead to a durable change in overall function of a gut microbial community with potential for long-term health benefit while probiotics are live microorganisms that when administered in adequate amounts can confer a health benefit even in the short term.
• • Prebiotics ferment to short-chain fatty acids known to positively influence human metabolism and immunity. Commercial prebiotics may be beneficial in some individuals but intolerable in others.
• • Further research is needed to determine the specificity of prebiotics in terms of their biological effects. Other dietary fibers/proteins may have similar health benefits that have not yet been determined.

These tips are from “Prebiotics 101,” the first of a four-part CME series in AGA University, agau.gastro.org, titled, “The Microbiome and Digestive Health: A Look at Prebiotics.” Part two, “Diet vs. Prebiotics” is also available.

Looking for more information on prebiotics?

AGA has educational materials for patients on probiotics (also available in Spanish) at gastro.org/patient.
 

[email protected]

Stephen R. Lindemann, PhD, assistant professor of food science and nutrition science, Purdue University, shares four talking points to use when your patients ask about prebiotics.

Explaining prebiotics:

• • Prebiotics serve as food for specific microbes in the gut but their health benefits are likely due to broader changes in the function of communities of microbes.
• • Prebiotics can lead to a durable change in overall function of a gut microbial community with potential for long-term health benefit while probiotics are live microorganisms that when administered in adequate amounts can confer a health benefit even in the short term.
• • Prebiotics ferment to short-chain fatty acids known to positively influence human metabolism and immunity. Commercial prebiotics may be beneficial in some individuals but intolerable in others.
• • Further research is needed to determine the specificity of prebiotics in terms of their biological effects. Other dietary fibers/proteins may have similar health benefits that have not yet been determined.

These tips are from “Prebiotics 101,” the first of a four-part CME series in AGA University, agau.gastro.org, titled, “The Microbiome and Digestive Health: A Look at Prebiotics.” Part two, “Diet vs. Prebiotics” is also available.

Looking for more information on prebiotics?

AGA has educational materials for patients on probiotics (also available in Spanish) at gastro.org/patient.
 

[email protected]

Stephen R. Lindemann, PhD, assistant professor of food science and nutrition science, Purdue University, shares four talking points to use when your patients ask about prebiotics.

Explaining prebiotics:

• • Prebiotics serve as food for specific microbes in the gut but their health benefits are likely due to broader changes in the function of communities of microbes.
• • Prebiotics can lead to a durable change in overall function of a gut microbial community with potential for long-term health benefit while probiotics are live microorganisms that when administered in adequate amounts can confer a health benefit even in the short term.
• • Prebiotics ferment to short-chain fatty acids known to positively influence human metabolism and immunity. Commercial prebiotics may be beneficial in some individuals but intolerable in others.
• • Further research is needed to determine the specificity of prebiotics in terms of their biological effects. Other dietary fibers/proteins may have similar health benefits that have not yet been determined.

These tips are from “Prebiotics 101,” the first of a four-part CME series in AGA University, agau.gastro.org, titled, “The Microbiome and Digestive Health: A Look at Prebiotics.” Part two, “Diet vs. Prebiotics” is also available.

Looking for more information on prebiotics?

AGA has educational materials for patients on probiotics (also available in Spanish) at gastro.org/patient.
 

[email protected]

AGA and our sister societies met with Medicare staff in Washington, DC, to voice our opposition to its proposal that would require physicians to inform patients about potential colorectal cancer (CRC) screening costs. Under the proposal, physicians who plan to perform a CRC screening for a Medicare beneficiary must tell the beneficiary in advance that they may have to pay coinsurance under the Medicare program if the screening finds polyps that are removed as part of the screening procedure and document the conversation in the beneficiary’s medical record starting Jan. 1, 2020.

Under the Affordable Care Act, Medicare beneficiaries do not need to pay for screenings that receive an A or B from the U.S. Preventive Services Task Force (USPSTF), such as screening colonoscopy. However, because of Medicare’s interpretation of the coding rules, when a polyp is found and removed during a screening colonoscopy, it is considered a diagnostic procedure and the patient is required to pay the coinsurance. Medicare’s new proposal does not solve the underlying problem — fixing the coinsurance issue for Medicare beneficiaries; instead, it shifts responsibility to notify Medicare beneficiaries to the physician.

The gastroenterology community, together with patient advocates, has been asking CMS since 2011 to use its authority to fix the Medicare screening colonoscopy coinsurance problem. It was never the intention of Congress for polypectomy resulting from the initial screening to be excluded from the screening benefit. The Obama administration provided guidance for commercial plans on this screening benefit and stated that plans should not impose coinsurance since “removal of polyp is integral to the screening” and thus most private insurers recognize the benefit of waiving the coinsurance.

In our meeting with Medicare, we told them that beneficiaries should not be penalized because of the agency’s misinterpretation of Congress’ legislation. We also urged Medicare not to add to physician burden, to take responsibility for notifying patients of its own coverage and payment policies, and to focus on ways to help patients avoid unfair financial penalties resulting from its misinterpretation of Congress’s mandate for free CRC screening.

Medicare needs to hear from you today. Sign our letter on gastro.org/advocacy to let your voice be heard.
 

[email protected]

AGA and our sister societies met with Medicare staff in Washington, DC, to voice our opposition to its proposal that would require physicians to inform patients about potential colorectal cancer (CRC) screening costs. Under the proposal, physicians who plan to perform a CRC screening for a Medicare beneficiary must tell the beneficiary in advance that they may have to pay coinsurance under the Medicare program if the screening finds polyps that are removed as part of the screening procedure and document the conversation in the beneficiary’s medical record starting Jan. 1, 2020.

Under the Affordable Care Act, Medicare beneficiaries do not need to pay for screenings that receive an A or B from the U.S. Preventive Services Task Force (USPSTF), such as screening colonoscopy. However, because of Medicare’s interpretation of the coding rules, when a polyp is found and removed during a screening colonoscopy, it is considered a diagnostic procedure and the patient is required to pay the coinsurance. Medicare’s new proposal does not solve the underlying problem — fixing the coinsurance issue for Medicare beneficiaries; instead, it shifts responsibility to notify Medicare beneficiaries to the physician.

The gastroenterology community, together with patient advocates, has been asking CMS since 2011 to use its authority to fix the Medicare screening colonoscopy coinsurance problem. It was never the intention of Congress for polypectomy resulting from the initial screening to be excluded from the screening benefit. The Obama administration provided guidance for commercial plans on this screening benefit and stated that plans should not impose coinsurance since “removal of polyp is integral to the screening” and thus most private insurers recognize the benefit of waiving the coinsurance.

In our meeting with Medicare, we told them that beneficiaries should not be penalized because of the agency’s misinterpretation of Congress’ legislation. We also urged Medicare not to add to physician burden, to take responsibility for notifying patients of its own coverage and payment policies, and to focus on ways to help patients avoid unfair financial penalties resulting from its misinterpretation of Congress’s mandate for free CRC screening.

Medicare needs to hear from you today. Sign our letter on gastro.org/advocacy to let your voice be heard.
 

[email protected]

AGA and our sister societies met with Medicare staff in Washington, DC, to voice our opposition to its proposal that would require physicians to inform patients about potential colorectal cancer (CRC) screening costs. Under the proposal, physicians who plan to perform a CRC screening for a Medicare beneficiary must tell the beneficiary in advance that they may have to pay coinsurance under the Medicare program if the screening finds polyps that are removed as part of the screening procedure and document the conversation in the beneficiary’s medical record starting Jan. 1, 2020.

Under the Affordable Care Act, Medicare beneficiaries do not need to pay for screenings that receive an A or B from the U.S. Preventive Services Task Force (USPSTF), such as screening colonoscopy. However, because of Medicare’s interpretation of the coding rules, when a polyp is found and removed during a screening colonoscopy, it is considered a diagnostic procedure and the patient is required to pay the coinsurance. Medicare’s new proposal does not solve the underlying problem — fixing the coinsurance issue for Medicare beneficiaries; instead, it shifts responsibility to notify Medicare beneficiaries to the physician.

The gastroenterology community, together with patient advocates, has been asking CMS since 2011 to use its authority to fix the Medicare screening colonoscopy coinsurance problem. It was never the intention of Congress for polypectomy resulting from the initial screening to be excluded from the screening benefit. The Obama administration provided guidance for commercial plans on this screening benefit and stated that plans should not impose coinsurance since “removal of polyp is integral to the screening” and thus most private insurers recognize the benefit of waiving the coinsurance.

In our meeting with Medicare, we told them that beneficiaries should not be penalized because of the agency’s misinterpretation of Congress’ legislation. We also urged Medicare not to add to physician burden, to take responsibility for notifying patients of its own coverage and payment policies, and to focus on ways to help patients avoid unfair financial penalties resulting from its misinterpretation of Congress’s mandate for free CRC screening.

Medicare needs to hear from you today. Sign our letter on gastro.org/advocacy to let your voice be heard.
 

[email protected]

Gifts to charitable organizations, such as the AGA Research Foundation, in your future plans ensure your support for our mission continues even after your lifetime. Review these goals to turn financial aspiration into charitable action to achieve your philanthropic vision.

Goal: Take care of those you love

Use your will or living trust to clearly communicate your intentions for how you would like to provide for your loved ones and favorite causes, including the AGA Research Foundation. You can feel secure knowing you will maintain control of your assets until after your lifetime and that your gifts are revocable so you can change your mind at any time.

Goal: Eliminate capital gains tax on stocks

When you donate appreciated securities – that is, stocks you’ve owned for more than 1 year that are now worth more than you originally paid for them – you can benefit yourself and the AGA Research Foundation. You can reduce or even eliminate federal capital gains taxes on the stock transfer, and you may be entitled to a federal income tax charitable deduction.

Tip: There are a number of ways to give appreciated securities, such as outright giving or funding a charitable gift annuity or a charitable remainder trust.
 

Goal: Conserve today’s finances

Save critical funds now by naming the AGA Research Foundation as the beneficiary of all or a percentage (1%-100%) of your IRA. Leaving all or part of your IRA to charity after your lifetime dramatically lowers future taxes for your beneficiaries. Naming a charity, like the AGA Research Foundation, as a beneficiary can eliminate federal income taxes that could consume a substantial portion of your account.

Want to learn more about including a gift to the AGA Research Foundation in your future plans? Visit our website at https://gastro.planmylegacy.org or contact Harmony Excellent at 301-272-1602 or [email protected].

[email protected]

Gifts to charitable organizations, such as the AGA Research Foundation, in your future plans ensure your support for our mission continues even after your lifetime. Review these goals to turn financial aspiration into charitable action to achieve your philanthropic vision.

Goal: Take care of those you love

Use your will or living trust to clearly communicate your intentions for how you would like to provide for your loved ones and favorite causes, including the AGA Research Foundation. You can feel secure knowing you will maintain control of your assets until after your lifetime and that your gifts are revocable so you can change your mind at any time.

Goal: Eliminate capital gains tax on stocks

When you donate appreciated securities – that is, stocks you’ve owned for more than 1 year that are now worth more than you originally paid for them – you can benefit yourself and the AGA Research Foundation. You can reduce or even eliminate federal capital gains taxes on the stock transfer, and you may be entitled to a federal income tax charitable deduction.

Tip: There are a number of ways to give appreciated securities, such as outright giving or funding a charitable gift annuity or a charitable remainder trust.
 

Goal: Conserve today’s finances

Save critical funds now by naming the AGA Research Foundation as the beneficiary of all or a percentage (1%-100%) of your IRA. Leaving all or part of your IRA to charity after your lifetime dramatically lowers future taxes for your beneficiaries. Naming a charity, like the AGA Research Foundation, as a beneficiary can eliminate federal income taxes that could consume a substantial portion of your account.

Want to learn more about including a gift to the AGA Research Foundation in your future plans? Visit our website at https://gastro.planmylegacy.org or contact Harmony Excellent at 301-272-1602 or [email protected].

[email protected]

Gifts to charitable organizations, such as the AGA Research Foundation, in your future plans ensure your support for our mission continues even after your lifetime. Review these goals to turn financial aspiration into charitable action to achieve your philanthropic vision.

Goal: Take care of those you love

Use your will or living trust to clearly communicate your intentions for how you would like to provide for your loved ones and favorite causes, including the AGA Research Foundation. You can feel secure knowing you will maintain control of your assets until after your lifetime and that your gifts are revocable so you can change your mind at any time.

Goal: Eliminate capital gains tax on stocks

When you donate appreciated securities – that is, stocks you’ve owned for more than 1 year that are now worth more than you originally paid for them – you can benefit yourself and the AGA Research Foundation. You can reduce or even eliminate federal capital gains taxes on the stock transfer, and you may be entitled to a federal income tax charitable deduction.

Tip: There are a number of ways to give appreciated securities, such as outright giving or funding a charitable gift annuity or a charitable remainder trust.
 

Goal: Conserve today’s finances

Save critical funds now by naming the AGA Research Foundation as the beneficiary of all or a percentage (1%-100%) of your IRA. Leaving all or part of your IRA to charity after your lifetime dramatically lowers future taxes for your beneficiaries. Naming a charity, like the AGA Research Foundation, as a beneficiary can eliminate federal income taxes that could consume a substantial portion of your account.

Want to learn more about including a gift to the AGA Research Foundation in your future plans? Visit our website at https://gastro.planmylegacy.org or contact Harmony Excellent at 301-272-1602 or [email protected].

[email protected]

Infection transmission from duodenoscopes is a serious and complex issue for our patients and our practices.

As previously shared with our members late last year, the U.S. Food and Drug Administration (FDA) reported on preliminary data from manufacturer testing of duodenoscopes following reprocessing (cleaning). The report showed that, in about 5% of cases, samples tested positive for “high concern” bacteria after the scopes had been reprocessed as recommended. According to FDA, these are bacteria that are more often associated with disease. The final results and more granular detail are expected later this year.

This is a serious and complex issue for our patients and our practices. Duodenoscopes are necessary for performing endoscopic retrograde cholangiopancreatography (ERCP). This minimally invasive procedure is typically performed in patients with diseases of the liver, pancreas, and gallbladder and obviates the necessity for more morbid surgical and radiologic procedures.

A recent article in The New York Times reviewing this issue largely understated the value of duodenoscopes and the procedure for which they are used. This is a potentially life-saving procedure for nearly 700,000 patients each year in the United States. When a doctor recommends ERCP, it often is because the patient is seriously ill, and the benefits of the procedure far outweigh the risks. ERCPs also spare patients more invasive alternatives, including surgery. Withdrawal of these instruments from the marketplace is simply not feasible and would be a major step backward in our ability to treat common and complex disease in the most beneficial manner.

We do agree and support the identification and development of safe and effective solutions that eliminate risk of infection transmission as a top priority. This cannot happen overnight: We cannot adopt new technologies, such as disposable duodenoscopes, without first understanding the new and unintentional risks we may be introducing to our patients such as an increased risk of procedural failure, perforation, or pancreatitis.

The GI societies have been working closely with FDA and industry to identify and properly vet potential solutions. FDA has already reviewed and cleared new reprocessing and sterilization technologies and revised designs for some duodenoscopes; all are intended to enhance ease of cleaning and reprocessing, thereby improving safety from transmitted infection. Other redesigns and new technologies for endoscope reprocessing, as well as single-use instruments, are in the pipeline. All of these options, and others, will likely enter the marketplace in the coming months and years after FDA vetting and approval and with postmarketing studies to ensure the efficacy of the technology and patient safety.

AGA is currently seeking feedback from AGA members to provide to FDA for consideration as they make upcoming review and approval decisions. If you are concerned about losing access to ERCP, a valuable procedure, please share your comments in the AGA Community. We will be sharing these comments with FDA to ensure their decisions reflect the needs of our members.

Since it was discovered several years ago that cases of infection transmission associated with duodenoscopes had been experienced by hospitals in the United States and Europe, health care organizations across the board recognized the need to escalate infection control efforts and to swiftly identify and disseminate best practices. FDA, the Centers for Disease Control and Prevention, state and local health departments, scope manufacturers, and medical societies have collaborated continuously to determine best practices for identifying and reporting sources of infection and effectively cleaning equipment.

Since this problem was identified, vigilance has been raised and infection rates have improved. As with all medical procedures, physicians should discuss the risks and benefits with their patients who require ERCP.

This article was developed in collaboration with American Society for Gastrointestinal Endoscopy (ASGE) and the Society of Gastroenterology Nurses and Associates (SGNA).

[email protected]

Infection transmission from duodenoscopes is a serious and complex issue for our patients and our practices.

As previously shared with our members late last year, the U.S. Food and Drug Administration (FDA) reported on preliminary data from manufacturer testing of duodenoscopes following reprocessing (cleaning). The report showed that, in about 5% of cases, samples tested positive for “high concern” bacteria after the scopes had been reprocessed as recommended. According to FDA, these are bacteria that are more often associated with disease. The final results and more granular detail are expected later this year.

This is a serious and complex issue for our patients and our practices. Duodenoscopes are necessary for performing endoscopic retrograde cholangiopancreatography (ERCP). This minimally invasive procedure is typically performed in patients with diseases of the liver, pancreas, and gallbladder and obviates the necessity for more morbid surgical and radiologic procedures.

A recent article in The New York Times reviewing this issue largely understated the value of duodenoscopes and the procedure for which they are used. This is a potentially life-saving procedure for nearly 700,000 patients each year in the United States. When a doctor recommends ERCP, it often is because the patient is seriously ill, and the benefits of the procedure far outweigh the risks. ERCPs also spare patients more invasive alternatives, including surgery. Withdrawal of these instruments from the marketplace is simply not feasible and would be a major step backward in our ability to treat common and complex disease in the most beneficial manner.

We do agree and support the identification and development of safe and effective solutions that eliminate risk of infection transmission as a top priority. This cannot happen overnight: We cannot adopt new technologies, such as disposable duodenoscopes, without first understanding the new and unintentional risks we may be introducing to our patients such as an increased risk of procedural failure, perforation, or pancreatitis.

The GI societies have been working closely with FDA and industry to identify and properly vet potential solutions. FDA has already reviewed and cleared new reprocessing and sterilization technologies and revised designs for some duodenoscopes; all are intended to enhance ease of cleaning and reprocessing, thereby improving safety from transmitted infection. Other redesigns and new technologies for endoscope reprocessing, as well as single-use instruments, are in the pipeline. All of these options, and others, will likely enter the marketplace in the coming months and years after FDA vetting and approval and with postmarketing studies to ensure the efficacy of the technology and patient safety.

AGA is currently seeking feedback from AGA members to provide to FDA for consideration as they make upcoming review and approval decisions. If you are concerned about losing access to ERCP, a valuable procedure, please share your comments in the AGA Community. We will be sharing these comments with FDA to ensure their decisions reflect the needs of our members.

Since it was discovered several years ago that cases of infection transmission associated with duodenoscopes had been experienced by hospitals in the United States and Europe, health care organizations across the board recognized the need to escalate infection control efforts and to swiftly identify and disseminate best practices. FDA, the Centers for Disease Control and Prevention, state and local health departments, scope manufacturers, and medical societies have collaborated continuously to determine best practices for identifying and reporting sources of infection and effectively cleaning equipment.

Since this problem was identified, vigilance has been raised and infection rates have improved. As with all medical procedures, physicians should discuss the risks and benefits with their patients who require ERCP.

This article was developed in collaboration with American Society for Gastrointestinal Endoscopy (ASGE) and the Society of Gastroenterology Nurses and Associates (SGNA).

[email protected]

Infection transmission from duodenoscopes is a serious and complex issue for our patients and our practices.

As previously shared with our members late last year, the U.S. Food and Drug Administration (FDA) reported on preliminary data from manufacturer testing of duodenoscopes following reprocessing (cleaning). The report showed that, in about 5% of cases, samples tested positive for “high concern” bacteria after the scopes had been reprocessed as recommended. According to FDA, these are bacteria that are more often associated with disease. The final results and more granular detail are expected later this year.

This is a serious and complex issue for our patients and our practices. Duodenoscopes are necessary for performing endoscopic retrograde cholangiopancreatography (ERCP). This minimally invasive procedure is typically performed in patients with diseases of the liver, pancreas, and gallbladder and obviates the necessity for more morbid surgical and radiologic procedures.

A recent article in The New York Times reviewing this issue largely understated the value of duodenoscopes and the procedure for which they are used. This is a potentially life-saving procedure for nearly 700,000 patients each year in the United States. When a doctor recommends ERCP, it often is because the patient is seriously ill, and the benefits of the procedure far outweigh the risks. ERCPs also spare patients more invasive alternatives, including surgery. Withdrawal of these instruments from the marketplace is simply not feasible and would be a major step backward in our ability to treat common and complex disease in the most beneficial manner.

We do agree and support the identification and development of safe and effective solutions that eliminate risk of infection transmission as a top priority. This cannot happen overnight: We cannot adopt new technologies, such as disposable duodenoscopes, without first understanding the new and unintentional risks we may be introducing to our patients such as an increased risk of procedural failure, perforation, or pancreatitis.

The GI societies have been working closely with FDA and industry to identify and properly vet potential solutions. FDA has already reviewed and cleared new reprocessing and sterilization technologies and revised designs for some duodenoscopes; all are intended to enhance ease of cleaning and reprocessing, thereby improving safety from transmitted infection. Other redesigns and new technologies for endoscope reprocessing, as well as single-use instruments, are in the pipeline. All of these options, and others, will likely enter the marketplace in the coming months and years after FDA vetting and approval and with postmarketing studies to ensure the efficacy of the technology and patient safety.

AGA is currently seeking feedback from AGA members to provide to FDA for consideration as they make upcoming review and approval decisions. If you are concerned about losing access to ERCP, a valuable procedure, please share your comments in the AGA Community. We will be sharing these comments with FDA to ensure their decisions reflect the needs of our members.

Since it was discovered several years ago that cases of infection transmission associated with duodenoscopes had been experienced by hospitals in the United States and Europe, health care organizations across the board recognized the need to escalate infection control efforts and to swiftly identify and disseminate best practices. FDA, the Centers for Disease Control and Prevention, state and local health departments, scope manufacturers, and medical societies have collaborated continuously to determine best practices for identifying and reporting sources of infection and effectively cleaning equipment.

Since this problem was identified, vigilance has been raised and infection rates have improved. As with all medical procedures, physicians should discuss the risks and benefits with their patients who require ERCP.

This article was developed in collaboration with American Society for Gastrointestinal Endoscopy (ASGE) and the Society of Gastroenterology Nurses and Associates (SGNA).

[email protected]

Patients with nonalcoholic steatohepatitis (NASH) and advanced fibrosis reported lower quality of life that is worsened in those who develop cirrhosis, based on data from 1,667 individuals.

NASH is becoming an increasingly common cause of liver disease, cirrhosis, and hepatocellular carcinoma and can have a negative effect on patients’ quality of life and other patient-reported outcomes (PROs), but studies of the impact on PROs in these patients are limited, wrote Zobair M. Younossi, MD, of the Inova Health System, Falls Church, Va., and colleagues.

In a study published in Clinical Gastroenterology and Hepatology, the researchers reviewed data from 870 adults with NASH cirrhosis and 797 with NASH and bridging fibrosis. The average age of the patients was 58 years, 73% were white, 40% were male, 52% had cirrhosis, and 74% had diabetes.

The researchers used four tools to assess quality of life: the SF-36 (36-Item Short Form Health Survey), the EQ-5D (Euroqol, a generic health questionnaire), the CLDQ-NASH (Chronic Liver Disease Questionnaire-NASH), and the WPAI:SHP (Work Productivity and Activity Impairment: Specific Health Problem).

The SF-36 score is based on eight domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health.

Overall, patients with NASH and cirrhosis had significantly lower scores on domains of the SF-36 that related to physical function, compared with bridging fibrosis patients (70.3 vs. 73.6), as well as role physical (71.6 vs. 75.4) and bodily pain (65.0 vs. 68.6). The other areas of significant impairment in NASH patients with cirrhosis, compared with NASH patients with fibrosis, appeared in four domains of the disease-specific CLDQ-NASH: activity, emotional, fatigue, and worry. In addition, the EQ-5D utility score was significantly lower in cirrhosis patients, compared with fibrosis patients.

Older age, male sex, Asian race, and U.S. location of study enrollment were independent predictors of higher PRO scores in a multivariate analysis, while black race, history of smoking, history of diabetes, higher body mass index, cirrhosis, and history of comorbidities that were gastrointestinal, musculoskeletal, psychiatric, or neurologic were independent predictors of lower PRO scores in patients with advanced fibrosis and NASH.

WPAI:SHP scores, which focused on work productivity impairment and absenteeism, were not significantly different between the groups.

The study findings were limited by several factors including the specific nature of the study population and absence of non-NASH controls, the potential of false positives because of the use of self-reports, and the lack of longitudinal data, the researchers said. The results should be verified in a larger, diverse patient population, the researchers noted, but the data highlight the impairment in quality of life and productivity among patients with NASH and “can inform patients, clinicians, payers, and policymakers about the total burden of the disease and also the comprehensive benefit of treatment,” they concluded.

The study was supported by Gilead Sciences. Dr. Younossi disclosed relationships with Gilead Sciences, as well as Intercept, NovoNordisk, BMS, Allergan/Tobira, Terns, Viking, AbbVie, Novartis, and Quest Diagnostics.

SOURCE: Younossi ZM et al. Clin Gastroenterol Hepatol. 2019. doi: 10.1016/j.cgh.2019.02.024.

Patients with nonalcoholic steatohepatitis (NASH) and advanced fibrosis reported lower quality of life that is worsened in those who develop cirrhosis, based on data from 1,667 individuals.

NASH is becoming an increasingly common cause of liver disease, cirrhosis, and hepatocellular carcinoma and can have a negative effect on patients’ quality of life and other patient-reported outcomes (PROs), but studies of the impact on PROs in these patients are limited, wrote Zobair M. Younossi, MD, of the Inova Health System, Falls Church, Va., and colleagues.

In a study published in Clinical Gastroenterology and Hepatology, the researchers reviewed data from 870 adults with NASH cirrhosis and 797 with NASH and bridging fibrosis. The average age of the patients was 58 years, 73% were white, 40% were male, 52% had cirrhosis, and 74% had diabetes.

The researchers used four tools to assess quality of life: the SF-36 (36-Item Short Form Health Survey), the EQ-5D (Euroqol, a generic health questionnaire), the CLDQ-NASH (Chronic Liver Disease Questionnaire-NASH), and the WPAI:SHP (Work Productivity and Activity Impairment: Specific Health Problem).

The SF-36 score is based on eight domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health.

Overall, patients with NASH and cirrhosis had significantly lower scores on domains of the SF-36 that related to physical function, compared with bridging fibrosis patients (70.3 vs. 73.6), as well as role physical (71.6 vs. 75.4) and bodily pain (65.0 vs. 68.6). The other areas of significant impairment in NASH patients with cirrhosis, compared with NASH patients with fibrosis, appeared in four domains of the disease-specific CLDQ-NASH: activity, emotional, fatigue, and worry. In addition, the EQ-5D utility score was significantly lower in cirrhosis patients, compared with fibrosis patients.

Older age, male sex, Asian race, and U.S. location of study enrollment were independent predictors of higher PRO scores in a multivariate analysis, while black race, history of smoking, history of diabetes, higher body mass index, cirrhosis, and history of comorbidities that were gastrointestinal, musculoskeletal, psychiatric, or neurologic were independent predictors of lower PRO scores in patients with advanced fibrosis and NASH.

WPAI:SHP scores, which focused on work productivity impairment and absenteeism, were not significantly different between the groups.

The study findings were limited by several factors including the specific nature of the study population and absence of non-NASH controls, the potential of false positives because of the use of self-reports, and the lack of longitudinal data, the researchers said. The results should be verified in a larger, diverse patient population, the researchers noted, but the data highlight the impairment in quality of life and productivity among patients with NASH and “can inform patients, clinicians, payers, and policymakers about the total burden of the disease and also the comprehensive benefit of treatment,” they concluded.

The study was supported by Gilead Sciences. Dr. Younossi disclosed relationships with Gilead Sciences, as well as Intercept, NovoNordisk, BMS, Allergan/Tobira, Terns, Viking, AbbVie, Novartis, and Quest Diagnostics.

SOURCE: Younossi ZM et al. Clin Gastroenterol Hepatol. 2019. doi: 10.1016/j.cgh.2019.02.024.

Patients with nonalcoholic steatohepatitis (NASH) and advanced fibrosis reported lower quality of life that is worsened in those who develop cirrhosis, based on data from 1,667 individuals.

NASH is becoming an increasingly common cause of liver disease, cirrhosis, and hepatocellular carcinoma and can have a negative effect on patients’ quality of life and other patient-reported outcomes (PROs), but studies of the impact on PROs in these patients are limited, wrote Zobair M. Younossi, MD, of the Inova Health System, Falls Church, Va., and colleagues.

In a study published in Clinical Gastroenterology and Hepatology, the researchers reviewed data from 870 adults with NASH cirrhosis and 797 with NASH and bridging fibrosis. The average age of the patients was 58 years, 73% were white, 40% were male, 52% had cirrhosis, and 74% had diabetes.

The researchers used four tools to assess quality of life: the SF-36 (36-Item Short Form Health Survey), the EQ-5D (Euroqol, a generic health questionnaire), the CLDQ-NASH (Chronic Liver Disease Questionnaire-NASH), and the WPAI:SHP (Work Productivity and Activity Impairment: Specific Health Problem).

The SF-36 score is based on eight domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health.

Overall, patients with NASH and cirrhosis had significantly lower scores on domains of the SF-36 that related to physical function, compared with bridging fibrosis patients (70.3 vs. 73.6), as well as role physical (71.6 vs. 75.4) and bodily pain (65.0 vs. 68.6). The other areas of significant impairment in NASH patients with cirrhosis, compared with NASH patients with fibrosis, appeared in four domains of the disease-specific CLDQ-NASH: activity, emotional, fatigue, and worry. In addition, the EQ-5D utility score was significantly lower in cirrhosis patients, compared with fibrosis patients.

Older age, male sex, Asian race, and U.S. location of study enrollment were independent predictors of higher PRO scores in a multivariate analysis, while black race, history of smoking, history of diabetes, higher body mass index, cirrhosis, and history of comorbidities that were gastrointestinal, musculoskeletal, psychiatric, or neurologic were independent predictors of lower PRO scores in patients with advanced fibrosis and NASH.

WPAI:SHP scores, which focused on work productivity impairment and absenteeism, were not significantly different between the groups.

The study findings were limited by several factors including the specific nature of the study population and absence of non-NASH controls, the potential of false positives because of the use of self-reports, and the lack of longitudinal data, the researchers said. The results should be verified in a larger, diverse patient population, the researchers noted, but the data highlight the impairment in quality of life and productivity among patients with NASH and “can inform patients, clinicians, payers, and policymakers about the total burden of the disease and also the comprehensive benefit of treatment,” they concluded.

The study was supported by Gilead Sciences. Dr. Younossi disclosed relationships with Gilead Sciences, as well as Intercept, NovoNordisk, BMS, Allergan/Tobira, Terns, Viking, AbbVie, Novartis, and Quest Diagnostics.

SOURCE: Younossi ZM et al. Clin Gastroenterol Hepatol. 2019. doi: 10.1016/j.cgh.2019.02.024.

Three experts share their takeaways from the 2019 James W. Freston Conference: Food at the Intersection of Gut Health and Disease.

During your 4 years of medical school, you likely received only 4 hours of nutrition training. Yet we know diet is integral to the care of GI patients. That’s why AGA focused the 2019 James W. Freston Conference on the topic of food.

Our course directors William Chey, MD, AGAF, Sheila E. Crowe, MD, AGAF, and Gerard E. Mullin, MD, AGAF, share eight points from the meeting that stuck with them and can help all practicing GIs as they consider dietary treatments for their patients.

• 1. Personalized nutrition is important. Genetic differences lead to differences in health outcomes. One size or recommendation does not fit all. This is why certain diets only work on certain people. There is no one diet for all and for all disease states. Genetic tests can be helpful, but they rely on reporting that isn’t readily available yet.

• 2. Dietary therapy is key to managing eosinophilic esophagitis (EoE). EoE is becoming more and more prevalent. Genes can’t change that fast, but epigenetic factors can, and the evidence seems to be in food. EoE is not an IgE-mediated disease and therefore most allergy tests will not prove useful; however, food is often the trigger — most common, dairy. Dietary therapy is likely the best way to manage. You want to reduce the number of eliminated foods by way of a reintroduction protocol. The six-food elimination diet is standard, though some are moving to a four-food elimination diet (dairy, wheat, egg and soy).

• 3. There has been a reported increase in those with food allergies, sensitivities, celiac disease, and other adverse reactions to food. Many of the food allergy tests available are not helpful. In addition, many afflicted patients are conducting self-imposed diets rather than working with a GI, allergist, or dietitian. This needs to change.

• 4. There is currently insufficient evidence to support a gluten-free diet for irritable bowel syndrome (IBS). It is possible that fructans, more than gluten, are causing the GI issues. Typically, the low-FODMAP diet is beneficial to IBS patients if done correctly with the guidance of a dietitian; however, not everyone with IBS improves on it. All the steps are important though, including reintroduction and maintenance.

•5. When working with patients on the low-FODMAP or other restrictive diets, it is important to know their food and eating history. Avoidance/Restrictive Food Intake Disorder (ARFID) is something we need to be aware of when it comes to patients with a history or likelihood to develop disordered eating/eating disorders. The patient team may need to include an eating disorder therapist.

•6. The general population in the U.S. has increased the adoption of a gluten-free diet although the number of cases of celiac disease has not increased. Many have self-reported gluten sensitivities. Those that have removed gluten following trends are more at risk of bowel irregularity (low fiber), weight gain, and disordered eating. Celiac disease is not a do-it-yourself disease, patients will be best served working with a dietitian and GI.

• 7. Food can induce symptoms in patients with inflammatory bowel disease (IBD). It can also trigger gut inflammation resulting in incident or relapse. There is experimental plausibility for some factors of the relationship to be causal and we may be able to modify the diet to prevent and manage IBD.

• 8. The focus on nutrition education must continue! Nutrition should be a required part of continuing medical education for physicians. And physicians should work with dietitians to improve the care of GI patients.

For resources to help your patients understand how diet and nutrition can affect their digestive health, visit the AGA GI Patient Center, gastro.org/patient. Each disease-based resource provides tips from leading experts on the role of diet in managing GI health.

The 2019 James W. Freston Single Topic Conference took place Aug. 9 and 10 in Chicago. The Freston conference is the only conference organized by the AGA Institute Council in which the agenda is determined through an open call for proposals from AGA membership. The purpose of the conference is to focus on scientific dialogue, present opportunities for scientific collaboration, and explore new ideas that may lead to enhanced patient therapies or potential opportunities for cures of digestive diseases. The 2019 conference was sponsored by the AGA Institute Council Obesity, Metabolism & Nutrition Section. Vice chair of the section, Dr. Gerard Mullin, served as co-course director.

[email protected]

Three experts share their takeaways from the 2019 James W. Freston Conference: Food at the Intersection of Gut Health and Disease.

During your 4 years of medical school, you likely received only 4 hours of nutrition training. Yet we know diet is integral to the care of GI patients. That’s why AGA focused the 2019 James W. Freston Conference on the topic of food.

Our course directors William Chey, MD, AGAF, Sheila E. Crowe, MD, AGAF, and Gerard E. Mullin, MD, AGAF, share eight points from the meeting that stuck with them and can help all practicing GIs as they consider dietary treatments for their patients.

• 1. Personalized nutrition is important. Genetic differences lead to differences in health outcomes. One size or recommendation does not fit all. This is why certain diets only work on certain people. There is no one diet for all and for all disease states. Genetic tests can be helpful, but they rely on reporting that isn’t readily available yet.

• 2. Dietary therapy is key to managing eosinophilic esophagitis (EoE). EoE is becoming more and more prevalent. Genes can’t change that fast, but epigenetic factors can, and the evidence seems to be in food. EoE is not an IgE-mediated disease and therefore most allergy tests will not prove useful; however, food is often the trigger — most common, dairy. Dietary therapy is likely the best way to manage. You want to reduce the number of eliminated foods by way of a reintroduction protocol. The six-food elimination diet is standard, though some are moving to a four-food elimination diet (dairy, wheat, egg and soy).

• 3. There has been a reported increase in those with food allergies, sensitivities, celiac disease, and other adverse reactions to food. Many of the food allergy tests available are not helpful. In addition, many afflicted patients are conducting self-imposed diets rather than working with a GI, allergist, or dietitian. This needs to change.

• 4. There is currently insufficient evidence to support a gluten-free diet for irritable bowel syndrome (IBS). It is possible that fructans, more than gluten, are causing the GI issues. Typically, the low-FODMAP diet is beneficial to IBS patients if done correctly with the guidance of a dietitian; however, not everyone with IBS improves on it. All the steps are important though, including reintroduction and maintenance.

•5. When working with patients on the low-FODMAP or other restrictive diets, it is important to know their food and eating history. Avoidance/Restrictive Food Intake Disorder (ARFID) is something we need to be aware of when it comes to patients with a history or likelihood to develop disordered eating/eating disorders. The patient team may need to include an eating disorder therapist.

•6. The general population in the U.S. has increased the adoption of a gluten-free diet although the number of cases of celiac disease has not increased. Many have self-reported gluten sensitivities. Those that have removed gluten following trends are more at risk of bowel irregularity (low fiber), weight gain, and disordered eating. Celiac disease is not a do-it-yourself disease, patients will be best served working with a dietitian and GI.

• 7. Food can induce symptoms in patients with inflammatory bowel disease (IBD). It can also trigger gut inflammation resulting in incident or relapse. There is experimental plausibility for some factors of the relationship to be causal and we may be able to modify the diet to prevent and manage IBD.

• 8. The focus on nutrition education must continue! Nutrition should be a required part of continuing medical education for physicians. And physicians should work with dietitians to improve the care of GI patients.

For resources to help your patients understand how diet and nutrition can affect their digestive health, visit the AGA GI Patient Center, gastro.org/patient. Each disease-based resource provides tips from leading experts on the role of diet in managing GI health.

The 2019 James W. Freston Single Topic Conference took place Aug. 9 and 10 in Chicago. The Freston conference is the only conference organized by the AGA Institute Council in which the agenda is determined through an open call for proposals from AGA membership. The purpose of the conference is to focus on scientific dialogue, present opportunities for scientific collaboration, and explore new ideas that may lead to enhanced patient therapies or potential opportunities for cures of digestive diseases. The 2019 conference was sponsored by the AGA Institute Council Obesity, Metabolism & Nutrition Section. Vice chair of the section, Dr. Gerard Mullin, served as co-course director.

[email protected]

Three experts share their takeaways from the 2019 James W. Freston Conference: Food at the Intersection of Gut Health and Disease.

During your 4 years of medical school, you likely received only 4 hours of nutrition training. Yet we know diet is integral to the care of GI patients. That’s why AGA focused the 2019 James W. Freston Conference on the topic of food.

Our course directors William Chey, MD, AGAF, Sheila E. Crowe, MD, AGAF, and Gerard E. Mullin, MD, AGAF, share eight points from the meeting that stuck with them and can help all practicing GIs as they consider dietary treatments for their patients.

• 1. Personalized nutrition is important. Genetic differences lead to differences in health outcomes. One size or recommendation does not fit all. This is why certain diets only work on certain people. There is no one diet for all and for all disease states. Genetic tests can be helpful, but they rely on reporting that isn’t readily available yet.

• 2. Dietary therapy is key to managing eosinophilic esophagitis (EoE). EoE is becoming more and more prevalent. Genes can’t change that fast, but epigenetic factors can, and the evidence seems to be in food. EoE is not an IgE-mediated disease and therefore most allergy tests will not prove useful; however, food is often the trigger — most common, dairy. Dietary therapy is likely the best way to manage. You want to reduce the number of eliminated foods by way of a reintroduction protocol. The six-food elimination diet is standard, though some are moving to a four-food elimination diet (dairy, wheat, egg and soy).

• 3. There has been a reported increase in those with food allergies, sensitivities, celiac disease, and other adverse reactions to food. Many of the food allergy tests available are not helpful. In addition, many afflicted patients are conducting self-imposed diets rather than working with a GI, allergist, or dietitian. This needs to change.

• 4. There is currently insufficient evidence to support a gluten-free diet for irritable bowel syndrome (IBS). It is possible that fructans, more than gluten, are causing the GI issues. Typically, the low-FODMAP diet is beneficial to IBS patients if done correctly with the guidance of a dietitian; however, not everyone with IBS improves on it. All the steps are important though, including reintroduction and maintenance.

•5. When working with patients on the low-FODMAP or other restrictive diets, it is important to know their food and eating history. Avoidance/Restrictive Food Intake Disorder (ARFID) is something we need to be aware of when it comes to patients with a history or likelihood to develop disordered eating/eating disorders. The patient team may need to include an eating disorder therapist.

•6. The general population in the U.S. has increased the adoption of a gluten-free diet although the number of cases of celiac disease has not increased. Many have self-reported gluten sensitivities. Those that have removed gluten following trends are more at risk of bowel irregularity (low fiber), weight gain, and disordered eating. Celiac disease is not a do-it-yourself disease, patients will be best served working with a dietitian and GI.

• 7. Food can induce symptoms in patients with inflammatory bowel disease (IBD). It can also trigger gut inflammation resulting in incident or relapse. There is experimental plausibility for some factors of the relationship to be causal and we may be able to modify the diet to prevent and manage IBD.

• 8. The focus on nutrition education must continue! Nutrition should be a required part of continuing medical education for physicians. And physicians should work with dietitians to improve the care of GI patients.

For resources to help your patients understand how diet and nutrition can affect their digestive health, visit the AGA GI Patient Center, gastro.org/patient. Each disease-based resource provides tips from leading experts on the role of diet in managing GI health.

The 2019 James W. Freston Single Topic Conference took place Aug. 9 and 10 in Chicago. The Freston conference is the only conference organized by the AGA Institute Council in which the agenda is determined through an open call for proposals from AGA membership. The purpose of the conference is to focus on scientific dialogue, present opportunities for scientific collaboration, and explore new ideas that may lead to enhanced patient therapies or potential opportunities for cures of digestive diseases. The 2019 conference was sponsored by the AGA Institute Council Obesity, Metabolism & Nutrition Section. Vice chair of the section, Dr. Gerard Mullin, served as co-course director.

[email protected]

To the Editor:

Leiomyomas are benign smooth muscle tumors. There are 3 types of cutaneous leiomyomas: (1) piloleiomyomas, arising from the arrector pili muscles; (2) angioleiomyomas, arising from the muscles surrounding dermal blood vessels; and (3) leiomyomas of the external genitalia, arising from the dartoic, vulvar, or mammary smooth muscles.¹ There is no gender predilection for cutaneous leiomyomas, and lesions present on average at approximately 40 to 45 years of age.²

Piloleiomyomas are the most common type of cutaneous leiomyomas and typically present as red-brown papules and nodules on the trunk, arms, and legs.³ Piloleiomyomas often are associated with spontaneous or induced pain (eg, with cold exposure). The pain associated with piloleiomyomas can be severely debilitating to patients and may have a considerable impact on their quality of life.

A 40-year-old woman presented to our clinic with numerous widespread, painful, red-brown papules and nodules on the head, neck, chest, abdomen, back, arms, and legs of 6 years’ duration that were increasing in number (Figure 1). She had a history of uterine leiomyomas and type 2 renal papillary carcinoma following a left nephrectomy at 38 years of age. The patient’s mother had a history of similar skin lesions as well as uterine cancer. Multiple excisional biopsies were performed, all of which showed piloleiomyomas on histopathology (Figure 2). The pain associated with the patient’s extensive cutaneous leiomyomas considerably impaired her quality of life. Although she experienced pain in all affected areas of the body, the pain was the worst in the upper arms. She reported having requested a nerve ablation procedure from an outside pain management clinic, which was denied for unknown reasons.

Two years prior to the current presentation, the patient had been treated by a pain management specialist with gabapentin 300 mg twice daily as needed for pain associated with leiomyomas. The patient followed this regimen approximately 3 times weekly for the preceding 1 to 2 years with reduction in her pain symptoms; however, the painful episodes became more frequent and severe over time. The patient reported being unable to further increase the gabapentin dosing frequency because it made her too drowsy and impacted her ability to work a job that required heavy lifting. Thus, the patient requested additional therapy and was subsequently treated at our clinic with numerous excisional biopsies of the most painful lesions during the 2 years prior to her current presentation.

When the patient re-presented to our clinic, she requested additional lesion excisions given that she had experienced some pain relief from this treatment modality in the past; however, these prior excisions only resulted in local pain relief limited to the site of the excision. Because of the extent of the lesions and the patient’s inability to tolerate pain from the lidocaine injections, we did not feel multiple excisions were a practical treatment option. The patient subsequently was offered a trial of cryotherapy for symptom relief based on a reported case in which this modality was successfully used.⁴ After discussing the risks and benefits associated with this treatment, cryotherapy was attempted on a few of the leiomyomas on the patient’s right shoulder; however, she experienced severe pain during cryotherapy treatment, and the procedure had to be aborted.

We then increased the patient’s gabapentin regimen to 300 mg in the morning and 600 mg in the evening, as tolerated. The patient reported that she was better able to tolerate the sedating side effects of the increased dose of gabapentin because she had stopped working due to her severe pain episodes. We also added oral nifedipine 10 mg 3 times daily, as needed. Within 30 minutes of starting this treatment regimen, the pain associated with the lesions remarkably improved (10/10 severity before starting treatment vs 3/10 after starting treatment). Her pain levels remained stable (3/10 severity) during 3 weeks of treatment with this combination regimen, but unfortunately she developed headaches and malaise, which she associated with the nifedipine at the 3 times daily dose.

The patient was able to better tolerate the nifedipine after reducing the dose to once daily on an as-needed basis. On average, the patient took nifedipine once every 3 days; however, she reported that she had to periodically increase the frequency of the nifedipine to once daily for up to 2 weeks at a time for periods of more frequent pain flares. The patient reported a consistent pattern of the breakthrough symptoms rapidly improving with each dose of nifedipine, though she did feel that taking consistent gabapentin enhanced baseline symptom control. The patient also noticed on a few occasions when she did not have access to her nifedipine that her pain would flare to 10/10 severity and would decrease to 4/10 severity 30 minutes after restarting nifedipine at 10 mg once daily. She experienced breakthrough pain due to exacerbating factors including her menstrual cycle; exposure to the sun and cold temperatures or water; excessive physical activity; and mild trauma. Due to exacerbations from sun exposure, the patient often wore long-sleeved shirts, which helped reduce the severity of the pain episodes while she was outdoors.

The exact mechanism for the pain associated with cutaneous leiomyomas is unknown but is thought to be due to infringement of the lesion on the surrounding cutaneous nerves. In addition, norepinephrine activates alpha receptors on the smooth muscle to contract through an influx of ions such as calcium. When smooth muscle contracts, the compression of nerves likely is worsened.

There are a limited number of case reports in the literature that have demonstrated successful treatment of the pain associated with cutaneous leiomyomas. Previously reported treatment modalities have included phenoxybenzamine, an alpha-blocking agent that may reduce pain through its antiadrenergic effects²; nitroglycerin, a venous and arterial dilator that may reduce pain by decreasing muscle oxygen requirements²; gabapentin, an antiepileptic and analgesic medication with structural similarity to the gamma-aminobutyric acid neurotransmitter for which the exact mechanism of action is unknown³; botulinum toxin, a neuromuscular blocker that prevents the release of presynaptic acetylcholine and may decrease neuropathic pain by reducing hyperactive nerves^5,6; hyoscine butylbromide and topical hyoscine hydrobromide, both antispasmodics that may reduce pain through their anticholinergic effects, which relax smooth muscle^7,8; and the CO₂ laser, a treatment that has been utilized for its resurfacing, excisional, and ablative properties.^9,10

Calcium channel blockers such as amlodipine, verapamil, and nifedipine also have been used to treat the pain associated with piloleiomyomas.¹¹ Calcium ion channel antagonists inhibit the influx of calcium ions across the cell membrane; therefore, nifedipine and other calcium channel blockers may prevent the smooth muscle contraction that is hypothesized to cause pain in patients with cutaneous leiomyomas.¹²

Mean plasma concentration of nifedipine has been shown to reach maximum values of 160 +/− 49 µg/L after 30 to 60 minutes following oral administration of 10 mg of nifedipine.¹³ After 8 hours, the mean concentration drops to 3.4 +/− 1.2 µg/L. The clinical response in our patient appeared consistent with the reported pharmacokinetics of the drug, as she was able to consistently obtain considerable reduction in her pain symptoms within 30 minutes of starting nifedipine, coinciding with the period of time it takes for the nifedipine to reach maximum plasma concentrations.¹³

Interestingly, our patient had worsening pain episodes associated with sun exposure, which typically is not reported as one of the usual triggers for cutaneous leiomyomas. We are not aware of any described mechanisms that would explain this phenomenon.

Importantly, any patient presenting with multiple cutaneous and uterine (if female) leiomyomas should be screened for hereditary leiomyomatosis and renal cell carcinoma syndrome (HLRCC), an autosomal-dominant disorder linked to a mutation in the fumarate hydratase tumor suppressor gene. Clinically, HLRCC patients typically present with multiple cutaneous leiomyomas, uterine leiomyomas, and renal cell cancer (most often type 2 papillary renal cell carcinoma).¹⁴ Hereditary leiomyomatosis and renal cell carcinoma syndrome (also known as multiple cutaneous and uterine leiomyomatosis syndrome) previously was thought to be a separate disease entity from Reed syndrome; however, after the same mutation in the fumarate hydratase tumor suppressor gene was found to be responsible for both Reed syndrome and HLRCC, they are now thought to be the same disease process.¹⁵

Diagnosis of HLRCC is likely when the patient meets the major criterion of multiple cutaneous piloleiomyomas confirmed histopathologically. Clinical diagnosis of HLRCC is suspected if 2 or more of the following minor criteria are present: type 2 papillary renal cell carcinoma before 40 years of age; onset of severely symptomatic (requiring surgery) uterine fibroids before 40 years of age in females; and first-degree family member who meets 1 or more of these criteria.¹⁵ At the time of presentation, the patient met clinical criteria for HLRCC, including multiple cutaneous leiomyomas (major criterion) and type 2 papillary renal cell carcinoma before 40 years of age (minor criterion). The patient also had a history of uterine leiomyomas, but these lesions did not fulfill the criterion of being severely symptomatic requiring surgery. Furthermore, the patient’s mother had similar cutaneous leiomyomas and a history of uterine cancer, which fulfilled additional minor criterion, consistent with an autosomal-dominant inheritance pattern (with variable penetrance) seen in HLRCC. An important issue for counseling and monitoring patients is that premenopausal women with HLRCC are at an increased risk of developing uterine leiomyosarcoma.¹⁵ Our patient followed up with an oncologist for tumor surveillance and subsequently underwent genetic testing, which revealed a mutation in the fumarate hydratase gene.

Treatment of painful cutaneous leiomyomas, particularly in patients with HLRCC, remains a therapeutic challenge. Although surgical and/or destructive treatments can provide pain relief for patients who have a limited number of lesions, these options are impracticable when a patient has numerous widespread leiomyomas; therefore, systemic therapies may be more beneficial. Clinicians should be aware of nifedipine, which may be used in combination with gabapentin as a viable treatment option in the management of acute and breakthrough pain associated with cutaneous leiomyomas.

Acknowledgment
The authors thank Alejandra Encalada, MA, for her assistance in the care and follow-up of the patient.

To the Editor:

Leiomyomas are benign smooth muscle tumors. There are 3 types of cutaneous leiomyomas: (1) piloleiomyomas, arising from the arrector pili muscles; (2) angioleiomyomas, arising from the muscles surrounding dermal blood vessels; and (3) leiomyomas of the external genitalia, arising from the dartoic, vulvar, or mammary smooth muscles.¹ There is no gender predilection for cutaneous leiomyomas, and lesions present on average at approximately 40 to 45 years of age.²

Piloleiomyomas are the most common type of cutaneous leiomyomas and typically present as red-brown papules and nodules on the trunk, arms, and legs.³ Piloleiomyomas often are associated with spontaneous or induced pain (eg, with cold exposure). The pain associated with piloleiomyomas can be severely debilitating to patients and may have a considerable impact on their quality of life.

A 40-year-old woman presented to our clinic with numerous widespread, painful, red-brown papules and nodules on the head, neck, chest, abdomen, back, arms, and legs of 6 years’ duration that were increasing in number (Figure 1). She had a history of uterine leiomyomas and type 2 renal papillary carcinoma following a left nephrectomy at 38 years of age. The patient’s mother had a history of similar skin lesions as well as uterine cancer. Multiple excisional biopsies were performed, all of which showed piloleiomyomas on histopathology (Figure 2). The pain associated with the patient’s extensive cutaneous leiomyomas considerably impaired her quality of life. Although she experienced pain in all affected areas of the body, the pain was the worst in the upper arms. She reported having requested a nerve ablation procedure from an outside pain management clinic, which was denied for unknown reasons.

Two years prior to the current presentation, the patient had been treated by a pain management specialist with gabapentin 300 mg twice daily as needed for pain associated with leiomyomas. The patient followed this regimen approximately 3 times weekly for the preceding 1 to 2 years with reduction in her pain symptoms; however, the painful episodes became more frequent and severe over time. The patient reported being unable to further increase the gabapentin dosing frequency because it made her too drowsy and impacted her ability to work a job that required heavy lifting. Thus, the patient requested additional therapy and was subsequently treated at our clinic with numerous excisional biopsies of the most painful lesions during the 2 years prior to her current presentation.

When the patient re-presented to our clinic, she requested additional lesion excisions given that she had experienced some pain relief from this treatment modality in the past; however, these prior excisions only resulted in local pain relief limited to the site of the excision. Because of the extent of the lesions and the patient’s inability to tolerate pain from the lidocaine injections, we did not feel multiple excisions were a practical treatment option. The patient subsequently was offered a trial of cryotherapy for symptom relief based on a reported case in which this modality was successfully used.⁴ After discussing the risks and benefits associated with this treatment, cryotherapy was attempted on a few of the leiomyomas on the patient’s right shoulder; however, she experienced severe pain during cryotherapy treatment, and the procedure had to be aborted.

We then increased the patient’s gabapentin regimen to 300 mg in the morning and 600 mg in the evening, as tolerated. The patient reported that she was better able to tolerate the sedating side effects of the increased dose of gabapentin because she had stopped working due to her severe pain episodes. We also added oral nifedipine 10 mg 3 times daily, as needed. Within 30 minutes of starting this treatment regimen, the pain associated with the lesions remarkably improved (10/10 severity before starting treatment vs 3/10 after starting treatment). Her pain levels remained stable (3/10 severity) during 3 weeks of treatment with this combination regimen, but unfortunately she developed headaches and malaise, which she associated with the nifedipine at the 3 times daily dose.

The patient was able to better tolerate the nifedipine after reducing the dose to once daily on an as-needed basis. On average, the patient took nifedipine once every 3 days; however, she reported that she had to periodically increase the frequency of the nifedipine to once daily for up to 2 weeks at a time for periods of more frequent pain flares. The patient reported a consistent pattern of the breakthrough symptoms rapidly improving with each dose of nifedipine, though she did feel that taking consistent gabapentin enhanced baseline symptom control. The patient also noticed on a few occasions when she did not have access to her nifedipine that her pain would flare to 10/10 severity and would decrease to 4/10 severity 30 minutes after restarting nifedipine at 10 mg once daily. She experienced breakthrough pain due to exacerbating factors including her menstrual cycle; exposure to the sun and cold temperatures or water; excessive physical activity; and mild trauma. Due to exacerbations from sun exposure, the patient often wore long-sleeved shirts, which helped reduce the severity of the pain episodes while she was outdoors.

The exact mechanism for the pain associated with cutaneous leiomyomas is unknown but is thought to be due to infringement of the lesion on the surrounding cutaneous nerves. In addition, norepinephrine activates alpha receptors on the smooth muscle to contract through an influx of ions such as calcium. When smooth muscle contracts, the compression of nerves likely is worsened.

There are a limited number of case reports in the literature that have demonstrated successful treatment of the pain associated with cutaneous leiomyomas. Previously reported treatment modalities have included phenoxybenzamine, an alpha-blocking agent that may reduce pain through its antiadrenergic effects²; nitroglycerin, a venous and arterial dilator that may reduce pain by decreasing muscle oxygen requirements²; gabapentin, an antiepileptic and analgesic medication with structural similarity to the gamma-aminobutyric acid neurotransmitter for which the exact mechanism of action is unknown³; botulinum toxin, a neuromuscular blocker that prevents the release of presynaptic acetylcholine and may decrease neuropathic pain by reducing hyperactive nerves^5,6; hyoscine butylbromide and topical hyoscine hydrobromide, both antispasmodics that may reduce pain through their anticholinergic effects, which relax smooth muscle^7,8; and the CO₂ laser, a treatment that has been utilized for its resurfacing, excisional, and ablative properties.^9,10

Calcium channel blockers such as amlodipine, verapamil, and nifedipine also have been used to treat the pain associated with piloleiomyomas.¹¹ Calcium ion channel antagonists inhibit the influx of calcium ions across the cell membrane; therefore, nifedipine and other calcium channel blockers may prevent the smooth muscle contraction that is hypothesized to cause pain in patients with cutaneous leiomyomas.¹²

Mean plasma concentration of nifedipine has been shown to reach maximum values of 160 +/− 49 µg/L after 30 to 60 minutes following oral administration of 10 mg of nifedipine.¹³ After 8 hours, the mean concentration drops to 3.4 +/− 1.2 µg/L. The clinical response in our patient appeared consistent with the reported pharmacokinetics of the drug, as she was able to consistently obtain considerable reduction in her pain symptoms within 30 minutes of starting nifedipine, coinciding with the period of time it takes for the nifedipine to reach maximum plasma concentrations.¹³

Interestingly, our patient had worsening pain episodes associated with sun exposure, which typically is not reported as one of the usual triggers for cutaneous leiomyomas. We are not aware of any described mechanisms that would explain this phenomenon.

Importantly, any patient presenting with multiple cutaneous and uterine (if female) leiomyomas should be screened for hereditary leiomyomatosis and renal cell carcinoma syndrome (HLRCC), an autosomal-dominant disorder linked to a mutation in the fumarate hydratase tumor suppressor gene. Clinically, HLRCC patients typically present with multiple cutaneous leiomyomas, uterine leiomyomas, and renal cell cancer (most often type 2 papillary renal cell carcinoma).¹⁴ Hereditary leiomyomatosis and renal cell carcinoma syndrome (also known as multiple cutaneous and uterine leiomyomatosis syndrome) previously was thought to be a separate disease entity from Reed syndrome; however, after the same mutation in the fumarate hydratase tumor suppressor gene was found to be responsible for both Reed syndrome and HLRCC, they are now thought to be the same disease process.¹⁵

Diagnosis of HLRCC is likely when the patient meets the major criterion of multiple cutaneous piloleiomyomas confirmed histopathologically. Clinical diagnosis of HLRCC is suspected if 2 or more of the following minor criteria are present: type 2 papillary renal cell carcinoma before 40 years of age; onset of severely symptomatic (requiring surgery) uterine fibroids before 40 years of age in females; and first-degree family member who meets 1 or more of these criteria.¹⁵ At the time of presentation, the patient met clinical criteria for HLRCC, including multiple cutaneous leiomyomas (major criterion) and type 2 papillary renal cell carcinoma before 40 years of age (minor criterion). The patient also had a history of uterine leiomyomas, but these lesions did not fulfill the criterion of being severely symptomatic requiring surgery. Furthermore, the patient’s mother had similar cutaneous leiomyomas and a history of uterine cancer, which fulfilled additional minor criterion, consistent with an autosomal-dominant inheritance pattern (with variable penetrance) seen in HLRCC. An important issue for counseling and monitoring patients is that premenopausal women with HLRCC are at an increased risk of developing uterine leiomyosarcoma.¹⁵ Our patient followed up with an oncologist for tumor surveillance and subsequently underwent genetic testing, which revealed a mutation in the fumarate hydratase gene.

Treatment of painful cutaneous leiomyomas, particularly in patients with HLRCC, remains a therapeutic challenge. Although surgical and/or destructive treatments can provide pain relief for patients who have a limited number of lesions, these options are impracticable when a patient has numerous widespread leiomyomas; therefore, systemic therapies may be more beneficial. Clinicians should be aware of nifedipine, which may be used in combination with gabapentin as a viable treatment option in the management of acute and breakthrough pain associated with cutaneous leiomyomas.

Acknowledgment
The authors thank Alejandra Encalada, MA, for her assistance in the care and follow-up of the patient.

To the Editor:

Leiomyomas are benign smooth muscle tumors. There are 3 types of cutaneous leiomyomas: (1) piloleiomyomas, arising from the arrector pili muscles; (2) angioleiomyomas, arising from the muscles surrounding dermal blood vessels; and (3) leiomyomas of the external genitalia, arising from the dartoic, vulvar, or mammary smooth muscles.¹ There is no gender predilection for cutaneous leiomyomas, and lesions present on average at approximately 40 to 45 years of age.²

Piloleiomyomas are the most common type of cutaneous leiomyomas and typically present as red-brown papules and nodules on the trunk, arms, and legs.³ Piloleiomyomas often are associated with spontaneous or induced pain (eg, with cold exposure). The pain associated with piloleiomyomas can be severely debilitating to patients and may have a considerable impact on their quality of life.

A 40-year-old woman presented to our clinic with numerous widespread, painful, red-brown papules and nodules on the head, neck, chest, abdomen, back, arms, and legs of 6 years’ duration that were increasing in number (Figure 1). She had a history of uterine leiomyomas and type 2 renal papillary carcinoma following a left nephrectomy at 38 years of age. The patient’s mother had a history of similar skin lesions as well as uterine cancer. Multiple excisional biopsies were performed, all of which showed piloleiomyomas on histopathology (Figure 2). The pain associated with the patient’s extensive cutaneous leiomyomas considerably impaired her quality of life. Although she experienced pain in all affected areas of the body, the pain was the worst in the upper arms. She reported having requested a nerve ablation procedure from an outside pain management clinic, which was denied for unknown reasons.

Two years prior to the current presentation, the patient had been treated by a pain management specialist with gabapentin 300 mg twice daily as needed for pain associated with leiomyomas. The patient followed this regimen approximately 3 times weekly for the preceding 1 to 2 years with reduction in her pain symptoms; however, the painful episodes became more frequent and severe over time. The patient reported being unable to further increase the gabapentin dosing frequency because it made her too drowsy and impacted her ability to work a job that required heavy lifting. Thus, the patient requested additional therapy and was subsequently treated at our clinic with numerous excisional biopsies of the most painful lesions during the 2 years prior to her current presentation.

When the patient re-presented to our clinic, she requested additional lesion excisions given that she had experienced some pain relief from this treatment modality in the past; however, these prior excisions only resulted in local pain relief limited to the site of the excision. Because of the extent of the lesions and the patient’s inability to tolerate pain from the lidocaine injections, we did not feel multiple excisions were a practical treatment option. The patient subsequently was offered a trial of cryotherapy for symptom relief based on a reported case in which this modality was successfully used.⁴ After discussing the risks and benefits associated with this treatment, cryotherapy was attempted on a few of the leiomyomas on the patient’s right shoulder; however, she experienced severe pain during cryotherapy treatment, and the procedure had to be aborted.

We then increased the patient’s gabapentin regimen to 300 mg in the morning and 600 mg in the evening, as tolerated. The patient reported that she was better able to tolerate the sedating side effects of the increased dose of gabapentin because she had stopped working due to her severe pain episodes. We also added oral nifedipine 10 mg 3 times daily, as needed. Within 30 minutes of starting this treatment regimen, the pain associated with the lesions remarkably improved (10/10 severity before starting treatment vs 3/10 after starting treatment). Her pain levels remained stable (3/10 severity) during 3 weeks of treatment with this combination regimen, but unfortunately she developed headaches and malaise, which she associated with the nifedipine at the 3 times daily dose.

The patient was able to better tolerate the nifedipine after reducing the dose to once daily on an as-needed basis. On average, the patient took nifedipine once every 3 days; however, she reported that she had to periodically increase the frequency of the nifedipine to once daily for up to 2 weeks at a time for periods of more frequent pain flares. The patient reported a consistent pattern of the breakthrough symptoms rapidly improving with each dose of nifedipine, though she did feel that taking consistent gabapentin enhanced baseline symptom control. The patient also noticed on a few occasions when she did not have access to her nifedipine that her pain would flare to 10/10 severity and would decrease to 4/10 severity 30 minutes after restarting nifedipine at 10 mg once daily. She experienced breakthrough pain due to exacerbating factors including her menstrual cycle; exposure to the sun and cold temperatures or water; excessive physical activity; and mild trauma. Due to exacerbations from sun exposure, the patient often wore long-sleeved shirts, which helped reduce the severity of the pain episodes while she was outdoors.

The exact mechanism for the pain associated with cutaneous leiomyomas is unknown but is thought to be due to infringement of the lesion on the surrounding cutaneous nerves. In addition, norepinephrine activates alpha receptors on the smooth muscle to contract through an influx of ions such as calcium. When smooth muscle contracts, the compression of nerves likely is worsened.

There are a limited number of case reports in the literature that have demonstrated successful treatment of the pain associated with cutaneous leiomyomas. Previously reported treatment modalities have included phenoxybenzamine, an alpha-blocking agent that may reduce pain through its antiadrenergic effects²; nitroglycerin, a venous and arterial dilator that may reduce pain by decreasing muscle oxygen requirements²; gabapentin, an antiepileptic and analgesic medication with structural similarity to the gamma-aminobutyric acid neurotransmitter for which the exact mechanism of action is unknown³; botulinum toxin, a neuromuscular blocker that prevents the release of presynaptic acetylcholine and may decrease neuropathic pain by reducing hyperactive nerves^5,6; hyoscine butylbromide and topical hyoscine hydrobromide, both antispasmodics that may reduce pain through their anticholinergic effects, which relax smooth muscle^7,8; and the CO₂ laser, a treatment that has been utilized for its resurfacing, excisional, and ablative properties.^9,10

Calcium channel blockers such as amlodipine, verapamil, and nifedipine also have been used to treat the pain associated with piloleiomyomas.¹¹ Calcium ion channel antagonists inhibit the influx of calcium ions across the cell membrane; therefore, nifedipine and other calcium channel blockers may prevent the smooth muscle contraction that is hypothesized to cause pain in patients with cutaneous leiomyomas.¹²

Mean plasma concentration of nifedipine has been shown to reach maximum values of 160 +/− 49 µg/L after 30 to 60 minutes following oral administration of 10 mg of nifedipine.¹³ After 8 hours, the mean concentration drops to 3.4 +/− 1.2 µg/L. The clinical response in our patient appeared consistent with the reported pharmacokinetics of the drug, as she was able to consistently obtain considerable reduction in her pain symptoms within 30 minutes of starting nifedipine, coinciding with the period of time it takes for the nifedipine to reach maximum plasma concentrations.¹³

Interestingly, our patient had worsening pain episodes associated with sun exposure, which typically is not reported as one of the usual triggers for cutaneous leiomyomas. We are not aware of any described mechanisms that would explain this phenomenon.

Importantly, any patient presenting with multiple cutaneous and uterine (if female) leiomyomas should be screened for hereditary leiomyomatosis and renal cell carcinoma syndrome (HLRCC), an autosomal-dominant disorder linked to a mutation in the fumarate hydratase tumor suppressor gene. Clinically, HLRCC patients typically present with multiple cutaneous leiomyomas, uterine leiomyomas, and renal cell cancer (most often type 2 papillary renal cell carcinoma).¹⁴ Hereditary leiomyomatosis and renal cell carcinoma syndrome (also known as multiple cutaneous and uterine leiomyomatosis syndrome) previously was thought to be a separate disease entity from Reed syndrome; however, after the same mutation in the fumarate hydratase tumor suppressor gene was found to be responsible for both Reed syndrome and HLRCC, they are now thought to be the same disease process.¹⁵

Diagnosis of HLRCC is likely when the patient meets the major criterion of multiple cutaneous piloleiomyomas confirmed histopathologically. Clinical diagnosis of HLRCC is suspected if 2 or more of the following minor criteria are present: type 2 papillary renal cell carcinoma before 40 years of age; onset of severely symptomatic (requiring surgery) uterine fibroids before 40 years of age in females; and first-degree family member who meets 1 or more of these criteria.¹⁵ At the time of presentation, the patient met clinical criteria for HLRCC, including multiple cutaneous leiomyomas (major criterion) and type 2 papillary renal cell carcinoma before 40 years of age (minor criterion). The patient also had a history of uterine leiomyomas, but these lesions did not fulfill the criterion of being severely symptomatic requiring surgery. Furthermore, the patient’s mother had similar cutaneous leiomyomas and a history of uterine cancer, which fulfilled additional minor criterion, consistent with an autosomal-dominant inheritance pattern (with variable penetrance) seen in HLRCC. An important issue for counseling and monitoring patients is that premenopausal women with HLRCC are at an increased risk of developing uterine leiomyosarcoma.¹⁵ Our patient followed up with an oncologist for tumor surveillance and subsequently underwent genetic testing, which revealed a mutation in the fumarate hydratase gene.

Treatment of painful cutaneous leiomyomas, particularly in patients with HLRCC, remains a therapeutic challenge. Although surgical and/or destructive treatments can provide pain relief for patients who have a limited number of lesions, these options are impracticable when a patient has numerous widespread leiomyomas; therefore, systemic therapies may be more beneficial. Clinicians should be aware of nifedipine, which may be used in combination with gabapentin as a viable treatment option in the management of acute and breakthrough pain associated with cutaneous leiomyomas.

Acknowledgment
The authors thank Alejandra Encalada, MA, for her assistance in the care and follow-up of the patient.