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Benefits of low-dose CT scanning for lung cancer screening explained
According to the Centers for Disease Control and Prevention, lung cancer is the third-most common cancer in the United States and the leading cause of cancer deaths in both men and women. Approximately, 150,000 Americans die every year from this disease.
In fact, it has been shown that low-dose CT scan screening can reduce lung cancer deaths by 20%-30% in high-risk populations.
In the United States, low-dose CT scan screening for lung cancer has largely become the norm. In July 2021, CHEST released new clinical guidelines. These guidelines cover 18 evidence-based recommendations as well as inclusion of further evidence regarding the benefits, risks, and use of CT screening.
In doing the risk assessment of low-dose CT scan as a method of lung cancer screening, meta-analyses were performed on evidence obtained through a literature search using PubMed, Embase, and the Cochrane Library. It was concluded that the benefits outweigh the risks as a method of lung cancer screening and can be utilized in reducing lung cancer deaths.
Low-dose CT scan screening was recommended for the following patients:
- Asymptomatic individuals aged 55-77 years with a history of smoking 30 or more pack-years. (This includes those who continue to smoke or who have quit in the previous 15 years. Annual screening is advised.)
- Asymptomatic individuals aged 55-80 years with a history of smoking 20-30 pack-years who either continue to smoke or have quit in the previous 15 years.
- For asymptomatic individuals who do not meet the above criteria but are predicted to benefit based on life-year gained calculations.
Don’t screen these patients
CT scan screening should not be performed on any person who does not meet any of the above three criteria.
Additionally, if a person has significant comorbidities that would limit their life expectancy, it is recommended not to do CT scan screening. Symptomatic patients should have appropriate diagnostic testing rather than screening.
Additional recommendations from the updated guidelines include developing appropriate counseling strategies as well as deciding what constitutes a positive test.
A positive test should be anything that warrants further evaluation rather than a return to annual screening. It was also advised that overtreatment strategies should be implemented. Additionally, smoking cessation treatment should be provided.
CHEST suggested undertaking a comprehensive approach involving multiple specialists including pulmonologists, radiologists, oncologists, etc. Strategies to ensure compliance with annual screening should also be devised, the guidelines say.
USPSTF’s updated guidelines
It should be noted that the U.S. Preventative Task Force released their own set of updated guidelines in March 2021. In these guidelines, the age at which lung cancer screening should be started was lowered from 55 years to 50 years.
Also, the USPSTF lowered the minimum required smoking history in order to be screened from 30 to 20 pack-years. Their purpose for doing this was to include more high-risk women as well as minorities.
With the changes, 14.5 million individuals living in the United States would be eligible for lung cancer screening by low-dose CT scan, an increase of 6.5 million people, compared with the previous guidelines.
While only small differences exist between the set of guidelines issued by CHEST and the ones issues by the USPSTF, lung cancer screening is still largely underutilized.
One of the barriers to screening may be patients’ lacking insurance coverage for it. As physicians, we need to advocate for these screening tools to be covered.
Other barriers include lack of patient knowledge regarding low-dose CT scans as a screening tool, patient time, and patient visits with their doctors being too short.
Key message
Part of the duties of physicians is to give our patients the best information. We can reduce lung cancer mortality in high risk patients by performing annual low-dose CT scans.
Whichever set of guidelines we chose to follow, we fail our patients if we don’t follow either set of them. The evidence is clear that a low-dose CT scan is a valuable screening tool to add to our practice of medicine.
Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].
According to the Centers for Disease Control and Prevention, lung cancer is the third-most common cancer in the United States and the leading cause of cancer deaths in both men and women. Approximately, 150,000 Americans die every year from this disease.
In fact, it has been shown that low-dose CT scan screening can reduce lung cancer deaths by 20%-30% in high-risk populations.
In the United States, low-dose CT scan screening for lung cancer has largely become the norm. In July 2021, CHEST released new clinical guidelines. These guidelines cover 18 evidence-based recommendations as well as inclusion of further evidence regarding the benefits, risks, and use of CT screening.
In doing the risk assessment of low-dose CT scan as a method of lung cancer screening, meta-analyses were performed on evidence obtained through a literature search using PubMed, Embase, and the Cochrane Library. It was concluded that the benefits outweigh the risks as a method of lung cancer screening and can be utilized in reducing lung cancer deaths.
Low-dose CT scan screening was recommended for the following patients:
- Asymptomatic individuals aged 55-77 years with a history of smoking 30 or more pack-years. (This includes those who continue to smoke or who have quit in the previous 15 years. Annual screening is advised.)
- Asymptomatic individuals aged 55-80 years with a history of smoking 20-30 pack-years who either continue to smoke or have quit in the previous 15 years.
- For asymptomatic individuals who do not meet the above criteria but are predicted to benefit based on life-year gained calculations.
Don’t screen these patients
CT scan screening should not be performed on any person who does not meet any of the above three criteria.
Additionally, if a person has significant comorbidities that would limit their life expectancy, it is recommended not to do CT scan screening. Symptomatic patients should have appropriate diagnostic testing rather than screening.
Additional recommendations from the updated guidelines include developing appropriate counseling strategies as well as deciding what constitutes a positive test.
A positive test should be anything that warrants further evaluation rather than a return to annual screening. It was also advised that overtreatment strategies should be implemented. Additionally, smoking cessation treatment should be provided.
CHEST suggested undertaking a comprehensive approach involving multiple specialists including pulmonologists, radiologists, oncologists, etc. Strategies to ensure compliance with annual screening should also be devised, the guidelines say.
USPSTF’s updated guidelines
It should be noted that the U.S. Preventative Task Force released their own set of updated guidelines in March 2021. In these guidelines, the age at which lung cancer screening should be started was lowered from 55 years to 50 years.
Also, the USPSTF lowered the minimum required smoking history in order to be screened from 30 to 20 pack-years. Their purpose for doing this was to include more high-risk women as well as minorities.
With the changes, 14.5 million individuals living in the United States would be eligible for lung cancer screening by low-dose CT scan, an increase of 6.5 million people, compared with the previous guidelines.
While only small differences exist between the set of guidelines issued by CHEST and the ones issues by the USPSTF, lung cancer screening is still largely underutilized.
One of the barriers to screening may be patients’ lacking insurance coverage for it. As physicians, we need to advocate for these screening tools to be covered.
Other barriers include lack of patient knowledge regarding low-dose CT scans as a screening tool, patient time, and patient visits with their doctors being too short.
Key message
Part of the duties of physicians is to give our patients the best information. We can reduce lung cancer mortality in high risk patients by performing annual low-dose CT scans.
Whichever set of guidelines we chose to follow, we fail our patients if we don’t follow either set of them. The evidence is clear that a low-dose CT scan is a valuable screening tool to add to our practice of medicine.
Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].
According to the Centers for Disease Control and Prevention, lung cancer is the third-most common cancer in the United States and the leading cause of cancer deaths in both men and women. Approximately, 150,000 Americans die every year from this disease.
In fact, it has been shown that low-dose CT scan screening can reduce lung cancer deaths by 20%-30% in high-risk populations.
In the United States, low-dose CT scan screening for lung cancer has largely become the norm. In July 2021, CHEST released new clinical guidelines. These guidelines cover 18 evidence-based recommendations as well as inclusion of further evidence regarding the benefits, risks, and use of CT screening.
In doing the risk assessment of low-dose CT scan as a method of lung cancer screening, meta-analyses were performed on evidence obtained through a literature search using PubMed, Embase, and the Cochrane Library. It was concluded that the benefits outweigh the risks as a method of lung cancer screening and can be utilized in reducing lung cancer deaths.
Low-dose CT scan screening was recommended for the following patients:
- Asymptomatic individuals aged 55-77 years with a history of smoking 30 or more pack-years. (This includes those who continue to smoke or who have quit in the previous 15 years. Annual screening is advised.)
- Asymptomatic individuals aged 55-80 years with a history of smoking 20-30 pack-years who either continue to smoke or have quit in the previous 15 years.
- For asymptomatic individuals who do not meet the above criteria but are predicted to benefit based on life-year gained calculations.
Don’t screen these patients
CT scan screening should not be performed on any person who does not meet any of the above three criteria.
Additionally, if a person has significant comorbidities that would limit their life expectancy, it is recommended not to do CT scan screening. Symptomatic patients should have appropriate diagnostic testing rather than screening.
Additional recommendations from the updated guidelines include developing appropriate counseling strategies as well as deciding what constitutes a positive test.
A positive test should be anything that warrants further evaluation rather than a return to annual screening. It was also advised that overtreatment strategies should be implemented. Additionally, smoking cessation treatment should be provided.
CHEST suggested undertaking a comprehensive approach involving multiple specialists including pulmonologists, radiologists, oncologists, etc. Strategies to ensure compliance with annual screening should also be devised, the guidelines say.
USPSTF’s updated guidelines
It should be noted that the U.S. Preventative Task Force released their own set of updated guidelines in March 2021. In these guidelines, the age at which lung cancer screening should be started was lowered from 55 years to 50 years.
Also, the USPSTF lowered the minimum required smoking history in order to be screened from 30 to 20 pack-years. Their purpose for doing this was to include more high-risk women as well as minorities.
With the changes, 14.5 million individuals living in the United States would be eligible for lung cancer screening by low-dose CT scan, an increase of 6.5 million people, compared with the previous guidelines.
While only small differences exist between the set of guidelines issued by CHEST and the ones issues by the USPSTF, lung cancer screening is still largely underutilized.
One of the barriers to screening may be patients’ lacking insurance coverage for it. As physicians, we need to advocate for these screening tools to be covered.
Other barriers include lack of patient knowledge regarding low-dose CT scans as a screening tool, patient time, and patient visits with their doctors being too short.
Key message
Part of the duties of physicians is to give our patients the best information. We can reduce lung cancer mortality in high risk patients by performing annual low-dose CT scans.
Whichever set of guidelines we chose to follow, we fail our patients if we don’t follow either set of them. The evidence is clear that a low-dose CT scan is a valuable screening tool to add to our practice of medicine.
Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].
FDA OKs emergency use of Merck pill for COVID-19
Similar to FDA authorization of another antiviral pill regimen – ritonavir plus nirmatrelvir, or Paxlovid – granted to Pfizer on Wednesday, molnupiravir (brand name Lagevrio) should be taken early in the course of COVID-19 illness.
Pfizer’s drug is authorized for anyone aged 12 and up. But Merck’s is only for adults aged 18 and older.
Merck filed an application for emergency use authorization with the FDA in October. The company included results of its phase 3 study showing the treatment could lead to a 50% reduction in COVID-19 hospitalizations. Data later showed this efficacy at closer to a 30% reduction. In November, an FDA advisory panel narrowly recommended the agency grant authorization by a 13-10 vote.
Animal studies found the drug may harm a fetus, so it is not recommended for pregnant people, the FDA says. It may be prescribed to a pregnant person only after their doctor determines the benefits outweigh the risks and the patient is told of those risks.
Women who may get pregnant should use a reliable method of birth control if being treated with molnupiravir and for 4 days after the final dose.
Two weapons against COVID
Two antiviral pills could be better than one, at least in terms of making more COVID-19 treatments available in early 2022. It is yet to be seen if the drugmakers will be able to keep up with demand, which could substantially increase with an expected surge in Omicron variant cases.
Ritonavir and molnupiravir join remdesivir (brand name Veklury) as available antivirals to treat COVID-19. Remdesivir is fully approved by the FDA but is given only through an IV to people in the hospital.
Officials point out that COVID-19 treatments in tablet form are more convenient for patients in the United States and across the globe, particularly where IV infusion services may be limited.
In March 2021, experts accurately predicted that the molnupiravir pill would be available by year’s end.
Interestingly, in September, Merck announced the findings of laboratory studies suggesting that molnupiravir would work against variants of SARS-CoV-2 because the agent does not target the virus’s spike protein.
Perhaps in part because of early promising results, the U.S. government announced in November intentions to purchase $1 billion worth of molnupiravir. That new order came on top of $1.2 billion worth of the pills the U.S. ordered in June.
A version of this article first appeared on WebMD.com.
Similar to FDA authorization of another antiviral pill regimen – ritonavir plus nirmatrelvir, or Paxlovid – granted to Pfizer on Wednesday, molnupiravir (brand name Lagevrio) should be taken early in the course of COVID-19 illness.
Pfizer’s drug is authorized for anyone aged 12 and up. But Merck’s is only for adults aged 18 and older.
Merck filed an application for emergency use authorization with the FDA in October. The company included results of its phase 3 study showing the treatment could lead to a 50% reduction in COVID-19 hospitalizations. Data later showed this efficacy at closer to a 30% reduction. In November, an FDA advisory panel narrowly recommended the agency grant authorization by a 13-10 vote.
Animal studies found the drug may harm a fetus, so it is not recommended for pregnant people, the FDA says. It may be prescribed to a pregnant person only after their doctor determines the benefits outweigh the risks and the patient is told of those risks.
Women who may get pregnant should use a reliable method of birth control if being treated with molnupiravir and for 4 days after the final dose.
Two weapons against COVID
Two antiviral pills could be better than one, at least in terms of making more COVID-19 treatments available in early 2022. It is yet to be seen if the drugmakers will be able to keep up with demand, which could substantially increase with an expected surge in Omicron variant cases.
Ritonavir and molnupiravir join remdesivir (brand name Veklury) as available antivirals to treat COVID-19. Remdesivir is fully approved by the FDA but is given only through an IV to people in the hospital.
Officials point out that COVID-19 treatments in tablet form are more convenient for patients in the United States and across the globe, particularly where IV infusion services may be limited.
In March 2021, experts accurately predicted that the molnupiravir pill would be available by year’s end.
Interestingly, in September, Merck announced the findings of laboratory studies suggesting that molnupiravir would work against variants of SARS-CoV-2 because the agent does not target the virus’s spike protein.
Perhaps in part because of early promising results, the U.S. government announced in November intentions to purchase $1 billion worth of molnupiravir. That new order came on top of $1.2 billion worth of the pills the U.S. ordered in June.
A version of this article first appeared on WebMD.com.
Similar to FDA authorization of another antiviral pill regimen – ritonavir plus nirmatrelvir, or Paxlovid – granted to Pfizer on Wednesday, molnupiravir (brand name Lagevrio) should be taken early in the course of COVID-19 illness.
Pfizer’s drug is authorized for anyone aged 12 and up. But Merck’s is only for adults aged 18 and older.
Merck filed an application for emergency use authorization with the FDA in October. The company included results of its phase 3 study showing the treatment could lead to a 50% reduction in COVID-19 hospitalizations. Data later showed this efficacy at closer to a 30% reduction. In November, an FDA advisory panel narrowly recommended the agency grant authorization by a 13-10 vote.
Animal studies found the drug may harm a fetus, so it is not recommended for pregnant people, the FDA says. It may be prescribed to a pregnant person only after their doctor determines the benefits outweigh the risks and the patient is told of those risks.
Women who may get pregnant should use a reliable method of birth control if being treated with molnupiravir and for 4 days after the final dose.
Two weapons against COVID
Two antiviral pills could be better than one, at least in terms of making more COVID-19 treatments available in early 2022. It is yet to be seen if the drugmakers will be able to keep up with demand, which could substantially increase with an expected surge in Omicron variant cases.
Ritonavir and molnupiravir join remdesivir (brand name Veklury) as available antivirals to treat COVID-19. Remdesivir is fully approved by the FDA but is given only through an IV to people in the hospital.
Officials point out that COVID-19 treatments in tablet form are more convenient for patients in the United States and across the globe, particularly where IV infusion services may be limited.
In March 2021, experts accurately predicted that the molnupiravir pill would be available by year’s end.
Interestingly, in September, Merck announced the findings of laboratory studies suggesting that molnupiravir would work against variants of SARS-CoV-2 because the agent does not target the virus’s spike protein.
Perhaps in part because of early promising results, the U.S. government announced in November intentions to purchase $1 billion worth of molnupiravir. That new order came on top of $1.2 billion worth of the pills the U.S. ordered in June.
A version of this article first appeared on WebMD.com.
iPLEDGE rollout: As frustration mounts, FDA agrees to help solve issues
, according to dermatologists, pharmacists, and patients.
When the new website and call center launched Dec. 13, hours-long hold times and repeated crashing of the website were reported as the norm, not the exception, triggering the American Academy of Dermatology Association (AADA) to request – and get – an emergency meeting on Dec. 16 with the U.S. Food and Drug Administration, which mandates the risk evaluation and mitigation strategy (REMS) for isotretinoin due to the teratogenicity of the acne medication.
At that meeting, ‘’the FDA and HHS [U.S. Department of Health and Human Services] acknowledged the concerns of dermatologists and the need for stakeholders to work collaboratively to find a solution,” Ilona Frieden, MD, chair of the AADA’s iPLEDGE workgroup and professor of dermatology at the University of California, San Francisco, said in an email interview. At the meeting, the AADA representatives described the severe impact on patient access to treatment that is resulting from the issues. The AADA also ‘’reiterated our call for a temporary pause to the program while stakeholders work to resolve the urgent issues with the platform,” she said.
The new approach, which is intended to make the experience more inclusive for transgender patients, reduces the previous three risk categories (females of reproductive potential, females not of reproductive potential, and males) to just two (those capable of getting pregnant and those not capable). The program requires physicians, patients, and pharmacists who prescribe, use, or dispense the drug to be registered, with requirements that include the use of two forms of an effective contraceptive and regular pregnancy tests by patients capable of becoming pregnant.
With reduced or no access during the technology glitches, access to the medicine was delayed for some patients. And dermatologists, pharmacists, and their staffs reported grueling hold times trying to reach the call center when the website had issues.
While the FDA agreed to help find a solution, it noted that the solution ‘’was to be found with dermatologists and pharmacists who are on the ground living the program every day,” Dr. Frieden said. No timeline for solving the issues was provided, so on Dec. 21, the AADA asked the FDA for a constructive dialogue among stakeholders within the next 24 hours, Dr. Frieden told this news organization.
While Dr. Frieden sees progress, ‘’we are disappointed that this situation continues to drag on for more than a week later, with more patients losing access to their needed medication each day.” While some prescribers have been able to log onto the portal and enter the information required, confirming some patients, large gaps remain, she said. Patients and pharmacists still report difficulties logging on. When that happens and they try to reach the call center, there are often hours-long hold times, dropped calls, or a message saying to call back.
The iPLEDGE administrator is Syneos Health, but a spokesperson for Syneos, Gary Gatyas, said the company does not maintain the system or the contact center.
So who does manage the call center and website? “The AADA has asked stakeholders, including Syneos Health, for clarification on who manages the call center and website but has not received a response,” Dr. Frieden said. “In the meeting [Dec. 16], representatives from the FDA made clear that the iPLEDGE sponsors are ultimately responsible for this REMS program,” Dr. Frieden said.
According to the FDA, isotretinoin manufacturers are part of the iPLEDGE program. On the iPLEDGE website, 12 isotretinoin products are listed, made by eight different companies.
One dermatologist maneuvering the new website who registered successfully as a provider told this news organization that he received a follow-up survey from United BioSource about the new website. This news organization contacted that company to confirm it runs the website but has not yet received a response.
Meanwhile, dermatologists continue to help frustrated patients cope with the new website and registration details. Neil S. Goldberg, MD, a dermatologist in Westchester County, New York, heard from two mothers who helped their teen daughters complete the forms by attesting they would use abstinence as contraception but then couldn’t figure out how to answer another question. As a result, their answers were interpreted as the patients saying they were using abstinence but didn’t commit to not having sexual contact with a partner capable of impregnating them. So Dr. Goldberg got an automated message back from the iPLEDGE program that the answers were a mismatch.
And in the comments section following a previous story on the problematic rollout, one reader offered a suggestion for reducing hold times to the call center: choose the Spanish option.
Dr. Frieden and Dr. Goldberg have no relevant disclosures.
A version of this article first appeared on Medscape.com.
, according to dermatologists, pharmacists, and patients.
When the new website and call center launched Dec. 13, hours-long hold times and repeated crashing of the website were reported as the norm, not the exception, triggering the American Academy of Dermatology Association (AADA) to request – and get – an emergency meeting on Dec. 16 with the U.S. Food and Drug Administration, which mandates the risk evaluation and mitigation strategy (REMS) for isotretinoin due to the teratogenicity of the acne medication.
At that meeting, ‘’the FDA and HHS [U.S. Department of Health and Human Services] acknowledged the concerns of dermatologists and the need for stakeholders to work collaboratively to find a solution,” Ilona Frieden, MD, chair of the AADA’s iPLEDGE workgroup and professor of dermatology at the University of California, San Francisco, said in an email interview. At the meeting, the AADA representatives described the severe impact on patient access to treatment that is resulting from the issues. The AADA also ‘’reiterated our call for a temporary pause to the program while stakeholders work to resolve the urgent issues with the platform,” she said.
The new approach, which is intended to make the experience more inclusive for transgender patients, reduces the previous three risk categories (females of reproductive potential, females not of reproductive potential, and males) to just two (those capable of getting pregnant and those not capable). The program requires physicians, patients, and pharmacists who prescribe, use, or dispense the drug to be registered, with requirements that include the use of two forms of an effective contraceptive and regular pregnancy tests by patients capable of becoming pregnant.
With reduced or no access during the technology glitches, access to the medicine was delayed for some patients. And dermatologists, pharmacists, and their staffs reported grueling hold times trying to reach the call center when the website had issues.
While the FDA agreed to help find a solution, it noted that the solution ‘’was to be found with dermatologists and pharmacists who are on the ground living the program every day,” Dr. Frieden said. No timeline for solving the issues was provided, so on Dec. 21, the AADA asked the FDA for a constructive dialogue among stakeholders within the next 24 hours, Dr. Frieden told this news organization.
While Dr. Frieden sees progress, ‘’we are disappointed that this situation continues to drag on for more than a week later, with more patients losing access to their needed medication each day.” While some prescribers have been able to log onto the portal and enter the information required, confirming some patients, large gaps remain, she said. Patients and pharmacists still report difficulties logging on. When that happens and they try to reach the call center, there are often hours-long hold times, dropped calls, or a message saying to call back.
The iPLEDGE administrator is Syneos Health, but a spokesperson for Syneos, Gary Gatyas, said the company does not maintain the system or the contact center.
So who does manage the call center and website? “The AADA has asked stakeholders, including Syneos Health, for clarification on who manages the call center and website but has not received a response,” Dr. Frieden said. “In the meeting [Dec. 16], representatives from the FDA made clear that the iPLEDGE sponsors are ultimately responsible for this REMS program,” Dr. Frieden said.
According to the FDA, isotretinoin manufacturers are part of the iPLEDGE program. On the iPLEDGE website, 12 isotretinoin products are listed, made by eight different companies.
One dermatologist maneuvering the new website who registered successfully as a provider told this news organization that he received a follow-up survey from United BioSource about the new website. This news organization contacted that company to confirm it runs the website but has not yet received a response.
Meanwhile, dermatologists continue to help frustrated patients cope with the new website and registration details. Neil S. Goldberg, MD, a dermatologist in Westchester County, New York, heard from two mothers who helped their teen daughters complete the forms by attesting they would use abstinence as contraception but then couldn’t figure out how to answer another question. As a result, their answers were interpreted as the patients saying they were using abstinence but didn’t commit to not having sexual contact with a partner capable of impregnating them. So Dr. Goldberg got an automated message back from the iPLEDGE program that the answers were a mismatch.
And in the comments section following a previous story on the problematic rollout, one reader offered a suggestion for reducing hold times to the call center: choose the Spanish option.
Dr. Frieden and Dr. Goldberg have no relevant disclosures.
A version of this article first appeared on Medscape.com.
, according to dermatologists, pharmacists, and patients.
When the new website and call center launched Dec. 13, hours-long hold times and repeated crashing of the website were reported as the norm, not the exception, triggering the American Academy of Dermatology Association (AADA) to request – and get – an emergency meeting on Dec. 16 with the U.S. Food and Drug Administration, which mandates the risk evaluation and mitigation strategy (REMS) for isotretinoin due to the teratogenicity of the acne medication.
At that meeting, ‘’the FDA and HHS [U.S. Department of Health and Human Services] acknowledged the concerns of dermatologists and the need for stakeholders to work collaboratively to find a solution,” Ilona Frieden, MD, chair of the AADA’s iPLEDGE workgroup and professor of dermatology at the University of California, San Francisco, said in an email interview. At the meeting, the AADA representatives described the severe impact on patient access to treatment that is resulting from the issues. The AADA also ‘’reiterated our call for a temporary pause to the program while stakeholders work to resolve the urgent issues with the platform,” she said.
The new approach, which is intended to make the experience more inclusive for transgender patients, reduces the previous three risk categories (females of reproductive potential, females not of reproductive potential, and males) to just two (those capable of getting pregnant and those not capable). The program requires physicians, patients, and pharmacists who prescribe, use, or dispense the drug to be registered, with requirements that include the use of two forms of an effective contraceptive and regular pregnancy tests by patients capable of becoming pregnant.
With reduced or no access during the technology glitches, access to the medicine was delayed for some patients. And dermatologists, pharmacists, and their staffs reported grueling hold times trying to reach the call center when the website had issues.
While the FDA agreed to help find a solution, it noted that the solution ‘’was to be found with dermatologists and pharmacists who are on the ground living the program every day,” Dr. Frieden said. No timeline for solving the issues was provided, so on Dec. 21, the AADA asked the FDA for a constructive dialogue among stakeholders within the next 24 hours, Dr. Frieden told this news organization.
While Dr. Frieden sees progress, ‘’we are disappointed that this situation continues to drag on for more than a week later, with more patients losing access to their needed medication each day.” While some prescribers have been able to log onto the portal and enter the information required, confirming some patients, large gaps remain, she said. Patients and pharmacists still report difficulties logging on. When that happens and they try to reach the call center, there are often hours-long hold times, dropped calls, or a message saying to call back.
The iPLEDGE administrator is Syneos Health, but a spokesperson for Syneos, Gary Gatyas, said the company does not maintain the system or the contact center.
So who does manage the call center and website? “The AADA has asked stakeholders, including Syneos Health, for clarification on who manages the call center and website but has not received a response,” Dr. Frieden said. “In the meeting [Dec. 16], representatives from the FDA made clear that the iPLEDGE sponsors are ultimately responsible for this REMS program,” Dr. Frieden said.
According to the FDA, isotretinoin manufacturers are part of the iPLEDGE program. On the iPLEDGE website, 12 isotretinoin products are listed, made by eight different companies.
One dermatologist maneuvering the new website who registered successfully as a provider told this news organization that he received a follow-up survey from United BioSource about the new website. This news organization contacted that company to confirm it runs the website but has not yet received a response.
Meanwhile, dermatologists continue to help frustrated patients cope with the new website and registration details. Neil S. Goldberg, MD, a dermatologist in Westchester County, New York, heard from two mothers who helped their teen daughters complete the forms by attesting they would use abstinence as contraception but then couldn’t figure out how to answer another question. As a result, their answers were interpreted as the patients saying they were using abstinence but didn’t commit to not having sexual contact with a partner capable of impregnating them. So Dr. Goldberg got an automated message back from the iPLEDGE program that the answers were a mismatch.
And in the comments section following a previous story on the problematic rollout, one reader offered a suggestion for reducing hold times to the call center: choose the Spanish option.
Dr. Frieden and Dr. Goldberg have no relevant disclosures.
A version of this article first appeared on Medscape.com.
New studies suggest Omicron infections are less severe than Delta ones
People who get COVID-19 infections caused by the Omicron variant are less likely to need hospital care, compared with those infected by the Delta variant, according to two large new studies from the U.K. and South Africa.
The findings, which were released ahead of peer review, add to previous glimmers of evidence suggesting that Omicron – while extremely contagious -– may result in less severe symptoms than its predecessors.
“This is helping us quantify how much less severe Omicron is than Delta, and it appears to be between 40 to 75% reduced risk of hospitalizations, adjusted for many factors, which is very good,” said Eric Topol, MD, the editor-in-chief of Medscape and a cardiologist at Scripps Research Translational Institute in La Jolla, CA.
The first analysis, which was done by the World Health Organization Collaborating Centre for Infectious Disease Modelling and Imperial College London, found that overall, people infected by Omicron had about a 20% reduced risk of needing any hospital care for their infections and a 40% lower risk of an overnight hospital stay, compared to those infected with Delta.
Meanwhile, people who were re-infected – meaning they caught Omicron after recovering from a previous COVID-19 infection – had a 50%-60% lower risk of needing hospital care, likely reflecting the benefits of having some prior immunity against the same family of viruses.
The study included everyone with polymerase chain reaction-confirmed COVID-19 in the U.K. during the first 2 weeks of December – roughly 56,000 Omicron cases and 269,000 Delta infections.
The second study, from researchers at the National Institute for Communicable Diseases in South Africa, included more than 29,000 COVID-19 cases that had lab results highly suggestive of Omicron infections. Compared to people infected with the Delta variant, those with presumed Omicron infections were about 70% less likely to have severe disease.
While the news is hopeful for individuals, on a population level, health care systems may still be stressed, the study authors warned.
“Given the high transmissibility of the Omicron virus, there remains the potential for health services to face increasing demand if Omicron cases continue to grow at the rate that has been seen in recent weeks,” said study author Neil Ferguson, PhD, who studies how infectious diseases spread at Imperial College London.
The study authors say their findings are specific to the U.K. and South Africa, where substantial portions of the population have some immune protection from past infection. In other words, they may not apply to countries where fewer people have been vaccinated or recovered from a bout with COVID-19.
A version of this article first appeared on WebMD.com.
People who get COVID-19 infections caused by the Omicron variant are less likely to need hospital care, compared with those infected by the Delta variant, according to two large new studies from the U.K. and South Africa.
The findings, which were released ahead of peer review, add to previous glimmers of evidence suggesting that Omicron – while extremely contagious -– may result in less severe symptoms than its predecessors.
“This is helping us quantify how much less severe Omicron is than Delta, and it appears to be between 40 to 75% reduced risk of hospitalizations, adjusted for many factors, which is very good,” said Eric Topol, MD, the editor-in-chief of Medscape and a cardiologist at Scripps Research Translational Institute in La Jolla, CA.
The first analysis, which was done by the World Health Organization Collaborating Centre for Infectious Disease Modelling and Imperial College London, found that overall, people infected by Omicron had about a 20% reduced risk of needing any hospital care for their infections and a 40% lower risk of an overnight hospital stay, compared to those infected with Delta.
Meanwhile, people who were re-infected – meaning they caught Omicron after recovering from a previous COVID-19 infection – had a 50%-60% lower risk of needing hospital care, likely reflecting the benefits of having some prior immunity against the same family of viruses.
The study included everyone with polymerase chain reaction-confirmed COVID-19 in the U.K. during the first 2 weeks of December – roughly 56,000 Omicron cases and 269,000 Delta infections.
The second study, from researchers at the National Institute for Communicable Diseases in South Africa, included more than 29,000 COVID-19 cases that had lab results highly suggestive of Omicron infections. Compared to people infected with the Delta variant, those with presumed Omicron infections were about 70% less likely to have severe disease.
While the news is hopeful for individuals, on a population level, health care systems may still be stressed, the study authors warned.
“Given the high transmissibility of the Omicron virus, there remains the potential for health services to face increasing demand if Omicron cases continue to grow at the rate that has been seen in recent weeks,” said study author Neil Ferguson, PhD, who studies how infectious diseases spread at Imperial College London.
The study authors say their findings are specific to the U.K. and South Africa, where substantial portions of the population have some immune protection from past infection. In other words, they may not apply to countries where fewer people have been vaccinated or recovered from a bout with COVID-19.
A version of this article first appeared on WebMD.com.
People who get COVID-19 infections caused by the Omicron variant are less likely to need hospital care, compared with those infected by the Delta variant, according to two large new studies from the U.K. and South Africa.
The findings, which were released ahead of peer review, add to previous glimmers of evidence suggesting that Omicron – while extremely contagious -– may result in less severe symptoms than its predecessors.
“This is helping us quantify how much less severe Omicron is than Delta, and it appears to be between 40 to 75% reduced risk of hospitalizations, adjusted for many factors, which is very good,” said Eric Topol, MD, the editor-in-chief of Medscape and a cardiologist at Scripps Research Translational Institute in La Jolla, CA.
The first analysis, which was done by the World Health Organization Collaborating Centre for Infectious Disease Modelling and Imperial College London, found that overall, people infected by Omicron had about a 20% reduced risk of needing any hospital care for their infections and a 40% lower risk of an overnight hospital stay, compared to those infected with Delta.
Meanwhile, people who were re-infected – meaning they caught Omicron after recovering from a previous COVID-19 infection – had a 50%-60% lower risk of needing hospital care, likely reflecting the benefits of having some prior immunity against the same family of viruses.
The study included everyone with polymerase chain reaction-confirmed COVID-19 in the U.K. during the first 2 weeks of December – roughly 56,000 Omicron cases and 269,000 Delta infections.
The second study, from researchers at the National Institute for Communicable Diseases in South Africa, included more than 29,000 COVID-19 cases that had lab results highly suggestive of Omicron infections. Compared to people infected with the Delta variant, those with presumed Omicron infections were about 70% less likely to have severe disease.
While the news is hopeful for individuals, on a population level, health care systems may still be stressed, the study authors warned.
“Given the high transmissibility of the Omicron virus, there remains the potential for health services to face increasing demand if Omicron cases continue to grow at the rate that has been seen in recent weeks,” said study author Neil Ferguson, PhD, who studies how infectious diseases spread at Imperial College London.
The study authors say their findings are specific to the U.K. and South Africa, where substantial portions of the population have some immune protection from past infection. In other words, they may not apply to countries where fewer people have been vaccinated or recovered from a bout with COVID-19.
A version of this article first appeared on WebMD.com.
Could Fabkin hormonal complex spell the end of diabetes?
A hitherto unknown hormonal complex that regulates extracellular energy production in pancreatic islet (beta) cells could be a novel target to not only treat both type 1 and type 2 diabetes but also potentially to prevent their development in the first place, suggests basic science research led by U.S. investigators.
Fatty acid–binding protein 4 (FABP4), a recently identified hormone, was known to be elevated in type 2 diabetes, but the researchers now show that it is not only increased in type 1 diabetes but also that those increases predate its development.
They also show that antibodies against the hormone in mice models prevent type 1 diabetes and improve glycemic control in type 2 disease.
Moreover, it forms a complex with two other proteins that the researchers termed “Fabkin.”
The research, published in Nature, indicates that increased levels of the complex blunts beta cell function, while antibody treatment improves beta cell function.
“For many decades, we have been searching for the signal that communicates the status of energy reserves in adipocytes (fat cells) to generate appropriate endocrine responses, such as the insulin production from pancreatic beta cells,” said senior author Gökhan S. Hotamisligil, MD, PhD, in a press release. “We now have identified Fabkin as a novel hormone that controls this critical function through a very unusual molecular mechanism.”
Still a long way to go
Dr. Hotamisligil, who is director of the Sabri Ülker Center for Metabolic Research at the Harvard School of Public Health, Boston, explained in an interview that taking the findings to the clinic entails answering a number of questions.
“That will keep us busy for a long time, and there are also translational questions, which are extremely exciting,” but the team is very “optimistic” that the findings will transfer well into humans, he said.
One reason is that, in mice and humans with type 1 and type 2 diabetes, “we see exactly the same pattern of regulation” of Fabkin levels and that, “equally importantly,” sustained high levels of the hormone “correlate with poor diabetes control” in type 1 diabetes and disease severity in type 2 disease.
“This is the first strong indication that it will translate well, and the second is that, if we take human islets ... and then apply this hormone into those islets, we see the same suppression of insulin secretion and viability that we see in mice islets,” Dr. Hotamisligil said.
Moreover, blocking the hormone prevents the “negative effects” that we see on the islets, which is a “really critical” factor in suggesting that Fabkin could be a viable treatment target in humans, Dr. Hotamisligil explained.
He continued that, encouragingly, “nature has done some experiments in humans” with Fabkin, showing that “you can have a safe and healthy life with a mutation in the components of this complex ... that reduces levels of the hormone.
“These individuals have a greatly reduced risk for both diabetes and cardiovascular disease,” he said, “so this tells us that, if we can establish a safe agent that can be used in humans, this will be well tolerated for life, and it will have beneficial effects.”
Lastly, Dr. Hotamisligil said that such an agent already exists, “so it’s really just a matter of making it suitable for human use and taking it through the testing procedures.”
He cautioned, however, that “these are important pillars” for translational research “that we rarely, if ever, find in many of our projects,” and there is still a long way to go.
Study details: FABP4 levels associated with glycemic control
The team said the research was “inspired” by previous studies showing that FABP4 knockout mice had higher beta-cell mass in the pancreas and significantly increased glucose-stimulated insulin secretion.
While it is “well established” that FABP4 is increased in type 2 diabetes, they initially examined whether levels are also regulated in type 1 diabetes, independently of adiposity and insulin resistance.
Looking at serum samples from normoglycemic individuals and those with new-onset type 1 diabetes in the BABYDIAB and DiMELLI cohorts, they found that FABP4 was increased approximately 1.6-fold in the latter.
In another cohort of older patients with type 1 diabetes of variation durations, serum FABP4 levels were correlated with hemoglobin A1c levels (P = .005), “which suggests that FABP4 is associated with glycemic control.”
Mouse studies indicate that FABP4 levels are increased both shortly before and during new-onset type 1 diabetes, implying that the hormone “may have a role in beta-cell failure and pathogenesis” in both type 1 and type 2 diabetes.
Antibody targeting of FABP4 levels in mice also revealed that treatment from 10 weeks of age protected against the development of type 1 diabetes, while antibody-treated mice with diabetes had significantly reduced blood glucose and increased plasma insulin levels versus mice given control antibodies.
This, the team said, “suggests that these mice had a less severe diabetes phenotype” with the protection against type 1 diabetes similar to that seen in FABP4 knockout mice.
Mice with diet-induced obesity and nonobese mice with diabetes treated with anti-FABP4 antibodies had improved glucose tolerance tests and a significant increase in islet number and beta-cell mass versus controls.
Further work enabled the team to identify a complex formed by circulating FABP4, adenosine kinase, and nucleoside diphosphate kinase, which could be targeted by anti-FABP4 antibodies via both FABP4 and NPDK.
“We propose the name Fabkin for this new hormone complex formed by NDPK to indicate its unique constitution of a fatty acid–binding protein and kinases,” the researchers wrote.
The team then found that the Fabkin complex alters calcium homeostasis in the endoplasmic reticulum.
This, “results in [endoplasmic reticulum] dysfunction, increased sensitivity to environmental stress and potentiation of beta-cell death in vitro,” which are mechanisms “critical” to the pathogenesis of both type 1 and 2 diabetes.
Finally, they showed that targeting Fabkin with anti-FABP4 antibodies “preserves beta-cell mass and enhances beta-cell function to protect against diabetes in multiple models.”
Funding for this study came from National Institutes of Health and Juvenile Diabetes Research Foundation grants. The Hotamisligil Lab at the Sabri Ülker Center has generated intellectual property (assigned to Harvard University) related to hormonal FABP4 and its therapeutic targeting and receives funding for this project from Lab1636, an affiliate of Deerfield Management. Dr. Hotamisligil is on the scientific advisory board of Crescenta Pharmaceuticals and holds equity. The other authors have no conflicts of interest to declare.
A version of this article first appeared on Medscape.com.
A hitherto unknown hormonal complex that regulates extracellular energy production in pancreatic islet (beta) cells could be a novel target to not only treat both type 1 and type 2 diabetes but also potentially to prevent their development in the first place, suggests basic science research led by U.S. investigators.
Fatty acid–binding protein 4 (FABP4), a recently identified hormone, was known to be elevated in type 2 diabetes, but the researchers now show that it is not only increased in type 1 diabetes but also that those increases predate its development.
They also show that antibodies against the hormone in mice models prevent type 1 diabetes and improve glycemic control in type 2 disease.
Moreover, it forms a complex with two other proteins that the researchers termed “Fabkin.”
The research, published in Nature, indicates that increased levels of the complex blunts beta cell function, while antibody treatment improves beta cell function.
“For many decades, we have been searching for the signal that communicates the status of energy reserves in adipocytes (fat cells) to generate appropriate endocrine responses, such as the insulin production from pancreatic beta cells,” said senior author Gökhan S. Hotamisligil, MD, PhD, in a press release. “We now have identified Fabkin as a novel hormone that controls this critical function through a very unusual molecular mechanism.”
Still a long way to go
Dr. Hotamisligil, who is director of the Sabri Ülker Center for Metabolic Research at the Harvard School of Public Health, Boston, explained in an interview that taking the findings to the clinic entails answering a number of questions.
“That will keep us busy for a long time, and there are also translational questions, which are extremely exciting,” but the team is very “optimistic” that the findings will transfer well into humans, he said.
One reason is that, in mice and humans with type 1 and type 2 diabetes, “we see exactly the same pattern of regulation” of Fabkin levels and that, “equally importantly,” sustained high levels of the hormone “correlate with poor diabetes control” in type 1 diabetes and disease severity in type 2 disease.
“This is the first strong indication that it will translate well, and the second is that, if we take human islets ... and then apply this hormone into those islets, we see the same suppression of insulin secretion and viability that we see in mice islets,” Dr. Hotamisligil said.
Moreover, blocking the hormone prevents the “negative effects” that we see on the islets, which is a “really critical” factor in suggesting that Fabkin could be a viable treatment target in humans, Dr. Hotamisligil explained.
He continued that, encouragingly, “nature has done some experiments in humans” with Fabkin, showing that “you can have a safe and healthy life with a mutation in the components of this complex ... that reduces levels of the hormone.
“These individuals have a greatly reduced risk for both diabetes and cardiovascular disease,” he said, “so this tells us that, if we can establish a safe agent that can be used in humans, this will be well tolerated for life, and it will have beneficial effects.”
Lastly, Dr. Hotamisligil said that such an agent already exists, “so it’s really just a matter of making it suitable for human use and taking it through the testing procedures.”
He cautioned, however, that “these are important pillars” for translational research “that we rarely, if ever, find in many of our projects,” and there is still a long way to go.
Study details: FABP4 levels associated with glycemic control
The team said the research was “inspired” by previous studies showing that FABP4 knockout mice had higher beta-cell mass in the pancreas and significantly increased glucose-stimulated insulin secretion.
While it is “well established” that FABP4 is increased in type 2 diabetes, they initially examined whether levels are also regulated in type 1 diabetes, independently of adiposity and insulin resistance.
Looking at serum samples from normoglycemic individuals and those with new-onset type 1 diabetes in the BABYDIAB and DiMELLI cohorts, they found that FABP4 was increased approximately 1.6-fold in the latter.
In another cohort of older patients with type 1 diabetes of variation durations, serum FABP4 levels were correlated with hemoglobin A1c levels (P = .005), “which suggests that FABP4 is associated with glycemic control.”
Mouse studies indicate that FABP4 levels are increased both shortly before and during new-onset type 1 diabetes, implying that the hormone “may have a role in beta-cell failure and pathogenesis” in both type 1 and type 2 diabetes.
Antibody targeting of FABP4 levels in mice also revealed that treatment from 10 weeks of age protected against the development of type 1 diabetes, while antibody-treated mice with diabetes had significantly reduced blood glucose and increased plasma insulin levels versus mice given control antibodies.
This, the team said, “suggests that these mice had a less severe diabetes phenotype” with the protection against type 1 diabetes similar to that seen in FABP4 knockout mice.
Mice with diet-induced obesity and nonobese mice with diabetes treated with anti-FABP4 antibodies had improved glucose tolerance tests and a significant increase in islet number and beta-cell mass versus controls.
Further work enabled the team to identify a complex formed by circulating FABP4, adenosine kinase, and nucleoside diphosphate kinase, which could be targeted by anti-FABP4 antibodies via both FABP4 and NPDK.
“We propose the name Fabkin for this new hormone complex formed by NDPK to indicate its unique constitution of a fatty acid–binding protein and kinases,” the researchers wrote.
The team then found that the Fabkin complex alters calcium homeostasis in the endoplasmic reticulum.
This, “results in [endoplasmic reticulum] dysfunction, increased sensitivity to environmental stress and potentiation of beta-cell death in vitro,” which are mechanisms “critical” to the pathogenesis of both type 1 and 2 diabetes.
Finally, they showed that targeting Fabkin with anti-FABP4 antibodies “preserves beta-cell mass and enhances beta-cell function to protect against diabetes in multiple models.”
Funding for this study came from National Institutes of Health and Juvenile Diabetes Research Foundation grants. The Hotamisligil Lab at the Sabri Ülker Center has generated intellectual property (assigned to Harvard University) related to hormonal FABP4 and its therapeutic targeting and receives funding for this project from Lab1636, an affiliate of Deerfield Management. Dr. Hotamisligil is on the scientific advisory board of Crescenta Pharmaceuticals and holds equity. The other authors have no conflicts of interest to declare.
A version of this article first appeared on Medscape.com.
A hitherto unknown hormonal complex that regulates extracellular energy production in pancreatic islet (beta) cells could be a novel target to not only treat both type 1 and type 2 diabetes but also potentially to prevent their development in the first place, suggests basic science research led by U.S. investigators.
Fatty acid–binding protein 4 (FABP4), a recently identified hormone, was known to be elevated in type 2 diabetes, but the researchers now show that it is not only increased in type 1 diabetes but also that those increases predate its development.
They also show that antibodies against the hormone in mice models prevent type 1 diabetes and improve glycemic control in type 2 disease.
Moreover, it forms a complex with two other proteins that the researchers termed “Fabkin.”
The research, published in Nature, indicates that increased levels of the complex blunts beta cell function, while antibody treatment improves beta cell function.
“For many decades, we have been searching for the signal that communicates the status of energy reserves in adipocytes (fat cells) to generate appropriate endocrine responses, such as the insulin production from pancreatic beta cells,” said senior author Gökhan S. Hotamisligil, MD, PhD, in a press release. “We now have identified Fabkin as a novel hormone that controls this critical function through a very unusual molecular mechanism.”
Still a long way to go
Dr. Hotamisligil, who is director of the Sabri Ülker Center for Metabolic Research at the Harvard School of Public Health, Boston, explained in an interview that taking the findings to the clinic entails answering a number of questions.
“That will keep us busy for a long time, and there are also translational questions, which are extremely exciting,” but the team is very “optimistic” that the findings will transfer well into humans, he said.
One reason is that, in mice and humans with type 1 and type 2 diabetes, “we see exactly the same pattern of regulation” of Fabkin levels and that, “equally importantly,” sustained high levels of the hormone “correlate with poor diabetes control” in type 1 diabetes and disease severity in type 2 disease.
“This is the first strong indication that it will translate well, and the second is that, if we take human islets ... and then apply this hormone into those islets, we see the same suppression of insulin secretion and viability that we see in mice islets,” Dr. Hotamisligil said.
Moreover, blocking the hormone prevents the “negative effects” that we see on the islets, which is a “really critical” factor in suggesting that Fabkin could be a viable treatment target in humans, Dr. Hotamisligil explained.
He continued that, encouragingly, “nature has done some experiments in humans” with Fabkin, showing that “you can have a safe and healthy life with a mutation in the components of this complex ... that reduces levels of the hormone.
“These individuals have a greatly reduced risk for both diabetes and cardiovascular disease,” he said, “so this tells us that, if we can establish a safe agent that can be used in humans, this will be well tolerated for life, and it will have beneficial effects.”
Lastly, Dr. Hotamisligil said that such an agent already exists, “so it’s really just a matter of making it suitable for human use and taking it through the testing procedures.”
He cautioned, however, that “these are important pillars” for translational research “that we rarely, if ever, find in many of our projects,” and there is still a long way to go.
Study details: FABP4 levels associated with glycemic control
The team said the research was “inspired” by previous studies showing that FABP4 knockout mice had higher beta-cell mass in the pancreas and significantly increased glucose-stimulated insulin secretion.
While it is “well established” that FABP4 is increased in type 2 diabetes, they initially examined whether levels are also regulated in type 1 diabetes, independently of adiposity and insulin resistance.
Looking at serum samples from normoglycemic individuals and those with new-onset type 1 diabetes in the BABYDIAB and DiMELLI cohorts, they found that FABP4 was increased approximately 1.6-fold in the latter.
In another cohort of older patients with type 1 diabetes of variation durations, serum FABP4 levels were correlated with hemoglobin A1c levels (P = .005), “which suggests that FABP4 is associated with glycemic control.”
Mouse studies indicate that FABP4 levels are increased both shortly before and during new-onset type 1 diabetes, implying that the hormone “may have a role in beta-cell failure and pathogenesis” in both type 1 and type 2 diabetes.
Antibody targeting of FABP4 levels in mice also revealed that treatment from 10 weeks of age protected against the development of type 1 diabetes, while antibody-treated mice with diabetes had significantly reduced blood glucose and increased plasma insulin levels versus mice given control antibodies.
This, the team said, “suggests that these mice had a less severe diabetes phenotype” with the protection against type 1 diabetes similar to that seen in FABP4 knockout mice.
Mice with diet-induced obesity and nonobese mice with diabetes treated with anti-FABP4 antibodies had improved glucose tolerance tests and a significant increase in islet number and beta-cell mass versus controls.
Further work enabled the team to identify a complex formed by circulating FABP4, adenosine kinase, and nucleoside diphosphate kinase, which could be targeted by anti-FABP4 antibodies via both FABP4 and NPDK.
“We propose the name Fabkin for this new hormone complex formed by NDPK to indicate its unique constitution of a fatty acid–binding protein and kinases,” the researchers wrote.
The team then found that the Fabkin complex alters calcium homeostasis in the endoplasmic reticulum.
This, “results in [endoplasmic reticulum] dysfunction, increased sensitivity to environmental stress and potentiation of beta-cell death in vitro,” which are mechanisms “critical” to the pathogenesis of both type 1 and 2 diabetes.
Finally, they showed that targeting Fabkin with anti-FABP4 antibodies “preserves beta-cell mass and enhances beta-cell function to protect against diabetes in multiple models.”
Funding for this study came from National Institutes of Health and Juvenile Diabetes Research Foundation grants. The Hotamisligil Lab at the Sabri Ülker Center has generated intellectual property (assigned to Harvard University) related to hormonal FABP4 and its therapeutic targeting and receives funding for this project from Lab1636, an affiliate of Deerfield Management. Dr. Hotamisligil is on the scientific advisory board of Crescenta Pharmaceuticals and holds equity. The other authors have no conflicts of interest to declare.
A version of this article first appeared on Medscape.com.
FROM NATURE
Hyperprolactinemia – When, why, and how to evaluate prolactin
Because of the increasing popularity and success of in vitro fertilization, the field of reproductive endocrinology and infertility has steadily morphed toward the treatment of infertility. Nevertheless, a physician board certified in reproductive endocrinology and infertility is the referring physician of choice regarding prolactin disorders and gynecologists should be familiar with the symptoms and sequela of prolactin elevations. This month’s column will address when to obtain a serum prolactin and how to appropriately manage hyperprolactinemia.
Of all the anterior pituitary hormones (adrenocorticotropic hormone, follicle-stimulating hormone, growth hormone, luteinizing hormone, prolactin, thyroid-stimulating hormone ), prolactin is the only one under tonic inhibition by dopamine. Disturbances in this dopaminergic pathway result in elevated serum prolactin. The normal range for prolactin is approximately 5-20 ng/mL.
In the nonpregnant state, little is known regarding the purpose of prolactin, which is produced by the anterior pituitary cluster of cells called lactotrophs. To prepare the breast for postpartum lactation, increases in prolactin are necessary and sustained throughout pregnancy. Second to pregnancy, amenorrhea can occur in 10%-20% of cases of hyperprolactinemia. Outside of pregnancy, elevations in prolactin result in hypogonadism, through gonadotropin-releasing hormone suppression, resulting in infertility (48%), headache (39%), oligomenorrhea (29%) and galactorrhea (24%).1 Most hypogonadal symptoms are more likely to occur with prolactin levels greater than 100 ng/mL, whereas infertility and ovulation dysfunction can occur with mild to moderate hyperprolactinemia, respectively. Prolonged amenorrhea can risk bone mineral density loss.
While the focus of our discussion is the effect of prolactin on women, men with hyperprolactinemia can experience hypogonadotropic hypogonadism with resultant decreased libido, impotence, infertility, gynecomastia, or, rarely, galactorrhea.2
The three Ps – physiological, pharmacologic, pathological
Physiological causes of hyperprolactinemia include rising estradiol during the late follicular phase and into the secretory phase of the menstrual cycle or while taking combined oral contraception, nipple stimulation, pregnancy, lactation, meals, sleep, and stress.
Drugs can interrupt the dopaminergic pathway, thereby elevating serum prolactin but usually not above 100 ng/mL, except for the antipsychotic drug risperidone, which can cause marked elevation up to 300 or even 400 ng/mL. Medications that can cause hyperprolactinemia are estrogens, neuroleptic drugs such as risperidone, metoclopramide, antidepressant drugs, cimetidine, methyldopa, and verapamil.
A pituitary MRI can diagnose an adenoma, that is, a collection of cells in the pituitary that are responsible for hyperprolactinemia and is named based on its size. Microadenomas are less than 1 cm and are typically associated with serum prolactin values below 200 ng/mL. Macroadenomas can worsen while a patient is on combined oral contraception and during pregnancy; fortunately, this is not the case with a microadenoma.
Hypothyroidism can elevate serum prolactin since thyrotropin releasing hormone is known to stimulate prolactin secretion.3 Consequently, when a patient presents with both hypothyroidism and hyperprolactinemia, thyroid replacement should be initiated for thyroid regulation and potential restoration of prolactin levels. If hyperprolactinemia persists, then further evaluation is required. Chronic renal impairment can also elevate prolactin levels due to decreased clearance.
Management
The appropriate evaluation of hyperprolactinemia consists of a history to disclose medications, identify galactorrhea, and visual changes. Because of an adenoma compressing the optic chiasm, partial blindness may occur where vision is lost in the outer half of both the right and left visual field, called bitemporal hemianopsia. Mild elevations in prolactin should be tested at a time when physiological influences are at a minimum, that is, during menses, fasting, and in late morning.4 Persistent elevations should be appropriately evaluated rather than by using the empiric “shotgun” approach of prescribing a dopamine agonist. Laboratory testing for repeated elevations in prolactin includes a pituitary MRI looking for a mass in the hypothalamic-pituitary region that interrupts dopamine suppression.
Treatment of hyperprolactinemia begins with a dopamine agonist and is indicated when there is hypogonadism or intolerable galactorrhea. Cabergoline is the first choice because of effectiveness (reduced adenoma size in greater than 90% of patients) and lesser side effects, particularly nausea, than bromocriptine. Dopamine agonists, such as bromocriptine and cabergoline, belong to the category of ergot-derived dopamine agonists and have been used to treat Parkinson’s disease. At high doses used to treat Parkinson’s, cabergoline is associated with an increased risk of valvular heart disease. In the United States, pergolide was voluntarily withdrawn from the market in March 2007 because of this risk. At the lower doses generally used for the treatment of hyperprolactinemia, cabergoline is probably not associated with excess risk.5
Newer dopamine agonists are known as nonergot. These are pramipexole, ropinirole, rotigotine, and apomorphine. They have not been associated with a risk of heart damage and can be prescribed.
The initial prescribing dose of cabergoline should be 0.25 mg twice a week or 0.5 mg once a week. If bromocriptine is used, the starting dose is 1.25 mg after dinner or at bedtime for 1 week, then increasing to 1.25 mg twice a day (after breakfast and after dinner or at bedtime to reduce nausea and fatigue). After 1 month of a dopamine agonist, the patient should be evaluated for side effects and a serum prolactin level should be obtained. With a normal prolactin level, gonadal function will probably return within a few months. The dopamine agonist should typically be discontinued with pregnancy as pregnancy increases prolactin physiologically.
Treatment of a macroadenoma is essential when the tumor is large enough to cause neurologic symptoms, such as visual impairment or headache, and is preferable when it is invasive or when there are enlarging microadenomas since they are likely to continue to grow and become symptomatic. About 95% of microadenomas have not been shown to increase in size during 4-6 years of observation.6
Transsphenoidal surgery should be considered when there is:
- Persistent hyperprolactinemia and/or size of the adenoma, with associated symptoms or signs despite several months of dopamine agonist treatment at high doses.
- Presence of a giant lactotroph adenoma (e.g., >3 cm) with pregnancy desired including those whose adenoma responds to a dopamine agonist – to avoid significant growth during pregnancy while off medication.
Data from over 6,000 pregnancies suggest that the administration of bromocriptine during the first month of pregnancy does not harm the fetus.7
Discontinuing treatment
Three scenarios may allow for cessation of dopamine agonist therapy. The first is when a patient has had a normal serum prolactin test following 2 years of low-dose dopamine agonist. Another is the patient who had hyperprolactinemia and a microadenoma that responded to treatment with a normal prolactin level and no further evidence of an adenoma by MRI for at least 2 years. Lastly, the patient who had a macroadenoma prior to treatment and a subsequent normal serum prolactin level without an adenoma for at least 2 years.
Like the management of thyroid dysfunction, our field must be aware of prolactin disorders for early detection, prompt referral, and appropriate management to minimize long-term consequences.
Dr. Trolice is director of Fertility CARE – The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando.
References
1. Bayrak A et al. Fertil Steril. 2005 Jul;84(1):181-5.
2. Carter JN et al. N Engl J Med. 1978 Oct 19;299(16):847-52.
3. Sachson R et al. N Engl J Med. 1972;287:972.
4. Singh SP and Singh TP. Ann Endocrinol (Paris). 1984;45(2):137-41.
5. Valassi E et al. J Clin Endocrinol Metab. 2010 Mar;95(3):1025-33.
6. Sisam DA et al. Fertil Steril. 1987 Jul;48(1):67-71.
7. Molitch ME. Best Pract Res Clin Endocrinol Metab. 2011 Dec;25(6):885-96.
Because of the increasing popularity and success of in vitro fertilization, the field of reproductive endocrinology and infertility has steadily morphed toward the treatment of infertility. Nevertheless, a physician board certified in reproductive endocrinology and infertility is the referring physician of choice regarding prolactin disorders and gynecologists should be familiar with the symptoms and sequela of prolactin elevations. This month’s column will address when to obtain a serum prolactin and how to appropriately manage hyperprolactinemia.
Of all the anterior pituitary hormones (adrenocorticotropic hormone, follicle-stimulating hormone, growth hormone, luteinizing hormone, prolactin, thyroid-stimulating hormone ), prolactin is the only one under tonic inhibition by dopamine. Disturbances in this dopaminergic pathway result in elevated serum prolactin. The normal range for prolactin is approximately 5-20 ng/mL.
In the nonpregnant state, little is known regarding the purpose of prolactin, which is produced by the anterior pituitary cluster of cells called lactotrophs. To prepare the breast for postpartum lactation, increases in prolactin are necessary and sustained throughout pregnancy. Second to pregnancy, amenorrhea can occur in 10%-20% of cases of hyperprolactinemia. Outside of pregnancy, elevations in prolactin result in hypogonadism, through gonadotropin-releasing hormone suppression, resulting in infertility (48%), headache (39%), oligomenorrhea (29%) and galactorrhea (24%).1 Most hypogonadal symptoms are more likely to occur with prolactin levels greater than 100 ng/mL, whereas infertility and ovulation dysfunction can occur with mild to moderate hyperprolactinemia, respectively. Prolonged amenorrhea can risk bone mineral density loss.
While the focus of our discussion is the effect of prolactin on women, men with hyperprolactinemia can experience hypogonadotropic hypogonadism with resultant decreased libido, impotence, infertility, gynecomastia, or, rarely, galactorrhea.2
The three Ps – physiological, pharmacologic, pathological
Physiological causes of hyperprolactinemia include rising estradiol during the late follicular phase and into the secretory phase of the menstrual cycle or while taking combined oral contraception, nipple stimulation, pregnancy, lactation, meals, sleep, and stress.
Drugs can interrupt the dopaminergic pathway, thereby elevating serum prolactin but usually not above 100 ng/mL, except for the antipsychotic drug risperidone, which can cause marked elevation up to 300 or even 400 ng/mL. Medications that can cause hyperprolactinemia are estrogens, neuroleptic drugs such as risperidone, metoclopramide, antidepressant drugs, cimetidine, methyldopa, and verapamil.
A pituitary MRI can diagnose an adenoma, that is, a collection of cells in the pituitary that are responsible for hyperprolactinemia and is named based on its size. Microadenomas are less than 1 cm and are typically associated with serum prolactin values below 200 ng/mL. Macroadenomas can worsen while a patient is on combined oral contraception and during pregnancy; fortunately, this is not the case with a microadenoma.
Hypothyroidism can elevate serum prolactin since thyrotropin releasing hormone is known to stimulate prolactin secretion.3 Consequently, when a patient presents with both hypothyroidism and hyperprolactinemia, thyroid replacement should be initiated for thyroid regulation and potential restoration of prolactin levels. If hyperprolactinemia persists, then further evaluation is required. Chronic renal impairment can also elevate prolactin levels due to decreased clearance.
Management
The appropriate evaluation of hyperprolactinemia consists of a history to disclose medications, identify galactorrhea, and visual changes. Because of an adenoma compressing the optic chiasm, partial blindness may occur where vision is lost in the outer half of both the right and left visual field, called bitemporal hemianopsia. Mild elevations in prolactin should be tested at a time when physiological influences are at a minimum, that is, during menses, fasting, and in late morning.4 Persistent elevations should be appropriately evaluated rather than by using the empiric “shotgun” approach of prescribing a dopamine agonist. Laboratory testing for repeated elevations in prolactin includes a pituitary MRI looking for a mass in the hypothalamic-pituitary region that interrupts dopamine suppression.
Treatment of hyperprolactinemia begins with a dopamine agonist and is indicated when there is hypogonadism or intolerable galactorrhea. Cabergoline is the first choice because of effectiveness (reduced adenoma size in greater than 90% of patients) and lesser side effects, particularly nausea, than bromocriptine. Dopamine agonists, such as bromocriptine and cabergoline, belong to the category of ergot-derived dopamine agonists and have been used to treat Parkinson’s disease. At high doses used to treat Parkinson’s, cabergoline is associated with an increased risk of valvular heart disease. In the United States, pergolide was voluntarily withdrawn from the market in March 2007 because of this risk. At the lower doses generally used for the treatment of hyperprolactinemia, cabergoline is probably not associated with excess risk.5
Newer dopamine agonists are known as nonergot. These are pramipexole, ropinirole, rotigotine, and apomorphine. They have not been associated with a risk of heart damage and can be prescribed.
The initial prescribing dose of cabergoline should be 0.25 mg twice a week or 0.5 mg once a week. If bromocriptine is used, the starting dose is 1.25 mg after dinner or at bedtime for 1 week, then increasing to 1.25 mg twice a day (after breakfast and after dinner or at bedtime to reduce nausea and fatigue). After 1 month of a dopamine agonist, the patient should be evaluated for side effects and a serum prolactin level should be obtained. With a normal prolactin level, gonadal function will probably return within a few months. The dopamine agonist should typically be discontinued with pregnancy as pregnancy increases prolactin physiologically.
Treatment of a macroadenoma is essential when the tumor is large enough to cause neurologic symptoms, such as visual impairment or headache, and is preferable when it is invasive or when there are enlarging microadenomas since they are likely to continue to grow and become symptomatic. About 95% of microadenomas have not been shown to increase in size during 4-6 years of observation.6
Transsphenoidal surgery should be considered when there is:
- Persistent hyperprolactinemia and/or size of the adenoma, with associated symptoms or signs despite several months of dopamine agonist treatment at high doses.
- Presence of a giant lactotroph adenoma (e.g., >3 cm) with pregnancy desired including those whose adenoma responds to a dopamine agonist – to avoid significant growth during pregnancy while off medication.
Data from over 6,000 pregnancies suggest that the administration of bromocriptine during the first month of pregnancy does not harm the fetus.7
Discontinuing treatment
Three scenarios may allow for cessation of dopamine agonist therapy. The first is when a patient has had a normal serum prolactin test following 2 years of low-dose dopamine agonist. Another is the patient who had hyperprolactinemia and a microadenoma that responded to treatment with a normal prolactin level and no further evidence of an adenoma by MRI for at least 2 years. Lastly, the patient who had a macroadenoma prior to treatment and a subsequent normal serum prolactin level without an adenoma for at least 2 years.
Like the management of thyroid dysfunction, our field must be aware of prolactin disorders for early detection, prompt referral, and appropriate management to minimize long-term consequences.
Dr. Trolice is director of Fertility CARE – The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando.
References
1. Bayrak A et al. Fertil Steril. 2005 Jul;84(1):181-5.
2. Carter JN et al. N Engl J Med. 1978 Oct 19;299(16):847-52.
3. Sachson R et al. N Engl J Med. 1972;287:972.
4. Singh SP and Singh TP. Ann Endocrinol (Paris). 1984;45(2):137-41.
5. Valassi E et al. J Clin Endocrinol Metab. 2010 Mar;95(3):1025-33.
6. Sisam DA et al. Fertil Steril. 1987 Jul;48(1):67-71.
7. Molitch ME. Best Pract Res Clin Endocrinol Metab. 2011 Dec;25(6):885-96.
Because of the increasing popularity and success of in vitro fertilization, the field of reproductive endocrinology and infertility has steadily morphed toward the treatment of infertility. Nevertheless, a physician board certified in reproductive endocrinology and infertility is the referring physician of choice regarding prolactin disorders and gynecologists should be familiar with the symptoms and sequela of prolactin elevations. This month’s column will address when to obtain a serum prolactin and how to appropriately manage hyperprolactinemia.
Of all the anterior pituitary hormones (adrenocorticotropic hormone, follicle-stimulating hormone, growth hormone, luteinizing hormone, prolactin, thyroid-stimulating hormone ), prolactin is the only one under tonic inhibition by dopamine. Disturbances in this dopaminergic pathway result in elevated serum prolactin. The normal range for prolactin is approximately 5-20 ng/mL.
In the nonpregnant state, little is known regarding the purpose of prolactin, which is produced by the anterior pituitary cluster of cells called lactotrophs. To prepare the breast for postpartum lactation, increases in prolactin are necessary and sustained throughout pregnancy. Second to pregnancy, amenorrhea can occur in 10%-20% of cases of hyperprolactinemia. Outside of pregnancy, elevations in prolactin result in hypogonadism, through gonadotropin-releasing hormone suppression, resulting in infertility (48%), headache (39%), oligomenorrhea (29%) and galactorrhea (24%).1 Most hypogonadal symptoms are more likely to occur with prolactin levels greater than 100 ng/mL, whereas infertility and ovulation dysfunction can occur with mild to moderate hyperprolactinemia, respectively. Prolonged amenorrhea can risk bone mineral density loss.
While the focus of our discussion is the effect of prolactin on women, men with hyperprolactinemia can experience hypogonadotropic hypogonadism with resultant decreased libido, impotence, infertility, gynecomastia, or, rarely, galactorrhea.2
The three Ps – physiological, pharmacologic, pathological
Physiological causes of hyperprolactinemia include rising estradiol during the late follicular phase and into the secretory phase of the menstrual cycle or while taking combined oral contraception, nipple stimulation, pregnancy, lactation, meals, sleep, and stress.
Drugs can interrupt the dopaminergic pathway, thereby elevating serum prolactin but usually not above 100 ng/mL, except for the antipsychotic drug risperidone, which can cause marked elevation up to 300 or even 400 ng/mL. Medications that can cause hyperprolactinemia are estrogens, neuroleptic drugs such as risperidone, metoclopramide, antidepressant drugs, cimetidine, methyldopa, and verapamil.
A pituitary MRI can diagnose an adenoma, that is, a collection of cells in the pituitary that are responsible for hyperprolactinemia and is named based on its size. Microadenomas are less than 1 cm and are typically associated with serum prolactin values below 200 ng/mL. Macroadenomas can worsen while a patient is on combined oral contraception and during pregnancy; fortunately, this is not the case with a microadenoma.
Hypothyroidism can elevate serum prolactin since thyrotropin releasing hormone is known to stimulate prolactin secretion.3 Consequently, when a patient presents with both hypothyroidism and hyperprolactinemia, thyroid replacement should be initiated for thyroid regulation and potential restoration of prolactin levels. If hyperprolactinemia persists, then further evaluation is required. Chronic renal impairment can also elevate prolactin levels due to decreased clearance.
Management
The appropriate evaluation of hyperprolactinemia consists of a history to disclose medications, identify galactorrhea, and visual changes. Because of an adenoma compressing the optic chiasm, partial blindness may occur where vision is lost in the outer half of both the right and left visual field, called bitemporal hemianopsia. Mild elevations in prolactin should be tested at a time when physiological influences are at a minimum, that is, during menses, fasting, and in late morning.4 Persistent elevations should be appropriately evaluated rather than by using the empiric “shotgun” approach of prescribing a dopamine agonist. Laboratory testing for repeated elevations in prolactin includes a pituitary MRI looking for a mass in the hypothalamic-pituitary region that interrupts dopamine suppression.
Treatment of hyperprolactinemia begins with a dopamine agonist and is indicated when there is hypogonadism or intolerable galactorrhea. Cabergoline is the first choice because of effectiveness (reduced adenoma size in greater than 90% of patients) and lesser side effects, particularly nausea, than bromocriptine. Dopamine agonists, such as bromocriptine and cabergoline, belong to the category of ergot-derived dopamine agonists and have been used to treat Parkinson’s disease. At high doses used to treat Parkinson’s, cabergoline is associated with an increased risk of valvular heart disease. In the United States, pergolide was voluntarily withdrawn from the market in March 2007 because of this risk. At the lower doses generally used for the treatment of hyperprolactinemia, cabergoline is probably not associated with excess risk.5
Newer dopamine agonists are known as nonergot. These are pramipexole, ropinirole, rotigotine, and apomorphine. They have not been associated with a risk of heart damage and can be prescribed.
The initial prescribing dose of cabergoline should be 0.25 mg twice a week or 0.5 mg once a week. If bromocriptine is used, the starting dose is 1.25 mg after dinner or at bedtime for 1 week, then increasing to 1.25 mg twice a day (after breakfast and after dinner or at bedtime to reduce nausea and fatigue). After 1 month of a dopamine agonist, the patient should be evaluated for side effects and a serum prolactin level should be obtained. With a normal prolactin level, gonadal function will probably return within a few months. The dopamine agonist should typically be discontinued with pregnancy as pregnancy increases prolactin physiologically.
Treatment of a macroadenoma is essential when the tumor is large enough to cause neurologic symptoms, such as visual impairment or headache, and is preferable when it is invasive or when there are enlarging microadenomas since they are likely to continue to grow and become symptomatic. About 95% of microadenomas have not been shown to increase in size during 4-6 years of observation.6
Transsphenoidal surgery should be considered when there is:
- Persistent hyperprolactinemia and/or size of the adenoma, with associated symptoms or signs despite several months of dopamine agonist treatment at high doses.
- Presence of a giant lactotroph adenoma (e.g., >3 cm) with pregnancy desired including those whose adenoma responds to a dopamine agonist – to avoid significant growth during pregnancy while off medication.
Data from over 6,000 pregnancies suggest that the administration of bromocriptine during the first month of pregnancy does not harm the fetus.7
Discontinuing treatment
Three scenarios may allow for cessation of dopamine agonist therapy. The first is when a patient has had a normal serum prolactin test following 2 years of low-dose dopamine agonist. Another is the patient who had hyperprolactinemia and a microadenoma that responded to treatment with a normal prolactin level and no further evidence of an adenoma by MRI for at least 2 years. Lastly, the patient who had a macroadenoma prior to treatment and a subsequent normal serum prolactin level without an adenoma for at least 2 years.
Like the management of thyroid dysfunction, our field must be aware of prolactin disorders for early detection, prompt referral, and appropriate management to minimize long-term consequences.
Dr. Trolice is director of Fertility CARE – The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando.
References
1. Bayrak A et al. Fertil Steril. 2005 Jul;84(1):181-5.
2. Carter JN et al. N Engl J Med. 1978 Oct 19;299(16):847-52.
3. Sachson R et al. N Engl J Med. 1972;287:972.
4. Singh SP and Singh TP. Ann Endocrinol (Paris). 1984;45(2):137-41.
5. Valassi E et al. J Clin Endocrinol Metab. 2010 Mar;95(3):1025-33.
6. Sisam DA et al. Fertil Steril. 1987 Jul;48(1):67-71.
7. Molitch ME. Best Pract Res Clin Endocrinol Metab. 2011 Dec;25(6):885-96.
Last call? Moderate alcohol’s health benefits look increasingly doubtful
When holiday shoppers recently went to their local liquor stores in search of some liquid spirit, many were instead greeted by the sight of increasingly barren shelves.
Although partly a result of global supply chain issues, this was also yet more evidence of the rising demand for alcohol among adults during these difficult COVID years. It’s a trend that has led to concerns of an echo pandemic of alcohol-related morbidity, which has begun to play out in the form of rising rates of gastrointestinal and liver disease, hospital admissions for alcoholic hepatitis, and alcohol-related incidents of domestic violence.
Those who imbibe alcohol in low to moderate levels may not see themselves reflected in such stories of drinking’s hefty tolls. They’re instead following established health guidance that a little bit of alcohol now and then actually has robust health benefits. Yet the past few of years have seen a notable fraying of this idea, as emerging data calls into question whether alcohol in moderation should really continue to be just what the doctor ordered.
Behind the curve: Alcohol’s diminishing cardioprotective value
Perhaps the most resonant argument for the benefits of light to moderate alcohol consumption – usually defined as between one to two drinks a day – has been its proposed cardioprotective value. In this way, alcohol differs from tobacco, which is unsafe at any level. Alcohol’s proposed cardioprotective effects are often represented as a J-shaped curve, with moderate drinking occupying the sweet spot between teetotaling and heavy/binge drinking when it comes to reduced mortality.
In reality, this association is more likely “a statistical artifact” largely derived from low-quality observational studies, according to Christopher Labos, MD, CM, MSc, an epidemiologist and cardiologist at the Queen Elizabeth Health Complex in Montreal.
“When you look at studies that correct for things like reverse causation, or the fact that some people who drink zero alcohol are former drinkers who used to drink alcohol, then you realize that the protective benefit of alcohol is either minimal or nonexistent and that alcohol does more harm than good to our society,” said Dr. Labos, who detailed the reasons underpinning alcohol’s unearned cardioprotective reputation in a 2020 Medscape commentary.
This statistical limitation was on display in July 2021 when BMC Medicine published results from meta-analyses suggesting that current drinkers need not stop consuming small amounts of alcohol for the secondary prevention of cardiovascular disease (CVD). The study’s own investigators noted that it likely overestimated the reduced risk of CVD by including former heavy drinkers as nondrinkers.
Even if the J-shaped curve exists, its simplicity is deceiving. CVD risk increases alongside alcohol consumption owning to a complicated array of genetic and lifestyle factors. The curve also presents something of a catch-22. If you like alcohol enough to drink it every day, staying at the nadir of the curve where you’d gain the most benefits may prove challenging.
Another factor dimming alcohol’s cardioprotective reputation came via recent data that atrial fibrillation episodes can be triggered by acute alcohol use. A randomized, controlled trial published in the New England Journal of Medicine concluded that abstinence reduced arrhythmia recurrences in regular drinkers with atrial fibrillation.
“If we can replicate that, I think we’ll find that reducing alcohol consumption might be a very effective way to prevent and treat atrial fibrillation,” said Dr. Labos.
However, J-curve proponents will note the publication of study data from the UK Biobank indicating that low levels of alcohol consumption confers the greatest reduction in atrial fibrillation risk.
An overlooked carcinogen no longer
Surveys indicate that less than half of Americans realize alcohol increases cancer risk. That might have changed just a bit this year. In early 2021, an epidemiological analysis estimated that alcohol contributed to 4.8% of cancer cases and 3.2% of cancer deaths in the United States. Then the Lancet Oncology published the results of a high-profile, population-based study on the global burden of cancer as a result of alcoho. Although the main takeaway message was that 4% of new cancer cases worldwide in 2020 were attributable to alcohol, it was also noteworthy that moderate drinking accounted for 103,100 out of 741,300 of these projected annual cases.
“The risk of cancer increases even with low or moderate levels of drinking,” said the study’s lead author Harriet Rumgay, BSc, from the International Agency for Research on Cancer in Lyon, France. “Drinking less means you’ll have a lower risk of cancer than if you drink heavily, but there is no safe limit of alcohol consumption.”
The study linked alcohol consumption with an increased risk of at least seven different cancer types, including cancers of the oral cavity, pharynx, larynx, esophagus, colon, rectum, liver, and breast.
Although in North America men represented about two-thirds of the burden of cancer caused by alcohol, Ms. Rumgay added that “low and moderate levels of drinking [one or two alcoholic drinks per day] contributed relatively more cancer cases among women than among men.”
Yet more negative news for moderate alcohol drinkers arrived in August 2021, when a team of South Korean researchers published data in JAMA Network Open showing that, when it came to the risk of developing gastrointestinal cancers, even binge drinking may be preferable to continuous but moderate consumption.
who in updating its guidelines in 2020 after an 8-year interim offered this succinct piece of advice: “It is best not to drink alcohol.”
Neurotoxic implications
There has similarly been a reconsideration of the effects of moderate alcohol consumption on brain health.
A recent report of multimodal MRI brain and cognitive testing data from over 25,000 participants in the UK Biobank study indicate that alcohol may have no safe dosage . Even moderate consumption reduced gray matter volume and functional connectivity, negative associations that were increased in those with higher blood pressure and body mass index.
Speaking with this news organization in May 2021, an investigator said: “The size of the effect is small, albeit greater than any other modifiable risk factor,” noting that the changes have been linked to decreased memory and dementia.
Louise Mewton, PhD, from the Center for Healthy Brain Aging at the University of New South Wales, Sydney, said that these results provide an interesting comparison with others into the association between alcohol and dementia.
“A recent study of over 1 million dementia cases in France indicated that problematic alcohol use (alcohol use disorders) were one of the strongest risk factors for dementia – even more so than things like high blood pressure and diabetes,” Dr. Mewton said in an interview. In comparison, “the most-recent reviews indicate that 4 drinks/week is associated with the lowest risk for dementia – so we’re talking about very low levels of alcohol use in terms of maintaining brain health.
“Understanding why very small amounts of alcohol appear to be protective in terms of dementia but damaging when we look at brain scans is something that would be really interesting to unpack.”
Dr. Mewton and colleagues recently published data suggesting that there are three periods when the brain might be particularly susceptible to alcohol’s neurotoxic effects: gestation (from conception to birth), later adolescence (15-19 years), and older adulthood (over 65 years). Directing behavioral interventions to patients in these stages may therefore be beneficial.
And there’s no time too soon to promote abstinence among those with alcohol use disorder, as brain damage is shown to still occur even in the immediate period after people cease drinking.
Although in one more argument for the J-shaped curve’s relevance, data from the Massachusetts General Brigham Biobank recently indicated that moderate alcohol use, unlike low and heavy use, lowered both stress-related neurobiological activity and major adverse cardiovascular events.
Getting patients to reconsider alcohol’s ‘benefits’
These new findings mean physicians will find themselves imparting a more nuanced message about the health impacts of moderate alcohol consumption than in prior years. To aid those efforts, Ms. Rumgay advised clinicians to consult a special issue of the journal Nutrients that features review articles of alcohol›s impact on various health outcomes.
Ms. Rumgay also supports broader policy changes.
“There is some evidence that adding cancer warnings to alcohol labels, similar to those used on cigarette packages, might deter people from purchasing alcohol products and increase awareness of the causal link with cancer,” she said. “But the most effective ways of reducing alcohol use in the population are through increasing the price of alcohol through higher taxes, limiting purchasing availability, and reducing marketing of alcohol brands to the public.”
Dr. Mewton recommended various interventions for patients who still find it difficult to curtail their drinking.
“For less severe, problematic use, things like cognitive-behavioral therapy and motivational therapy are very effective in reducing alcohol consumption,” she said in an interview.
For all the discussion about how the COVID-19 pandemic has exacerbated problematic drinking, it has also provided an opportunity for getting patients to reexamine their relationship to alcohol. And as Dr. Labos noted, emerging data on alcohol’s negative effects probably won’t be considered earth-shattering to most patients.
“Deep down, I think most people know that alcohol is not healthy, but it is part of our social culture and so we find ways to justify our own behavior,” he said in an interview.
Dr. Labos suggested that clinicians reframe alcohol in their patients’ minds for what it really is – “an indulgence that we shouldn’t have too much of very often.
“Just like junk food, that doesn’t mean we can’t enjoy small amounts occasionally, but we have to stop presenting that it is good for us, because it isn’t.”
A version of this article first appeared on Medscape.com.
When holiday shoppers recently went to their local liquor stores in search of some liquid spirit, many were instead greeted by the sight of increasingly barren shelves.
Although partly a result of global supply chain issues, this was also yet more evidence of the rising demand for alcohol among adults during these difficult COVID years. It’s a trend that has led to concerns of an echo pandemic of alcohol-related morbidity, which has begun to play out in the form of rising rates of gastrointestinal and liver disease, hospital admissions for alcoholic hepatitis, and alcohol-related incidents of domestic violence.
Those who imbibe alcohol in low to moderate levels may not see themselves reflected in such stories of drinking’s hefty tolls. They’re instead following established health guidance that a little bit of alcohol now and then actually has robust health benefits. Yet the past few of years have seen a notable fraying of this idea, as emerging data calls into question whether alcohol in moderation should really continue to be just what the doctor ordered.
Behind the curve: Alcohol’s diminishing cardioprotective value
Perhaps the most resonant argument for the benefits of light to moderate alcohol consumption – usually defined as between one to two drinks a day – has been its proposed cardioprotective value. In this way, alcohol differs from tobacco, which is unsafe at any level. Alcohol’s proposed cardioprotective effects are often represented as a J-shaped curve, with moderate drinking occupying the sweet spot between teetotaling and heavy/binge drinking when it comes to reduced mortality.
In reality, this association is more likely “a statistical artifact” largely derived from low-quality observational studies, according to Christopher Labos, MD, CM, MSc, an epidemiologist and cardiologist at the Queen Elizabeth Health Complex in Montreal.
“When you look at studies that correct for things like reverse causation, or the fact that some people who drink zero alcohol are former drinkers who used to drink alcohol, then you realize that the protective benefit of alcohol is either minimal or nonexistent and that alcohol does more harm than good to our society,” said Dr. Labos, who detailed the reasons underpinning alcohol’s unearned cardioprotective reputation in a 2020 Medscape commentary.
This statistical limitation was on display in July 2021 when BMC Medicine published results from meta-analyses suggesting that current drinkers need not stop consuming small amounts of alcohol for the secondary prevention of cardiovascular disease (CVD). The study’s own investigators noted that it likely overestimated the reduced risk of CVD by including former heavy drinkers as nondrinkers.
Even if the J-shaped curve exists, its simplicity is deceiving. CVD risk increases alongside alcohol consumption owning to a complicated array of genetic and lifestyle factors. The curve also presents something of a catch-22. If you like alcohol enough to drink it every day, staying at the nadir of the curve where you’d gain the most benefits may prove challenging.
Another factor dimming alcohol’s cardioprotective reputation came via recent data that atrial fibrillation episodes can be triggered by acute alcohol use. A randomized, controlled trial published in the New England Journal of Medicine concluded that abstinence reduced arrhythmia recurrences in regular drinkers with atrial fibrillation.
“If we can replicate that, I think we’ll find that reducing alcohol consumption might be a very effective way to prevent and treat atrial fibrillation,” said Dr. Labos.
However, J-curve proponents will note the publication of study data from the UK Biobank indicating that low levels of alcohol consumption confers the greatest reduction in atrial fibrillation risk.
An overlooked carcinogen no longer
Surveys indicate that less than half of Americans realize alcohol increases cancer risk. That might have changed just a bit this year. In early 2021, an epidemiological analysis estimated that alcohol contributed to 4.8% of cancer cases and 3.2% of cancer deaths in the United States. Then the Lancet Oncology published the results of a high-profile, population-based study on the global burden of cancer as a result of alcoho. Although the main takeaway message was that 4% of new cancer cases worldwide in 2020 were attributable to alcohol, it was also noteworthy that moderate drinking accounted for 103,100 out of 741,300 of these projected annual cases.
“The risk of cancer increases even with low or moderate levels of drinking,” said the study’s lead author Harriet Rumgay, BSc, from the International Agency for Research on Cancer in Lyon, France. “Drinking less means you’ll have a lower risk of cancer than if you drink heavily, but there is no safe limit of alcohol consumption.”
The study linked alcohol consumption with an increased risk of at least seven different cancer types, including cancers of the oral cavity, pharynx, larynx, esophagus, colon, rectum, liver, and breast.
Although in North America men represented about two-thirds of the burden of cancer caused by alcohol, Ms. Rumgay added that “low and moderate levels of drinking [one or two alcoholic drinks per day] contributed relatively more cancer cases among women than among men.”
Yet more negative news for moderate alcohol drinkers arrived in August 2021, when a team of South Korean researchers published data in JAMA Network Open showing that, when it came to the risk of developing gastrointestinal cancers, even binge drinking may be preferable to continuous but moderate consumption.
who in updating its guidelines in 2020 after an 8-year interim offered this succinct piece of advice: “It is best not to drink alcohol.”
Neurotoxic implications
There has similarly been a reconsideration of the effects of moderate alcohol consumption on brain health.
A recent report of multimodal MRI brain and cognitive testing data from over 25,000 participants in the UK Biobank study indicate that alcohol may have no safe dosage . Even moderate consumption reduced gray matter volume and functional connectivity, negative associations that were increased in those with higher blood pressure and body mass index.
Speaking with this news organization in May 2021, an investigator said: “The size of the effect is small, albeit greater than any other modifiable risk factor,” noting that the changes have been linked to decreased memory and dementia.
Louise Mewton, PhD, from the Center for Healthy Brain Aging at the University of New South Wales, Sydney, said that these results provide an interesting comparison with others into the association between alcohol and dementia.
“A recent study of over 1 million dementia cases in France indicated that problematic alcohol use (alcohol use disorders) were one of the strongest risk factors for dementia – even more so than things like high blood pressure and diabetes,” Dr. Mewton said in an interview. In comparison, “the most-recent reviews indicate that 4 drinks/week is associated with the lowest risk for dementia – so we’re talking about very low levels of alcohol use in terms of maintaining brain health.
“Understanding why very small amounts of alcohol appear to be protective in terms of dementia but damaging when we look at brain scans is something that would be really interesting to unpack.”
Dr. Mewton and colleagues recently published data suggesting that there are three periods when the brain might be particularly susceptible to alcohol’s neurotoxic effects: gestation (from conception to birth), later adolescence (15-19 years), and older adulthood (over 65 years). Directing behavioral interventions to patients in these stages may therefore be beneficial.
And there’s no time too soon to promote abstinence among those with alcohol use disorder, as brain damage is shown to still occur even in the immediate period after people cease drinking.
Although in one more argument for the J-shaped curve’s relevance, data from the Massachusetts General Brigham Biobank recently indicated that moderate alcohol use, unlike low and heavy use, lowered both stress-related neurobiological activity and major adverse cardiovascular events.
Getting patients to reconsider alcohol’s ‘benefits’
These new findings mean physicians will find themselves imparting a more nuanced message about the health impacts of moderate alcohol consumption than in prior years. To aid those efforts, Ms. Rumgay advised clinicians to consult a special issue of the journal Nutrients that features review articles of alcohol›s impact on various health outcomes.
Ms. Rumgay also supports broader policy changes.
“There is some evidence that adding cancer warnings to alcohol labels, similar to those used on cigarette packages, might deter people from purchasing alcohol products and increase awareness of the causal link with cancer,” she said. “But the most effective ways of reducing alcohol use in the population are through increasing the price of alcohol through higher taxes, limiting purchasing availability, and reducing marketing of alcohol brands to the public.”
Dr. Mewton recommended various interventions for patients who still find it difficult to curtail their drinking.
“For less severe, problematic use, things like cognitive-behavioral therapy and motivational therapy are very effective in reducing alcohol consumption,” she said in an interview.
For all the discussion about how the COVID-19 pandemic has exacerbated problematic drinking, it has also provided an opportunity for getting patients to reexamine their relationship to alcohol. And as Dr. Labos noted, emerging data on alcohol’s negative effects probably won’t be considered earth-shattering to most patients.
“Deep down, I think most people know that alcohol is not healthy, but it is part of our social culture and so we find ways to justify our own behavior,” he said in an interview.
Dr. Labos suggested that clinicians reframe alcohol in their patients’ minds for what it really is – “an indulgence that we shouldn’t have too much of very often.
“Just like junk food, that doesn’t mean we can’t enjoy small amounts occasionally, but we have to stop presenting that it is good for us, because it isn’t.”
A version of this article first appeared on Medscape.com.
When holiday shoppers recently went to their local liquor stores in search of some liquid spirit, many were instead greeted by the sight of increasingly barren shelves.
Although partly a result of global supply chain issues, this was also yet more evidence of the rising demand for alcohol among adults during these difficult COVID years. It’s a trend that has led to concerns of an echo pandemic of alcohol-related morbidity, which has begun to play out in the form of rising rates of gastrointestinal and liver disease, hospital admissions for alcoholic hepatitis, and alcohol-related incidents of domestic violence.
Those who imbibe alcohol in low to moderate levels may not see themselves reflected in such stories of drinking’s hefty tolls. They’re instead following established health guidance that a little bit of alcohol now and then actually has robust health benefits. Yet the past few of years have seen a notable fraying of this idea, as emerging data calls into question whether alcohol in moderation should really continue to be just what the doctor ordered.
Behind the curve: Alcohol’s diminishing cardioprotective value
Perhaps the most resonant argument for the benefits of light to moderate alcohol consumption – usually defined as between one to two drinks a day – has been its proposed cardioprotective value. In this way, alcohol differs from tobacco, which is unsafe at any level. Alcohol’s proposed cardioprotective effects are often represented as a J-shaped curve, with moderate drinking occupying the sweet spot between teetotaling and heavy/binge drinking when it comes to reduced mortality.
In reality, this association is more likely “a statistical artifact” largely derived from low-quality observational studies, according to Christopher Labos, MD, CM, MSc, an epidemiologist and cardiologist at the Queen Elizabeth Health Complex in Montreal.
“When you look at studies that correct for things like reverse causation, or the fact that some people who drink zero alcohol are former drinkers who used to drink alcohol, then you realize that the protective benefit of alcohol is either minimal or nonexistent and that alcohol does more harm than good to our society,” said Dr. Labos, who detailed the reasons underpinning alcohol’s unearned cardioprotective reputation in a 2020 Medscape commentary.
This statistical limitation was on display in July 2021 when BMC Medicine published results from meta-analyses suggesting that current drinkers need not stop consuming small amounts of alcohol for the secondary prevention of cardiovascular disease (CVD). The study’s own investigators noted that it likely overestimated the reduced risk of CVD by including former heavy drinkers as nondrinkers.
Even if the J-shaped curve exists, its simplicity is deceiving. CVD risk increases alongside alcohol consumption owning to a complicated array of genetic and lifestyle factors. The curve also presents something of a catch-22. If you like alcohol enough to drink it every day, staying at the nadir of the curve where you’d gain the most benefits may prove challenging.
Another factor dimming alcohol’s cardioprotective reputation came via recent data that atrial fibrillation episodes can be triggered by acute alcohol use. A randomized, controlled trial published in the New England Journal of Medicine concluded that abstinence reduced arrhythmia recurrences in regular drinkers with atrial fibrillation.
“If we can replicate that, I think we’ll find that reducing alcohol consumption might be a very effective way to prevent and treat atrial fibrillation,” said Dr. Labos.
However, J-curve proponents will note the publication of study data from the UK Biobank indicating that low levels of alcohol consumption confers the greatest reduction in atrial fibrillation risk.
An overlooked carcinogen no longer
Surveys indicate that less than half of Americans realize alcohol increases cancer risk. That might have changed just a bit this year. In early 2021, an epidemiological analysis estimated that alcohol contributed to 4.8% of cancer cases and 3.2% of cancer deaths in the United States. Then the Lancet Oncology published the results of a high-profile, population-based study on the global burden of cancer as a result of alcoho. Although the main takeaway message was that 4% of new cancer cases worldwide in 2020 were attributable to alcohol, it was also noteworthy that moderate drinking accounted for 103,100 out of 741,300 of these projected annual cases.
“The risk of cancer increases even with low or moderate levels of drinking,” said the study’s lead author Harriet Rumgay, BSc, from the International Agency for Research on Cancer in Lyon, France. “Drinking less means you’ll have a lower risk of cancer than if you drink heavily, but there is no safe limit of alcohol consumption.”
The study linked alcohol consumption with an increased risk of at least seven different cancer types, including cancers of the oral cavity, pharynx, larynx, esophagus, colon, rectum, liver, and breast.
Although in North America men represented about two-thirds of the burden of cancer caused by alcohol, Ms. Rumgay added that “low and moderate levels of drinking [one or two alcoholic drinks per day] contributed relatively more cancer cases among women than among men.”
Yet more negative news for moderate alcohol drinkers arrived in August 2021, when a team of South Korean researchers published data in JAMA Network Open showing that, when it came to the risk of developing gastrointestinal cancers, even binge drinking may be preferable to continuous but moderate consumption.
who in updating its guidelines in 2020 after an 8-year interim offered this succinct piece of advice: “It is best not to drink alcohol.”
Neurotoxic implications
There has similarly been a reconsideration of the effects of moderate alcohol consumption on brain health.
A recent report of multimodal MRI brain and cognitive testing data from over 25,000 participants in the UK Biobank study indicate that alcohol may have no safe dosage . Even moderate consumption reduced gray matter volume and functional connectivity, negative associations that were increased in those with higher blood pressure and body mass index.
Speaking with this news organization in May 2021, an investigator said: “The size of the effect is small, albeit greater than any other modifiable risk factor,” noting that the changes have been linked to decreased memory and dementia.
Louise Mewton, PhD, from the Center for Healthy Brain Aging at the University of New South Wales, Sydney, said that these results provide an interesting comparison with others into the association between alcohol and dementia.
“A recent study of over 1 million dementia cases in France indicated that problematic alcohol use (alcohol use disorders) were one of the strongest risk factors for dementia – even more so than things like high blood pressure and diabetes,” Dr. Mewton said in an interview. In comparison, “the most-recent reviews indicate that 4 drinks/week is associated with the lowest risk for dementia – so we’re talking about very low levels of alcohol use in terms of maintaining brain health.
“Understanding why very small amounts of alcohol appear to be protective in terms of dementia but damaging when we look at brain scans is something that would be really interesting to unpack.”
Dr. Mewton and colleagues recently published data suggesting that there are three periods when the brain might be particularly susceptible to alcohol’s neurotoxic effects: gestation (from conception to birth), later adolescence (15-19 years), and older adulthood (over 65 years). Directing behavioral interventions to patients in these stages may therefore be beneficial.
And there’s no time too soon to promote abstinence among those with alcohol use disorder, as brain damage is shown to still occur even in the immediate period after people cease drinking.
Although in one more argument for the J-shaped curve’s relevance, data from the Massachusetts General Brigham Biobank recently indicated that moderate alcohol use, unlike low and heavy use, lowered both stress-related neurobiological activity and major adverse cardiovascular events.
Getting patients to reconsider alcohol’s ‘benefits’
These new findings mean physicians will find themselves imparting a more nuanced message about the health impacts of moderate alcohol consumption than in prior years. To aid those efforts, Ms. Rumgay advised clinicians to consult a special issue of the journal Nutrients that features review articles of alcohol›s impact on various health outcomes.
Ms. Rumgay also supports broader policy changes.
“There is some evidence that adding cancer warnings to alcohol labels, similar to those used on cigarette packages, might deter people from purchasing alcohol products and increase awareness of the causal link with cancer,” she said. “But the most effective ways of reducing alcohol use in the population are through increasing the price of alcohol through higher taxes, limiting purchasing availability, and reducing marketing of alcohol brands to the public.”
Dr. Mewton recommended various interventions for patients who still find it difficult to curtail their drinking.
“For less severe, problematic use, things like cognitive-behavioral therapy and motivational therapy are very effective in reducing alcohol consumption,” she said in an interview.
For all the discussion about how the COVID-19 pandemic has exacerbated problematic drinking, it has also provided an opportunity for getting patients to reexamine their relationship to alcohol. And as Dr. Labos noted, emerging data on alcohol’s negative effects probably won’t be considered earth-shattering to most patients.
“Deep down, I think most people know that alcohol is not healthy, but it is part of our social culture and so we find ways to justify our own behavior,” he said in an interview.
Dr. Labos suggested that clinicians reframe alcohol in their patients’ minds for what it really is – “an indulgence that we shouldn’t have too much of very often.
“Just like junk food, that doesn’t mean we can’t enjoy small amounts occasionally, but we have to stop presenting that it is good for us, because it isn’t.”
A version of this article first appeared on Medscape.com.
Pruritic Eruption on the Trunk and Extremities
THE DIAGNOSIS:
Acquired Perforating Disorder of Renal Disease
A papule with the central plug removed left a pitlike depression, representing Kyrle disease (Figure 1). A punch biopsy of the left forearm revealed epidermal hyperplasia (Figure 2A) surrounding a keratin plug that contained degenerated basophilic material (Figure 2B), confirming the diagnosis of acquired perforating disorder of renal disease (APDRD), classically described as Kyrle disease.
Acquired perforating disorder of renal disease is an uncommon condition in the general population. It is associated with systemic disease, commonly diabetes mellitus and chronic renal failure, and is seen in up to 10% patients receiving hemodialysis.1 The underlying etiology and pathogenesis of APDRD remains unknown. It has been proposed to be a variant of prurigo nodularis, representing end-stage excoriated folliculitis.1 Given that most cases appear in patients with systemic disease and metabolic abnormalities, APDRD also has been classified under the spectrum of acquired perforating dermatoses, a group of disorders defined by transepithelial elimination of dermal connective tissue. Elevated levels of serum and tissue fibronectin, uremia, and hyperphosphatemia have been observed in patients with APDRD.1,2 Fibronectin stimulates epithelial migration and proliferation and may lead to expulsion of keratin. Furthermore, dermal deposition of excess urea and/or phosphate could initiate transepithelial elimination of material. Alternative hypotheses implicate abnormal keratinization or an imbalance between the rates of epidermal proliferation/ differentiation and keratin production, whereby keratin production outpaces the former. Keratin deposited within the dermis subsequently elicits an inflammatory response along with alterations in the local dermis and connective tissue. These components become intermixed and are extruded through the plug opening.3 Lastly, immune dysregulation resulting from systemic disease could contribute to APDRD through increased expression of IL-31, a cytokine thought to play a role in several pruritic inflammatory skin diseases.4
Although standardized treatment guidelines for APDRD have not been established, the mainstay of therapy is control of the underlying systemic disorder. Intense pruritus and repeated scratching may contribute to microtrauma and subsequent koebnerization of new lesions.3 Thus, ameliorating pruritus can provide both symptomatic relief and prevent the development of new lesions. Retinoids, UV light, oral antibiotics, antihistamines, corticosteroids, keratolytic agents, and immunosuppressants (eg, allopurinol, tacrolimus) have shown some benefit.4
The differential diagnoses for APDRD include arthropod hypersensitivity reactions, eruptive keratoacanthomas, keratosis pilaris, and prurigo nodularis. Arthropod hypersensitivity reactions are seen in patients with a history of a bite or sting from arthropods such as bees, fleas, mites, ticks, and spiders. These reactions cause symptoms of pain, burning, or pruritus and present heterogeneously. They can be edematous and appear as single or multiple papules, pustules, plaques, vesicles, and/or bullae. A central punctum or crusting also may be present. Eruptive keratoacanthomas are seen in Grzybowski syndrome and Ferguson-Smith disease. Grzybowski syndrome arises in the fifth to seventh decades of life and is characterized by the eruptive onset of hundreds to thousands of pruritic, dome-shaped, follicular papules with or without central keratin plugs. Ectropion, mucosal lesions, and masklike facies are other clinical characteristics of Grzybowski syndrome. Ferguson-Smith disease begins in the second decade of life. The eruption of multiple keratoacanthomas and/or squamous cell carcinomas occurs in crops, rapidly growing over 2 to 4 weeks, and then self-resolves. This disease is inherited in an autosomal-dominant manner and is associated with chromosome 9q22. Keratosis pilaris is a benign condition of follicular hyperkeratosis that can appear in any age group and usually is absent of symptoms. It is not associated with any systemic disease. Clinically, the condition appears as folliculocentric keratotic papules with varying degrees of perifollicular erythema located along the extensor surfaces. Keratosis pilaris and APDRD share features of a follicular hyperkeratosis and dilated infundibulum; however, perforation is absent in keratosis pilaris. Lastly, prurigo nodularis is another intensely pruritic dermatosis associated with renal disease that presents as papulonodules on the extensor surfaces of the arms and legs. A biopsy can help to distinguish prurigo nodularis from APDRD.
- Rice AS, Zedek D. Kyrle disease. StatPearls [internet]. StatPearls Publishing; 2020. https://www.ncbi.nlm.nih.gov/books/NBK532886/
- McKinley-Grant L, Peebles J. Renal disease. In: Kelly A, Taylor SC, Lim HW, et al, eds. Taylor and Kelly’s Dermatology for Skin of Color. 2nd ed. McGraw-Hill; 2016
- Patterson JW. The perforating disorders. J Am Acad Dermatol. 1984;10:561-581. doi:10.1016/s0190-9622(84)80259-5
- Forouzandeh M, Stratman S, Yosipovitch G. The treatment of Kyrle’s disease: a systematic review. J Eur Acad Dermatol Venereol. 2020;34:1457-1463. doi:10.1111/jdv.16182
THE DIAGNOSIS:
Acquired Perforating Disorder of Renal Disease
A papule with the central plug removed left a pitlike depression, representing Kyrle disease (Figure 1). A punch biopsy of the left forearm revealed epidermal hyperplasia (Figure 2A) surrounding a keratin plug that contained degenerated basophilic material (Figure 2B), confirming the diagnosis of acquired perforating disorder of renal disease (APDRD), classically described as Kyrle disease.
Acquired perforating disorder of renal disease is an uncommon condition in the general population. It is associated with systemic disease, commonly diabetes mellitus and chronic renal failure, and is seen in up to 10% patients receiving hemodialysis.1 The underlying etiology and pathogenesis of APDRD remains unknown. It has been proposed to be a variant of prurigo nodularis, representing end-stage excoriated folliculitis.1 Given that most cases appear in patients with systemic disease and metabolic abnormalities, APDRD also has been classified under the spectrum of acquired perforating dermatoses, a group of disorders defined by transepithelial elimination of dermal connective tissue. Elevated levels of serum and tissue fibronectin, uremia, and hyperphosphatemia have been observed in patients with APDRD.1,2 Fibronectin stimulates epithelial migration and proliferation and may lead to expulsion of keratin. Furthermore, dermal deposition of excess urea and/or phosphate could initiate transepithelial elimination of material. Alternative hypotheses implicate abnormal keratinization or an imbalance between the rates of epidermal proliferation/ differentiation and keratin production, whereby keratin production outpaces the former. Keratin deposited within the dermis subsequently elicits an inflammatory response along with alterations in the local dermis and connective tissue. These components become intermixed and are extruded through the plug opening.3 Lastly, immune dysregulation resulting from systemic disease could contribute to APDRD through increased expression of IL-31, a cytokine thought to play a role in several pruritic inflammatory skin diseases.4
Although standardized treatment guidelines for APDRD have not been established, the mainstay of therapy is control of the underlying systemic disorder. Intense pruritus and repeated scratching may contribute to microtrauma and subsequent koebnerization of new lesions.3 Thus, ameliorating pruritus can provide both symptomatic relief and prevent the development of new lesions. Retinoids, UV light, oral antibiotics, antihistamines, corticosteroids, keratolytic agents, and immunosuppressants (eg, allopurinol, tacrolimus) have shown some benefit.4
The differential diagnoses for APDRD include arthropod hypersensitivity reactions, eruptive keratoacanthomas, keratosis pilaris, and prurigo nodularis. Arthropod hypersensitivity reactions are seen in patients with a history of a bite or sting from arthropods such as bees, fleas, mites, ticks, and spiders. These reactions cause symptoms of pain, burning, or pruritus and present heterogeneously. They can be edematous and appear as single or multiple papules, pustules, plaques, vesicles, and/or bullae. A central punctum or crusting also may be present. Eruptive keratoacanthomas are seen in Grzybowski syndrome and Ferguson-Smith disease. Grzybowski syndrome arises in the fifth to seventh decades of life and is characterized by the eruptive onset of hundreds to thousands of pruritic, dome-shaped, follicular papules with or without central keratin plugs. Ectropion, mucosal lesions, and masklike facies are other clinical characteristics of Grzybowski syndrome. Ferguson-Smith disease begins in the second decade of life. The eruption of multiple keratoacanthomas and/or squamous cell carcinomas occurs in crops, rapidly growing over 2 to 4 weeks, and then self-resolves. This disease is inherited in an autosomal-dominant manner and is associated with chromosome 9q22. Keratosis pilaris is a benign condition of follicular hyperkeratosis that can appear in any age group and usually is absent of symptoms. It is not associated with any systemic disease. Clinically, the condition appears as folliculocentric keratotic papules with varying degrees of perifollicular erythema located along the extensor surfaces. Keratosis pilaris and APDRD share features of a follicular hyperkeratosis and dilated infundibulum; however, perforation is absent in keratosis pilaris. Lastly, prurigo nodularis is another intensely pruritic dermatosis associated with renal disease that presents as papulonodules on the extensor surfaces of the arms and legs. A biopsy can help to distinguish prurigo nodularis from APDRD.
THE DIAGNOSIS:
Acquired Perforating Disorder of Renal Disease
A papule with the central plug removed left a pitlike depression, representing Kyrle disease (Figure 1). A punch biopsy of the left forearm revealed epidermal hyperplasia (Figure 2A) surrounding a keratin plug that contained degenerated basophilic material (Figure 2B), confirming the diagnosis of acquired perforating disorder of renal disease (APDRD), classically described as Kyrle disease.
Acquired perforating disorder of renal disease is an uncommon condition in the general population. It is associated with systemic disease, commonly diabetes mellitus and chronic renal failure, and is seen in up to 10% patients receiving hemodialysis.1 The underlying etiology and pathogenesis of APDRD remains unknown. It has been proposed to be a variant of prurigo nodularis, representing end-stage excoriated folliculitis.1 Given that most cases appear in patients with systemic disease and metabolic abnormalities, APDRD also has been classified under the spectrum of acquired perforating dermatoses, a group of disorders defined by transepithelial elimination of dermal connective tissue. Elevated levels of serum and tissue fibronectin, uremia, and hyperphosphatemia have been observed in patients with APDRD.1,2 Fibronectin stimulates epithelial migration and proliferation and may lead to expulsion of keratin. Furthermore, dermal deposition of excess urea and/or phosphate could initiate transepithelial elimination of material. Alternative hypotheses implicate abnormal keratinization or an imbalance between the rates of epidermal proliferation/ differentiation and keratin production, whereby keratin production outpaces the former. Keratin deposited within the dermis subsequently elicits an inflammatory response along with alterations in the local dermis and connective tissue. These components become intermixed and are extruded through the plug opening.3 Lastly, immune dysregulation resulting from systemic disease could contribute to APDRD through increased expression of IL-31, a cytokine thought to play a role in several pruritic inflammatory skin diseases.4
Although standardized treatment guidelines for APDRD have not been established, the mainstay of therapy is control of the underlying systemic disorder. Intense pruritus and repeated scratching may contribute to microtrauma and subsequent koebnerization of new lesions.3 Thus, ameliorating pruritus can provide both symptomatic relief and prevent the development of new lesions. Retinoids, UV light, oral antibiotics, antihistamines, corticosteroids, keratolytic agents, and immunosuppressants (eg, allopurinol, tacrolimus) have shown some benefit.4
The differential diagnoses for APDRD include arthropod hypersensitivity reactions, eruptive keratoacanthomas, keratosis pilaris, and prurigo nodularis. Arthropod hypersensitivity reactions are seen in patients with a history of a bite or sting from arthropods such as bees, fleas, mites, ticks, and spiders. These reactions cause symptoms of pain, burning, or pruritus and present heterogeneously. They can be edematous and appear as single or multiple papules, pustules, plaques, vesicles, and/or bullae. A central punctum or crusting also may be present. Eruptive keratoacanthomas are seen in Grzybowski syndrome and Ferguson-Smith disease. Grzybowski syndrome arises in the fifth to seventh decades of life and is characterized by the eruptive onset of hundreds to thousands of pruritic, dome-shaped, follicular papules with or without central keratin plugs. Ectropion, mucosal lesions, and masklike facies are other clinical characteristics of Grzybowski syndrome. Ferguson-Smith disease begins in the second decade of life. The eruption of multiple keratoacanthomas and/or squamous cell carcinomas occurs in crops, rapidly growing over 2 to 4 weeks, and then self-resolves. This disease is inherited in an autosomal-dominant manner and is associated with chromosome 9q22. Keratosis pilaris is a benign condition of follicular hyperkeratosis that can appear in any age group and usually is absent of symptoms. It is not associated with any systemic disease. Clinically, the condition appears as folliculocentric keratotic papules with varying degrees of perifollicular erythema located along the extensor surfaces. Keratosis pilaris and APDRD share features of a follicular hyperkeratosis and dilated infundibulum; however, perforation is absent in keratosis pilaris. Lastly, prurigo nodularis is another intensely pruritic dermatosis associated with renal disease that presents as papulonodules on the extensor surfaces of the arms and legs. A biopsy can help to distinguish prurigo nodularis from APDRD.
- Rice AS, Zedek D. Kyrle disease. StatPearls [internet]. StatPearls Publishing; 2020. https://www.ncbi.nlm.nih.gov/books/NBK532886/
- McKinley-Grant L, Peebles J. Renal disease. In: Kelly A, Taylor SC, Lim HW, et al, eds. Taylor and Kelly’s Dermatology for Skin of Color. 2nd ed. McGraw-Hill; 2016
- Patterson JW. The perforating disorders. J Am Acad Dermatol. 1984;10:561-581. doi:10.1016/s0190-9622(84)80259-5
- Forouzandeh M, Stratman S, Yosipovitch G. The treatment of Kyrle’s disease: a systematic review. J Eur Acad Dermatol Venereol. 2020;34:1457-1463. doi:10.1111/jdv.16182
- Rice AS, Zedek D. Kyrle disease. StatPearls [internet]. StatPearls Publishing; 2020. https://www.ncbi.nlm.nih.gov/books/NBK532886/
- McKinley-Grant L, Peebles J. Renal disease. In: Kelly A, Taylor SC, Lim HW, et al, eds. Taylor and Kelly’s Dermatology for Skin of Color. 2nd ed. McGraw-Hill; 2016
- Patterson JW. The perforating disorders. J Am Acad Dermatol. 1984;10:561-581. doi:10.1016/s0190-9622(84)80259-5
- Forouzandeh M, Stratman S, Yosipovitch G. The treatment of Kyrle’s disease: a systematic review. J Eur Acad Dermatol Venereol. 2020;34:1457-1463. doi:10.1111/jdv.16182
A 74-year-old woman with a 30-year history of type 2 diabetes mellitus presented to our dermatology clinic with a pruritic eruption on the trunk, arms, and legs of 2 months’ duration. Several over-the-counter moisturizers had been used without improvement, and the pruritus was notably impacting her sleep. Physical examination revealed discrete, hyperkeratotic, predominantly follicular, eruptive papules with hyperkeratotic plugs diffusely distributed on the trunk, arms, and legs.
Wrist rash
The gradual development of a rash in an area of frequent direct contact between metal and skin is pathognomonic for allergic contact dermatitis (ACD). Contact dermatitis often results from exposure to metals. Stainless steel is a group of ferrous alloys composed of a variety of elements including nickel, which is added to increase corrosion resistance. Unfortunately, nickel is a metal commonly known to induce a delayed hypersensitivity response. In the upper left corner of the image shown here, one can see the metal plate of the watch band.
ACD is a T-cell mediated, delayed, type IV hypersensitivity response to foreign materials.1 These reactions typically occur around 48 to 72 hours following contact with the metal but can take weeks to appear, depending on the amount of T-cell activation. Symptoms may appear more rapidly on repeat exposures. Lesions manifest as erythematous, scaly plaques, which may include vesicles and bullae in severe cases.
The mainstay of treatment for allergic contact dermatitis is avoidance of the allergen once it has been identified. Nickel is commonly found in metal parts on clothing and in jewelry. One method of protection from nickel in these cases is to cover the metal that touches the skin with a clear nail polish or another clear barrier (commercial options are available). Duct tape or fabric can also be used to cover the metal.
Topical corticosteroids are the first-line therapy to treat lesions. Topical calcineurin inhibitors are an alternative. Systemic corticosteroids may be indicated if there is extensive body surface area involvement. Phototherapy or systemic immunosuppression may be considered in severe refractory cases.
Our patient was counseled on the nature of the disease process and educated on strategies to avoid future exposures. Treatment was initiated with topical triamcinolone 0.1% ointment with follow-up as needed.
Image courtesy of Daniel Stulberg, MD. Text courtesy of Spenser Squire, MD, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.
1. Mowad CM, Anderson B, Scheinman P, et al. Allergic contact dermatitis: patient diagnosis and evaluation. J Am Acad Dermatol. 2016;74:1029-1040. doi: 10.1016/j.jaad.2015.02.1139
The gradual development of a rash in an area of frequent direct contact between metal and skin is pathognomonic for allergic contact dermatitis (ACD). Contact dermatitis often results from exposure to metals. Stainless steel is a group of ferrous alloys composed of a variety of elements including nickel, which is added to increase corrosion resistance. Unfortunately, nickel is a metal commonly known to induce a delayed hypersensitivity response. In the upper left corner of the image shown here, one can see the metal plate of the watch band.
ACD is a T-cell mediated, delayed, type IV hypersensitivity response to foreign materials.1 These reactions typically occur around 48 to 72 hours following contact with the metal but can take weeks to appear, depending on the amount of T-cell activation. Symptoms may appear more rapidly on repeat exposures. Lesions manifest as erythematous, scaly plaques, which may include vesicles and bullae in severe cases.
The mainstay of treatment for allergic contact dermatitis is avoidance of the allergen once it has been identified. Nickel is commonly found in metal parts on clothing and in jewelry. One method of protection from nickel in these cases is to cover the metal that touches the skin with a clear nail polish or another clear barrier (commercial options are available). Duct tape or fabric can also be used to cover the metal.
Topical corticosteroids are the first-line therapy to treat lesions. Topical calcineurin inhibitors are an alternative. Systemic corticosteroids may be indicated if there is extensive body surface area involvement. Phototherapy or systemic immunosuppression may be considered in severe refractory cases.
Our patient was counseled on the nature of the disease process and educated on strategies to avoid future exposures. Treatment was initiated with topical triamcinolone 0.1% ointment with follow-up as needed.
Image courtesy of Daniel Stulberg, MD. Text courtesy of Spenser Squire, MD, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.
The gradual development of a rash in an area of frequent direct contact between metal and skin is pathognomonic for allergic contact dermatitis (ACD). Contact dermatitis often results from exposure to metals. Stainless steel is a group of ferrous alloys composed of a variety of elements including nickel, which is added to increase corrosion resistance. Unfortunately, nickel is a metal commonly known to induce a delayed hypersensitivity response. In the upper left corner of the image shown here, one can see the metal plate of the watch band.
ACD is a T-cell mediated, delayed, type IV hypersensitivity response to foreign materials.1 These reactions typically occur around 48 to 72 hours following contact with the metal but can take weeks to appear, depending on the amount of T-cell activation. Symptoms may appear more rapidly on repeat exposures. Lesions manifest as erythematous, scaly plaques, which may include vesicles and bullae in severe cases.
The mainstay of treatment for allergic contact dermatitis is avoidance of the allergen once it has been identified. Nickel is commonly found in metal parts on clothing and in jewelry. One method of protection from nickel in these cases is to cover the metal that touches the skin with a clear nail polish or another clear barrier (commercial options are available). Duct tape or fabric can also be used to cover the metal.
Topical corticosteroids are the first-line therapy to treat lesions. Topical calcineurin inhibitors are an alternative. Systemic corticosteroids may be indicated if there is extensive body surface area involvement. Phototherapy or systemic immunosuppression may be considered in severe refractory cases.
Our patient was counseled on the nature of the disease process and educated on strategies to avoid future exposures. Treatment was initiated with topical triamcinolone 0.1% ointment with follow-up as needed.
Image courtesy of Daniel Stulberg, MD. Text courtesy of Spenser Squire, MD, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.
1. Mowad CM, Anderson B, Scheinman P, et al. Allergic contact dermatitis: patient diagnosis and evaluation. J Am Acad Dermatol. 2016;74:1029-1040. doi: 10.1016/j.jaad.2015.02.1139
1. Mowad CM, Anderson B, Scheinman P, et al. Allergic contact dermatitis: patient diagnosis and evaluation. J Am Acad Dermatol. 2016;74:1029-1040. doi: 10.1016/j.jaad.2015.02.1139
Epilepsy in older adults: Misdiagnosis and case complexity are common
, a neurologist told an audience at the annual meeting of the American Epilepsy Society. She urged colleagues to focus on possible interactions with other neurological conditions, consider various complicating factors, and embrace a team strategy.
“There are lots of nuances,” said Rebecca O’Dwyer, MD, an adult epilepsy specialist with Rush Epilepsy Center in Chicago. “It takes a lot of time and requires a multidisciplinary approach. Taking care of older individuals with epilepsy truly is a team sport.”
According to a 2014 report highlighted by Dr. O’Dwyer, “nearly 25% of new-onset seizures occur after age 65. The incidence of epilepsy in this age group is almost twice the rate in children, and in people over age 80, it is triple the rate in children.”
Research suggests it can take up to 2 years to correctly diagnose epilepsy in older people, Dr. O’Dwyer said, and nearly two-thirds of cases may be misdiagnosed. “Some of it is just limited awareness. There’s this perception in the public that epilepsy is something that occurs in younger adults or young children, and that when you come to a certain age, you cannot have epilepsy. Also, there are differences in the clinical manifestations of their seizures, and many comorbid possibilities could also present in similar fashion to epilepsy. Some of our usual tools that we use to come to the diagnosis such as EEG are also known to be less sensitive in this age group.”
According to the 2014 report, research finds that the elderly are much more likely than young adults to have postictal sleepiness or unresponsiveness and seizures manifesting as brief moments of subtle confusion. They’re much less likely to have epileptic aura and generalized tonic seizures.
“An epileptic seizure in an older adult tends to be less dramatic with fewer motor manifestations, and they often tend to be monophasic. They may be so subtle that they’re missed by family members and other medical providers,” Dr. O’Dwyer said. “I had a patient whose seizure consisted of her tapping her left shoulder. She had been doing this for at least 6 months, and she came to my clinic after her daughter realized that she was a little confused afterward. She’d already seen a behavioral neurologist and been given the diagnosis of dementia. We were fortunate enough to catch one of these episodes while we were doing an EEG, and we diagnosed her with focal epilepsy. With one antiseizure medication, we stopped the seizures, and her memory came back.”
Make sure to take detailed histories and keep an eye out for descriptions of behaviors that are episodic but perhaps not typical of seizures, she said.
Epilepsy can be misdiagnosed as a variety of conditions, she said, such as syncope, Alzheimer’s disease, stroke, Parkinson’s disease, and atrial fibrillation. “When you do diagnose somebody older with new-onset epilepsy, you should work them up for a stroke. Because we know that within the first 4 weeks after their first seizure the likelihood that they could have a stroke is three times higher.”
It’s also possible that neurological conditions can be followed by new-onset epilepsy, she said, making dementia even worse. Low-dose antiepileptic drugs can be helpful in these patients.
But seniors are especially vulnerable to side effects of antiepileptic drugs such as sedation, dizziness, and cardiac-conduction abnormalities. “You must adhere to the mantra of going low and going slow because they are exquisitely susceptible,” Dr. O’Dwyer said.
She recommends lamotrigine, which is well tolerated with helpful mood-stabilizing effects, and levetiracetam, which attenuates cognitive decline in dementia but may cause side effects such as irritable mood. Zonisamide is showing promise in patients with parkinsonian syndromes, she said, and it may be helpful to maximize drugs that patients are already taking such as gabapentin or pregabalin.
Finally, Dr. O’Dwyer urged colleagues to work in teams that include caregivers, primary care doctors, social workers, and pharmacists. “Sometimes in all this,” she said, “my job is the easiest.”
Dr. O’Dwyer discloses research support from the Shapiro Foundation.
, a neurologist told an audience at the annual meeting of the American Epilepsy Society. She urged colleagues to focus on possible interactions with other neurological conditions, consider various complicating factors, and embrace a team strategy.
“There are lots of nuances,” said Rebecca O’Dwyer, MD, an adult epilepsy specialist with Rush Epilepsy Center in Chicago. “It takes a lot of time and requires a multidisciplinary approach. Taking care of older individuals with epilepsy truly is a team sport.”
According to a 2014 report highlighted by Dr. O’Dwyer, “nearly 25% of new-onset seizures occur after age 65. The incidence of epilepsy in this age group is almost twice the rate in children, and in people over age 80, it is triple the rate in children.”
Research suggests it can take up to 2 years to correctly diagnose epilepsy in older people, Dr. O’Dwyer said, and nearly two-thirds of cases may be misdiagnosed. “Some of it is just limited awareness. There’s this perception in the public that epilepsy is something that occurs in younger adults or young children, and that when you come to a certain age, you cannot have epilepsy. Also, there are differences in the clinical manifestations of their seizures, and many comorbid possibilities could also present in similar fashion to epilepsy. Some of our usual tools that we use to come to the diagnosis such as EEG are also known to be less sensitive in this age group.”
According to the 2014 report, research finds that the elderly are much more likely than young adults to have postictal sleepiness or unresponsiveness and seizures manifesting as brief moments of subtle confusion. They’re much less likely to have epileptic aura and generalized tonic seizures.
“An epileptic seizure in an older adult tends to be less dramatic with fewer motor manifestations, and they often tend to be monophasic. They may be so subtle that they’re missed by family members and other medical providers,” Dr. O’Dwyer said. “I had a patient whose seizure consisted of her tapping her left shoulder. She had been doing this for at least 6 months, and she came to my clinic after her daughter realized that she was a little confused afterward. She’d already seen a behavioral neurologist and been given the diagnosis of dementia. We were fortunate enough to catch one of these episodes while we were doing an EEG, and we diagnosed her with focal epilepsy. With one antiseizure medication, we stopped the seizures, and her memory came back.”
Make sure to take detailed histories and keep an eye out for descriptions of behaviors that are episodic but perhaps not typical of seizures, she said.
Epilepsy can be misdiagnosed as a variety of conditions, she said, such as syncope, Alzheimer’s disease, stroke, Parkinson’s disease, and atrial fibrillation. “When you do diagnose somebody older with new-onset epilepsy, you should work them up for a stroke. Because we know that within the first 4 weeks after their first seizure the likelihood that they could have a stroke is three times higher.”
It’s also possible that neurological conditions can be followed by new-onset epilepsy, she said, making dementia even worse. Low-dose antiepileptic drugs can be helpful in these patients.
But seniors are especially vulnerable to side effects of antiepileptic drugs such as sedation, dizziness, and cardiac-conduction abnormalities. “You must adhere to the mantra of going low and going slow because they are exquisitely susceptible,” Dr. O’Dwyer said.
She recommends lamotrigine, which is well tolerated with helpful mood-stabilizing effects, and levetiracetam, which attenuates cognitive decline in dementia but may cause side effects such as irritable mood. Zonisamide is showing promise in patients with parkinsonian syndromes, she said, and it may be helpful to maximize drugs that patients are already taking such as gabapentin or pregabalin.
Finally, Dr. O’Dwyer urged colleagues to work in teams that include caregivers, primary care doctors, social workers, and pharmacists. “Sometimes in all this,” she said, “my job is the easiest.”
Dr. O’Dwyer discloses research support from the Shapiro Foundation.
, a neurologist told an audience at the annual meeting of the American Epilepsy Society. She urged colleagues to focus on possible interactions with other neurological conditions, consider various complicating factors, and embrace a team strategy.
“There are lots of nuances,” said Rebecca O’Dwyer, MD, an adult epilepsy specialist with Rush Epilepsy Center in Chicago. “It takes a lot of time and requires a multidisciplinary approach. Taking care of older individuals with epilepsy truly is a team sport.”
According to a 2014 report highlighted by Dr. O’Dwyer, “nearly 25% of new-onset seizures occur after age 65. The incidence of epilepsy in this age group is almost twice the rate in children, and in people over age 80, it is triple the rate in children.”
Research suggests it can take up to 2 years to correctly diagnose epilepsy in older people, Dr. O’Dwyer said, and nearly two-thirds of cases may be misdiagnosed. “Some of it is just limited awareness. There’s this perception in the public that epilepsy is something that occurs in younger adults or young children, and that when you come to a certain age, you cannot have epilepsy. Also, there are differences in the clinical manifestations of their seizures, and many comorbid possibilities could also present in similar fashion to epilepsy. Some of our usual tools that we use to come to the diagnosis such as EEG are also known to be less sensitive in this age group.”
According to the 2014 report, research finds that the elderly are much more likely than young adults to have postictal sleepiness or unresponsiveness and seizures manifesting as brief moments of subtle confusion. They’re much less likely to have epileptic aura and generalized tonic seizures.
“An epileptic seizure in an older adult tends to be less dramatic with fewer motor manifestations, and they often tend to be monophasic. They may be so subtle that they’re missed by family members and other medical providers,” Dr. O’Dwyer said. “I had a patient whose seizure consisted of her tapping her left shoulder. She had been doing this for at least 6 months, and she came to my clinic after her daughter realized that she was a little confused afterward. She’d already seen a behavioral neurologist and been given the diagnosis of dementia. We were fortunate enough to catch one of these episodes while we were doing an EEG, and we diagnosed her with focal epilepsy. With one antiseizure medication, we stopped the seizures, and her memory came back.”
Make sure to take detailed histories and keep an eye out for descriptions of behaviors that are episodic but perhaps not typical of seizures, she said.
Epilepsy can be misdiagnosed as a variety of conditions, she said, such as syncope, Alzheimer’s disease, stroke, Parkinson’s disease, and atrial fibrillation. “When you do diagnose somebody older with new-onset epilepsy, you should work them up for a stroke. Because we know that within the first 4 weeks after their first seizure the likelihood that they could have a stroke is three times higher.”
It’s also possible that neurological conditions can be followed by new-onset epilepsy, she said, making dementia even worse. Low-dose antiepileptic drugs can be helpful in these patients.
But seniors are especially vulnerable to side effects of antiepileptic drugs such as sedation, dizziness, and cardiac-conduction abnormalities. “You must adhere to the mantra of going low and going slow because they are exquisitely susceptible,” Dr. O’Dwyer said.
She recommends lamotrigine, which is well tolerated with helpful mood-stabilizing effects, and levetiracetam, which attenuates cognitive decline in dementia but may cause side effects such as irritable mood. Zonisamide is showing promise in patients with parkinsonian syndromes, she said, and it may be helpful to maximize drugs that patients are already taking such as gabapentin or pregabalin.
Finally, Dr. O’Dwyer urged colleagues to work in teams that include caregivers, primary care doctors, social workers, and pharmacists. “Sometimes in all this,” she said, “my job is the easiest.”
Dr. O’Dwyer discloses research support from the Shapiro Foundation.
FROM AES 2021