I passed the neurology boards, for the first time, in 1998. Then again in 2009, and most recently in 2019.

So I’m up again in 2029. Regrettably, I missed grandfathering in for life by a few years.

Some people don’t study for them, but I’m a little too compulsive not to. I’d guess I put 40-50 hours into doing so in the 3 months beforehand. I didn’t want to fail and have to pay a hefty fee to retake them (the test fee for once is enough as it is).

I’ll be 63 when my next certification is due.

So I wonder (if I’m still in practice) will it even be worthwhile to do it all again? I like what I do, but certainly don’t plan on practicing forever.

Board certification looks good on paper, but certainly isn’t a requirement to practice. One of the best cardiologists I know has never bothered to get his board certification and I don’t think any less of him for it. He also isn’t wanting for patients, and those he has think he’s awesome.

That said, there are things, like being involved in research and legal work, where board certification is strongly recommended, if not mandatory. Since I do both, I certainly wouldn’t want to do anything that might affect my participating in them – if I’m still doing this in 8 years.

By the same token, my office lease runs out when I’m 62. At that point I’ll have been in the same place for 17 years. I don’t consider that a bad thing. I like my current office, and will be perfectly happy to wrap up my career here.

It brings up the same question, though, with logistics that are an even bigger PIA. The last thing I want to do is move my office as my career is winding down. But a lease extension for a few years can be negotiated, a board certification can’t.

I can’t help but wonder: What is the point of recertification over time? If I’ve already passed it three times, hopefully that means I know what I’m doing. One side will argue that it’s purely greed, as the people who run the boards need money and a way to justify their existence. On the other side are those who argue that maintenance of certification, while not perfect, is the only way we have of making sure practicing physicians are staying up to snuff.

The truth, as always, is somewhere in between.

But it still raises a question that I, fortunately, have another 8 years to think about. Because I’m not in a position to debate if it’s right or wrong, I just have to play by the rules.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

I passed the neurology boards, for the first time, in 1998. Then again in 2009, and most recently in 2019.

So I’m up again in 2029. Regrettably, I missed grandfathering in for life by a few years.

Some people don’t study for them, but I’m a little too compulsive not to. I’d guess I put 40-50 hours into doing so in the 3 months beforehand. I didn’t want to fail and have to pay a hefty fee to retake them (the test fee for once is enough as it is).

I’ll be 63 when my next certification is due.

So I wonder (if I’m still in practice) will it even be worthwhile to do it all again? I like what I do, but certainly don’t plan on practicing forever.

Board certification looks good on paper, but certainly isn’t a requirement to practice. One of the best cardiologists I know has never bothered to get his board certification and I don’t think any less of him for it. He also isn’t wanting for patients, and those he has think he’s awesome.

That said, there are things, like being involved in research and legal work, where board certification is strongly recommended, if not mandatory. Since I do both, I certainly wouldn’t want to do anything that might affect my participating in them – if I’m still doing this in 8 years.

By the same token, my office lease runs out when I’m 62. At that point I’ll have been in the same place for 17 years. I don’t consider that a bad thing. I like my current office, and will be perfectly happy to wrap up my career here.

It brings up the same question, though, with logistics that are an even bigger PIA. The last thing I want to do is move my office as my career is winding down. But a lease extension for a few years can be negotiated, a board certification can’t.

I can’t help but wonder: What is the point of recertification over time? If I’ve already passed it three times, hopefully that means I know what I’m doing. One side will argue that it’s purely greed, as the people who run the boards need money and a way to justify their existence. On the other side are those who argue that maintenance of certification, while not perfect, is the only way we have of making sure practicing physicians are staying up to snuff.

The truth, as always, is somewhere in between.

But it still raises a question that I, fortunately, have another 8 years to think about. Because I’m not in a position to debate if it’s right or wrong, I just have to play by the rules.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

I passed the neurology boards, for the first time, in 1998. Then again in 2009, and most recently in 2019.

So I’m up again in 2029. Regrettably, I missed grandfathering in for life by a few years.

Some people don’t study for them, but I’m a little too compulsive not to. I’d guess I put 40-50 hours into doing so in the 3 months beforehand. I didn’t want to fail and have to pay a hefty fee to retake them (the test fee for once is enough as it is).

I’ll be 63 when my next certification is due.

So I wonder (if I’m still in practice) will it even be worthwhile to do it all again? I like what I do, but certainly don’t plan on practicing forever.

Board certification looks good on paper, but certainly isn’t a requirement to practice. One of the best cardiologists I know has never bothered to get his board certification and I don’t think any less of him for it. He also isn’t wanting for patients, and those he has think he’s awesome.

That said, there are things, like being involved in research and legal work, where board certification is strongly recommended, if not mandatory. Since I do both, I certainly wouldn’t want to do anything that might affect my participating in them – if I’m still doing this in 8 years.

By the same token, my office lease runs out when I’m 62. At that point I’ll have been in the same place for 17 years. I don’t consider that a bad thing. I like my current office, and will be perfectly happy to wrap up my career here.

It brings up the same question, though, with logistics that are an even bigger PIA. The last thing I want to do is move my office as my career is winding down. But a lease extension for a few years can be negotiated, a board certification can’t.

I can’t help but wonder: What is the point of recertification over time? If I’ve already passed it three times, hopefully that means I know what I’m doing. One side will argue that it’s purely greed, as the people who run the boards need money and a way to justify their existence. On the other side are those who argue that maintenance of certification, while not perfect, is the only way we have of making sure practicing physicians are staying up to snuff.

The truth, as always, is somewhere in between.

But it still raises a question that I, fortunately, have another 8 years to think about. Because I’m not in a position to debate if it’s right or wrong, I just have to play by the rules.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Non-Hispanic Black and Hispanic patients are underrepresented on many liver transplant waiting lists, whereas non-Hispanic White patients are often overrepresented, according to data from 109 centers.

pixelheadphoto/Thinkstock

While racial disparities “greatly diminished” after placement on a waiting list, which suggests recent progress in the field, pre–wait-listing disparities may be more challenging to overcome, reported lead author Curtis Warren, MPH, CPH, of the University of Florida, Gainesville, and colleagues.

“In 2020, the Organ Procurement and Transplantation Network implemented a new allocation system for liver transplantation based on concentric circles of geographic proximity rather than somewhat arbitrarily delineated Donor Service Areas (DSAs),” the investigators wrote in Journal of the American College of Surgeons. “Although this was a step toward improving and equalizing access to lifesaving organs for those on the liver transplant wait list, the listing process determining which patients will be considered for transplantation has continued to be a significant hurdle.”

The process is “rife with impediments to equal access to listing,” according to Dr. Warren and colleagues; getting on a waiting list can be affected by factors such as inequitable access to primary care, lack of private health insurance, and subjective selection by transplant centers.

To better characterize these impediments, the investigators gathered center-specific data from the Scientific Registry of Transplant Recipients and the U.S. Census Bureau. The final dataset included 30,353 patients from treated at 109 transplant centers, each of which performed more than 250 transplants between January 2013 and December 2018. The investigators compared waiting list data for each center with demographics from its DSA. Primary variables included race/ethnicity, education level, poverty, and insurance coverage.

Multiple logistic regression analysis was used to compare expected waiting list demographics with observed waiting list demographics with the aid of observed/expected ratios for each race/ethnicity. Univariate and multivariate analyses were used to identify significant predictors, including covariates such as age at listing, distance traveled to transplant center, and center type.

On an adjusted basis, the observed/expected ratios showed that non-Hispanic Black patients were underrepresented on waiting lists at 88 out of 109 centers (81%) and Hispanic patients were underrepresented at 68 centers (62%). In contrast, non-Hispanic White patients were overrepresented on waiting lists at 65 centers (58%). Non-Hispanic White patients were underrepresented on waiting lists at 49 centers, or 45%. Minority underrepresentation was further supported by mean MELD (Model for End-Stage Liver Disease) scores, which were significantly higher among non-Hispanic Black patients (20.2) and Hispanic patients (19.4), compared with non-Hispanic White patients (18.7) (P < .0001 for all) at the time of wait-listing.

Based on the multivariate model, underrepresentation among Black patients was most common in areas with a higher proportion of Black individuals in the population, longer travel distances to transplant centers, and a higher rate of private insurance among transplant recipients. For Hispanic patients, rates of private insurance alone predicted underrepresentation.

Once patients were listed, however, these disparities faded. Non-Hispanic Black patients accounted for 9.8% of all transplants across all hospitals, compared with 7.9% of wait-listed individuals (P < .0001). At approximately two out of three hospitals (65%), the transplanted percentage of Black patients exceeded the wait-listed percentage (P = .002).

“Data from this study show that the wait lists at many transplant centers in the United States underrepresent minority populations, compared with what would be expected based on their service areas,” the investigators concluded. “Future work will need to be devoted to increasing awareness of these trends to promote equitable access to listing for liver transplantation.”

Looking at social determinants of health

According to Lauren D. Nephew, MD, MSc, MAE, of Indiana University, Indianapolis, “The question of access to care is particularly important at this juncture as we examine the inequities that COVID-19 exposed in access to care for racial minorities, and as we prepare for potential changes to health insurance coverage with the new administration.”

Dr. Nephew noted that the reported racial disparities stem from social determinants of health, such as proximity to transplant centers and type of insurance coverage.

“Another striking finding was that the disparity in wait-listing non-Hispanic Black patients increased with the percentage of non-Hispanic Black patients living in the area, further highlighting barriers in access to care in majority Black neighborhoods,” she said. “Inequities such as these are unacceptable, given our mandate to distribute organs in a fair and equitable fashion, and they require prospective studies for further examination.”
 

Identifying discrimination

Lanla Conteh, MD, MPH, of the Ohio State University Wexner Medical Center, Columbus, described how these inequities are magnified through bias in patient selection.

“Often times two very similar patients may present with the same medical profile and social circumstances; however, one is turned down,” she said. “Often the patient turned down is the non-Hispanic Black patient while the non-Hispanic White patient is given a pass.”

Dr. Conteh suggested that the first step in fixing this bias is recognizing that it is a problem and calling it by its proper name.

“As transplant centers, in order to address and change these significant disparities, we must first be willing to acknowledge that they do exist,” she said. “Only then can we move to the next step of developing awareness and methods to actively combat what we should label as systemic discrimination in medicine. Transplantation is a lifesaving treatment for many patients with decompensated liver disease or liver cancer. Ensuring equitable access for all patients and populations is of paramount importance.”

The study was supported by a Health Resources and Services Administration contract, as well as grants from the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases. The investigators and interviewees reported no conflicts of interest.

Non-Hispanic Black and Hispanic patients are underrepresented on many liver transplant waiting lists, whereas non-Hispanic White patients are often overrepresented, according to data from 109 centers.

pixelheadphoto/Thinkstock

While racial disparities “greatly diminished” after placement on a waiting list, which suggests recent progress in the field, pre–wait-listing disparities may be more challenging to overcome, reported lead author Curtis Warren, MPH, CPH, of the University of Florida, Gainesville, and colleagues.

“In 2020, the Organ Procurement and Transplantation Network implemented a new allocation system for liver transplantation based on concentric circles of geographic proximity rather than somewhat arbitrarily delineated Donor Service Areas (DSAs),” the investigators wrote in Journal of the American College of Surgeons. “Although this was a step toward improving and equalizing access to lifesaving organs for those on the liver transplant wait list, the listing process determining which patients will be considered for transplantation has continued to be a significant hurdle.”

The process is “rife with impediments to equal access to listing,” according to Dr. Warren and colleagues; getting on a waiting list can be affected by factors such as inequitable access to primary care, lack of private health insurance, and subjective selection by transplant centers.

To better characterize these impediments, the investigators gathered center-specific data from the Scientific Registry of Transplant Recipients and the U.S. Census Bureau. The final dataset included 30,353 patients from treated at 109 transplant centers, each of which performed more than 250 transplants between January 2013 and December 2018. The investigators compared waiting list data for each center with demographics from its DSA. Primary variables included race/ethnicity, education level, poverty, and insurance coverage.

Multiple logistic regression analysis was used to compare expected waiting list demographics with observed waiting list demographics with the aid of observed/expected ratios for each race/ethnicity. Univariate and multivariate analyses were used to identify significant predictors, including covariates such as age at listing, distance traveled to transplant center, and center type.

On an adjusted basis, the observed/expected ratios showed that non-Hispanic Black patients were underrepresented on waiting lists at 88 out of 109 centers (81%) and Hispanic patients were underrepresented at 68 centers (62%). In contrast, non-Hispanic White patients were overrepresented on waiting lists at 65 centers (58%). Non-Hispanic White patients were underrepresented on waiting lists at 49 centers, or 45%. Minority underrepresentation was further supported by mean MELD (Model for End-Stage Liver Disease) scores, which were significantly higher among non-Hispanic Black patients (20.2) and Hispanic patients (19.4), compared with non-Hispanic White patients (18.7) (P < .0001 for all) at the time of wait-listing.

Based on the multivariate model, underrepresentation among Black patients was most common in areas with a higher proportion of Black individuals in the population, longer travel distances to transplant centers, and a higher rate of private insurance among transplant recipients. For Hispanic patients, rates of private insurance alone predicted underrepresentation.

Once patients were listed, however, these disparities faded. Non-Hispanic Black patients accounted for 9.8% of all transplants across all hospitals, compared with 7.9% of wait-listed individuals (P < .0001). At approximately two out of three hospitals (65%), the transplanted percentage of Black patients exceeded the wait-listed percentage (P = .002).

“Data from this study show that the wait lists at many transplant centers in the United States underrepresent minority populations, compared with what would be expected based on their service areas,” the investigators concluded. “Future work will need to be devoted to increasing awareness of these trends to promote equitable access to listing for liver transplantation.”

Looking at social determinants of health

According to Lauren D. Nephew, MD, MSc, MAE, of Indiana University, Indianapolis, “The question of access to care is particularly important at this juncture as we examine the inequities that COVID-19 exposed in access to care for racial minorities, and as we prepare for potential changes to health insurance coverage with the new administration.”

Dr. Nephew noted that the reported racial disparities stem from social determinants of health, such as proximity to transplant centers and type of insurance coverage.

“Another striking finding was that the disparity in wait-listing non-Hispanic Black patients increased with the percentage of non-Hispanic Black patients living in the area, further highlighting barriers in access to care in majority Black neighborhoods,” she said. “Inequities such as these are unacceptable, given our mandate to distribute organs in a fair and equitable fashion, and they require prospective studies for further examination.”
 

Identifying discrimination

Lanla Conteh, MD, MPH, of the Ohio State University Wexner Medical Center, Columbus, described how these inequities are magnified through bias in patient selection.

“Often times two very similar patients may present with the same medical profile and social circumstances; however, one is turned down,” she said. “Often the patient turned down is the non-Hispanic Black patient while the non-Hispanic White patient is given a pass.”

Dr. Conteh suggested that the first step in fixing this bias is recognizing that it is a problem and calling it by its proper name.

“As transplant centers, in order to address and change these significant disparities, we must first be willing to acknowledge that they do exist,” she said. “Only then can we move to the next step of developing awareness and methods to actively combat what we should label as systemic discrimination in medicine. Transplantation is a lifesaving treatment for many patients with decompensated liver disease or liver cancer. Ensuring equitable access for all patients and populations is of paramount importance.”

The study was supported by a Health Resources and Services Administration contract, as well as grants from the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases. The investigators and interviewees reported no conflicts of interest.

Non-Hispanic Black and Hispanic patients are underrepresented on many liver transplant waiting lists, whereas non-Hispanic White patients are often overrepresented, according to data from 109 centers.

pixelheadphoto/Thinkstock

While racial disparities “greatly diminished” after placement on a waiting list, which suggests recent progress in the field, pre–wait-listing disparities may be more challenging to overcome, reported lead author Curtis Warren, MPH, CPH, of the University of Florida, Gainesville, and colleagues.

“In 2020, the Organ Procurement and Transplantation Network implemented a new allocation system for liver transplantation based on concentric circles of geographic proximity rather than somewhat arbitrarily delineated Donor Service Areas (DSAs),” the investigators wrote in Journal of the American College of Surgeons. “Although this was a step toward improving and equalizing access to lifesaving organs for those on the liver transplant wait list, the listing process determining which patients will be considered for transplantation has continued to be a significant hurdle.”

The process is “rife with impediments to equal access to listing,” according to Dr. Warren and colleagues; getting on a waiting list can be affected by factors such as inequitable access to primary care, lack of private health insurance, and subjective selection by transplant centers.

To better characterize these impediments, the investigators gathered center-specific data from the Scientific Registry of Transplant Recipients and the U.S. Census Bureau. The final dataset included 30,353 patients from treated at 109 transplant centers, each of which performed more than 250 transplants between January 2013 and December 2018. The investigators compared waiting list data for each center with demographics from its DSA. Primary variables included race/ethnicity, education level, poverty, and insurance coverage.

Multiple logistic regression analysis was used to compare expected waiting list demographics with observed waiting list demographics with the aid of observed/expected ratios for each race/ethnicity. Univariate and multivariate analyses were used to identify significant predictors, including covariates such as age at listing, distance traveled to transplant center, and center type.

On an adjusted basis, the observed/expected ratios showed that non-Hispanic Black patients were underrepresented on waiting lists at 88 out of 109 centers (81%) and Hispanic patients were underrepresented at 68 centers (62%). In contrast, non-Hispanic White patients were overrepresented on waiting lists at 65 centers (58%). Non-Hispanic White patients were underrepresented on waiting lists at 49 centers, or 45%. Minority underrepresentation was further supported by mean MELD (Model for End-Stage Liver Disease) scores, which were significantly higher among non-Hispanic Black patients (20.2) and Hispanic patients (19.4), compared with non-Hispanic White patients (18.7) (P < .0001 for all) at the time of wait-listing.

Based on the multivariate model, underrepresentation among Black patients was most common in areas with a higher proportion of Black individuals in the population, longer travel distances to transplant centers, and a higher rate of private insurance among transplant recipients. For Hispanic patients, rates of private insurance alone predicted underrepresentation.

Once patients were listed, however, these disparities faded. Non-Hispanic Black patients accounted for 9.8% of all transplants across all hospitals, compared with 7.9% of wait-listed individuals (P < .0001). At approximately two out of three hospitals (65%), the transplanted percentage of Black patients exceeded the wait-listed percentage (P = .002).

“Data from this study show that the wait lists at many transplant centers in the United States underrepresent minority populations, compared with what would be expected based on their service areas,” the investigators concluded. “Future work will need to be devoted to increasing awareness of these trends to promote equitable access to listing for liver transplantation.”

Looking at social determinants of health

According to Lauren D. Nephew, MD, MSc, MAE, of Indiana University, Indianapolis, “The question of access to care is particularly important at this juncture as we examine the inequities that COVID-19 exposed in access to care for racial minorities, and as we prepare for potential changes to health insurance coverage with the new administration.”

Dr. Nephew noted that the reported racial disparities stem from social determinants of health, such as proximity to transplant centers and type of insurance coverage.

“Another striking finding was that the disparity in wait-listing non-Hispanic Black patients increased with the percentage of non-Hispanic Black patients living in the area, further highlighting barriers in access to care in majority Black neighborhoods,” she said. “Inequities such as these are unacceptable, given our mandate to distribute organs in a fair and equitable fashion, and they require prospective studies for further examination.”
 

Identifying discrimination

Lanla Conteh, MD, MPH, of the Ohio State University Wexner Medical Center, Columbus, described how these inequities are magnified through bias in patient selection.

“Often times two very similar patients may present with the same medical profile and social circumstances; however, one is turned down,” she said. “Often the patient turned down is the non-Hispanic Black patient while the non-Hispanic White patient is given a pass.”

Dr. Conteh suggested that the first step in fixing this bias is recognizing that it is a problem and calling it by its proper name.

“As transplant centers, in order to address and change these significant disparities, we must first be willing to acknowledge that they do exist,” she said. “Only then can we move to the next step of developing awareness and methods to actively combat what we should label as systemic discrimination in medicine. Transplantation is a lifesaving treatment for many patients with decompensated liver disease or liver cancer. Ensuring equitable access for all patients and populations is of paramount importance.”

The study was supported by a Health Resources and Services Administration contract, as well as grants from the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases. The investigators and interviewees reported no conflicts of interest.

For patients with triple-negative breast cancer (TNBC), neoadjuvant carboplatin plus docetaxel yields the same pathologic complete response and survival rates as a standard anthracycline-based neoadjuvant regimen – carboplatin and paclitaxel followed by doxorubicin/cyclophosphamide – but with less toxicity, higher completion rates, and at lower cost.

The results come from a phase 2 trial that involved 100 women. The study was published online in February in Clinical Cancer Research.

The doublet provides a safe, effective alternative for patients who are not candidates for treatment with anthracyclines and should be explored further for neoadjuvant deescalation, according to investigators led by Priyanka Sharma, MD, TNBC specialist and professor at the University of Kansas Medical Center, Westwood.

The trial wasn’t powered to demonstrate noninferiority, so it “probably does not provide enough evidence to state that [taxane/platinum] should replace other regimens,” Dr. Sharma said in an interview.

A proper noninferiority trial would require more than 2,500 participants, she said, adding that such a trial is unlikely, because companies are focused on immunotherapies for neoadjuvant TNBC.

“Our study does, however, provide a very effective alternative for patients and providers who want to use or prefer an anthracycline-sparing neoadjuvant chemotherapy regimen. We are very encouraged” by the findings, Dr. Sharma said.

This is “a provocative study that should make us pause and reevaluate our current approach. Further study of this approach in early-stage TNBC is warranted,” Melinda L. Telli, MD, associate professor of medicine and director of the breast cancer program at Stanford (Calif.) University, said when asked for comment.

Avoiding the risks associated with anthracycline “is great. I would be particularly enthusiastic using this regimen in patients with known increased risk of cardiac toxicity,” said Amy Tiersten, MD, a breast cancer specialist and professor at Mount Sinai Hospital, New York.

Anthracycline-based regimens are the standard of care for neoadjuvant TNBC. They typically include a taxane with or without carboplatin plus an anthracycline/cyclophosphamide combination. The regimen is highly active, but there is a small but serious risk for cardiomyopathy and leukemia with anthracycline/cyclophosphamide. In the current trial, one woman in the anthracycline arm died of secondary acute myeloid leukemia.

Given its tolerability and effectiveness, a taxane/carboplatin doublet might serve as a good backbone for the addition of novel immunotherapies in trials. Dr. Sharma is the principal investigator in one such trial, a phase 2 trial of carboplatin/docetaxel plus pembrolizumab for stage I–III TNBC.
 

Study details

The Neoadjuvant Study of Two Platinum Regimens in Stage I–III Triple Negative Breast Cancer (NeoSTOP) involved 100 women with stage I–III TNBC.

In the experimental arm, 52 women received carboplatin AUC 6 plus docetaxel 75 mg/m² every 21 days for six cycles.

In the standard-of-care anthracycline arm, 48 women received carboplatin AUC 6 every 21 days for four cycles plus paclitaxel 80 mg/m² weekly for 12 weeks, followed by doxorubicin 60 mg/m² plus cyclophosphamide 600 mg/m² every 2 weeks for four cycles.

Docetaxel and paclitaxel in the two regimens are interchangeable because they have shown equal efficacy in adjuvant trials, Dr. Sharma said.

At surgery, 54% of women in both arms had a breast/axilla pathologic complete response – the primary endpoint – and 67% in both arms had a residual cancer burden of 0-1. Event-free and overall survival (about 55% at 3 years for both) were similar with the two regimens.

Grade 3/4 adverse events were more common in the anthracycline arm. They included neutropenia, which occurred in 60% of women in the anthracycline arm, vs. 8% with the doublet; and febrile neutropenia, which occurred in 19% with anthracycline, vs. none with the doublet.

The toxicity profile of the anthracycline regimen was comparable to those in previous reports.

Ninety-two percent of the docetaxel/carboplatin group completed all six cycles; 72% of women in the anthracycline arm completed 10 or more doses of paclitaxel, and 85% completed all 4 carboplatin doses.

Mean costs of treatment, patient transportation, and lost productivity were $36,720 in the anthracycline arm, vs. $33,148 with the doublet.

The two arms were well balanced with respect to patient characteristics. The median age was 51 years, 30% of patients had axillary lymph node–positive disease, and 16% had ER/PgR expression of 1% to 10%. Of the study population, 17% carried deleterious BRCA1/2 mutations. Women were enrolled from July 2015 to May 2018. Median follow-up was 38 months.

Of the study population, 17% had stage I disease, so NeoSTOP included a lower-risk population than some neoadjuvant trials. However, there was no significant change in pathologic complete response rates in the two arms after exclusion of women with stage I disease (doublet, 50%; anthracycline, 54%).

The study was funded by the University of Kansas Cancer Center, the Breast Cancer Research Foundation, and the National Institute of General Medical Sciences. The investigators disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

For patients with triple-negative breast cancer (TNBC), neoadjuvant carboplatin plus docetaxel yields the same pathologic complete response and survival rates as a standard anthracycline-based neoadjuvant regimen – carboplatin and paclitaxel followed by doxorubicin/cyclophosphamide – but with less toxicity, higher completion rates, and at lower cost.

The results come from a phase 2 trial that involved 100 women. The study was published online in February in Clinical Cancer Research.

The doublet provides a safe, effective alternative for patients who are not candidates for treatment with anthracyclines and should be explored further for neoadjuvant deescalation, according to investigators led by Priyanka Sharma, MD, TNBC specialist and professor at the University of Kansas Medical Center, Westwood.

The trial wasn’t powered to demonstrate noninferiority, so it “probably does not provide enough evidence to state that [taxane/platinum] should replace other regimens,” Dr. Sharma said in an interview.

A proper noninferiority trial would require more than 2,500 participants, she said, adding that such a trial is unlikely, because companies are focused on immunotherapies for neoadjuvant TNBC.

“Our study does, however, provide a very effective alternative for patients and providers who want to use or prefer an anthracycline-sparing neoadjuvant chemotherapy regimen. We are very encouraged” by the findings, Dr. Sharma said.

This is “a provocative study that should make us pause and reevaluate our current approach. Further study of this approach in early-stage TNBC is warranted,” Melinda L. Telli, MD, associate professor of medicine and director of the breast cancer program at Stanford (Calif.) University, said when asked for comment.

Avoiding the risks associated with anthracycline “is great. I would be particularly enthusiastic using this regimen in patients with known increased risk of cardiac toxicity,” said Amy Tiersten, MD, a breast cancer specialist and professor at Mount Sinai Hospital, New York.

Anthracycline-based regimens are the standard of care for neoadjuvant TNBC. They typically include a taxane with or without carboplatin plus an anthracycline/cyclophosphamide combination. The regimen is highly active, but there is a small but serious risk for cardiomyopathy and leukemia with anthracycline/cyclophosphamide. In the current trial, one woman in the anthracycline arm died of secondary acute myeloid leukemia.

Given its tolerability and effectiveness, a taxane/carboplatin doublet might serve as a good backbone for the addition of novel immunotherapies in trials. Dr. Sharma is the principal investigator in one such trial, a phase 2 trial of carboplatin/docetaxel plus pembrolizumab for stage I–III TNBC.
 

Study details

The Neoadjuvant Study of Two Platinum Regimens in Stage I–III Triple Negative Breast Cancer (NeoSTOP) involved 100 women with stage I–III TNBC.

In the experimental arm, 52 women received carboplatin AUC 6 plus docetaxel 75 mg/m² every 21 days for six cycles.

In the standard-of-care anthracycline arm, 48 women received carboplatin AUC 6 every 21 days for four cycles plus paclitaxel 80 mg/m² weekly for 12 weeks, followed by doxorubicin 60 mg/m² plus cyclophosphamide 600 mg/m² every 2 weeks for four cycles.

Docetaxel and paclitaxel in the two regimens are interchangeable because they have shown equal efficacy in adjuvant trials, Dr. Sharma said.

At surgery, 54% of women in both arms had a breast/axilla pathologic complete response – the primary endpoint – and 67% in both arms had a residual cancer burden of 0-1. Event-free and overall survival (about 55% at 3 years for both) were similar with the two regimens.

Grade 3/4 adverse events were more common in the anthracycline arm. They included neutropenia, which occurred in 60% of women in the anthracycline arm, vs. 8% with the doublet; and febrile neutropenia, which occurred in 19% with anthracycline, vs. none with the doublet.

The toxicity profile of the anthracycline regimen was comparable to those in previous reports.

Ninety-two percent of the docetaxel/carboplatin group completed all six cycles; 72% of women in the anthracycline arm completed 10 or more doses of paclitaxel, and 85% completed all 4 carboplatin doses.

Mean costs of treatment, patient transportation, and lost productivity were $36,720 in the anthracycline arm, vs. $33,148 with the doublet.

The two arms were well balanced with respect to patient characteristics. The median age was 51 years, 30% of patients had axillary lymph node–positive disease, and 16% had ER/PgR expression of 1% to 10%. Of the study population, 17% carried deleterious BRCA1/2 mutations. Women were enrolled from July 2015 to May 2018. Median follow-up was 38 months.

Of the study population, 17% had stage I disease, so NeoSTOP included a lower-risk population than some neoadjuvant trials. However, there was no significant change in pathologic complete response rates in the two arms after exclusion of women with stage I disease (doublet, 50%; anthracycline, 54%).

The study was funded by the University of Kansas Cancer Center, the Breast Cancer Research Foundation, and the National Institute of General Medical Sciences. The investigators disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

For patients with triple-negative breast cancer (TNBC), neoadjuvant carboplatin plus docetaxel yields the same pathologic complete response and survival rates as a standard anthracycline-based neoadjuvant regimen – carboplatin and paclitaxel followed by doxorubicin/cyclophosphamide – but with less toxicity, higher completion rates, and at lower cost.

The results come from a phase 2 trial that involved 100 women. The study was published online in February in Clinical Cancer Research.

The doublet provides a safe, effective alternative for patients who are not candidates for treatment with anthracyclines and should be explored further for neoadjuvant deescalation, according to investigators led by Priyanka Sharma, MD, TNBC specialist and professor at the University of Kansas Medical Center, Westwood.

The trial wasn’t powered to demonstrate noninferiority, so it “probably does not provide enough evidence to state that [taxane/platinum] should replace other regimens,” Dr. Sharma said in an interview.

A proper noninferiority trial would require more than 2,500 participants, she said, adding that such a trial is unlikely, because companies are focused on immunotherapies for neoadjuvant TNBC.

“Our study does, however, provide a very effective alternative for patients and providers who want to use or prefer an anthracycline-sparing neoadjuvant chemotherapy regimen. We are very encouraged” by the findings, Dr. Sharma said.

This is “a provocative study that should make us pause and reevaluate our current approach. Further study of this approach in early-stage TNBC is warranted,” Melinda L. Telli, MD, associate professor of medicine and director of the breast cancer program at Stanford (Calif.) University, said when asked for comment.

Avoiding the risks associated with anthracycline “is great. I would be particularly enthusiastic using this regimen in patients with known increased risk of cardiac toxicity,” said Amy Tiersten, MD, a breast cancer specialist and professor at Mount Sinai Hospital, New York.

Anthracycline-based regimens are the standard of care for neoadjuvant TNBC. They typically include a taxane with or without carboplatin plus an anthracycline/cyclophosphamide combination. The regimen is highly active, but there is a small but serious risk for cardiomyopathy and leukemia with anthracycline/cyclophosphamide. In the current trial, one woman in the anthracycline arm died of secondary acute myeloid leukemia.

Given its tolerability and effectiveness, a taxane/carboplatin doublet might serve as a good backbone for the addition of novel immunotherapies in trials. Dr. Sharma is the principal investigator in one such trial, a phase 2 trial of carboplatin/docetaxel plus pembrolizumab for stage I–III TNBC.
 

Study details

The Neoadjuvant Study of Two Platinum Regimens in Stage I–III Triple Negative Breast Cancer (NeoSTOP) involved 100 women with stage I–III TNBC.

In the experimental arm, 52 women received carboplatin AUC 6 plus docetaxel 75 mg/m² every 21 days for six cycles.

In the standard-of-care anthracycline arm, 48 women received carboplatin AUC 6 every 21 days for four cycles plus paclitaxel 80 mg/m² weekly for 12 weeks, followed by doxorubicin 60 mg/m² plus cyclophosphamide 600 mg/m² every 2 weeks for four cycles.

Docetaxel and paclitaxel in the two regimens are interchangeable because they have shown equal efficacy in adjuvant trials, Dr. Sharma said.

At surgery, 54% of women in both arms had a breast/axilla pathologic complete response – the primary endpoint – and 67% in both arms had a residual cancer burden of 0-1. Event-free and overall survival (about 55% at 3 years for both) were similar with the two regimens.

Grade 3/4 adverse events were more common in the anthracycline arm. They included neutropenia, which occurred in 60% of women in the anthracycline arm, vs. 8% with the doublet; and febrile neutropenia, which occurred in 19% with anthracycline, vs. none with the doublet.

The toxicity profile of the anthracycline regimen was comparable to those in previous reports.

Ninety-two percent of the docetaxel/carboplatin group completed all six cycles; 72% of women in the anthracycline arm completed 10 or more doses of paclitaxel, and 85% completed all 4 carboplatin doses.

Mean costs of treatment, patient transportation, and lost productivity were $36,720 in the anthracycline arm, vs. $33,148 with the doublet.

The two arms were well balanced with respect to patient characteristics. The median age was 51 years, 30% of patients had axillary lymph node–positive disease, and 16% had ER/PgR expression of 1% to 10%. Of the study population, 17% carried deleterious BRCA1/2 mutations. Women were enrolled from July 2015 to May 2018. Median follow-up was 38 months.

Of the study population, 17% had stage I disease, so NeoSTOP included a lower-risk population than some neoadjuvant trials. However, there was no significant change in pathologic complete response rates in the two arms after exclusion of women with stage I disease (doublet, 50%; anthracycline, 54%).

The study was funded by the University of Kansas Cancer Center, the Breast Cancer Research Foundation, and the National Institute of General Medical Sciences. The investigators disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Vaping cannabis significantly increased the risk of respiratory symptoms in adolescents, according to findings of a study based on a national sample of teens.

HAZEMMKAMAL/Getty Images

Most studies of electronic nicotine delivery systems (ENDS) use in teens have not addressed cannabis vaping, although e-cigarette– or vaping product use–associated lung injury (EVALI) has been predominately associated with cannabis products, wrote Carol J. Boyd, PhD, of the University of Michigan School of Nursing, Ann Arbor, and colleagues.

“At this time, relatively little is known about the population-level health consequences of adolescents’ use of ENDS, including use with cannabis and controlling for a history of asthma,” they said.

In a study published in the Journal of Adolescent Health, the researchers identified 14,798 adolescents aged 12-17 years using Wave 4 data from the Population Assessment of Tobacco and Health Study. Of these, 17.6% had a baseline asthma diagnosis, 8.9% reported ever using cannabis in ENDS, and 4.7% reported any cannabis use. In addition, 4.2% reported current e-cigarette use, 3.1% reported current cigarette use, 51% were male, and 69.2% were white.
 

Any cannabis vaping makes impact

In a fully-adjusted model, teens who had ever vaped cannabis had higher odds of five respiratory symptoms in the past year, compared with those with no history of cannabis vaping: wheezing or whistling in the chest (adjusted odds ratio, 1.81); sleep disturbed by wheezing or whistling (AOR, 1.71); speech limited because of wheezing (AOR, 1.96); wheezy during and after exercise (AOR, 1.33), and a dry cough at night independent of a cold or chest infection (AOR, 1.26).

Neither e-cigarettes nor cigarettes were significantly associated with any of these five respiratory symptoms in the fully adjusted models. In addition, “past 30-day use of cigarettes, e-cigarettes and cannabis use were associated with some respiratory symptoms in bivariate analyses but not in the adjusted models,” the researchers noted. In addition, the associations of an asthma diagnosis and respiratory symptoms had greater magnitudes than either cigarette, e-cigarette, and cannabis use or vaping cannabis with ENDS.

The study findings were limited by several factors including the inherent limitations of secondary database analysis, the researchers noted. “Another limitation is that co-use of cannabis and tobacco/nicotine was not assessed and, in the future, should be examined: Researchers have found that co-use is related to EVALI symptoms among young adults,” they said.

However, the study is the first known to include ENDS product use and respiratory symptoms while accounting for baseline asthma, and an asthma diagnosis was even more strongly associated with all five respiratory symptoms, the researchers said.

The results suggest that “the inhalation of cannabis via vaping is associated with some pulmonary irritation and symptoms of lung diseases (both known and unknown),” that may be predictive of later EVALI, they concluded.
 

Product details aid in diagnosis

“As we continue to see patients presenting with EVALI in pediatric hospitals, it is important for us to identify if there are specific products (or categories) that are more likely to cause it,” said Brandon Seay, MD, FCCP, a pediatric pulmonologist and sleep specialist at Children’s Healthcare of Atlanta, in an interview. “When we are trying to diagnose EVALI, we should be asking appropriate questions about exposures to specific products to get the best answers. If we simply ask ‘Are you smoking e-cigarettes?’ the patient may not [equate] e-cigarette smoking to vaping cannabis products,” he said. 

Dr. Seay said he was not surprised by the study findings. “A lot of the patients I see with EVALI have reported vaping THC products, and most of them also report that the products were mixed by a friend or an individual instead of being a commercially produced product,” he noted. “This is not surprising, as THC is still illegal in most states and there would not be any commercially available products,” he said. “The mixing of these products by individuals increases the risk of ingredients being more toxic or irritating to the lungs,” Dr. Seay added. “This does highlight the need for more regulation of vaping products. As more states legalize marijuana, more of these products will become available, which will provide an opportunity for increased regulation, he said. 

The take-home message for clinicians is to seek specific details from their young patients, Dr. Seay emphasized. “When we are educating our patients on the dangers of vaping/e-cigarettes, we need to make sure we are asking specifically which products they are using and know the terminology,” he said. “The use of THC-containing products will be increasing across the country with more legalization, so we need to keep ourselves apprised of the different risks between THC- and nicotine-containing devices,” he added.  

As for additional research, it would be interesting to know whether patients were asked where they had gotten their products (commercially available products vs. those mixed by individuals) and explore any difference between the two, said Dr. Seay. “Also, as these products are relatively new to the market, compared to cigarettes, data on the longitudinal effects of vaping (nicotine and THC) over a long period of time, compared to traditional combustible cigarettes, will be needed,” he said.

The study was funded by grants from the National Institutes of Health, National Institute on Drug Abuse, and National Cancer Institute. The researchers had no financial conflicts to disclose.

Dr. Seay had no financial disclosures, but serves as a member of the CHEST Physician editorial board.

Vaping cannabis significantly increased the risk of respiratory symptoms in adolescents, according to findings of a study based on a national sample of teens.

HAZEMMKAMAL/Getty Images

Most studies of electronic nicotine delivery systems (ENDS) use in teens have not addressed cannabis vaping, although e-cigarette– or vaping product use–associated lung injury (EVALI) has been predominately associated with cannabis products, wrote Carol J. Boyd, PhD, of the University of Michigan School of Nursing, Ann Arbor, and colleagues.

“At this time, relatively little is known about the population-level health consequences of adolescents’ use of ENDS, including use with cannabis and controlling for a history of asthma,” they said.

In a study published in the Journal of Adolescent Health, the researchers identified 14,798 adolescents aged 12-17 years using Wave 4 data from the Population Assessment of Tobacco and Health Study. Of these, 17.6% had a baseline asthma diagnosis, 8.9% reported ever using cannabis in ENDS, and 4.7% reported any cannabis use. In addition, 4.2% reported current e-cigarette use, 3.1% reported current cigarette use, 51% were male, and 69.2% were white.
 

Any cannabis vaping makes impact

In a fully-adjusted model, teens who had ever vaped cannabis had higher odds of five respiratory symptoms in the past year, compared with those with no history of cannabis vaping: wheezing or whistling in the chest (adjusted odds ratio, 1.81); sleep disturbed by wheezing or whistling (AOR, 1.71); speech limited because of wheezing (AOR, 1.96); wheezy during and after exercise (AOR, 1.33), and a dry cough at night independent of a cold or chest infection (AOR, 1.26).

Neither e-cigarettes nor cigarettes were significantly associated with any of these five respiratory symptoms in the fully adjusted models. In addition, “past 30-day use of cigarettes, e-cigarettes and cannabis use were associated with some respiratory symptoms in bivariate analyses but not in the adjusted models,” the researchers noted. In addition, the associations of an asthma diagnosis and respiratory symptoms had greater magnitudes than either cigarette, e-cigarette, and cannabis use or vaping cannabis with ENDS.

The study findings were limited by several factors including the inherent limitations of secondary database analysis, the researchers noted. “Another limitation is that co-use of cannabis and tobacco/nicotine was not assessed and, in the future, should be examined: Researchers have found that co-use is related to EVALI symptoms among young adults,” they said.

However, the study is the first known to include ENDS product use and respiratory symptoms while accounting for baseline asthma, and an asthma diagnosis was even more strongly associated with all five respiratory symptoms, the researchers said.

The results suggest that “the inhalation of cannabis via vaping is associated with some pulmonary irritation and symptoms of lung diseases (both known and unknown),” that may be predictive of later EVALI, they concluded.
 

Product details aid in diagnosis

“As we continue to see patients presenting with EVALI in pediatric hospitals, it is important for us to identify if there are specific products (or categories) that are more likely to cause it,” said Brandon Seay, MD, FCCP, a pediatric pulmonologist and sleep specialist at Children’s Healthcare of Atlanta, in an interview. “When we are trying to diagnose EVALI, we should be asking appropriate questions about exposures to specific products to get the best answers. If we simply ask ‘Are you smoking e-cigarettes?’ the patient may not [equate] e-cigarette smoking to vaping cannabis products,” he said. 

Dr. Seay said he was not surprised by the study findings. “A lot of the patients I see with EVALI have reported vaping THC products, and most of them also report that the products were mixed by a friend or an individual instead of being a commercially produced product,” he noted. “This is not surprising, as THC is still illegal in most states and there would not be any commercially available products,” he said. “The mixing of these products by individuals increases the risk of ingredients being more toxic or irritating to the lungs,” Dr. Seay added. “This does highlight the need for more regulation of vaping products. As more states legalize marijuana, more of these products will become available, which will provide an opportunity for increased regulation, he said. 

The take-home message for clinicians is to seek specific details from their young patients, Dr. Seay emphasized. “When we are educating our patients on the dangers of vaping/e-cigarettes, we need to make sure we are asking specifically which products they are using and know the terminology,” he said. “The use of THC-containing products will be increasing across the country with more legalization, so we need to keep ourselves apprised of the different risks between THC- and nicotine-containing devices,” he added.  

As for additional research, it would be interesting to know whether patients were asked where they had gotten their products (commercially available products vs. those mixed by individuals) and explore any difference between the two, said Dr. Seay. “Also, as these products are relatively new to the market, compared to cigarettes, data on the longitudinal effects of vaping (nicotine and THC) over a long period of time, compared to traditional combustible cigarettes, will be needed,” he said.

The study was funded by grants from the National Institutes of Health, National Institute on Drug Abuse, and National Cancer Institute. The researchers had no financial conflicts to disclose.

Dr. Seay had no financial disclosures, but serves as a member of the CHEST Physician editorial board.

Vaping cannabis significantly increased the risk of respiratory symptoms in adolescents, according to findings of a study based on a national sample of teens.

HAZEMMKAMAL/Getty Images

Most studies of electronic nicotine delivery systems (ENDS) use in teens have not addressed cannabis vaping, although e-cigarette– or vaping product use–associated lung injury (EVALI) has been predominately associated with cannabis products, wrote Carol J. Boyd, PhD, of the University of Michigan School of Nursing, Ann Arbor, and colleagues.

“At this time, relatively little is known about the population-level health consequences of adolescents’ use of ENDS, including use with cannabis and controlling for a history of asthma,” they said.

In a study published in the Journal of Adolescent Health, the researchers identified 14,798 adolescents aged 12-17 years using Wave 4 data from the Population Assessment of Tobacco and Health Study. Of these, 17.6% had a baseline asthma diagnosis, 8.9% reported ever using cannabis in ENDS, and 4.7% reported any cannabis use. In addition, 4.2% reported current e-cigarette use, 3.1% reported current cigarette use, 51% were male, and 69.2% were white.
 

Any cannabis vaping makes impact

In a fully-adjusted model, teens who had ever vaped cannabis had higher odds of five respiratory symptoms in the past year, compared with those with no history of cannabis vaping: wheezing or whistling in the chest (adjusted odds ratio, 1.81); sleep disturbed by wheezing or whistling (AOR, 1.71); speech limited because of wheezing (AOR, 1.96); wheezy during and after exercise (AOR, 1.33), and a dry cough at night independent of a cold or chest infection (AOR, 1.26).

Neither e-cigarettes nor cigarettes were significantly associated with any of these five respiratory symptoms in the fully adjusted models. In addition, “past 30-day use of cigarettes, e-cigarettes and cannabis use were associated with some respiratory symptoms in bivariate analyses but not in the adjusted models,” the researchers noted. In addition, the associations of an asthma diagnosis and respiratory symptoms had greater magnitudes than either cigarette, e-cigarette, and cannabis use or vaping cannabis with ENDS.

The study findings were limited by several factors including the inherent limitations of secondary database analysis, the researchers noted. “Another limitation is that co-use of cannabis and tobacco/nicotine was not assessed and, in the future, should be examined: Researchers have found that co-use is related to EVALI symptoms among young adults,” they said.

However, the study is the first known to include ENDS product use and respiratory symptoms while accounting for baseline asthma, and an asthma diagnosis was even more strongly associated with all five respiratory symptoms, the researchers said.

The results suggest that “the inhalation of cannabis via vaping is associated with some pulmonary irritation and symptoms of lung diseases (both known and unknown),” that may be predictive of later EVALI, they concluded.
 

Product details aid in diagnosis

“As we continue to see patients presenting with EVALI in pediatric hospitals, it is important for us to identify if there are specific products (or categories) that are more likely to cause it,” said Brandon Seay, MD, FCCP, a pediatric pulmonologist and sleep specialist at Children’s Healthcare of Atlanta, in an interview. “When we are trying to diagnose EVALI, we should be asking appropriate questions about exposures to specific products to get the best answers. If we simply ask ‘Are you smoking e-cigarettes?’ the patient may not [equate] e-cigarette smoking to vaping cannabis products,” he said. 

Dr. Seay said he was not surprised by the study findings. “A lot of the patients I see with EVALI have reported vaping THC products, and most of them also report that the products were mixed by a friend or an individual instead of being a commercially produced product,” he noted. “This is not surprising, as THC is still illegal in most states and there would not be any commercially available products,” he said. “The mixing of these products by individuals increases the risk of ingredients being more toxic or irritating to the lungs,” Dr. Seay added. “This does highlight the need for more regulation of vaping products. As more states legalize marijuana, more of these products will become available, which will provide an opportunity for increased regulation, he said. 

The take-home message for clinicians is to seek specific details from their young patients, Dr. Seay emphasized. “When we are educating our patients on the dangers of vaping/e-cigarettes, we need to make sure we are asking specifically which products they are using and know the terminology,” he said. “The use of THC-containing products will be increasing across the country with more legalization, so we need to keep ourselves apprised of the different risks between THC- and nicotine-containing devices,” he added.  

As for additional research, it would be interesting to know whether patients were asked where they had gotten their products (commercially available products vs. those mixed by individuals) and explore any difference between the two, said Dr. Seay. “Also, as these products are relatively new to the market, compared to cigarettes, data on the longitudinal effects of vaping (nicotine and THC) over a long period of time, compared to traditional combustible cigarettes, will be needed,” he said.

The study was funded by grants from the National Institutes of Health, National Institute on Drug Abuse, and National Cancer Institute. The researchers had no financial conflicts to disclose.

Dr. Seay had no financial disclosures, but serves as a member of the CHEST Physician editorial board.

The terminology and classification scheme for heart failure (HF) is changing in ways that experts hope will directly impact patient outcomes.

In a new consensus statement, a multisociety group of experts proposed a new universal definition of heart failure and made substantial revisions to the way in which the disease is staged and classified.

The authors of the statement, led by writing committee chair and immediate past president of the Heart Failure Society of America Biykem Bozkurt, MD, PhD, hope their efforts will go far to improve standardization of terminology, but more importantly will facilitate better management of the disease in ways that keep pace with current knowledge and advances in the field.

“There is a great need for reframing and standardizing the terminology across societies and different stakeholders, and importantly for patients because a lot of the terminology we were using was understood by academicians, but were not being translated in important ways to ensure patients are being appropriately treated,” said Dr. Bozkurt, of Baylor College of Medicine, Houston.

The consensus statement was a group effort led by the HFSA, the Heart Failure Association of the European Society of Cardiology, and the Japanese Heart Failure Society, with endorsements from the Canadian Heart Failure Society, the Heart Failure Association of India, the Cardiac Society of Australia and New Zealand, and the Chinese Heart Failure Association.

The article was published March 1 in the Journal of Cardiac Failure and the European Journal of Heart Failure, authored by a writing committee of 38 individuals with domain expertise in HF, cardiomyopathy, and cardiovascular disease.

“This is a very thorough and very carefully written document that I think will be helpful for clinicians because they’ve tapped into important changes in the field that have occurred over the past 10 years and that now allow us to do more for patients than we could before,” Eugene Braunwald, MD, said in an interview.

A new universal definition

“[Heart failure] is a clinical syndrome with symptoms and or signs caused by a structural and/or functional cardiac abnormality and corroborated by elevated natriuretic peptide levels and/or objective evidence of pulmonary or systemic congestion.”

This proposed definition, said the authors, is designed to be contemporary and simple “but conceptually comprehensive, with near universal applicability, prognostic and therapeutic viability, and acceptable sensitivity and specificity.”

Both left and right HF qualifies under this definition, said the authors, but conditions that result in marked volume overload, such as chronic kidney disease, which may present with signs and symptoms of HF, do not.

“Although some of these patients may have concomitant HF, these patients have a primary abnormality that may require a specific treatment beyond that for HF,” said the consensus statement authors.

For his part, Douglas L. Mann, MD, is happy to see what he considers a more accurate and practical definition for heart failure.

Proposed revised stages of the HF continuum

Overall, minimal changes have been made to the HF stages, with tweaks intended to enhance understanding and address the evolving role of biomarkers.

The authors proposed an approach to staging of HF:

• At-risk for HF (stage A), for patients at risk for HF but without current or prior symptoms or signs of HF and without structural or biomarkers evidence of heart disease.
• Pre-HF (stage B), for patients without current or prior symptoms or signs of HF, but evidence of structural heart disease or abnormal cardiac function, or elevated natriuretic peptide levels.
• HF (stage C), for patients with current or prior symptoms and/or signs of HF caused by a structural and/or functional cardiac abnormality.
• Advanced HF (stage D), for patients with severe symptoms and/or signs of HF at rest, recurrent hospitalizations despite guideline-directed management and therapy (GDMT), refractory or intolerant to GDMT, requiring advanced therapies such as consideration for transplant, mechanical circulatory support, or palliative care.

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One notable change to the staging scheme is stage B, which the authors have reframed as “pre–heart failure.”

“Pre-cancer is a term widely understood and considered actionable and we wanted to tap into this successful messaging and embrace the pre–heart failure concept as something that is treatable and preventable,” said Dr. Bozkurt.

“We want patients and clinicians to understand that there are things we can do to prevent heart failure, strategies we didn’t have before, like SGLT2 inhibitors in patients with diabetes at risk for HF,” she added.

The revision also avoids the stigma of HF before the symptoms are manifest.

“Not calling it stage A and stage B heart failure you might say is semantics, but it’s important semantics,” said Dr. Braunwald. “When you’re talking to a patient or a relative and tell them they have stage A heart failure, it’s scares them unnecessarily. They don’t hear the stage A or B part, just the heart failure part.”
 

New classifications according to LVEF

And finally, in what some might consider the most obviously needed modification, the document proposes a new and revised classification of HF according to left ventricular ejection fraction (LVEF). Most agree on how to classify heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), but although the middle range has long been understood to be a clinically relevant, it has no proper name or clear delineation.

“For standardization across practice guidelines, to recognize clinical trajectories in HF, and to facilitate the recognition of different heart failure entities in a sensitive and specific manner that can guide therapy, we want to formalize the heart failure categories according to ejection fraction,” said Dr. Bozkurt.

To this end, the authors propose the following four classifications of EF:

• HF with reduced EF (HFrEF): LVEF of up to 40%.
• HF with mildly reduced EF (HFmrEF): LVEF of 41-49%.
• HF with preserved EF (HFpEF)HF with an LVEF of at least 50%.
• HF with improved EF (HFimpEF): HF with a baseline LVEF of 40% or less, an increase of at least 10 points from baseline LVEF, and a second measurement of LVEF of greater than 40%.

HFmrEF is usually a transition period, noted Dr. Bozkurt. “Patients with HF in this range may represent a population whose EF is likely to change, either increase or decrease over time and it’s important to be cognizant of that trajectory. Understanding where your patient is headed is crucial for prognosis and optimization of guideline-directed treatment,” she said.
 

Improved, not recovered, HF

The last classification of heart failure with improved ejection fraction (HFimpEF) represents an important change to the current classification scheme.

“We want to clarify what terms to use but also which not to use. For example, we don’t want people to use recovered heart failure or heart failure in remission, partly because we don’t want the medication to be stopped. We don’t want to give the false message that there has been full recovery,” said Dr. Bozkurt.

As seen in the TRED-HF trial, guideline-directed medical therapy should be continued in patients with HF with improved EF regardless of whether it has improved to a normal range of above 50% in subsequent measurements.

“This is a distinct group of people, and for a while the guidelines were lumping them in with HFpEF, which I think is totally wrong,” said Dr. Mann.

“I think it’s very important that we emphasize heart failure as a continuum, rather than a one-way street of [inevitable] progression. Because we do see improvements in ejection fraction and we do see that we can prevent heart failure if we do the right things, and this should be reflected in the terminology we use,” he added.

Dr. Bozkurt stressed that HFimpEF only applies if the EF improves to above 40%. A move from an EF of 10%-20% would still see the patient classified as having HFrEF, but a patient whose EF improved from, say, 30% to 45% would be classified as HFimpEF.

“The reason for this, again, is because a transition from, say an EF of 10%-20% does not change therapy, but a move upward over 40% might, especially regarding decisions for device therapies, so the trajectory as well as the absolute EF is important,” she added.

“Particularly in the early stages, people are responsive to therapy and it’s possible in some cases to reverse heart failure, so I think this change helps us understand when that’s happened,” said Dr. Braunwald.
 

One step toward universality

“The implementation of this terminology and nomenclature into practice will require a variety of tactics,” said Dr. Bozkurt. “For example, the current ICD 10 codes need to incorporate the at-risk and pre–heart failure categories, as well as the mid-range EF, preserved, and improved EF classifications, because the treatment differs between those three domains.”

In terms of how these proposed changes will be worked into practice guidelines, Dr. Bozkurt declined to comment on this to avoid any perception of conflict of interest as she is the cochair of the American College of Cardiology/American Heart Association HF guideline writing committee.

Dr. Braunwald and Dr. Antman suggest it may be premature to call the new terminology and classifications “universal.” In an interview, Dr. Braunwald lamented the absence of the World Heart Federation, the ACC, and the AHA as active participants in this effort and suggested this paper is only the first step of a multistep process that requires input from many stakeholders.

“It’s important that these organizations be involved, not just to bless it, but to contribute their expertise to the process,” he said.

For his part, Dr. Mann hopes these changes will gain widespread acceptance and clinical traction. “The problem sometimes with guidelines is that they’re so data driven that you just can’t come out and say the obvious, so making a position statement is a good first step. And they got good international representation on this, so I think these changes will be accepted in the next heart failure guidelines.”

To encourage further discussion and acceptance, Robert J. Mentz, MD, and Anuradha Lala, MD, editor-in-chief and deputy editor of the Journal of Cardiac Failure, respectively, announced a series of multidisciplinary perspective pieces to be published in the journal monthly, starting in May with editorials from Dr. Clyde W Yancy, MD, MSc, and Carolyn S.P. Lam, MBBS, PhD, both of whom were authors of the consensus statement.

Dr. Bozkurt reports being a consultant for Abbott, Amgen, Baxter, Bristol Myers Squibb, Liva Nova Relypsa/Vifor Pharma, Respicardia, and being on the registry steering committee for Sanofi-Aventis. Dr. Braunwald reports research grant support through Brigham and Women’s Hospital from AstraZeneca, Daiichi Sankyo, Merck, and Novartis; and consulting for Amgen, Boehringer-Ingelheim/Lilly, Cardurion, MyoKardia, Novo Nordisk, and Verve. Dr. Mann has been a consultant to Novartis, is on the steering committee for the PARADISE trial, and is on the scientific advisory board for MyoKardia/Bristol Myers Squibb.

The terminology and classification scheme for heart failure (HF) is changing in ways that experts hope will directly impact patient outcomes.

In a new consensus statement, a multisociety group of experts proposed a new universal definition of heart failure and made substantial revisions to the way in which the disease is staged and classified.

The authors of the statement, led by writing committee chair and immediate past president of the Heart Failure Society of America Biykem Bozkurt, MD, PhD, hope their efforts will go far to improve standardization of terminology, but more importantly will facilitate better management of the disease in ways that keep pace with current knowledge and advances in the field.

“There is a great need for reframing and standardizing the terminology across societies and different stakeholders, and importantly for patients because a lot of the terminology we were using was understood by academicians, but were not being translated in important ways to ensure patients are being appropriately treated,” said Dr. Bozkurt, of Baylor College of Medicine, Houston.

The consensus statement was a group effort led by the HFSA, the Heart Failure Association of the European Society of Cardiology, and the Japanese Heart Failure Society, with endorsements from the Canadian Heart Failure Society, the Heart Failure Association of India, the Cardiac Society of Australia and New Zealand, and the Chinese Heart Failure Association.

The article was published March 1 in the Journal of Cardiac Failure and the European Journal of Heart Failure, authored by a writing committee of 38 individuals with domain expertise in HF, cardiomyopathy, and cardiovascular disease.

“This is a very thorough and very carefully written document that I think will be helpful for clinicians because they’ve tapped into important changes in the field that have occurred over the past 10 years and that now allow us to do more for patients than we could before,” Eugene Braunwald, MD, said in an interview.

A new universal definition

“[Heart failure] is a clinical syndrome with symptoms and or signs caused by a structural and/or functional cardiac abnormality and corroborated by elevated natriuretic peptide levels and/or objective evidence of pulmonary or systemic congestion.”

This proposed definition, said the authors, is designed to be contemporary and simple “but conceptually comprehensive, with near universal applicability, prognostic and therapeutic viability, and acceptable sensitivity and specificity.”

Both left and right HF qualifies under this definition, said the authors, but conditions that result in marked volume overload, such as chronic kidney disease, which may present with signs and symptoms of HF, do not.

“Although some of these patients may have concomitant HF, these patients have a primary abnormality that may require a specific treatment beyond that for HF,” said the consensus statement authors.

For his part, Douglas L. Mann, MD, is happy to see what he considers a more accurate and practical definition for heart failure.

Proposed revised stages of the HF continuum

Overall, minimal changes have been made to the HF stages, with tweaks intended to enhance understanding and address the evolving role of biomarkers.

The authors proposed an approach to staging of HF:

• At-risk for HF (stage A), for patients at risk for HF but without current or prior symptoms or signs of HF and without structural or biomarkers evidence of heart disease.
• Pre-HF (stage B), for patients without current or prior symptoms or signs of HF, but evidence of structural heart disease or abnormal cardiac function, or elevated natriuretic peptide levels.
• HF (stage C), for patients with current or prior symptoms and/or signs of HF caused by a structural and/or functional cardiac abnormality.
• Advanced HF (stage D), for patients with severe symptoms and/or signs of HF at rest, recurrent hospitalizations despite guideline-directed management and therapy (GDMT), refractory or intolerant to GDMT, requiring advanced therapies such as consideration for transplant, mechanical circulatory support, or palliative care.

MDedge News

One notable change to the staging scheme is stage B, which the authors have reframed as “pre–heart failure.”

“Pre-cancer is a term widely understood and considered actionable and we wanted to tap into this successful messaging and embrace the pre–heart failure concept as something that is treatable and preventable,” said Dr. Bozkurt.

“We want patients and clinicians to understand that there are things we can do to prevent heart failure, strategies we didn’t have before, like SGLT2 inhibitors in patients with diabetes at risk for HF,” she added.

The revision also avoids the stigma of HF before the symptoms are manifest.

“Not calling it stage A and stage B heart failure you might say is semantics, but it’s important semantics,” said Dr. Braunwald. “When you’re talking to a patient or a relative and tell them they have stage A heart failure, it’s scares them unnecessarily. They don’t hear the stage A or B part, just the heart failure part.”
 

New classifications according to LVEF

And finally, in what some might consider the most obviously needed modification, the document proposes a new and revised classification of HF according to left ventricular ejection fraction (LVEF). Most agree on how to classify heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), but although the middle range has long been understood to be a clinically relevant, it has no proper name or clear delineation.

“For standardization across practice guidelines, to recognize clinical trajectories in HF, and to facilitate the recognition of different heart failure entities in a sensitive and specific manner that can guide therapy, we want to formalize the heart failure categories according to ejection fraction,” said Dr. Bozkurt.

To this end, the authors propose the following four classifications of EF:

• HF with reduced EF (HFrEF): LVEF of up to 40%.
• HF with mildly reduced EF (HFmrEF): LVEF of 41-49%.
• HF with preserved EF (HFpEF)HF with an LVEF of at least 50%.
• HF with improved EF (HFimpEF): HF with a baseline LVEF of 40% or less, an increase of at least 10 points from baseline LVEF, and a second measurement of LVEF of greater than 40%.

HFmrEF is usually a transition period, noted Dr. Bozkurt. “Patients with HF in this range may represent a population whose EF is likely to change, either increase or decrease over time and it’s important to be cognizant of that trajectory. Understanding where your patient is headed is crucial for prognosis and optimization of guideline-directed treatment,” she said.
 

Improved, not recovered, HF

The last classification of heart failure with improved ejection fraction (HFimpEF) represents an important change to the current classification scheme.

“We want to clarify what terms to use but also which not to use. For example, we don’t want people to use recovered heart failure or heart failure in remission, partly because we don’t want the medication to be stopped. We don’t want to give the false message that there has been full recovery,” said Dr. Bozkurt.

As seen in the TRED-HF trial, guideline-directed medical therapy should be continued in patients with HF with improved EF regardless of whether it has improved to a normal range of above 50% in subsequent measurements.

“This is a distinct group of people, and for a while the guidelines were lumping them in with HFpEF, which I think is totally wrong,” said Dr. Mann.

“I think it’s very important that we emphasize heart failure as a continuum, rather than a one-way street of [inevitable] progression. Because we do see improvements in ejection fraction and we do see that we can prevent heart failure if we do the right things, and this should be reflected in the terminology we use,” he added.

Dr. Bozkurt stressed that HFimpEF only applies if the EF improves to above 40%. A move from an EF of 10%-20% would still see the patient classified as having HFrEF, but a patient whose EF improved from, say, 30% to 45% would be classified as HFimpEF.

“The reason for this, again, is because a transition from, say an EF of 10%-20% does not change therapy, but a move upward over 40% might, especially regarding decisions for device therapies, so the trajectory as well as the absolute EF is important,” she added.

“Particularly in the early stages, people are responsive to therapy and it’s possible in some cases to reverse heart failure, so I think this change helps us understand when that’s happened,” said Dr. Braunwald.
 

One step toward universality

“The implementation of this terminology and nomenclature into practice will require a variety of tactics,” said Dr. Bozkurt. “For example, the current ICD 10 codes need to incorporate the at-risk and pre–heart failure categories, as well as the mid-range EF, preserved, and improved EF classifications, because the treatment differs between those three domains.”

In terms of how these proposed changes will be worked into practice guidelines, Dr. Bozkurt declined to comment on this to avoid any perception of conflict of interest as she is the cochair of the American College of Cardiology/American Heart Association HF guideline writing committee.

Dr. Braunwald and Dr. Antman suggest it may be premature to call the new terminology and classifications “universal.” In an interview, Dr. Braunwald lamented the absence of the World Heart Federation, the ACC, and the AHA as active participants in this effort and suggested this paper is only the first step of a multistep process that requires input from many stakeholders.

“It’s important that these organizations be involved, not just to bless it, but to contribute their expertise to the process,” he said.

For his part, Dr. Mann hopes these changes will gain widespread acceptance and clinical traction. “The problem sometimes with guidelines is that they’re so data driven that you just can’t come out and say the obvious, so making a position statement is a good first step. And they got good international representation on this, so I think these changes will be accepted in the next heart failure guidelines.”

To encourage further discussion and acceptance, Robert J. Mentz, MD, and Anuradha Lala, MD, editor-in-chief and deputy editor of the Journal of Cardiac Failure, respectively, announced a series of multidisciplinary perspective pieces to be published in the journal monthly, starting in May with editorials from Dr. Clyde W Yancy, MD, MSc, and Carolyn S.P. Lam, MBBS, PhD, both of whom were authors of the consensus statement.

Dr. Bozkurt reports being a consultant for Abbott, Amgen, Baxter, Bristol Myers Squibb, Liva Nova Relypsa/Vifor Pharma, Respicardia, and being on the registry steering committee for Sanofi-Aventis. Dr. Braunwald reports research grant support through Brigham and Women’s Hospital from AstraZeneca, Daiichi Sankyo, Merck, and Novartis; and consulting for Amgen, Boehringer-Ingelheim/Lilly, Cardurion, MyoKardia, Novo Nordisk, and Verve. Dr. Mann has been a consultant to Novartis, is on the steering committee for the PARADISE trial, and is on the scientific advisory board for MyoKardia/Bristol Myers Squibb.

The terminology and classification scheme for heart failure (HF) is changing in ways that experts hope will directly impact patient outcomes.

In a new consensus statement, a multisociety group of experts proposed a new universal definition of heart failure and made substantial revisions to the way in which the disease is staged and classified.

The authors of the statement, led by writing committee chair and immediate past president of the Heart Failure Society of America Biykem Bozkurt, MD, PhD, hope their efforts will go far to improve standardization of terminology, but more importantly will facilitate better management of the disease in ways that keep pace with current knowledge and advances in the field.

“There is a great need for reframing and standardizing the terminology across societies and different stakeholders, and importantly for patients because a lot of the terminology we were using was understood by academicians, but were not being translated in important ways to ensure patients are being appropriately treated,” said Dr. Bozkurt, of Baylor College of Medicine, Houston.

The consensus statement was a group effort led by the HFSA, the Heart Failure Association of the European Society of Cardiology, and the Japanese Heart Failure Society, with endorsements from the Canadian Heart Failure Society, the Heart Failure Association of India, the Cardiac Society of Australia and New Zealand, and the Chinese Heart Failure Association.

The article was published March 1 in the Journal of Cardiac Failure and the European Journal of Heart Failure, authored by a writing committee of 38 individuals with domain expertise in HF, cardiomyopathy, and cardiovascular disease.

“This is a very thorough and very carefully written document that I think will be helpful for clinicians because they’ve tapped into important changes in the field that have occurred over the past 10 years and that now allow us to do more for patients than we could before,” Eugene Braunwald, MD, said in an interview.

A new universal definition

“[Heart failure] is a clinical syndrome with symptoms and or signs caused by a structural and/or functional cardiac abnormality and corroborated by elevated natriuretic peptide levels and/or objective evidence of pulmonary or systemic congestion.”

This proposed definition, said the authors, is designed to be contemporary and simple “but conceptually comprehensive, with near universal applicability, prognostic and therapeutic viability, and acceptable sensitivity and specificity.”

Both left and right HF qualifies under this definition, said the authors, but conditions that result in marked volume overload, such as chronic kidney disease, which may present with signs and symptoms of HF, do not.

“Although some of these patients may have concomitant HF, these patients have a primary abnormality that may require a specific treatment beyond that for HF,” said the consensus statement authors.

For his part, Douglas L. Mann, MD, is happy to see what he considers a more accurate and practical definition for heart failure.

Proposed revised stages of the HF continuum

Overall, minimal changes have been made to the HF stages, with tweaks intended to enhance understanding and address the evolving role of biomarkers.

The authors proposed an approach to staging of HF:

• At-risk for HF (stage A), for patients at risk for HF but without current or prior symptoms or signs of HF and without structural or biomarkers evidence of heart disease.
• Pre-HF (stage B), for patients without current or prior symptoms or signs of HF, but evidence of structural heart disease or abnormal cardiac function, or elevated natriuretic peptide levels.
• HF (stage C), for patients with current or prior symptoms and/or signs of HF caused by a structural and/or functional cardiac abnormality.
• Advanced HF (stage D), for patients with severe symptoms and/or signs of HF at rest, recurrent hospitalizations despite guideline-directed management and therapy (GDMT), refractory or intolerant to GDMT, requiring advanced therapies such as consideration for transplant, mechanical circulatory support, or palliative care.

MDedge News

One notable change to the staging scheme is stage B, which the authors have reframed as “pre–heart failure.”

“Pre-cancer is a term widely understood and considered actionable and we wanted to tap into this successful messaging and embrace the pre–heart failure concept as something that is treatable and preventable,” said Dr. Bozkurt.

“We want patients and clinicians to understand that there are things we can do to prevent heart failure, strategies we didn’t have before, like SGLT2 inhibitors in patients with diabetes at risk for HF,” she added.

The revision also avoids the stigma of HF before the symptoms are manifest.

“Not calling it stage A and stage B heart failure you might say is semantics, but it’s important semantics,” said Dr. Braunwald. “When you’re talking to a patient or a relative and tell them they have stage A heart failure, it’s scares them unnecessarily. They don’t hear the stage A or B part, just the heart failure part.”
 

New classifications according to LVEF

And finally, in what some might consider the most obviously needed modification, the document proposes a new and revised classification of HF according to left ventricular ejection fraction (LVEF). Most agree on how to classify heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), but although the middle range has long been understood to be a clinically relevant, it has no proper name or clear delineation.

“For standardization across practice guidelines, to recognize clinical trajectories in HF, and to facilitate the recognition of different heart failure entities in a sensitive and specific manner that can guide therapy, we want to formalize the heart failure categories according to ejection fraction,” said Dr. Bozkurt.

To this end, the authors propose the following four classifications of EF:

• HF with reduced EF (HFrEF): LVEF of up to 40%.
• HF with mildly reduced EF (HFmrEF): LVEF of 41-49%.
• HF with preserved EF (HFpEF)HF with an LVEF of at least 50%.
• HF with improved EF (HFimpEF): HF with a baseline LVEF of 40% or less, an increase of at least 10 points from baseline LVEF, and a second measurement of LVEF of greater than 40%.

HFmrEF is usually a transition period, noted Dr. Bozkurt. “Patients with HF in this range may represent a population whose EF is likely to change, either increase or decrease over time and it’s important to be cognizant of that trajectory. Understanding where your patient is headed is crucial for prognosis and optimization of guideline-directed treatment,” she said.
 

Improved, not recovered, HF

The last classification of heart failure with improved ejection fraction (HFimpEF) represents an important change to the current classification scheme.

“We want to clarify what terms to use but also which not to use. For example, we don’t want people to use recovered heart failure or heart failure in remission, partly because we don’t want the medication to be stopped. We don’t want to give the false message that there has been full recovery,” said Dr. Bozkurt.

As seen in the TRED-HF trial, guideline-directed medical therapy should be continued in patients with HF with improved EF regardless of whether it has improved to a normal range of above 50% in subsequent measurements.

“This is a distinct group of people, and for a while the guidelines were lumping them in with HFpEF, which I think is totally wrong,” said Dr. Mann.

“I think it’s very important that we emphasize heart failure as a continuum, rather than a one-way street of [inevitable] progression. Because we do see improvements in ejection fraction and we do see that we can prevent heart failure if we do the right things, and this should be reflected in the terminology we use,” he added.

Dr. Bozkurt stressed that HFimpEF only applies if the EF improves to above 40%. A move from an EF of 10%-20% would still see the patient classified as having HFrEF, but a patient whose EF improved from, say, 30% to 45% would be classified as HFimpEF.

“The reason for this, again, is because a transition from, say an EF of 10%-20% does not change therapy, but a move upward over 40% might, especially regarding decisions for device therapies, so the trajectory as well as the absolute EF is important,” she added.

“Particularly in the early stages, people are responsive to therapy and it’s possible in some cases to reverse heart failure, so I think this change helps us understand when that’s happened,” said Dr. Braunwald.
 

One step toward universality

“The implementation of this terminology and nomenclature into practice will require a variety of tactics,” said Dr. Bozkurt. “For example, the current ICD 10 codes need to incorporate the at-risk and pre–heart failure categories, as well as the mid-range EF, preserved, and improved EF classifications, because the treatment differs between those three domains.”

In terms of how these proposed changes will be worked into practice guidelines, Dr. Bozkurt declined to comment on this to avoid any perception of conflict of interest as she is the cochair of the American College of Cardiology/American Heart Association HF guideline writing committee.

Dr. Braunwald and Dr. Antman suggest it may be premature to call the new terminology and classifications “universal.” In an interview, Dr. Braunwald lamented the absence of the World Heart Federation, the ACC, and the AHA as active participants in this effort and suggested this paper is only the first step of a multistep process that requires input from many stakeholders.

“It’s important that these organizations be involved, not just to bless it, but to contribute their expertise to the process,” he said.

For his part, Dr. Mann hopes these changes will gain widespread acceptance and clinical traction. “The problem sometimes with guidelines is that they’re so data driven that you just can’t come out and say the obvious, so making a position statement is a good first step. And they got good international representation on this, so I think these changes will be accepted in the next heart failure guidelines.”

To encourage further discussion and acceptance, Robert J. Mentz, MD, and Anuradha Lala, MD, editor-in-chief and deputy editor of the Journal of Cardiac Failure, respectively, announced a series of multidisciplinary perspective pieces to be published in the journal monthly, starting in May with editorials from Dr. Clyde W Yancy, MD, MSc, and Carolyn S.P. Lam, MBBS, PhD, both of whom were authors of the consensus statement.

Dr. Bozkurt reports being a consultant for Abbott, Amgen, Baxter, Bristol Myers Squibb, Liva Nova Relypsa/Vifor Pharma, Respicardia, and being on the registry steering committee for Sanofi-Aventis. Dr. Braunwald reports research grant support through Brigham and Women’s Hospital from AstraZeneca, Daiichi Sankyo, Merck, and Novartis; and consulting for Amgen, Boehringer-Ingelheim/Lilly, Cardurion, MyoKardia, Novo Nordisk, and Verve. Dr. Mann has been a consultant to Novartis, is on the steering committee for the PARADISE trial, and is on the scientific advisory board for MyoKardia/Bristol Myers Squibb.

Poor adherence and high discontinuance rates frequently compromise achieving optimal triptan therapy in managing acute migraine headaches, a new Danish study shows.

“Few people continue on triptans either due to lack of efficacy or too many adverse events,” said Alan Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles. “Some people overuse triptans when they are available and work well, but the patients are not properly informed, and do not listen.”

Migraine headaches fall among some of the most common neurologic disorders and claims the No. 2 spot in diseases that contribute to life lived with disability. An estimated 11.7% have migraine episodes annually, and the disorder carries a high prevalence through the duration of the patient’s life.

Triptans were noted as being a highly effective solution for acute migraine management when they were first introduced in the early 1990s and still remain the first-line treatment for acute migraine management not adequately controlled by ordinary analgesics and NSAIDs. As a drug class, the side-effect profile of triptans can vary, but frequent users run the risk of medication overuse headache, a condition noted by migraines of increased frequency and intensity.
 

25 years of triptan use

Study investigators conducted a nationwide, register-based cohort study using data collected from 7,435,758 Danish residents who accessed the public health care system between Jan. 1, 1994, and Oct. 31, 2019. The time frame accounts for a period of 139.0 million person-years when the residents were both alive and living in Denmark. Their findings were published online Feb. 14, 2021, in Cephalalgia.

Researchers evaluated and summarized purchases of all triptans in all dosage forms sold in Denmark during that time frame. These were sumatriptan, naratriptan, zolmitriptan, rizatriptan, almotriptan, eletriptan, and frovatriptan. Based on their finding, 381,695 patients purchased triptans at least one time. Triptan users were more likely to be female (75.7%) than male (24.3%).

Dr. Rapoport, who was not involved in the study, feels the differences in use between genders extrapolate to the U.S. migraine population as well. “Three times more women have migraines than men and buy triptans in that ratio,” he said.

Any patient who purchased at least one of any triptan at any point during the course of the study was classified as a triptan user. Triptan overuse is defined as using a triptan greater for at least 10 days a month for 3 consecutive months, as defined by the International Classification of Headache Disorders. It’s important to note that triptan are prescribed to patients for only two indications – migraines and cluster headaches. However, cluster headaches are extremely rare.

The study’s investigators summarized data collected throughout Denmark for more than a quarter of a century. The findings show an increase in triptan use from 345 defined daily doses to 945 defined daily doses per 1,000 residents per year along with an increased prevalence on triptan use from 5.17 to 14.57 per 1,000 inhabitants. In addition, 12.3% of the Danish residents who had migraines bought a triptan between 2014 and 2019 – data Dr. Rapoport noted falls in lines with trends in other Western countries, which range between 12% and 13%.

Nearly half of the first-time triptan buyers (43%) did not purchase another triptan for 5 years. In conflict with established guidelines, 90% of patients that discontinued triptan-based treatment had tried only one triptan type.

One important factor contributing to the ease of data collection is that the Danish population has free health care, coupled with sizable reimbursements for their spending. The country’s accessible health care system negates the effects of barriers related to price and availability while engendering data that more accurately reflects the patients’ experience based on treatment need and satisfaction.

“In a cohort with access to free clinical consultations and low medication costs, we observed low rates of triptan adherence, likely due to disappointing efficacy and/or unpleasant side effects rather than economic considerations. Triptan success continues to be hindered by poor implementation of clinical guidelines and high rates of treatment discontinuance,” the researchers concluded.

“The most surprising thing about this study is it is exactly what I would have expected if triptans in the U.S. were free,” Dr. Rapoport said.

Dr. Rapoport is the editor in chief of Neurology Reviews and serves as a consultant to several pharmaceutical companies.

Poor adherence and high discontinuance rates frequently compromise achieving optimal triptan therapy in managing acute migraine headaches, a new Danish study shows.

“Few people continue on triptans either due to lack of efficacy or too many adverse events,” said Alan Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles. “Some people overuse triptans when they are available and work well, but the patients are not properly informed, and do not listen.”

Migraine headaches fall among some of the most common neurologic disorders and claims the No. 2 spot in diseases that contribute to life lived with disability. An estimated 11.7% have migraine episodes annually, and the disorder carries a high prevalence through the duration of the patient’s life.

Triptans were noted as being a highly effective solution for acute migraine management when they were first introduced in the early 1990s and still remain the first-line treatment for acute migraine management not adequately controlled by ordinary analgesics and NSAIDs. As a drug class, the side-effect profile of triptans can vary, but frequent users run the risk of medication overuse headache, a condition noted by migraines of increased frequency and intensity.
 

25 years of triptan use

Study investigators conducted a nationwide, register-based cohort study using data collected from 7,435,758 Danish residents who accessed the public health care system between Jan. 1, 1994, and Oct. 31, 2019. The time frame accounts for a period of 139.0 million person-years when the residents were both alive and living in Denmark. Their findings were published online Feb. 14, 2021, in Cephalalgia.

Researchers evaluated and summarized purchases of all triptans in all dosage forms sold in Denmark during that time frame. These were sumatriptan, naratriptan, zolmitriptan, rizatriptan, almotriptan, eletriptan, and frovatriptan. Based on their finding, 381,695 patients purchased triptans at least one time. Triptan users were more likely to be female (75.7%) than male (24.3%).

Dr. Rapoport, who was not involved in the study, feels the differences in use between genders extrapolate to the U.S. migraine population as well. “Three times more women have migraines than men and buy triptans in that ratio,” he said.

Any patient who purchased at least one of any triptan at any point during the course of the study was classified as a triptan user. Triptan overuse is defined as using a triptan greater for at least 10 days a month for 3 consecutive months, as defined by the International Classification of Headache Disorders. It’s important to note that triptan are prescribed to patients for only two indications – migraines and cluster headaches. However, cluster headaches are extremely rare.

The study’s investigators summarized data collected throughout Denmark for more than a quarter of a century. The findings show an increase in triptan use from 345 defined daily doses to 945 defined daily doses per 1,000 residents per year along with an increased prevalence on triptan use from 5.17 to 14.57 per 1,000 inhabitants. In addition, 12.3% of the Danish residents who had migraines bought a triptan between 2014 and 2019 – data Dr. Rapoport noted falls in lines with trends in other Western countries, which range between 12% and 13%.

Nearly half of the first-time triptan buyers (43%) did not purchase another triptan for 5 years. In conflict with established guidelines, 90% of patients that discontinued triptan-based treatment had tried only one triptan type.

One important factor contributing to the ease of data collection is that the Danish population has free health care, coupled with sizable reimbursements for their spending. The country’s accessible health care system negates the effects of barriers related to price and availability while engendering data that more accurately reflects the patients’ experience based on treatment need and satisfaction.

“In a cohort with access to free clinical consultations and low medication costs, we observed low rates of triptan adherence, likely due to disappointing efficacy and/or unpleasant side effects rather than economic considerations. Triptan success continues to be hindered by poor implementation of clinical guidelines and high rates of treatment discontinuance,” the researchers concluded.

“The most surprising thing about this study is it is exactly what I would have expected if triptans in the U.S. were free,” Dr. Rapoport said.

Dr. Rapoport is the editor in chief of Neurology Reviews and serves as a consultant to several pharmaceutical companies.

Poor adherence and high discontinuance rates frequently compromise achieving optimal triptan therapy in managing acute migraine headaches, a new Danish study shows.

“Few people continue on triptans either due to lack of efficacy or too many adverse events,” said Alan Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles. “Some people overuse triptans when they are available and work well, but the patients are not properly informed, and do not listen.”

Migraine headaches fall among some of the most common neurologic disorders and claims the No. 2 spot in diseases that contribute to life lived with disability. An estimated 11.7% have migraine episodes annually, and the disorder carries a high prevalence through the duration of the patient’s life.

Triptans were noted as being a highly effective solution for acute migraine management when they were first introduced in the early 1990s and still remain the first-line treatment for acute migraine management not adequately controlled by ordinary analgesics and NSAIDs. As a drug class, the side-effect profile of triptans can vary, but frequent users run the risk of medication overuse headache, a condition noted by migraines of increased frequency and intensity.
 

25 years of triptan use

Study investigators conducted a nationwide, register-based cohort study using data collected from 7,435,758 Danish residents who accessed the public health care system between Jan. 1, 1994, and Oct. 31, 2019. The time frame accounts for a period of 139.0 million person-years when the residents were both alive and living in Denmark. Their findings were published online Feb. 14, 2021, in Cephalalgia.

Researchers evaluated and summarized purchases of all triptans in all dosage forms sold in Denmark during that time frame. These were sumatriptan, naratriptan, zolmitriptan, rizatriptan, almotriptan, eletriptan, and frovatriptan. Based on their finding, 381,695 patients purchased triptans at least one time. Triptan users were more likely to be female (75.7%) than male (24.3%).

Dr. Rapoport, who was not involved in the study, feels the differences in use between genders extrapolate to the U.S. migraine population as well. “Three times more women have migraines than men and buy triptans in that ratio,” he said.

Any patient who purchased at least one of any triptan at any point during the course of the study was classified as a triptan user. Triptan overuse is defined as using a triptan greater for at least 10 days a month for 3 consecutive months, as defined by the International Classification of Headache Disorders. It’s important to note that triptan are prescribed to patients for only two indications – migraines and cluster headaches. However, cluster headaches are extremely rare.

The study’s investigators summarized data collected throughout Denmark for more than a quarter of a century. The findings show an increase in triptan use from 345 defined daily doses to 945 defined daily doses per 1,000 residents per year along with an increased prevalence on triptan use from 5.17 to 14.57 per 1,000 inhabitants. In addition, 12.3% of the Danish residents who had migraines bought a triptan between 2014 and 2019 – data Dr. Rapoport noted falls in lines with trends in other Western countries, which range between 12% and 13%.

Nearly half of the first-time triptan buyers (43%) did not purchase another triptan for 5 years. In conflict with established guidelines, 90% of patients that discontinued triptan-based treatment had tried only one triptan type.

One important factor contributing to the ease of data collection is that the Danish population has free health care, coupled with sizable reimbursements for their spending. The country’s accessible health care system negates the effects of barriers related to price and availability while engendering data that more accurately reflects the patients’ experience based on treatment need and satisfaction.

“In a cohort with access to free clinical consultations and low medication costs, we observed low rates of triptan adherence, likely due to disappointing efficacy and/or unpleasant side effects rather than economic considerations. Triptan success continues to be hindered by poor implementation of clinical guidelines and high rates of treatment discontinuance,” the researchers concluded.

“The most surprising thing about this study is it is exactly what I would have expected if triptans in the U.S. were free,” Dr. Rapoport said.

Dr. Rapoport is the editor in chief of Neurology Reviews and serves as a consultant to several pharmaceutical companies.

In 2019, the   2 Current Procedural Terminology (CPT) codes for skin biopsies (11100 and 11101) were replaced with 6 new CPT codes that   specify biopsy technique   and associated procedural complexity. ^1,2 Prior to the coding changes, all biopsies were reimbursed at the same payment level, but a punch biopsy (11104; national nonfacility Medicare payment, $133.29) is now reimbursed more than a shave biopsy (11102; national nonfacility Medicare payment, $106.42). ³ We sought to evaluate whether the decrease in reimbursement for shave biopsies and concurrent increase in reimbursement for punch biopsies led to a shift from shave to punch biopsy utilization.

Methods

We examined shave and punch biopsies submitted for pathologic examination at Brigham and Women’s Hospital, Massachusetts General Hospital, and Massachusetts General Physician’s Organization (all in Boston, Massachusetts), and Penn Medicine, University of Pennsylvania Health System (Philadelphia, Pennsylvania), in May 2018 vs May 2019 (four months after new codes were implemented). This study was approved by Partners HealthCare (Boston, Massachusetts) and the University of Pennsylvania institutional review boards.

We included shave and punch biopsies of skin performed by physician dermatologists and mid-level providers (ie, physician assistants, nurse practitioners) at dermatology practices. All biopsies performed by a technique other than shave or punch, unspecified biopsy type, consultation cases, nonskin biopsies (eg, mucosa), and biopsies performed at nondermatology practices were excluded. We also excluded biopsies by providers who were not present during both study periods to account for provider mix.

Statistical Analysis
To evaluate for changes in the ratio of shave to punch biopsy utilization over time, we performed χ² tests. Because care practices may differ between private and academic settings as well as between physicians and mid-level providers, we performed subgroup analyses by practice setting and provider type.⁴

Results

We identified 11,785 biopsies (12.11% of which were punch) submitted for pathologic examination in May 2018 compared to 11,291 biopsies (12.08% of which were punch) in May 2019 (Table). The overall use of punch biopsies relative to shave biopsies did not change between the years. There was a relative decrease in punch biopsy use among academic practices (−1.88%; P=.032) and a relative increase in punch biopsy use among private practices (+0.90%; P=.043). Provider type was not associated with differing utilization of biopsy type.

Comment

Overall, there was not a considerable shift in utilization behavior from shave to punch biopsies after the introduction of new coding changes. However, our study does demonstrate a small yet significant increase in punch biopsy utilization among private practices, and a decrease among academic practices. Although the change in biopsy utilization behavior is small in magnitude, it may have a substantial impact when extrapolated to behavior across the entire United States.

We were unable to assess additional factors, such as clinical diagnosis, body site, and cosmetic concerns, that may impact biopsy type selection in this study. Although we included multiple study sites to improve generalizability, our findings may not be representative of all biopsies performed in the dermatology setting. The baseline difference in relative punch biopsy use in academic vs private practices may reflect differences in patient populations and chief concerns, but assuming these features are stable over a 1-year time period, our findings should remain valid. Future studies should focus on qualitative evaluations of physician decision-making and evaluate whether similar trends persist over time.

Conclusion

Skin biopsy utilization trends among differing practice and provider types should continue to be monitored to assess for longitudinal trends in utilization within the context of updated billing codes and associated reimbursements.

In 2019, the   2 Current Procedural Terminology (CPT) codes for skin biopsies (11100 and 11101) were replaced with 6 new CPT codes that   specify biopsy technique   and associated procedural complexity. ^1,2 Prior to the coding changes, all biopsies were reimbursed at the same payment level, but a punch biopsy (11104; national nonfacility Medicare payment, $133.29) is now reimbursed more than a shave biopsy (11102; national nonfacility Medicare payment, $106.42). ³ We sought to evaluate whether the decrease in reimbursement for shave biopsies and concurrent increase in reimbursement for punch biopsies led to a shift from shave to punch biopsy utilization.

Methods

We examined shave and punch biopsies submitted for pathologic examination at Brigham and Women’s Hospital, Massachusetts General Hospital, and Massachusetts General Physician’s Organization (all in Boston, Massachusetts), and Penn Medicine, University of Pennsylvania Health System (Philadelphia, Pennsylvania), in May 2018 vs May 2019 (four months after new codes were implemented). This study was approved by Partners HealthCare (Boston, Massachusetts) and the University of Pennsylvania institutional review boards.

We included shave and punch biopsies of skin performed by physician dermatologists and mid-level providers (ie, physician assistants, nurse practitioners) at dermatology practices. All biopsies performed by a technique other than shave or punch, unspecified biopsy type, consultation cases, nonskin biopsies (eg, mucosa), and biopsies performed at nondermatology practices were excluded. We also excluded biopsies by providers who were not present during both study periods to account for provider mix.

Statistical Analysis
To evaluate for changes in the ratio of shave to punch biopsy utilization over time, we performed χ² tests. Because care practices may differ between private and academic settings as well as between physicians and mid-level providers, we performed subgroup analyses by practice setting and provider type.⁴

Results

We identified 11,785 biopsies (12.11% of which were punch) submitted for pathologic examination in May 2018 compared to 11,291 biopsies (12.08% of which were punch) in May 2019 (Table). The overall use of punch biopsies relative to shave biopsies did not change between the years. There was a relative decrease in punch biopsy use among academic practices (−1.88%; P=.032) and a relative increase in punch biopsy use among private practices (+0.90%; P=.043). Provider type was not associated with differing utilization of biopsy type.

Comment

Overall, there was not a considerable shift in utilization behavior from shave to punch biopsies after the introduction of new coding changes. However, our study does demonstrate a small yet significant increase in punch biopsy utilization among private practices, and a decrease among academic practices. Although the change in biopsy utilization behavior is small in magnitude, it may have a substantial impact when extrapolated to behavior across the entire United States.

We were unable to assess additional factors, such as clinical diagnosis, body site, and cosmetic concerns, that may impact biopsy type selection in this study. Although we included multiple study sites to improve generalizability, our findings may not be representative of all biopsies performed in the dermatology setting. The baseline difference in relative punch biopsy use in academic vs private practices may reflect differences in patient populations and chief concerns, but assuming these features are stable over a 1-year time period, our findings should remain valid. Future studies should focus on qualitative evaluations of physician decision-making and evaluate whether similar trends persist over time.

Conclusion

Skin biopsy utilization trends among differing practice and provider types should continue to be monitored to assess for longitudinal trends in utilization within the context of updated billing codes and associated reimbursements.

In 2019, the   2 Current Procedural Terminology (CPT) codes for skin biopsies (11100 and 11101) were replaced with 6 new CPT codes that   specify biopsy technique   and associated procedural complexity. ^1,2 Prior to the coding changes, all biopsies were reimbursed at the same payment level, but a punch biopsy (11104; national nonfacility Medicare payment, $133.29) is now reimbursed more than a shave biopsy (11102; national nonfacility Medicare payment, $106.42). ³ We sought to evaluate whether the decrease in reimbursement for shave biopsies and concurrent increase in reimbursement for punch biopsies led to a shift from shave to punch biopsy utilization.

Methods

We examined shave and punch biopsies submitted for pathologic examination at Brigham and Women’s Hospital, Massachusetts General Hospital, and Massachusetts General Physician’s Organization (all in Boston, Massachusetts), and Penn Medicine, University of Pennsylvania Health System (Philadelphia, Pennsylvania), in May 2018 vs May 2019 (four months after new codes were implemented). This study was approved by Partners HealthCare (Boston, Massachusetts) and the University of Pennsylvania institutional review boards.

We included shave and punch biopsies of skin performed by physician dermatologists and mid-level providers (ie, physician assistants, nurse practitioners) at dermatology practices. All biopsies performed by a technique other than shave or punch, unspecified biopsy type, consultation cases, nonskin biopsies (eg, mucosa), and biopsies performed at nondermatology practices were excluded. We also excluded biopsies by providers who were not present during both study periods to account for provider mix.

Statistical Analysis
To evaluate for changes in the ratio of shave to punch biopsy utilization over time, we performed χ² tests. Because care practices may differ between private and academic settings as well as between physicians and mid-level providers, we performed subgroup analyses by practice setting and provider type.⁴

Results

We identified 11,785 biopsies (12.11% of which were punch) submitted for pathologic examination in May 2018 compared to 11,291 biopsies (12.08% of which were punch) in May 2019 (Table). The overall use of punch biopsies relative to shave biopsies did not change between the years. There was a relative decrease in punch biopsy use among academic practices (−1.88%; P=.032) and a relative increase in punch biopsy use among private practices (+0.90%; P=.043). Provider type was not associated with differing utilization of biopsy type.

Comment

Overall, there was not a considerable shift in utilization behavior from shave to punch biopsies after the introduction of new coding changes. However, our study does demonstrate a small yet significant increase in punch biopsy utilization among private practices, and a decrease among academic practices. Although the change in biopsy utilization behavior is small in magnitude, it may have a substantial impact when extrapolated to behavior across the entire United States.

We were unable to assess additional factors, such as clinical diagnosis, body site, and cosmetic concerns, that may impact biopsy type selection in this study. Although we included multiple study sites to improve generalizability, our findings may not be representative of all biopsies performed in the dermatology setting. The baseline difference in relative punch biopsy use in academic vs private practices may reflect differences in patient populations and chief concerns, but assuming these features are stable over a 1-year time period, our findings should remain valid. Future studies should focus on qualitative evaluations of physician decision-making and evaluate whether similar trends persist over time.

Conclusion

Skin biopsy utilization trends among differing practice and provider types should continue to be monitored to assess for longitudinal trends in utilization within the context of updated billing codes and associated reimbursements.

The upper lip poses challenges during reconstruction. Distortion of well-defined anatomic structures, including the vermilion border, oral commissures, Cupid’s bow, and philtrum, leads to noticeable deformities. Furthermore, maintenance of upper and lower lip function is essential for verbal communication, facial expression, and controlled opening of the oral cavity.

Similar to a prior review focused on the lower lip,¹ we conducted a review of the literature using the PubMed database (1976-2017) and the following search terms: upper lip, lower lip, anatomy, comparison, cadaver, histology, local flap, and reconstruction. We reviewed studies that assessed anatomic and histologic characteristics of the upper and the lower lips, function of the upper lip, mechanics of local flaps, and upper lip reconstruction techniques including local flaps and regional flaps. Articles with an emphasis on free flaps were excluded.

The initial search resulted in 1326 articles. Of these, 1201 were excluded after abstracts were screened. Full-text review of the remaining 125 articles resulted in exclusion of 85 papers (9 foreign language, 4 duplicates, and 72 irrelevant). Among the 40 articles eligible for inclusion, 12 articles discussed anatomy and histology of the upper lip, 9 examined function of the upper lip, and 19 reviewed available techniques for reconstruction of the upper lip.

In this article, we review the anatomy and function of the upper lip as well as various repair techniques to provide the reconstructive surgeon with greater familiarity with the local flaps and an algorithmic approach for upper lip reconstruction.

Anatomic Characteristics of the Upper Lip

The muscular component of the upper lip primarily is comprised of the orbicularis oris (OO) muscle divided into 2 distinct concentric components: pars peripheralis and pars marginalis.^2,3 It is discontinuous in some individuals.⁴ Although OO is the primary muscle of the lower lip, the upper lip is remarkably complex. Orbicularis oris and 3 additional muscles contribute to upper lip function: depressor septi nasi, the alar portion of the nasalis, and levator labii superioris alaeque nasi (LLSAN).⁵

The modiolus, a muscular structure located just lateral to the commissures, serves as a convergence point for facial muscle animation and lip function while distributing contraction forces between the lips and face.⁶ It is imperative to preserve its location in reconstruction to allow for good functional and aesthetic outcomes.

The upper lip is divided into 3 distinct aesthetic subunits: the philtrum and 1 lateral subunit on each side.^7,8 Its unique surface features include the Cupid’s bow, vermilion tubercle, and philtral columns. The philtral columns are created by the dermal insertion on each side of the OO, which originates from the modiolus, decussates, and inserts into the skin of the contralateral philtral groove.^2,9-11 The OO has additional insertions into the dermis lateral to the philtrum.⁵ During its course across the midline, it decreases its insertions, leading to the formation and thinness of the philtral dimple.⁹ The philtral shape primarily is due to the intermingling of LLSAN and the pars peripheralis in an axial plane. The LLSAN enters superolateral to the ipsilateral philtral ridge and courses along this ridge to contribute to the philtral shape.² Formation of the philtrum’s contour arises from the opposing force of both muscles pulling the skin in opposite directions.^2,5 The vermilion tubercle arises from the dermal insertion of the pars marginalis originating from the ipsilateral modiolus and follows the vermilion border.² The Cupid’s bow is part of the white roll at the vermilion-cutaneous junction produced by the anterior projection of the pars peripheralis.¹⁰ The complex anatomy of this structure explains the intricacy of lip reconstructions in this area.

Function of the Upper Lip

Although the primary purpose of OO is sphincteric function, the upper lip’s key role is coverage of dentition and facial animation.¹² The latter is achieved through the relationship of multiple muscles, including levator labii superioris, levator septi nasi, risorius, zygomaticus minor, zygomaticus major, levator anguli oris, and buccinator.^7,13-17 Their smooth coordination results in various facial expressions. In comparison, the lower lip is critical for preservation of oral competence, prevention of drooling, eating, and speech due to the actions of OO and vertical support from the mentalis muscle.^1,18-22

Reconstructive Methods for the Upper Lip

Multiple options are available for reconstruction of upper lip defects, with the aim to preserve facial animation and coverage of dentition. When animation muscles are involved, restoring function is the goal, which can be achieved by placing sutures to reapproximate the muscle edges in smaller defects or anchor the remaining muscle edge to preserve deep structures in larger defects, respecting the vector of contraction and attempting simulation of the muscle function. Additionally, restoration of the continuity of OO also is important for good aesthetic and functional outcomes.

Janis²³ proposed the rule of thirds to approach upper and lower lip reconstruction. Using these rules, we briefly analyze the available flaps focusing on animation, OO restoration, preservation of the modiolus position, and sensation for each (eTable).

Nasolabial (ie, melolabial) flaps are suggested for repair of defects up to one-third of the upper lip, especially when the vermilion is unaffected, or in lateral defects with or without commissure involvement.^7,24-28 This flap is based on the facial artery and may be used as a direct transposition, V-Y advancement, or island flap with good aesthetic and functional outcomes (Figure 1).^29,30 There is limited literature regarding the effects on animation. However, it may be beneficial in avoiding microstomia, as regional tissue is transferred from the cheek area, maintaining upper lip length. Additionally, the location of the modiolus often is unaffected, especially when the flap is harvested above the level of the muscle, providing superior facial animation function. Flap design is critical in areas lateral to the commissure and over the modiolus, as distortion of its position can occur.²⁶ Similar to crescentic advancement, it is important to exercise caution in male patients, as non–hair-bearing tissue can be transferred to the upper lip. Reported adverse outcomes of the nasolabial flap include a thin flat upper lip, obliteration of the Cupid’s bow, and hypoesthesia that may improve over time.³⁰

The Yu flap, a sensate single-stage rotational advancement flap, can be used in a variety of ways for repair of upper lip defects, depending on the size and location.²⁶ Lateral defects up to one-half of the upper lip should be repaired with a unilateral reverse Yu flap, central defects up to one-half of the upper lip can be reconstructed with bilateral reverse Yu flaps, and defects up to two-thirds of the upper lip can be repaired with bilateral Yu flaps. This flap restores OO continuity and thus preserves sphincter function, minimizes oral incompetence, and has a low risk of microstomia. The muscles of facial animation are preserved, yet the modiolus is not. Good aesthetic outcomes have been reported depending on the location of the Yu flap because scars can be placed in the nasolabial sulcus, commissures, or medially to recreate the philtrum.²⁶

The Estlander flap is a single-stage flap utilizing donor tissue from the opposing lip for reconstruction of lateral defects up to two-thirds of the upper lip with commissure and philtrum involvement (Figure 3).^8,23,32 It is an insensate flap that alters the position of the modiolus, distorting oral and facial animation.²³ The superomedial position of the modiolus is better tolerated in the upper lip because it increases the relaxation tone of the lower lip and simulates the vector of contraction of major animation muscles, positively impacting the sphincteric function of the reconstructed lip. Sphincteric function action is not as impaired compared with the lower lip because the new position of the modiolus tightens the lower lip and prevents drooling.³³ When designing the flap, one should consider that the inferior labial artery has been reported to remain with 10 mm of the superior border of the lower lip; therefore, pedicles of the Abbe and Estlander flaps should be at least 10 mm from the vermilion border to preserve vascular supply.^34,35

The Karapandzic flap, a modified Gilles fan flap, can be employed for repair of central defects up to two-thirds of the upper lip.^{8,23,32,36-39} The bilateral advancement of full-thickness adjacent tissue edges preserves neurovascular structures allowing sensation and restores OO continuation.⁴⁰ Prior studies have shown the average distance of the superior labial artery emergence from the facial artery and labial commissure is 12.1 mm; thus, at least 12.1 mm of tissue from the commissure should be preserved to prevent vascular compromise in Karapandzic flaps.^34,35 The modiolus position is altered, and facial animation muscles are disrupted, consequently impairing facial animation, especially elevation of the lip.³⁶ The philtrum is obliterated, producing unfavorable aesthetic outcomes. Finally, the upper lip is thinner and smaller in volume than the lower lip, increasing the risk for microstomia compared with the lower lip with a similar reconstructive technique.³⁶

Defects larger than two-thirds of the upper lip require a Bernard Burrow flap, distant free flap, or combination of multiple regional and local flaps dependent on the characteristics of the defect.^36,41 Distant free flaps are beyond the scope of this review. The Bernard Burrow flap consists of bilaterally opposing cheek advancement flaps. It is an insensate flap that does not restore OO continuity, producing minimal muscle function and poor animation. Microstomia is a common adverse outcome.³⁶

Conclusion

Comprehensive understanding of labial anatomy and its intimate relationship to function and aesthetics of the upper lip are critical. Flap anatomy and mechanics are key factors for successful reconstruction. The purpose of this article is to utilize knowledge of histology, anatomy, and function of the upper lip to improve the outcomes of reconstruction. The Abbe flap often is utilized for reconstruction of the philtrum and central upper lip defects, though it is a less desirable option for lower lip reconstruction. The Karapandzic flap, while sensate and restorative of OO continuity, may have less optimal functional and cosmetic results compared with its use in the lower lip. Regarding lateral defects involving the commissure, the Estlander flap provides a reasonable option for the upper lip when compared with its use in lower lip defects, where outcomes are usually inferior.

The upper lip poses challenges during reconstruction. Distortion of well-defined anatomic structures, including the vermilion border, oral commissures, Cupid’s bow, and philtrum, leads to noticeable deformities. Furthermore, maintenance of upper and lower lip function is essential for verbal communication, facial expression, and controlled opening of the oral cavity.

Similar to a prior review focused on the lower lip,¹ we conducted a review of the literature using the PubMed database (1976-2017) and the following search terms: upper lip, lower lip, anatomy, comparison, cadaver, histology, local flap, and reconstruction. We reviewed studies that assessed anatomic and histologic characteristics of the upper and the lower lips, function of the upper lip, mechanics of local flaps, and upper lip reconstruction techniques including local flaps and regional flaps. Articles with an emphasis on free flaps were excluded.

The initial search resulted in 1326 articles. Of these, 1201 were excluded after abstracts were screened. Full-text review of the remaining 125 articles resulted in exclusion of 85 papers (9 foreign language, 4 duplicates, and 72 irrelevant). Among the 40 articles eligible for inclusion, 12 articles discussed anatomy and histology of the upper lip, 9 examined function of the upper lip, and 19 reviewed available techniques for reconstruction of the upper lip.

In this article, we review the anatomy and function of the upper lip as well as various repair techniques to provide the reconstructive surgeon with greater familiarity with the local flaps and an algorithmic approach for upper lip reconstruction.

Anatomic Characteristics of the Upper Lip

The muscular component of the upper lip primarily is comprised of the orbicularis oris (OO) muscle divided into 2 distinct concentric components: pars peripheralis and pars marginalis.^2,3 It is discontinuous in some individuals.⁴ Although OO is the primary muscle of the lower lip, the upper lip is remarkably complex. Orbicularis oris and 3 additional muscles contribute to upper lip function: depressor septi nasi, the alar portion of the nasalis, and levator labii superioris alaeque nasi (LLSAN).⁵

The modiolus, a muscular structure located just lateral to the commissures, serves as a convergence point for facial muscle animation and lip function while distributing contraction forces between the lips and face.⁶ It is imperative to preserve its location in reconstruction to allow for good functional and aesthetic outcomes.

The upper lip is divided into 3 distinct aesthetic subunits: the philtrum and 1 lateral subunit on each side.^7,8 Its unique surface features include the Cupid’s bow, vermilion tubercle, and philtral columns. The philtral columns are created by the dermal insertion on each side of the OO, which originates from the modiolus, decussates, and inserts into the skin of the contralateral philtral groove.^2,9-11 The OO has additional insertions into the dermis lateral to the philtrum.⁵ During its course across the midline, it decreases its insertions, leading to the formation and thinness of the philtral dimple.⁹ The philtral shape primarily is due to the intermingling of LLSAN and the pars peripheralis in an axial plane. The LLSAN enters superolateral to the ipsilateral philtral ridge and courses along this ridge to contribute to the philtral shape.² Formation of the philtrum’s contour arises from the opposing force of both muscles pulling the skin in opposite directions.^2,5 The vermilion tubercle arises from the dermal insertion of the pars marginalis originating from the ipsilateral modiolus and follows the vermilion border.² The Cupid’s bow is part of the white roll at the vermilion-cutaneous junction produced by the anterior projection of the pars peripheralis.¹⁰ The complex anatomy of this structure explains the intricacy of lip reconstructions in this area.

Function of the Upper Lip

Although the primary purpose of OO is sphincteric function, the upper lip’s key role is coverage of dentition and facial animation.¹² The latter is achieved through the relationship of multiple muscles, including levator labii superioris, levator septi nasi, risorius, zygomaticus minor, zygomaticus major, levator anguli oris, and buccinator.^7,13-17 Their smooth coordination results in various facial expressions. In comparison, the lower lip is critical for preservation of oral competence, prevention of drooling, eating, and speech due to the actions of OO and vertical support from the mentalis muscle.^1,18-22

Reconstructive Methods for the Upper Lip

Multiple options are available for reconstruction of upper lip defects, with the aim to preserve facial animation and coverage of dentition. When animation muscles are involved, restoring function is the goal, which can be achieved by placing sutures to reapproximate the muscle edges in smaller defects or anchor the remaining muscle edge to preserve deep structures in larger defects, respecting the vector of contraction and attempting simulation of the muscle function. Additionally, restoration of the continuity of OO also is important for good aesthetic and functional outcomes.

Janis²³ proposed the rule of thirds to approach upper and lower lip reconstruction. Using these rules, we briefly analyze the available flaps focusing on animation, OO restoration, preservation of the modiolus position, and sensation for each (eTable).

Nasolabial (ie, melolabial) flaps are suggested for repair of defects up to one-third of the upper lip, especially when the vermilion is unaffected, or in lateral defects with or without commissure involvement.^7,24-28 This flap is based on the facial artery and may be used as a direct transposition, V-Y advancement, or island flap with good aesthetic and functional outcomes (Figure 1).^29,30 There is limited literature regarding the effects on animation. However, it may be beneficial in avoiding microstomia, as regional tissue is transferred from the cheek area, maintaining upper lip length. Additionally, the location of the modiolus often is unaffected, especially when the flap is harvested above the level of the muscle, providing superior facial animation function. Flap design is critical in areas lateral to the commissure and over the modiolus, as distortion of its position can occur.²⁶ Similar to crescentic advancement, it is important to exercise caution in male patients, as non–hair-bearing tissue can be transferred to the upper lip. Reported adverse outcomes of the nasolabial flap include a thin flat upper lip, obliteration of the Cupid’s bow, and hypoesthesia that may improve over time.³⁰

The Yu flap, a sensate single-stage rotational advancement flap, can be used in a variety of ways for repair of upper lip defects, depending on the size and location.²⁶ Lateral defects up to one-half of the upper lip should be repaired with a unilateral reverse Yu flap, central defects up to one-half of the upper lip can be reconstructed with bilateral reverse Yu flaps, and defects up to two-thirds of the upper lip can be repaired with bilateral Yu flaps. This flap restores OO continuity and thus preserves sphincter function, minimizes oral incompetence, and has a low risk of microstomia. The muscles of facial animation are preserved, yet the modiolus is not. Good aesthetic outcomes have been reported depending on the location of the Yu flap because scars can be placed in the nasolabial sulcus, commissures, or medially to recreate the philtrum.²⁶

The Estlander flap is a single-stage flap utilizing donor tissue from the opposing lip for reconstruction of lateral defects up to two-thirds of the upper lip with commissure and philtrum involvement (Figure 3).^8,23,32 It is an insensate flap that alters the position of the modiolus, distorting oral and facial animation.²³ The superomedial position of the modiolus is better tolerated in the upper lip because it increases the relaxation tone of the lower lip and simulates the vector of contraction of major animation muscles, positively impacting the sphincteric function of the reconstructed lip. Sphincteric function action is not as impaired compared with the lower lip because the new position of the modiolus tightens the lower lip and prevents drooling.³³ When designing the flap, one should consider that the inferior labial artery has been reported to remain with 10 mm of the superior border of the lower lip; therefore, pedicles of the Abbe and Estlander flaps should be at least 10 mm from the vermilion border to preserve vascular supply.^34,35

The Karapandzic flap, a modified Gilles fan flap, can be employed for repair of central defects up to two-thirds of the upper lip.^{8,23,32,36-39} The bilateral advancement of full-thickness adjacent tissue edges preserves neurovascular structures allowing sensation and restores OO continuation.⁴⁰ Prior studies have shown the average distance of the superior labial artery emergence from the facial artery and labial commissure is 12.1 mm; thus, at least 12.1 mm of tissue from the commissure should be preserved to prevent vascular compromise in Karapandzic flaps.^34,35 The modiolus position is altered, and facial animation muscles are disrupted, consequently impairing facial animation, especially elevation of the lip.³⁶ The philtrum is obliterated, producing unfavorable aesthetic outcomes. Finally, the upper lip is thinner and smaller in volume than the lower lip, increasing the risk for microstomia compared with the lower lip with a similar reconstructive technique.³⁶

Defects larger than two-thirds of the upper lip require a Bernard Burrow flap, distant free flap, or combination of multiple regional and local flaps dependent on the characteristics of the defect.^36,41 Distant free flaps are beyond the scope of this review. The Bernard Burrow flap consists of bilaterally opposing cheek advancement flaps. It is an insensate flap that does not restore OO continuity, producing minimal muscle function and poor animation. Microstomia is a common adverse outcome.³⁶

Conclusion

Comprehensive understanding of labial anatomy and its intimate relationship to function and aesthetics of the upper lip are critical. Flap anatomy and mechanics are key factors for successful reconstruction. The purpose of this article is to utilize knowledge of histology, anatomy, and function of the upper lip to improve the outcomes of reconstruction. The Abbe flap often is utilized for reconstruction of the philtrum and central upper lip defects, though it is a less desirable option for lower lip reconstruction. The Karapandzic flap, while sensate and restorative of OO continuity, may have less optimal functional and cosmetic results compared with its use in the lower lip. Regarding lateral defects involving the commissure, the Estlander flap provides a reasonable option for the upper lip when compared with its use in lower lip defects, where outcomes are usually inferior.

The upper lip poses challenges during reconstruction. Distortion of well-defined anatomic structures, including the vermilion border, oral commissures, Cupid’s bow, and philtrum, leads to noticeable deformities. Furthermore, maintenance of upper and lower lip function is essential for verbal communication, facial expression, and controlled opening of the oral cavity.

Similar to a prior review focused on the lower lip,¹ we conducted a review of the literature using the PubMed database (1976-2017) and the following search terms: upper lip, lower lip, anatomy, comparison, cadaver, histology, local flap, and reconstruction. We reviewed studies that assessed anatomic and histologic characteristics of the upper and the lower lips, function of the upper lip, mechanics of local flaps, and upper lip reconstruction techniques including local flaps and regional flaps. Articles with an emphasis on free flaps were excluded.

The initial search resulted in 1326 articles. Of these, 1201 were excluded after abstracts were screened. Full-text review of the remaining 125 articles resulted in exclusion of 85 papers (9 foreign language, 4 duplicates, and 72 irrelevant). Among the 40 articles eligible for inclusion, 12 articles discussed anatomy and histology of the upper lip, 9 examined function of the upper lip, and 19 reviewed available techniques for reconstruction of the upper lip.

In this article, we review the anatomy and function of the upper lip as well as various repair techniques to provide the reconstructive surgeon with greater familiarity with the local flaps and an algorithmic approach for upper lip reconstruction.

Anatomic Characteristics of the Upper Lip

The muscular component of the upper lip primarily is comprised of the orbicularis oris (OO) muscle divided into 2 distinct concentric components: pars peripheralis and pars marginalis.^2,3 It is discontinuous in some individuals.⁴ Although OO is the primary muscle of the lower lip, the upper lip is remarkably complex. Orbicularis oris and 3 additional muscles contribute to upper lip function: depressor septi nasi, the alar portion of the nasalis, and levator labii superioris alaeque nasi (LLSAN).⁵

The modiolus, a muscular structure located just lateral to the commissures, serves as a convergence point for facial muscle animation and lip function while distributing contraction forces between the lips and face.⁶ It is imperative to preserve its location in reconstruction to allow for good functional and aesthetic outcomes.

The upper lip is divided into 3 distinct aesthetic subunits: the philtrum and 1 lateral subunit on each side.^7,8 Its unique surface features include the Cupid’s bow, vermilion tubercle, and philtral columns. The philtral columns are created by the dermal insertion on each side of the OO, which originates from the modiolus, decussates, and inserts into the skin of the contralateral philtral groove.^2,9-11 The OO has additional insertions into the dermis lateral to the philtrum.⁵ During its course across the midline, it decreases its insertions, leading to the formation and thinness of the philtral dimple.⁹ The philtral shape primarily is due to the intermingling of LLSAN and the pars peripheralis in an axial plane. The LLSAN enters superolateral to the ipsilateral philtral ridge and courses along this ridge to contribute to the philtral shape.² Formation of the philtrum’s contour arises from the opposing force of both muscles pulling the skin in opposite directions.^2,5 The vermilion tubercle arises from the dermal insertion of the pars marginalis originating from the ipsilateral modiolus and follows the vermilion border.² The Cupid’s bow is part of the white roll at the vermilion-cutaneous junction produced by the anterior projection of the pars peripheralis.¹⁰ The complex anatomy of this structure explains the intricacy of lip reconstructions in this area.

Function of the Upper Lip

Although the primary purpose of OO is sphincteric function, the upper lip’s key role is coverage of dentition and facial animation.¹² The latter is achieved through the relationship of multiple muscles, including levator labii superioris, levator septi nasi, risorius, zygomaticus minor, zygomaticus major, levator anguli oris, and buccinator.^7,13-17 Their smooth coordination results in various facial expressions. In comparison, the lower lip is critical for preservation of oral competence, prevention of drooling, eating, and speech due to the actions of OO and vertical support from the mentalis muscle.^1,18-22

Reconstructive Methods for the Upper Lip

Multiple options are available for reconstruction of upper lip defects, with the aim to preserve facial animation and coverage of dentition. When animation muscles are involved, restoring function is the goal, which can be achieved by placing sutures to reapproximate the muscle edges in smaller defects or anchor the remaining muscle edge to preserve deep structures in larger defects, respecting the vector of contraction and attempting simulation of the muscle function. Additionally, restoration of the continuity of OO also is important for good aesthetic and functional outcomes.

Janis²³ proposed the rule of thirds to approach upper and lower lip reconstruction. Using these rules, we briefly analyze the available flaps focusing on animation, OO restoration, preservation of the modiolus position, and sensation for each (eTable).

Nasolabial (ie, melolabial) flaps are suggested for repair of defects up to one-third of the upper lip, especially when the vermilion is unaffected, or in lateral defects with or without commissure involvement.^7,24-28 This flap is based on the facial artery and may be used as a direct transposition, V-Y advancement, or island flap with good aesthetic and functional outcomes (Figure 1).^29,30 There is limited literature regarding the effects on animation. However, it may be beneficial in avoiding microstomia, as regional tissue is transferred from the cheek area, maintaining upper lip length. Additionally, the location of the modiolus often is unaffected, especially when the flap is harvested above the level of the muscle, providing superior facial animation function. Flap design is critical in areas lateral to the commissure and over the modiolus, as distortion of its position can occur.²⁶ Similar to crescentic advancement, it is important to exercise caution in male patients, as non–hair-bearing tissue can be transferred to the upper lip. Reported adverse outcomes of the nasolabial flap include a thin flat upper lip, obliteration of the Cupid’s bow, and hypoesthesia that may improve over time.³⁰

The Yu flap, a sensate single-stage rotational advancement flap, can be used in a variety of ways for repair of upper lip defects, depending on the size and location.²⁶ Lateral defects up to one-half of the upper lip should be repaired with a unilateral reverse Yu flap, central defects up to one-half of the upper lip can be reconstructed with bilateral reverse Yu flaps, and defects up to two-thirds of the upper lip can be repaired with bilateral Yu flaps. This flap restores OO continuity and thus preserves sphincter function, minimizes oral incompetence, and has a low risk of microstomia. The muscles of facial animation are preserved, yet the modiolus is not. Good aesthetic outcomes have been reported depending on the location of the Yu flap because scars can be placed in the nasolabial sulcus, commissures, or medially to recreate the philtrum.²⁶

The Estlander flap is a single-stage flap utilizing donor tissue from the opposing lip for reconstruction of lateral defects up to two-thirds of the upper lip with commissure and philtrum involvement (Figure 3).^8,23,32 It is an insensate flap that alters the position of the modiolus, distorting oral and facial animation.²³ The superomedial position of the modiolus is better tolerated in the upper lip because it increases the relaxation tone of the lower lip and simulates the vector of contraction of major animation muscles, positively impacting the sphincteric function of the reconstructed lip. Sphincteric function action is not as impaired compared with the lower lip because the new position of the modiolus tightens the lower lip and prevents drooling.³³ When designing the flap, one should consider that the inferior labial artery has been reported to remain with 10 mm of the superior border of the lower lip; therefore, pedicles of the Abbe and Estlander flaps should be at least 10 mm from the vermilion border to preserve vascular supply.^34,35

The Karapandzic flap, a modified Gilles fan flap, can be employed for repair of central defects up to two-thirds of the upper lip.^{8,23,32,36-39} The bilateral advancement of full-thickness adjacent tissue edges preserves neurovascular structures allowing sensation and restores OO continuation.⁴⁰ Prior studies have shown the average distance of the superior labial artery emergence from the facial artery and labial commissure is 12.1 mm; thus, at least 12.1 mm of tissue from the commissure should be preserved to prevent vascular compromise in Karapandzic flaps.^34,35 The modiolus position is altered, and facial animation muscles are disrupted, consequently impairing facial animation, especially elevation of the lip.³⁶ The philtrum is obliterated, producing unfavorable aesthetic outcomes. Finally, the upper lip is thinner and smaller in volume than the lower lip, increasing the risk for microstomia compared with the lower lip with a similar reconstructive technique.³⁶

Defects larger than two-thirds of the upper lip require a Bernard Burrow flap, distant free flap, or combination of multiple regional and local flaps dependent on the characteristics of the defect.^36,41 Distant free flaps are beyond the scope of this review. The Bernard Burrow flap consists of bilaterally opposing cheek advancement flaps. It is an insensate flap that does not restore OO continuity, producing minimal muscle function and poor animation. Microstomia is a common adverse outcome.³⁶

Conclusion

Comprehensive understanding of labial anatomy and its intimate relationship to function and aesthetics of the upper lip are critical. Flap anatomy and mechanics are key factors for successful reconstruction. The purpose of this article is to utilize knowledge of histology, anatomy, and function of the upper lip to improve the outcomes of reconstruction. The Abbe flap often is utilized for reconstruction of the philtrum and central upper lip defects, though it is a less desirable option for lower lip reconstruction. The Karapandzic flap, while sensate and restorative of OO continuity, may have less optimal functional and cosmetic results compared with its use in the lower lip. Regarding lateral defects involving the commissure, the Estlander flap provides a reasonable option for the upper lip when compared with its use in lower lip defects, where outcomes are usually inferior.

Hand dermatitis, also known as hand eczema, is common and affects a considerable number of individuals across all ages. The impact of hand dermatitis can be profound, as it can impair one’s ability to perform tasks at home and at work. As a result of the coronavirus disease 2019 (COVID-19) pandemic, there has been an increased focus on hand hygiene and subsequently hand dermatitis. There are many contributors to the severity of hand dermatitis, including genetic factors, immune reactions, and skin barrier disruption. In this column, we will explore irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD) of the hands, including epidemiology, potential causes, clinical characteristics, diagnosis, and management.

Epidemiology

The prevalence of hand dermatitis in the general population is 3% to 4%, with a 1‐year prevalence of 10% and a lifetime prevalence of 15%.¹ In a Swedish study of patients self-reporting hand eczema, contact dermatitis comprised 57% of the total cases (N=1385); ICD accounted for 35% of cases followed by ACD in 22%.² A recent study on hand dermatitis in North American specialty patch test clinics documented that the hands were the primary site of involvement in 24.2% of patients undergoing patch testing (N=37,113).³

The hands are particularly at risk for occupation-related contact dermatitis and are the primary site of involvement in 80% of cases, followed by the wrists and forearms.⁴ Occupations at greatest risk include cleaning, construction, metalworking, hairdressing, health care, housework, and mechanics.⁵ Even prior to the COVID-19 pandemic, occupational hand dermatitis was common; in a survey of inpatient nurses, the prevalence was 55% (N=167).⁶ More recently, a study from China demonstrated a 74.5% prevalence of hand dermatitis in frontline health care workers involved in COVID-19 patient care.⁷

Etiology of Hand ICD

The pathogenesis of ICD is multifactorial; although traditionally thought to be nonimmunologic, evidence has shown that it involves skin barrier disruption, infiltration by immunocompetent cells, and induction of inflammatory signal molecules. The degree of irritancy is related to the concentration, contact duration, and properties of the irritant. Irritant reactions can be acute, such as those following a single chemical exposure that results in a localized dermatitis, or chronic, such as after repetitive cumulative exposure to mild irritants such as soaps.

Hand hygiene products (eg, soaps, hand sanitizers) can be irritants and have recently gained notoriety given their increased use to prevent COVID-19 transmission.^8,9 Specific irritants include iodophors, antimicrobial soaps (chlorhexidine gluconate, chloroxylenol, triclosan), surfactants, and detergents. Wolfe et al¹⁰ showed that detergent-based hand cleansing products had the highest association with ICD, which was thought to be due to their propensity to remove protective lipids and reduce moisture content in the stratum corneum. Although hand sanitizers are better tolerated than detergents, they can still contribute to ICD by stripping precious lipids and disrupting the skin barrier.¹¹ Compared to ethanol, isopropanol and N-propanol cause more disruption of the stratum corneum.¹² In addition, N-propanol has the same irritant potential as the detergent sodium lauryl sulfate.¹³ Thus, ethanol-based sanitizers may be better tolerated. Disinfectant surface wipes may include the irritant N-alkyl dimethyl benzyl ammonium chloride. Conversely, hand and baby wipes are formulated specifically for the skin and may be less irritating.¹¹

Occupational contributors to hand ICD include chemical exposures and frequent handwashing. Wet work, mechanical trauma, warm dry air, and prolonged use of occlusive gloves also are well-known irritants.⁴ Fine or coarse particles encountered in some occupations or hobbies (eg, sand, sawdust, metal filings, plastic) can cause mechanical irritation. Exposure to physical friction from repeated handling of metal components, paper, cardboard, fabric, or steering wheels also has been implicated in hand ICD. Other common categories of occupational irritants include hydrocarbons, such as oils and petroleum.^5,14

In addition to environmental factors, atopic dermatitis is an important endogenous factor that increases the risk of ICD due to underlying deficiencies within the main lipid¹⁵ and structural¹⁶ barrier components. These deficiencies ultimately lead to a lower threshold for the activation of inflammation via water loss and a weakened barrier. Studies have demonstrated that atopic dermatitis increases the risk for developing hand ICD 2- to 4-fold.¹⁷

Etiology of Hand ACD

Allergic contact dermatitis is an immune-mediated type IV delayed hypersensitivity reaction. The North American Contact Dermatitis Group reported that the top 5 clinically relevant hand allergens were methylisothiazolinone (MI), nickel, formaldehyde, quaternium-15, and fragrance mix I.³ Similarly, the European Surveillance System on Contact Allergies demonstrated that the most common hand allergens were nickel, preservatives (quaternium-15 and formaldehyde), fragrances, and cobalt.¹⁸ In health care workers, rubber accelerators often are relevant in patients with hand ACD.^5,19 Hand hygiene products are known to contain potential allergens; a recent study demonstrated that the top 5 allergens in common hand sanitizers were tocopherol, fragrance, propylene glycol, benzoates, and cetylstearyl alcohol,²⁰ whereas the most common allergens in hand cleansers were fragrance, tocopherol, sodium benzoate, chloroxylenol, propylene glycol, and chlorhexidine gluconate.²¹

Preservatives
Preservatives can contribute to hand ACD. Methylisothiazolinone was the most commonly relevant allergen in a recent North American study of hand contact allergy,³ and a study of North American products confirmed its presence in dishwashing products (64%), shampoos (53%), household cleaners (47%), laundry softeners/additives (30%), soaps and cleansers (29%), and surface disinfectants (27%).²² In addition, in a study of 139 patients with refractory MI contact allergy, the hands were the most common site (69%) and had the highest rate of relapse.²³ Because of the common presence of this preservative in liquid-based personal care products, patients with MI hand contact allergy need to be vigilant.

The same North American study highlighted formaldehyde and the formaldehyde releaser quaternium-15 as commonly relevant hand contact allergens.³ Formaldehyde is not commonly found in personal care products, but formaldehyde-releasing preservatives frequently are found in cosmetic products, topical medicaments, detergents, soaps, and metal working fluids. Another study noted that the most relevant contact allergen in health care workers was quaternium-15, possibly due to increased hand hygiene and exposure to medical products used for patient care.^24,25

Metals
Nickel is used in metal objects and is found in many workplaces in the form of machines, office supplies, tools, electronics, uniforms, and jewelry. Occupationally related nickel ACD of the hands is most common in hairdressers/barbers/cosmetologists,²⁶ which is not surprising, as hairdressing tools such as scissors and hair clips can release nickel.^27,28

Although nickel contact allergy is more common than cobalt, these metals frequently co-react, with up to 25% of nickel-sensitive patients also having positive patch test reactions to cobalt.²⁹ Because cobalt is contained in alloys, the occupations most at risk pertain to hard metal manufacturing. Furthermore, cobalt is used in dentistry for dental tools, fillings, crowns, bridges, and dentures.³⁰ Cobalt also has been identified in leather, and leather gloves have been implicated in hand ACD.³¹

Fragrances
Fragrances can be added to products to infuse pleasing aromas or mask unpleasant chemical odors. In the North American study of hand ACD, fragrance mix I and balsam of Peru were the sixth and seventh most clinically relevant allergens, respectively.³ In another study, fragrances were found in 50% of waterless cleansers and 95% of rinse-off soaps and were the second most common allergens found in skin disinfectants.²¹ Fragrance is ubiquitous in personal care and cleansing products, which can make avoidance difficult.

Rubber Accelerators
Contact allergy to rubber additives in medical gloves is the most common cause of occupational hand ACD in health care workers.^5,19 Importantly, it usually is rubber accelerators that act as allergens in hand ACD and not natural rubber latex. Rubber accelerators known to cause ACD include thiurams, carbamates, 1,3-diphenylguanidine (DPG), mixed dialkyl thioureas, and benzothiazoles.³² In the setting of hand ACD in North America, reactions to thiuram mix and carba mix were the most common.³ Notably, DPG is a component of carba mix and can be present in rubber gloves. It has been shown that 40.3% of DPG reactions are missed by testing with carba mix alone; therefore, DPG must be patch tested separately.³³

Clinical Examination

It can be challenging to differentiate between hand ICD and ACD based on clinical appearance alone, and patch testing often is necessary for diagnosis. In the acute phase, both ICD and ACD can present as erythema, papules, vesicles, bullae, and/or crusting. In the chronic phase, scaling, lichenification, and/or fissures tend to prevail. Both acute and chronic ICD and ACD can be associated with pruritus and pain; however, ICD may be more likely associated with a burning or painful sensation, whereas ACD may be more associated with pruritus.

Other dermatoses may present as hand eruptions and should be kept in the differential diagnosis. Atopic dermatitis, psoriasis, dyshidrotic eczema, hyperkeratotic hand dermatitis, keratolysis exfoliativa, and palmoplantar pustulosis are other common causes of hand eruptions.^5,34

Patch Testing for Hand ACD
Consider patch testing for hand dermatitis that is refractory to conservative treatment. Patients with new-onset hand dermatitis without history of atopy and patients with a new worsening of chronic hand dermatitis also may need patch testing.

In addition to a medically appropriate screening series, patients with hand dermatitis often need supplemental patch testing. In a series of 37,113 patients with hand ACD, just over 20% of patients had positive patch test reactions to at least 1 supplemental allergen not on the screening series.³ Supplemental series should be selected based on the patient’s history and exposures; for example, nail salon technicians may need supplemental testing with the nail acrylate series, and massage therapists may need additional testing with the fragrance or essential oil series. Some of the most common supplemental series used for evaluation of hand dermatitis are the rubber, cosmetic, textile and dyes, plant, fragrance, essential oil, oil and coolants, nail or printing acrylates, and hairdressing series. If there is a high suspicion of occupational contact with allergens, obtaining material safety data sheets from the patient’s employer can be helpful to identify relevant allergens for testing.⁵ The thin-layer rapid use epicutaneous (T.R.U.E.) test may miss several common and relevant hand allergens, including benzalkonium chloride, lanolin, and iodopropynyl butylcarbamate.³

Management

Management of hand ICD requires avoidance of irritants and proper hand hygiene practices.^10,34 The hands should be washed using lukewarm water and mild fragrance-free soaps or cleansers,³⁵ keeping in mind that hand sanitizers may be better tolerated due to their lower lipid-stripping effects. The moisturizers with the best efficacy are combinations of humectants (topical urea, glycerin) and occlusive emollients (dimethicone, petrolatum).¹¹ When wet work is necessary, gloves should be worn; however, sweat and humidity from glove use can worsen ICD, and gloves should be changed regularly and applied only when hands are dry. Cotton gloves also can be worn underneath rubber gloves to prevent maceration from sweat.⁹

The mainstay of hand ACD management is allergen avoidance. The American Contact Dermatitis Society maintains the Contact Allergen Management Program (CAMP), a database that identifies products that do not contain patient allergens. The importance of reading ingredient labels of products should always be emphasized. For patients with rubber accelerator allergies, vinyl or accelerator-free gloves may be used. If the allergen is occupational, communication with the patient’s employer is necessary.⁵

When hand contact dermatitis does not improve with avoidance of irritants and allergens as well as gentle skin care, topical therapy, phototherapy, and in some cases systemic therapy may be required. High-potency topical corticosteroids or short courses of prednisone may be needed for quick relief. Topical calcineurin inhibitors (tacrolimus and pimecrolimus) and the phosphodiesterase 4 inhibitor crisaborole have shown some efficacy for hand dermatitis and can be used as steroid-sparing agents.^36,37 Narrowband UVB and UVA have been used with moderate efficacy to treat resistant hand dermatitis.^34,38 Oral immunosuppressant medications such as methotrexate, mycophenolate mofetil, azathioprine, and cyclosporine can be used for more severe cases.^34,39,40 Furthermore, oral retinoids have been used for chronic severe hand dermatitis with notable efficacy.⁴¹

Our Final Interpretation

The 2 major types of hand contact dermatitis are ICD and ACD. Hand ICD is more common than ACD in both occupational and nonoccupational settings. The hands are the most common sites in the setting of occupational dermatitis; in North American patch test populations, the hands were the primary site of involvement in just under 25% of patients.³ Many hand hygiene products contain irritants and allergens. The lipid-stripping effects of soaps, detergents, and hand sanitizers in conjunction with increased frequency of handwashing can trigger ICD. The most common allergens implicated in hand ACD include MI, nickel, formaldehyde, quaternium-15, and fragrances. Patch testing is important for diagnosis, and supplemental series should be considered. Management includes avoidance of irritants and allergens; liberal use of moisturizers and barrier creams; and prescription topical therapy, phototherapy, or systemic therapy when indicated.

Hand dermatitis, also known as hand eczema, is common and affects a considerable number of individuals across all ages. The impact of hand dermatitis can be profound, as it can impair one’s ability to perform tasks at home and at work. As a result of the coronavirus disease 2019 (COVID-19) pandemic, there has been an increased focus on hand hygiene and subsequently hand dermatitis. There are many contributors to the severity of hand dermatitis, including genetic factors, immune reactions, and skin barrier disruption. In this column, we will explore irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD) of the hands, including epidemiology, potential causes, clinical characteristics, diagnosis, and management.

Epidemiology

The prevalence of hand dermatitis in the general population is 3% to 4%, with a 1‐year prevalence of 10% and a lifetime prevalence of 15%.¹ In a Swedish study of patients self-reporting hand eczema, contact dermatitis comprised 57% of the total cases (N=1385); ICD accounted for 35% of cases followed by ACD in 22%.² A recent study on hand dermatitis in North American specialty patch test clinics documented that the hands were the primary site of involvement in 24.2% of patients undergoing patch testing (N=37,113).³

The hands are particularly at risk for occupation-related contact dermatitis and are the primary site of involvement in 80% of cases, followed by the wrists and forearms.⁴ Occupations at greatest risk include cleaning, construction, metalworking, hairdressing, health care, housework, and mechanics.⁵ Even prior to the COVID-19 pandemic, occupational hand dermatitis was common; in a survey of inpatient nurses, the prevalence was 55% (N=167).⁶ More recently, a study from China demonstrated a 74.5% prevalence of hand dermatitis in frontline health care workers involved in COVID-19 patient care.⁷

Etiology of Hand ICD

The pathogenesis of ICD is multifactorial; although traditionally thought to be nonimmunologic, evidence has shown that it involves skin barrier disruption, infiltration by immunocompetent cells, and induction of inflammatory signal molecules. The degree of irritancy is related to the concentration, contact duration, and properties of the irritant. Irritant reactions can be acute, such as those following a single chemical exposure that results in a localized dermatitis, or chronic, such as after repetitive cumulative exposure to mild irritants such as soaps.

Hand hygiene products (eg, soaps, hand sanitizers) can be irritants and have recently gained notoriety given their increased use to prevent COVID-19 transmission.^8,9 Specific irritants include iodophors, antimicrobial soaps (chlorhexidine gluconate, chloroxylenol, triclosan), surfactants, and detergents. Wolfe et al¹⁰ showed that detergent-based hand cleansing products had the highest association with ICD, which was thought to be due to their propensity to remove protective lipids and reduce moisture content in the stratum corneum. Although hand sanitizers are better tolerated than detergents, they can still contribute to ICD by stripping precious lipids and disrupting the skin barrier.¹¹ Compared to ethanol, isopropanol and N-propanol cause more disruption of the stratum corneum.¹² In addition, N-propanol has the same irritant potential as the detergent sodium lauryl sulfate.¹³ Thus, ethanol-based sanitizers may be better tolerated. Disinfectant surface wipes may include the irritant N-alkyl dimethyl benzyl ammonium chloride. Conversely, hand and baby wipes are formulated specifically for the skin and may be less irritating.¹¹

Occupational contributors to hand ICD include chemical exposures and frequent handwashing. Wet work, mechanical trauma, warm dry air, and prolonged use of occlusive gloves also are well-known irritants.⁴ Fine or coarse particles encountered in some occupations or hobbies (eg, sand, sawdust, metal filings, plastic) can cause mechanical irritation. Exposure to physical friction from repeated handling of metal components, paper, cardboard, fabric, or steering wheels also has been implicated in hand ICD. Other common categories of occupational irritants include hydrocarbons, such as oils and petroleum.^5,14

In addition to environmental factors, atopic dermatitis is an important endogenous factor that increases the risk of ICD due to underlying deficiencies within the main lipid¹⁵ and structural¹⁶ barrier components. These deficiencies ultimately lead to a lower threshold for the activation of inflammation via water loss and a weakened barrier. Studies have demonstrated that atopic dermatitis increases the risk for developing hand ICD 2- to 4-fold.¹⁷

Etiology of Hand ACD

Allergic contact dermatitis is an immune-mediated type IV delayed hypersensitivity reaction. The North American Contact Dermatitis Group reported that the top 5 clinically relevant hand allergens were methylisothiazolinone (MI), nickel, formaldehyde, quaternium-15, and fragrance mix I.³ Similarly, the European Surveillance System on Contact Allergies demonstrated that the most common hand allergens were nickel, preservatives (quaternium-15 and formaldehyde), fragrances, and cobalt.¹⁸ In health care workers, rubber accelerators often are relevant in patients with hand ACD.^5,19 Hand hygiene products are known to contain potential allergens; a recent study demonstrated that the top 5 allergens in common hand sanitizers were tocopherol, fragrance, propylene glycol, benzoates, and cetylstearyl alcohol,²⁰ whereas the most common allergens in hand cleansers were fragrance, tocopherol, sodium benzoate, chloroxylenol, propylene glycol, and chlorhexidine gluconate.²¹

Preservatives
Preservatives can contribute to hand ACD. Methylisothiazolinone was the most commonly relevant allergen in a recent North American study of hand contact allergy,³ and a study of North American products confirmed its presence in dishwashing products (64%), shampoos (53%), household cleaners (47%), laundry softeners/additives (30%), soaps and cleansers (29%), and surface disinfectants (27%).²² In addition, in a study of 139 patients with refractory MI contact allergy, the hands were the most common site (69%) and had the highest rate of relapse.²³ Because of the common presence of this preservative in liquid-based personal care products, patients with MI hand contact allergy need to be vigilant.

The same North American study highlighted formaldehyde and the formaldehyde releaser quaternium-15 as commonly relevant hand contact allergens.³ Formaldehyde is not commonly found in personal care products, but formaldehyde-releasing preservatives frequently are found in cosmetic products, topical medicaments, detergents, soaps, and metal working fluids. Another study noted that the most relevant contact allergen in health care workers was quaternium-15, possibly due to increased hand hygiene and exposure to medical products used for patient care.^24,25

Metals
Nickel is used in metal objects and is found in many workplaces in the form of machines, office supplies, tools, electronics, uniforms, and jewelry. Occupationally related nickel ACD of the hands is most common in hairdressers/barbers/cosmetologists,²⁶ which is not surprising, as hairdressing tools such as scissors and hair clips can release nickel.^27,28

Although nickel contact allergy is more common than cobalt, these metals frequently co-react, with up to 25% of nickel-sensitive patients also having positive patch test reactions to cobalt.²⁹ Because cobalt is contained in alloys, the occupations most at risk pertain to hard metal manufacturing. Furthermore, cobalt is used in dentistry for dental tools, fillings, crowns, bridges, and dentures.³⁰ Cobalt also has been identified in leather, and leather gloves have been implicated in hand ACD.³¹

Fragrances
Fragrances can be added to products to infuse pleasing aromas or mask unpleasant chemical odors. In the North American study of hand ACD, fragrance mix I and balsam of Peru were the sixth and seventh most clinically relevant allergens, respectively.³ In another study, fragrances were found in 50% of waterless cleansers and 95% of rinse-off soaps and were the second most common allergens found in skin disinfectants.²¹ Fragrance is ubiquitous in personal care and cleansing products, which can make avoidance difficult.

Rubber Accelerators
Contact allergy to rubber additives in medical gloves is the most common cause of occupational hand ACD in health care workers.^5,19 Importantly, it usually is rubber accelerators that act as allergens in hand ACD and not natural rubber latex. Rubber accelerators known to cause ACD include thiurams, carbamates, 1,3-diphenylguanidine (DPG), mixed dialkyl thioureas, and benzothiazoles.³² In the setting of hand ACD in North America, reactions to thiuram mix and carba mix were the most common.³ Notably, DPG is a component of carba mix and can be present in rubber gloves. It has been shown that 40.3% of DPG reactions are missed by testing with carba mix alone; therefore, DPG must be patch tested separately.³³

Clinical Examination

It can be challenging to differentiate between hand ICD and ACD based on clinical appearance alone, and patch testing often is necessary for diagnosis. In the acute phase, both ICD and ACD can present as erythema, papules, vesicles, bullae, and/or crusting. In the chronic phase, scaling, lichenification, and/or fissures tend to prevail. Both acute and chronic ICD and ACD can be associated with pruritus and pain; however, ICD may be more likely associated with a burning or painful sensation, whereas ACD may be more associated with pruritus.

Other dermatoses may present as hand eruptions and should be kept in the differential diagnosis. Atopic dermatitis, psoriasis, dyshidrotic eczema, hyperkeratotic hand dermatitis, keratolysis exfoliativa, and palmoplantar pustulosis are other common causes of hand eruptions.^5,34

Patch Testing for Hand ACD
Consider patch testing for hand dermatitis that is refractory to conservative treatment. Patients with new-onset hand dermatitis without history of atopy and patients with a new worsening of chronic hand dermatitis also may need patch testing.

In addition to a medically appropriate screening series, patients with hand dermatitis often need supplemental patch testing. In a series of 37,113 patients with hand ACD, just over 20% of patients had positive patch test reactions to at least 1 supplemental allergen not on the screening series.³ Supplemental series should be selected based on the patient’s history and exposures; for example, nail salon technicians may need supplemental testing with the nail acrylate series, and massage therapists may need additional testing with the fragrance or essential oil series. Some of the most common supplemental series used for evaluation of hand dermatitis are the rubber, cosmetic, textile and dyes, plant, fragrance, essential oil, oil and coolants, nail or printing acrylates, and hairdressing series. If there is a high suspicion of occupational contact with allergens, obtaining material safety data sheets from the patient’s employer can be helpful to identify relevant allergens for testing.⁵ The thin-layer rapid use epicutaneous (T.R.U.E.) test may miss several common and relevant hand allergens, including benzalkonium chloride, lanolin, and iodopropynyl butylcarbamate.³

Management

Management of hand ICD requires avoidance of irritants and proper hand hygiene practices.^10,34 The hands should be washed using lukewarm water and mild fragrance-free soaps or cleansers,³⁵ keeping in mind that hand sanitizers may be better tolerated due to their lower lipid-stripping effects. The moisturizers with the best efficacy are combinations of humectants (topical urea, glycerin) and occlusive emollients (dimethicone, petrolatum).¹¹ When wet work is necessary, gloves should be worn; however, sweat and humidity from glove use can worsen ICD, and gloves should be changed regularly and applied only when hands are dry. Cotton gloves also can be worn underneath rubber gloves to prevent maceration from sweat.⁹

The mainstay of hand ACD management is allergen avoidance. The American Contact Dermatitis Society maintains the Contact Allergen Management Program (CAMP), a database that identifies products that do not contain patient allergens. The importance of reading ingredient labels of products should always be emphasized. For patients with rubber accelerator allergies, vinyl or accelerator-free gloves may be used. If the allergen is occupational, communication with the patient’s employer is necessary.⁵

When hand contact dermatitis does not improve with avoidance of irritants and allergens as well as gentle skin care, topical therapy, phototherapy, and in some cases systemic therapy may be required. High-potency topical corticosteroids or short courses of prednisone may be needed for quick relief. Topical calcineurin inhibitors (tacrolimus and pimecrolimus) and the phosphodiesterase 4 inhibitor crisaborole have shown some efficacy for hand dermatitis and can be used as steroid-sparing agents.^36,37 Narrowband UVB and UVA have been used with moderate efficacy to treat resistant hand dermatitis.^34,38 Oral immunosuppressant medications such as methotrexate, mycophenolate mofetil, azathioprine, and cyclosporine can be used for more severe cases.^34,39,40 Furthermore, oral retinoids have been used for chronic severe hand dermatitis with notable efficacy.⁴¹

Our Final Interpretation

The 2 major types of hand contact dermatitis are ICD and ACD. Hand ICD is more common than ACD in both occupational and nonoccupational settings. The hands are the most common sites in the setting of occupational dermatitis; in North American patch test populations, the hands were the primary site of involvement in just under 25% of patients.³ Many hand hygiene products contain irritants and allergens. The lipid-stripping effects of soaps, detergents, and hand sanitizers in conjunction with increased frequency of handwashing can trigger ICD. The most common allergens implicated in hand ACD include MI, nickel, formaldehyde, quaternium-15, and fragrances. Patch testing is important for diagnosis, and supplemental series should be considered. Management includes avoidance of irritants and allergens; liberal use of moisturizers and barrier creams; and prescription topical therapy, phototherapy, or systemic therapy when indicated.

Hand dermatitis, also known as hand eczema, is common and affects a considerable number of individuals across all ages. The impact of hand dermatitis can be profound, as it can impair one’s ability to perform tasks at home and at work. As a result of the coronavirus disease 2019 (COVID-19) pandemic, there has been an increased focus on hand hygiene and subsequently hand dermatitis. There are many contributors to the severity of hand dermatitis, including genetic factors, immune reactions, and skin barrier disruption. In this column, we will explore irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD) of the hands, including epidemiology, potential causes, clinical characteristics, diagnosis, and management.

Epidemiology

The prevalence of hand dermatitis in the general population is 3% to 4%, with a 1‐year prevalence of 10% and a lifetime prevalence of 15%.¹ In a Swedish study of patients self-reporting hand eczema, contact dermatitis comprised 57% of the total cases (N=1385); ICD accounted for 35% of cases followed by ACD in 22%.² A recent study on hand dermatitis in North American specialty patch test clinics documented that the hands were the primary site of involvement in 24.2% of patients undergoing patch testing (N=37,113).³

The hands are particularly at risk for occupation-related contact dermatitis and are the primary site of involvement in 80% of cases, followed by the wrists and forearms.⁴ Occupations at greatest risk include cleaning, construction, metalworking, hairdressing, health care, housework, and mechanics.⁵ Even prior to the COVID-19 pandemic, occupational hand dermatitis was common; in a survey of inpatient nurses, the prevalence was 55% (N=167).⁶ More recently, a study from China demonstrated a 74.5% prevalence of hand dermatitis in frontline health care workers involved in COVID-19 patient care.⁷

Etiology of Hand ICD

The pathogenesis of ICD is multifactorial; although traditionally thought to be nonimmunologic, evidence has shown that it involves skin barrier disruption, infiltration by immunocompetent cells, and induction of inflammatory signal molecules. The degree of irritancy is related to the concentration, contact duration, and properties of the irritant. Irritant reactions can be acute, such as those following a single chemical exposure that results in a localized dermatitis, or chronic, such as after repetitive cumulative exposure to mild irritants such as soaps.

Hand hygiene products (eg, soaps, hand sanitizers) can be irritants and have recently gained notoriety given their increased use to prevent COVID-19 transmission.^8,9 Specific irritants include iodophors, antimicrobial soaps (chlorhexidine gluconate, chloroxylenol, triclosan), surfactants, and detergents. Wolfe et al¹⁰ showed that detergent-based hand cleansing products had the highest association with ICD, which was thought to be due to their propensity to remove protective lipids and reduce moisture content in the stratum corneum. Although hand sanitizers are better tolerated than detergents, they can still contribute to ICD by stripping precious lipids and disrupting the skin barrier.¹¹ Compared to ethanol, isopropanol and N-propanol cause more disruption of the stratum corneum.¹² In addition, N-propanol has the same irritant potential as the detergent sodium lauryl sulfate.¹³ Thus, ethanol-based sanitizers may be better tolerated. Disinfectant surface wipes may include the irritant N-alkyl dimethyl benzyl ammonium chloride. Conversely, hand and baby wipes are formulated specifically for the skin and may be less irritating.¹¹

Occupational contributors to hand ICD include chemical exposures and frequent handwashing. Wet work, mechanical trauma, warm dry air, and prolonged use of occlusive gloves also are well-known irritants.⁴ Fine or coarse particles encountered in some occupations or hobbies (eg, sand, sawdust, metal filings, plastic) can cause mechanical irritation. Exposure to physical friction from repeated handling of metal components, paper, cardboard, fabric, or steering wheels also has been implicated in hand ICD. Other common categories of occupational irritants include hydrocarbons, such as oils and petroleum.^5,14

In addition to environmental factors, atopic dermatitis is an important endogenous factor that increases the risk of ICD due to underlying deficiencies within the main lipid¹⁵ and structural¹⁶ barrier components. These deficiencies ultimately lead to a lower threshold for the activation of inflammation via water loss and a weakened barrier. Studies have demonstrated that atopic dermatitis increases the risk for developing hand ICD 2- to 4-fold.¹⁷

Etiology of Hand ACD

Allergic contact dermatitis is an immune-mediated type IV delayed hypersensitivity reaction. The North American Contact Dermatitis Group reported that the top 5 clinically relevant hand allergens were methylisothiazolinone (MI), nickel, formaldehyde, quaternium-15, and fragrance mix I.³ Similarly, the European Surveillance System on Contact Allergies demonstrated that the most common hand allergens were nickel, preservatives (quaternium-15 and formaldehyde), fragrances, and cobalt.¹⁸ In health care workers, rubber accelerators often are relevant in patients with hand ACD.^5,19 Hand hygiene products are known to contain potential allergens; a recent study demonstrated that the top 5 allergens in common hand sanitizers were tocopherol, fragrance, propylene glycol, benzoates, and cetylstearyl alcohol,²⁰ whereas the most common allergens in hand cleansers were fragrance, tocopherol, sodium benzoate, chloroxylenol, propylene glycol, and chlorhexidine gluconate.²¹

Preservatives
Preservatives can contribute to hand ACD. Methylisothiazolinone was the most commonly relevant allergen in a recent North American study of hand contact allergy,³ and a study of North American products confirmed its presence in dishwashing products (64%), shampoos (53%), household cleaners (47%), laundry softeners/additives (30%), soaps and cleansers (29%), and surface disinfectants (27%).²² In addition, in a study of 139 patients with refractory MI contact allergy, the hands were the most common site (69%) and had the highest rate of relapse.²³ Because of the common presence of this preservative in liquid-based personal care products, patients with MI hand contact allergy need to be vigilant.

The same North American study highlighted formaldehyde and the formaldehyde releaser quaternium-15 as commonly relevant hand contact allergens.³ Formaldehyde is not commonly found in personal care products, but formaldehyde-releasing preservatives frequently are found in cosmetic products, topical medicaments, detergents, soaps, and metal working fluids. Another study noted that the most relevant contact allergen in health care workers was quaternium-15, possibly due to increased hand hygiene and exposure to medical products used for patient care.^24,25

Metals
Nickel is used in metal objects and is found in many workplaces in the form of machines, office supplies, tools, electronics, uniforms, and jewelry. Occupationally related nickel ACD of the hands is most common in hairdressers/barbers/cosmetologists,²⁶ which is not surprising, as hairdressing tools such as scissors and hair clips can release nickel.^27,28

Although nickel contact allergy is more common than cobalt, these metals frequently co-react, with up to 25% of nickel-sensitive patients also having positive patch test reactions to cobalt.²⁹ Because cobalt is contained in alloys, the occupations most at risk pertain to hard metal manufacturing. Furthermore, cobalt is used in dentistry for dental tools, fillings, crowns, bridges, and dentures.³⁰ Cobalt also has been identified in leather, and leather gloves have been implicated in hand ACD.³¹

Fragrances
Fragrances can be added to products to infuse pleasing aromas or mask unpleasant chemical odors. In the North American study of hand ACD, fragrance mix I and balsam of Peru were the sixth and seventh most clinically relevant allergens, respectively.³ In another study, fragrances were found in 50% of waterless cleansers and 95% of rinse-off soaps and were the second most common allergens found in skin disinfectants.²¹ Fragrance is ubiquitous in personal care and cleansing products, which can make avoidance difficult.

Rubber Accelerators
Contact allergy to rubber additives in medical gloves is the most common cause of occupational hand ACD in health care workers.^5,19 Importantly, it usually is rubber accelerators that act as allergens in hand ACD and not natural rubber latex. Rubber accelerators known to cause ACD include thiurams, carbamates, 1,3-diphenylguanidine (DPG), mixed dialkyl thioureas, and benzothiazoles.³² In the setting of hand ACD in North America, reactions to thiuram mix and carba mix were the most common.³ Notably, DPG is a component of carba mix and can be present in rubber gloves. It has been shown that 40.3% of DPG reactions are missed by testing with carba mix alone; therefore, DPG must be patch tested separately.³³

Clinical Examination

It can be challenging to differentiate between hand ICD and ACD based on clinical appearance alone, and patch testing often is necessary for diagnosis. In the acute phase, both ICD and ACD can present as erythema, papules, vesicles, bullae, and/or crusting. In the chronic phase, scaling, lichenification, and/or fissures tend to prevail. Both acute and chronic ICD and ACD can be associated with pruritus and pain; however, ICD may be more likely associated with a burning or painful sensation, whereas ACD may be more associated with pruritus.

Other dermatoses may present as hand eruptions and should be kept in the differential diagnosis. Atopic dermatitis, psoriasis, dyshidrotic eczema, hyperkeratotic hand dermatitis, keratolysis exfoliativa, and palmoplantar pustulosis are other common causes of hand eruptions.^5,34

Patch Testing for Hand ACD
Consider patch testing for hand dermatitis that is refractory to conservative treatment. Patients with new-onset hand dermatitis without history of atopy and patients with a new worsening of chronic hand dermatitis also may need patch testing.

In addition to a medically appropriate screening series, patients with hand dermatitis often need supplemental patch testing. In a series of 37,113 patients with hand ACD, just over 20% of patients had positive patch test reactions to at least 1 supplemental allergen not on the screening series.³ Supplemental series should be selected based on the patient’s history and exposures; for example, nail salon technicians may need supplemental testing with the nail acrylate series, and massage therapists may need additional testing with the fragrance or essential oil series. Some of the most common supplemental series used for evaluation of hand dermatitis are the rubber, cosmetic, textile and dyes, plant, fragrance, essential oil, oil and coolants, nail or printing acrylates, and hairdressing series. If there is a high suspicion of occupational contact with allergens, obtaining material safety data sheets from the patient’s employer can be helpful to identify relevant allergens for testing.⁵ The thin-layer rapid use epicutaneous (T.R.U.E.) test may miss several common and relevant hand allergens, including benzalkonium chloride, lanolin, and iodopropynyl butylcarbamate.³

Management

Management of hand ICD requires avoidance of irritants and proper hand hygiene practices.^10,34 The hands should be washed using lukewarm water and mild fragrance-free soaps or cleansers,³⁵ keeping in mind that hand sanitizers may be better tolerated due to their lower lipid-stripping effects. The moisturizers with the best efficacy are combinations of humectants (topical urea, glycerin) and occlusive emollients (dimethicone, petrolatum).¹¹ When wet work is necessary, gloves should be worn; however, sweat and humidity from glove use can worsen ICD, and gloves should be changed regularly and applied only when hands are dry. Cotton gloves also can be worn underneath rubber gloves to prevent maceration from sweat.⁹

The mainstay of hand ACD management is allergen avoidance. The American Contact Dermatitis Society maintains the Contact Allergen Management Program (CAMP), a database that identifies products that do not contain patient allergens. The importance of reading ingredient labels of products should always be emphasized. For patients with rubber accelerator allergies, vinyl or accelerator-free gloves may be used. If the allergen is occupational, communication with the patient’s employer is necessary.⁵

When hand contact dermatitis does not improve with avoidance of irritants and allergens as well as gentle skin care, topical therapy, phototherapy, and in some cases systemic therapy may be required. High-potency topical corticosteroids or short courses of prednisone may be needed for quick relief. Topical calcineurin inhibitors (tacrolimus and pimecrolimus) and the phosphodiesterase 4 inhibitor crisaborole have shown some efficacy for hand dermatitis and can be used as steroid-sparing agents.^36,37 Narrowband UVB and UVA have been used with moderate efficacy to treat resistant hand dermatitis.^34,38 Oral immunosuppressant medications such as methotrexate, mycophenolate mofetil, azathioprine, and cyclosporine can be used for more severe cases.^34,39,40 Furthermore, oral retinoids have been used for chronic severe hand dermatitis with notable efficacy.⁴¹

Our Final Interpretation

The 2 major types of hand contact dermatitis are ICD and ACD. Hand ICD is more common than ACD in both occupational and nonoccupational settings. The hands are the most common sites in the setting of occupational dermatitis; in North American patch test populations, the hands were the primary site of involvement in just under 25% of patients.³ Many hand hygiene products contain irritants and allergens. The lipid-stripping effects of soaps, detergents, and hand sanitizers in conjunction with increased frequency of handwashing can trigger ICD. The most common allergens implicated in hand ACD include MI, nickel, formaldehyde, quaternium-15, and fragrances. Patch testing is important for diagnosis, and supplemental series should be considered. Management includes avoidance of irritants and allergens; liberal use of moisturizers and barrier creams; and prescription topical therapy, phototherapy, or systemic therapy when indicated.