‘Profound human toll’ in excess deaths from COVID-19 calculated in two studies

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More than 225,000 excess deaths occurred in the United States from March to July 2020, compared with historic norms, with approximately two-thirds directly attributable to COVID-19. However, additional deaths could be indirectly related because people avoided emergency care during the pandemic, new research shows.

Deaths linked to COVID-19 varied by state and phase of the pandemic, as reported in a study from researchers at Virginia Commonwealth University and Yale University that was published online October 12 in JAMA.

Another study published online simultaneously in JAMA took more of an international perspective. Investigators from the University of Pennsylvania and Harvard University found that in America there were more excess deaths and there was higher all-cause mortality during the pandemic than in 18 other countries.

Although the ongoing number of deaths attributable to COVID-19 continues to garner attention, there can be a lag of weeks or months in how long it takes some public health agencies to update their figures.

“For the public at large, the take-home message is twofold: that the number of deaths caused by the pandemic exceeds publicly reported COVID-19 death counts by 20% and that states that reopened or lifted restrictions early suffered a protracted surge in excess deaths that extended into the summer,” lead author of the US-focused study, Steven H. Woolf, MD, MPH, told Medscape Medical News.

The take-away for physicians is in the bigger picture – it is likely that the COVID-19 pandemic is responsible for deaths from other conditions as well. “Surges in COVID-19 were accompanied by an increase in deaths attributed to other causes, such as heart disease and Alzheimer’s disease and dementia,” said Woolf, director emeritus and senior adviser at the Center on Society and Health and professor in the Department of Family Medicine and Population Health at the Virginia Commonwealth University School of Medicine in Richmond, Virginia.

The investigators identified 225,530 excess US deaths in the 5 months from March to July. They report that 67% were directly attributable to COVID-19.

Deaths linked to COVID-19 included those in which the disease was listed as an underlying or contributing cause. US total death rates are “remarkably consistent” year after year, and the investigators calculated a 20% overall jump in mortality.

The study included data from the National Center for Health Statistics and the US Census Bureau for 48 states and the District of Columbia. Connecticut and North Carolina were excluded because of missing data.

Woolf and colleagues also found statistically higher rates of deaths from two other causes, heart disease and Alzheimer’s disease/dementia.
 

Altered states

New York, New Jersey, Massachusetts, Louisiana, Arizona, Mississippi, Maryland, Delaware, Rhode Island, and Michigan had the highest per capita excess death rates. Three states experienced the shortest epidemics during the study period: New York, New Jersey, and Massachusetts.

Some lessons could be learned by looking at how individual states managed large numbers of people with COVID-19. “Although we suspected that states that reopened early might have put themselves at risk of a pandemic surge, the consistency with which that occurred and the devastating numbers of deaths they suffered was a surprise,” Woolf said.

“The goal of our study is not to look in the rearview mirror and lament what happened months ago but to learn the lesson going forward: Our country will be unable to take control of this pandemic without more robust efforts to control community spread,” Woolf said. “Our study found that states that did this well, such as New York and New Jersey, experienced large surges but bent the curve and were back to baseline in less than 10 weeks.

“If we could do this as a country, countless lives could be saved.”
 

 

 

A global perspective

The United States experienced high mortality linked to COVID-19, as well as high all-cause mortality, compared with 18 other countries, as reported in the study by University of Pennsylvania and Harvard University researchers.

The United States ranked third, with 72 deaths per 100,000 people, among countries with moderate or high mortality. Although perhaps not surprising given the state of SARS-CoV-2 infection across the United States, a question remains as to what extent the relatively high mortality rate is linked to early outbreaks vs “poor long-term response,” the researchers note.

Alyssa Bilinski, MSc, and lead author Ezekiel J. Emanuel, MD, PhD, chair of the Department of Medical Ethics and Health Policy at the University of Pennsylvania Perelman School of Medicine in Philadelphia, calculated the difference in COVID-19 deaths among countries through Sept. 19, 2020. On this date, the United States reported a total 198,589 COVID-19 deaths.

They calculated that, if the US death rates were similar to those in Australia, the United States would have experienced 187,661 fewer COVID-19 deaths. If similar to those of Canada, there would have been 117,622 fewer deaths in the United States.

The US death rate was lower than six other countries with high COVID-19 mortality in the early spring, including Belgium, Spain, and the United Kingdom. However, after May 10, the per capita mortality rate in the United States exceeded the others.

Between May 10 and Sept. 19, the death rate in Italy was 9.1 per 100,000, vs 36.9 per 100,000.

“After the first peak in early spring, US death rates from COVID-19 and from all causes remained higher than even countries with high COVID-19 mortality,” the researchers note. “This may have been a result of several factors, including weak public health infrastructure and a decentralized, inconsistent US response to the pandemic.”
 

“Mortifying and motivating”

Woolf and colleagues estimate that more than 225,000 excess deaths occurred in recent months; this represents a 20% increase over expected deaths, note Harvey V. Fineberg, MD, PhD, of the Gordon and Betty Moore Foundation, in an accompanying editorial in JAMA.

“Importantly, a condition such as COVID-19 can contribute both directly and indirectly to excess mortality,” he writes.

Although the direct contribution to the mortality rates by those infected is straightforward, “the indirect contribution may relate to circumstances or choices due to the COVID-19 pandemic: for example, a patient who develops symptoms of a stroke is too concerned about COVID-19 to go to the emergency department, and a potentially reversible condition becomes fatal.”

Fineberg notes that “a general indication of the death toll from COVID-19 and the excess deaths related to the pandemic, as presented by Woolf et al, are sufficiently mortifying and motivating.”
 

“Profound human toll”

“The importance of the estimate by Woolf et al – which suggests that for the entirety of 2020, more than 400,000 excess deaths will occur – cannot be overstated, because it accounts for what could be declines in some causes of death, like motor vehicle crashes, but increases in others, like myocardial infarction,” write Howard Bauchner, MD, editor in chief of JAMA, and Phil B. Fontanarosa, MD, MBA, executive editor of JAMA, in another accompanying editorial.

“These deaths reflect a true measure of the human cost of the Great Pandemic of 2020,” they add.

The study from Emanuel and Bilinski was notable for calculating the excess COVID-19 and all-cause mortality to Sept. 2020, they note. “After the initial peak in early spring, US death rates from COVID-19 and from all causes remained higher than rates in countries with high COVID-19 mortality.”

“Few people will forget the Great Pandemic of 2020, where and how they lived, how it substantially changed their lives, and for many, the profound human toll it has taken,” Bauchner and Fontanarosa write.

The study by Woolf and colleagues was supported by National Center for Advancing Translational Sciences, the National Institute on Aging, and the National Institute of Allergy and Infectious Diseases. The study by Bilinski and Emanuel was partially funded by the Colton Foundation. Woolf, Emanuel, Fineberg, Bauchner, and Fontanarosa have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

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More than 225,000 excess deaths occurred in the United States from March to July 2020, compared with historic norms, with approximately two-thirds directly attributable to COVID-19. However, additional deaths could be indirectly related because people avoided emergency care during the pandemic, new research shows.

Deaths linked to COVID-19 varied by state and phase of the pandemic, as reported in a study from researchers at Virginia Commonwealth University and Yale University that was published online October 12 in JAMA.

Another study published online simultaneously in JAMA took more of an international perspective. Investigators from the University of Pennsylvania and Harvard University found that in America there were more excess deaths and there was higher all-cause mortality during the pandemic than in 18 other countries.

Although the ongoing number of deaths attributable to COVID-19 continues to garner attention, there can be a lag of weeks or months in how long it takes some public health agencies to update their figures.

“For the public at large, the take-home message is twofold: that the number of deaths caused by the pandemic exceeds publicly reported COVID-19 death counts by 20% and that states that reopened or lifted restrictions early suffered a protracted surge in excess deaths that extended into the summer,” lead author of the US-focused study, Steven H. Woolf, MD, MPH, told Medscape Medical News.

The take-away for physicians is in the bigger picture – it is likely that the COVID-19 pandemic is responsible for deaths from other conditions as well. “Surges in COVID-19 were accompanied by an increase in deaths attributed to other causes, such as heart disease and Alzheimer’s disease and dementia,” said Woolf, director emeritus and senior adviser at the Center on Society and Health and professor in the Department of Family Medicine and Population Health at the Virginia Commonwealth University School of Medicine in Richmond, Virginia.

The investigators identified 225,530 excess US deaths in the 5 months from March to July. They report that 67% were directly attributable to COVID-19.

Deaths linked to COVID-19 included those in which the disease was listed as an underlying or contributing cause. US total death rates are “remarkably consistent” year after year, and the investigators calculated a 20% overall jump in mortality.

The study included data from the National Center for Health Statistics and the US Census Bureau for 48 states and the District of Columbia. Connecticut and North Carolina were excluded because of missing data.

Woolf and colleagues also found statistically higher rates of deaths from two other causes, heart disease and Alzheimer’s disease/dementia.
 

Altered states

New York, New Jersey, Massachusetts, Louisiana, Arizona, Mississippi, Maryland, Delaware, Rhode Island, and Michigan had the highest per capita excess death rates. Three states experienced the shortest epidemics during the study period: New York, New Jersey, and Massachusetts.

Some lessons could be learned by looking at how individual states managed large numbers of people with COVID-19. “Although we suspected that states that reopened early might have put themselves at risk of a pandemic surge, the consistency with which that occurred and the devastating numbers of deaths they suffered was a surprise,” Woolf said.

“The goal of our study is not to look in the rearview mirror and lament what happened months ago but to learn the lesson going forward: Our country will be unable to take control of this pandemic without more robust efforts to control community spread,” Woolf said. “Our study found that states that did this well, such as New York and New Jersey, experienced large surges but bent the curve and were back to baseline in less than 10 weeks.

“If we could do this as a country, countless lives could be saved.”
 

 

 

A global perspective

The United States experienced high mortality linked to COVID-19, as well as high all-cause mortality, compared with 18 other countries, as reported in the study by University of Pennsylvania and Harvard University researchers.

The United States ranked third, with 72 deaths per 100,000 people, among countries with moderate or high mortality. Although perhaps not surprising given the state of SARS-CoV-2 infection across the United States, a question remains as to what extent the relatively high mortality rate is linked to early outbreaks vs “poor long-term response,” the researchers note.

Alyssa Bilinski, MSc, and lead author Ezekiel J. Emanuel, MD, PhD, chair of the Department of Medical Ethics and Health Policy at the University of Pennsylvania Perelman School of Medicine in Philadelphia, calculated the difference in COVID-19 deaths among countries through Sept. 19, 2020. On this date, the United States reported a total 198,589 COVID-19 deaths.

They calculated that, if the US death rates were similar to those in Australia, the United States would have experienced 187,661 fewer COVID-19 deaths. If similar to those of Canada, there would have been 117,622 fewer deaths in the United States.

The US death rate was lower than six other countries with high COVID-19 mortality in the early spring, including Belgium, Spain, and the United Kingdom. However, after May 10, the per capita mortality rate in the United States exceeded the others.

Between May 10 and Sept. 19, the death rate in Italy was 9.1 per 100,000, vs 36.9 per 100,000.

“After the first peak in early spring, US death rates from COVID-19 and from all causes remained higher than even countries with high COVID-19 mortality,” the researchers note. “This may have been a result of several factors, including weak public health infrastructure and a decentralized, inconsistent US response to the pandemic.”
 

“Mortifying and motivating”

Woolf and colleagues estimate that more than 225,000 excess deaths occurred in recent months; this represents a 20% increase over expected deaths, note Harvey V. Fineberg, MD, PhD, of the Gordon and Betty Moore Foundation, in an accompanying editorial in JAMA.

“Importantly, a condition such as COVID-19 can contribute both directly and indirectly to excess mortality,” he writes.

Although the direct contribution to the mortality rates by those infected is straightforward, “the indirect contribution may relate to circumstances or choices due to the COVID-19 pandemic: for example, a patient who develops symptoms of a stroke is too concerned about COVID-19 to go to the emergency department, and a potentially reversible condition becomes fatal.”

Fineberg notes that “a general indication of the death toll from COVID-19 and the excess deaths related to the pandemic, as presented by Woolf et al, are sufficiently mortifying and motivating.”
 

“Profound human toll”

“The importance of the estimate by Woolf et al – which suggests that for the entirety of 2020, more than 400,000 excess deaths will occur – cannot be overstated, because it accounts for what could be declines in some causes of death, like motor vehicle crashes, but increases in others, like myocardial infarction,” write Howard Bauchner, MD, editor in chief of JAMA, and Phil B. Fontanarosa, MD, MBA, executive editor of JAMA, in another accompanying editorial.

“These deaths reflect a true measure of the human cost of the Great Pandemic of 2020,” they add.

The study from Emanuel and Bilinski was notable for calculating the excess COVID-19 and all-cause mortality to Sept. 2020, they note. “After the initial peak in early spring, US death rates from COVID-19 and from all causes remained higher than rates in countries with high COVID-19 mortality.”

“Few people will forget the Great Pandemic of 2020, where and how they lived, how it substantially changed their lives, and for many, the profound human toll it has taken,” Bauchner and Fontanarosa write.

The study by Woolf and colleagues was supported by National Center for Advancing Translational Sciences, the National Institute on Aging, and the National Institute of Allergy and Infectious Diseases. The study by Bilinski and Emanuel was partially funded by the Colton Foundation. Woolf, Emanuel, Fineberg, Bauchner, and Fontanarosa have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

 

More than 225,000 excess deaths occurred in the United States from March to July 2020, compared with historic norms, with approximately two-thirds directly attributable to COVID-19. However, additional deaths could be indirectly related because people avoided emergency care during the pandemic, new research shows.

Deaths linked to COVID-19 varied by state and phase of the pandemic, as reported in a study from researchers at Virginia Commonwealth University and Yale University that was published online October 12 in JAMA.

Another study published online simultaneously in JAMA took more of an international perspective. Investigators from the University of Pennsylvania and Harvard University found that in America there were more excess deaths and there was higher all-cause mortality during the pandemic than in 18 other countries.

Although the ongoing number of deaths attributable to COVID-19 continues to garner attention, there can be a lag of weeks or months in how long it takes some public health agencies to update their figures.

“For the public at large, the take-home message is twofold: that the number of deaths caused by the pandemic exceeds publicly reported COVID-19 death counts by 20% and that states that reopened or lifted restrictions early suffered a protracted surge in excess deaths that extended into the summer,” lead author of the US-focused study, Steven H. Woolf, MD, MPH, told Medscape Medical News.

The take-away for physicians is in the bigger picture – it is likely that the COVID-19 pandemic is responsible for deaths from other conditions as well. “Surges in COVID-19 were accompanied by an increase in deaths attributed to other causes, such as heart disease and Alzheimer’s disease and dementia,” said Woolf, director emeritus and senior adviser at the Center on Society and Health and professor in the Department of Family Medicine and Population Health at the Virginia Commonwealth University School of Medicine in Richmond, Virginia.

The investigators identified 225,530 excess US deaths in the 5 months from March to July. They report that 67% were directly attributable to COVID-19.

Deaths linked to COVID-19 included those in which the disease was listed as an underlying or contributing cause. US total death rates are “remarkably consistent” year after year, and the investigators calculated a 20% overall jump in mortality.

The study included data from the National Center for Health Statistics and the US Census Bureau for 48 states and the District of Columbia. Connecticut and North Carolina were excluded because of missing data.

Woolf and colleagues also found statistically higher rates of deaths from two other causes, heart disease and Alzheimer’s disease/dementia.
 

Altered states

New York, New Jersey, Massachusetts, Louisiana, Arizona, Mississippi, Maryland, Delaware, Rhode Island, and Michigan had the highest per capita excess death rates. Three states experienced the shortest epidemics during the study period: New York, New Jersey, and Massachusetts.

Some lessons could be learned by looking at how individual states managed large numbers of people with COVID-19. “Although we suspected that states that reopened early might have put themselves at risk of a pandemic surge, the consistency with which that occurred and the devastating numbers of deaths they suffered was a surprise,” Woolf said.

“The goal of our study is not to look in the rearview mirror and lament what happened months ago but to learn the lesson going forward: Our country will be unable to take control of this pandemic without more robust efforts to control community spread,” Woolf said. “Our study found that states that did this well, such as New York and New Jersey, experienced large surges but bent the curve and were back to baseline in less than 10 weeks.

“If we could do this as a country, countless lives could be saved.”
 

 

 

A global perspective

The United States experienced high mortality linked to COVID-19, as well as high all-cause mortality, compared with 18 other countries, as reported in the study by University of Pennsylvania and Harvard University researchers.

The United States ranked third, with 72 deaths per 100,000 people, among countries with moderate or high mortality. Although perhaps not surprising given the state of SARS-CoV-2 infection across the United States, a question remains as to what extent the relatively high mortality rate is linked to early outbreaks vs “poor long-term response,” the researchers note.

Alyssa Bilinski, MSc, and lead author Ezekiel J. Emanuel, MD, PhD, chair of the Department of Medical Ethics and Health Policy at the University of Pennsylvania Perelman School of Medicine in Philadelphia, calculated the difference in COVID-19 deaths among countries through Sept. 19, 2020. On this date, the United States reported a total 198,589 COVID-19 deaths.

They calculated that, if the US death rates were similar to those in Australia, the United States would have experienced 187,661 fewer COVID-19 deaths. If similar to those of Canada, there would have been 117,622 fewer deaths in the United States.

The US death rate was lower than six other countries with high COVID-19 mortality in the early spring, including Belgium, Spain, and the United Kingdom. However, after May 10, the per capita mortality rate in the United States exceeded the others.

Between May 10 and Sept. 19, the death rate in Italy was 9.1 per 100,000, vs 36.9 per 100,000.

“After the first peak in early spring, US death rates from COVID-19 and from all causes remained higher than even countries with high COVID-19 mortality,” the researchers note. “This may have been a result of several factors, including weak public health infrastructure and a decentralized, inconsistent US response to the pandemic.”
 

“Mortifying and motivating”

Woolf and colleagues estimate that more than 225,000 excess deaths occurred in recent months; this represents a 20% increase over expected deaths, note Harvey V. Fineberg, MD, PhD, of the Gordon and Betty Moore Foundation, in an accompanying editorial in JAMA.

“Importantly, a condition such as COVID-19 can contribute both directly and indirectly to excess mortality,” he writes.

Although the direct contribution to the mortality rates by those infected is straightforward, “the indirect contribution may relate to circumstances or choices due to the COVID-19 pandemic: for example, a patient who develops symptoms of a stroke is too concerned about COVID-19 to go to the emergency department, and a potentially reversible condition becomes fatal.”

Fineberg notes that “a general indication of the death toll from COVID-19 and the excess deaths related to the pandemic, as presented by Woolf et al, are sufficiently mortifying and motivating.”
 

“Profound human toll”

“The importance of the estimate by Woolf et al – which suggests that for the entirety of 2020, more than 400,000 excess deaths will occur – cannot be overstated, because it accounts for what could be declines in some causes of death, like motor vehicle crashes, but increases in others, like myocardial infarction,” write Howard Bauchner, MD, editor in chief of JAMA, and Phil B. Fontanarosa, MD, MBA, executive editor of JAMA, in another accompanying editorial.

“These deaths reflect a true measure of the human cost of the Great Pandemic of 2020,” they add.

The study from Emanuel and Bilinski was notable for calculating the excess COVID-19 and all-cause mortality to Sept. 2020, they note. “After the initial peak in early spring, US death rates from COVID-19 and from all causes remained higher than rates in countries with high COVID-19 mortality.”

“Few people will forget the Great Pandemic of 2020, where and how they lived, how it substantially changed their lives, and for many, the profound human toll it has taken,” Bauchner and Fontanarosa write.

The study by Woolf and colleagues was supported by National Center for Advancing Translational Sciences, the National Institute on Aging, and the National Institute of Allergy and Infectious Diseases. The study by Bilinski and Emanuel was partially funded by the Colton Foundation. Woolf, Emanuel, Fineberg, Bauchner, and Fontanarosa have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

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Medscape Article

Intensive surveillance after CRC resection does not improve survival

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Changed
Wed, 05/26/2021 - 13:42

Intensive surveillance with carcinoembryonic antigen (CEA) testing and CT scans after colorectal cancer resection did not improve recurrence-free or overall survival when compared with standard abdominal ultrasound and chest x-ray monitoring in a phase 3 trial of almost 2,000 patients.

However, among patients with colon cancer recurrence, those randomized to intensive surveillance more often had a second surgery with curative intent. Even so, there was no overall survival benefit versus standard surveillance in this group.

In short, “none of the follow-up modalities resulted in a difference,” said investigator Come Lepage, MD, PhD, of Centre Hospitalier Universitaire de Dijon (France).

Dr. Lepage presented these findings at the European Society for Medical Oncology Virtual Congress 2020.

Dr. Lepage said the study’s results suggest guidelines that include CT and CEA monitoring should be amended, and the standard surveillance methods should be ultrasound and chest x-ray. Dr. LePage called CEA surveillance “useless” and said CT scans should be performed only in cases of suspected recurrence.

However, study discussant Tim Price, MBBS, DHSc, of the University of Adelaide, noted that both the intensive and standard arms in this study had abdominal imaging every 3 months, be it ultrasound or CT, so even in the standard arms, surveillance “was still fairly aggressive.”

Because of that, the study does not “suggest we should decrease our intensity,” Dr. Price said.

He added that the study’s major finding was that more intensive surveillance led to higher rates of secondary surgery with curative intent, probably because recurrences were caught earlier than they would have been with standard surveillance, when curative surgery was still possible.

Patients in the study were treated during 2009-2015, and that might have also made a difference. “We need to remember that, in 2020, care is very different,” Dr. Price said. This includes increased surgical interventions and options for oligometastatic disease, plus systemic therapies such as pembrolizumab. With modern treatments, detecting recurrences earlier “may well have an impact on survival.”

Perhaps patients would live longer with “earlier diagnosis in today’s setting with more active agents and more aggressive surgery and radiotherapy [e.g., stereotactic ablative radiation therapy],” Dr. Price said in an interview.
 

Study details

The trial, dubbed PRODIGE 13, was done to bring clarity to the surveillance issue. Intensive follow-up after curative surgery for colorectal cancer, including CT and CEA monitoring, is recommended by various scientific societies, but it’s based mainly on expert opinion. Results of the few clinical trials on the issue have been controversial, Dr. Lepage explained.

PRODIGE 13 included 1,995 subjects with colorectal cancer. About half of patients had stage II disease, and the other half had stage III. Most patients were 75 years or younger at baseline, and there were more men in the study than women. All patients underwent resection with curative intent and had no evidence of residual disease 3 months after surgery. Some patients received adjuvant chemotherapy.

Patients were first randomized to no CEA monitoring or CEA monitoring every 3 months for the first 2 years, then every 6 months for an additional 3 years. Members in both groups were then randomized a second time to either intensive or standard radiologic surveillance.

Surveillance in the standard arm consisted of an abdominal ultrasound every 3 months for the first 3 years, then biannually for an additional 2 years, plus chest x-rays every 6 months for 5 years. Intensive surveillance consisted of CT imaging, including thoracic imaging, alternating with abdominal ultrasound, every 3 months, then biannually for another 2 years.

At baseline, the surveillance groups were well balanced with regard to demographics, primary tumor location, and other factors, but stage III disease was more prevalent among patients randomized to standard radiologic monitoring without CEA.
 

 

 

Results

The median follow up was 6.5 years. There were no significant differences between the surveillance groups with regard to 5-year overall survival (P = .340) or recurrence-free survival (P = .473).

There were no significant differences in recurrence-free or overall survival when patients were stratified by age, sex, stage, CEA at a cut point of 5 mcg/L, and primary tumor characteristics including location, perineural invasion, and occlusion/perforation.

There were 356 recurrences in patients initially treated for colon cancer. CEA surveillance with or without CT scan was associated with an increased incidence of secondary resection with curative intent. The rate of secondary resection was 66.3% in the standard imaging with CEA arm, 59.5% in the CT plus CEA arm, 50.7% with CT imaging but no CEA, and 40.9% with standard imaging and no CEA (P = .0035).

The rates were similar among the 83 patients with recurrence after initial treatment for rectal cancer, but the between-arm differences were not significant. The rate of secondary resection with curative intent was 57.9% in the standard imaging with CEA arm, 47.8% in the CT plus CEA arm, 55% with CT imaging but no CEA, and 42.9% with standard imaging and no CEA.

The research is ongoing, and the team expects to report on secondary outcomes and ancillary studies of circulating tumor DNA, among other things, in 2021.

The study is being funded by the Federation Francophone de Cancerologie Digestive. Dr. Lepage disclosed ties with Novartis, Amgen, Bayer, Servier, and AAA. Dr. Price disclosed institutional research funding from Amgen and being an uncompensated adviser to Pierre-Fabre and Merck.

SOURCE: Lepage C et al. ESMO 2020, Abstract 398O.

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Intensive surveillance with carcinoembryonic antigen (CEA) testing and CT scans after colorectal cancer resection did not improve recurrence-free or overall survival when compared with standard abdominal ultrasound and chest x-ray monitoring in a phase 3 trial of almost 2,000 patients.

However, among patients with colon cancer recurrence, those randomized to intensive surveillance more often had a second surgery with curative intent. Even so, there was no overall survival benefit versus standard surveillance in this group.

In short, “none of the follow-up modalities resulted in a difference,” said investigator Come Lepage, MD, PhD, of Centre Hospitalier Universitaire de Dijon (France).

Dr. Lepage presented these findings at the European Society for Medical Oncology Virtual Congress 2020.

Dr. Lepage said the study’s results suggest guidelines that include CT and CEA monitoring should be amended, and the standard surveillance methods should be ultrasound and chest x-ray. Dr. LePage called CEA surveillance “useless” and said CT scans should be performed only in cases of suspected recurrence.

However, study discussant Tim Price, MBBS, DHSc, of the University of Adelaide, noted that both the intensive and standard arms in this study had abdominal imaging every 3 months, be it ultrasound or CT, so even in the standard arms, surveillance “was still fairly aggressive.”

Because of that, the study does not “suggest we should decrease our intensity,” Dr. Price said.

He added that the study’s major finding was that more intensive surveillance led to higher rates of secondary surgery with curative intent, probably because recurrences were caught earlier than they would have been with standard surveillance, when curative surgery was still possible.

Patients in the study were treated during 2009-2015, and that might have also made a difference. “We need to remember that, in 2020, care is very different,” Dr. Price said. This includes increased surgical interventions and options for oligometastatic disease, plus systemic therapies such as pembrolizumab. With modern treatments, detecting recurrences earlier “may well have an impact on survival.”

Perhaps patients would live longer with “earlier diagnosis in today’s setting with more active agents and more aggressive surgery and radiotherapy [e.g., stereotactic ablative radiation therapy],” Dr. Price said in an interview.
 

Study details

The trial, dubbed PRODIGE 13, was done to bring clarity to the surveillance issue. Intensive follow-up after curative surgery for colorectal cancer, including CT and CEA monitoring, is recommended by various scientific societies, but it’s based mainly on expert opinion. Results of the few clinical trials on the issue have been controversial, Dr. Lepage explained.

PRODIGE 13 included 1,995 subjects with colorectal cancer. About half of patients had stage II disease, and the other half had stage III. Most patients were 75 years or younger at baseline, and there were more men in the study than women. All patients underwent resection with curative intent and had no evidence of residual disease 3 months after surgery. Some patients received adjuvant chemotherapy.

Patients were first randomized to no CEA monitoring or CEA monitoring every 3 months for the first 2 years, then every 6 months for an additional 3 years. Members in both groups were then randomized a second time to either intensive or standard radiologic surveillance.

Surveillance in the standard arm consisted of an abdominal ultrasound every 3 months for the first 3 years, then biannually for an additional 2 years, plus chest x-rays every 6 months for 5 years. Intensive surveillance consisted of CT imaging, including thoracic imaging, alternating with abdominal ultrasound, every 3 months, then biannually for another 2 years.

At baseline, the surveillance groups were well balanced with regard to demographics, primary tumor location, and other factors, but stage III disease was more prevalent among patients randomized to standard radiologic monitoring without CEA.
 

 

 

Results

The median follow up was 6.5 years. There were no significant differences between the surveillance groups with regard to 5-year overall survival (P = .340) or recurrence-free survival (P = .473).

There were no significant differences in recurrence-free or overall survival when patients were stratified by age, sex, stage, CEA at a cut point of 5 mcg/L, and primary tumor characteristics including location, perineural invasion, and occlusion/perforation.

There were 356 recurrences in patients initially treated for colon cancer. CEA surveillance with or without CT scan was associated with an increased incidence of secondary resection with curative intent. The rate of secondary resection was 66.3% in the standard imaging with CEA arm, 59.5% in the CT plus CEA arm, 50.7% with CT imaging but no CEA, and 40.9% with standard imaging and no CEA (P = .0035).

The rates were similar among the 83 patients with recurrence after initial treatment for rectal cancer, but the between-arm differences were not significant. The rate of secondary resection with curative intent was 57.9% in the standard imaging with CEA arm, 47.8% in the CT plus CEA arm, 55% with CT imaging but no CEA, and 42.9% with standard imaging and no CEA.

The research is ongoing, and the team expects to report on secondary outcomes and ancillary studies of circulating tumor DNA, among other things, in 2021.

The study is being funded by the Federation Francophone de Cancerologie Digestive. Dr. Lepage disclosed ties with Novartis, Amgen, Bayer, Servier, and AAA. Dr. Price disclosed institutional research funding from Amgen and being an uncompensated adviser to Pierre-Fabre and Merck.

SOURCE: Lepage C et al. ESMO 2020, Abstract 398O.

Intensive surveillance with carcinoembryonic antigen (CEA) testing and CT scans after colorectal cancer resection did not improve recurrence-free or overall survival when compared with standard abdominal ultrasound and chest x-ray monitoring in a phase 3 trial of almost 2,000 patients.

However, among patients with colon cancer recurrence, those randomized to intensive surveillance more often had a second surgery with curative intent. Even so, there was no overall survival benefit versus standard surveillance in this group.

In short, “none of the follow-up modalities resulted in a difference,” said investigator Come Lepage, MD, PhD, of Centre Hospitalier Universitaire de Dijon (France).

Dr. Lepage presented these findings at the European Society for Medical Oncology Virtual Congress 2020.

Dr. Lepage said the study’s results suggest guidelines that include CT and CEA monitoring should be amended, and the standard surveillance methods should be ultrasound and chest x-ray. Dr. LePage called CEA surveillance “useless” and said CT scans should be performed only in cases of suspected recurrence.

However, study discussant Tim Price, MBBS, DHSc, of the University of Adelaide, noted that both the intensive and standard arms in this study had abdominal imaging every 3 months, be it ultrasound or CT, so even in the standard arms, surveillance “was still fairly aggressive.”

Because of that, the study does not “suggest we should decrease our intensity,” Dr. Price said.

He added that the study’s major finding was that more intensive surveillance led to higher rates of secondary surgery with curative intent, probably because recurrences were caught earlier than they would have been with standard surveillance, when curative surgery was still possible.

Patients in the study were treated during 2009-2015, and that might have also made a difference. “We need to remember that, in 2020, care is very different,” Dr. Price said. This includes increased surgical interventions and options for oligometastatic disease, plus systemic therapies such as pembrolizumab. With modern treatments, detecting recurrences earlier “may well have an impact on survival.”

Perhaps patients would live longer with “earlier diagnosis in today’s setting with more active agents and more aggressive surgery and radiotherapy [e.g., stereotactic ablative radiation therapy],” Dr. Price said in an interview.
 

Study details

The trial, dubbed PRODIGE 13, was done to bring clarity to the surveillance issue. Intensive follow-up after curative surgery for colorectal cancer, including CT and CEA monitoring, is recommended by various scientific societies, but it’s based mainly on expert opinion. Results of the few clinical trials on the issue have been controversial, Dr. Lepage explained.

PRODIGE 13 included 1,995 subjects with colorectal cancer. About half of patients had stage II disease, and the other half had stage III. Most patients were 75 years or younger at baseline, and there were more men in the study than women. All patients underwent resection with curative intent and had no evidence of residual disease 3 months after surgery. Some patients received adjuvant chemotherapy.

Patients were first randomized to no CEA monitoring or CEA monitoring every 3 months for the first 2 years, then every 6 months for an additional 3 years. Members in both groups were then randomized a second time to either intensive or standard radiologic surveillance.

Surveillance in the standard arm consisted of an abdominal ultrasound every 3 months for the first 3 years, then biannually for an additional 2 years, plus chest x-rays every 6 months for 5 years. Intensive surveillance consisted of CT imaging, including thoracic imaging, alternating with abdominal ultrasound, every 3 months, then biannually for another 2 years.

At baseline, the surveillance groups were well balanced with regard to demographics, primary tumor location, and other factors, but stage III disease was more prevalent among patients randomized to standard radiologic monitoring without CEA.
 

 

 

Results

The median follow up was 6.5 years. There were no significant differences between the surveillance groups with regard to 5-year overall survival (P = .340) or recurrence-free survival (P = .473).

There were no significant differences in recurrence-free or overall survival when patients were stratified by age, sex, stage, CEA at a cut point of 5 mcg/L, and primary tumor characteristics including location, perineural invasion, and occlusion/perforation.

There were 356 recurrences in patients initially treated for colon cancer. CEA surveillance with or without CT scan was associated with an increased incidence of secondary resection with curative intent. The rate of secondary resection was 66.3% in the standard imaging with CEA arm, 59.5% in the CT plus CEA arm, 50.7% with CT imaging but no CEA, and 40.9% with standard imaging and no CEA (P = .0035).

The rates were similar among the 83 patients with recurrence after initial treatment for rectal cancer, but the between-arm differences were not significant. The rate of secondary resection with curative intent was 57.9% in the standard imaging with CEA arm, 47.8% in the CT plus CEA arm, 55% with CT imaging but no CEA, and 42.9% with standard imaging and no CEA.

The research is ongoing, and the team expects to report on secondary outcomes and ancillary studies of circulating tumor DNA, among other things, in 2021.

The study is being funded by the Federation Francophone de Cancerologie Digestive. Dr. Lepage disclosed ties with Novartis, Amgen, Bayer, Servier, and AAA. Dr. Price disclosed institutional research funding from Amgen and being an uncompensated adviser to Pierre-Fabre and Merck.

SOURCE: Lepage C et al. ESMO 2020, Abstract 398O.

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Ruling out PE in pregnancy

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Ruling out PE in pregnancy

ILLUSTRATIVE CASE

A 28-year-old G2P1001 at 28 weeks’ gestation presents to your clinic with 1 day of dyspnea and palpitations. Her pregnancy has been otherwise uncomplicated. She reports worsening dyspnea with mild exertion but denies other symptoms, including leg swelling.

The current incidence of venous thromboembolism (VTE) in pregnant women is estimated to be a relatively low 5 to 12 events per 10,000 pregnancies, yet the condition is the leading cause of maternal mortality in developed countries.2,3,4 Currently, there are conflicting recommendations among relevant organization guidelines regarding the use of D-dimer testing to aid in the diagnosis of pulmonary embolism (PE) during pregnancy. Both the Working Group in Women’s Health of the Society of Thrombosis and Haemostasis (GTH) and the European Society of Cardiology (ESC) recommend using D-dimer testing to rule out PE in pregnant women (ESC Class IIa, level of evidence B based on small studies, retrospective studies, and observational studies; GTH provides no grade).5,6

Conversely, the Royal College of Obstetricians and Gynaecologists (RCOG), the Society of Obstetricians and Gynaecologists of Canada (SOGC), and the American Thoracic Society (ATS)/Society of Thoracic Radiology recommend against the use of D-dimer testing in pregnant women because pregnant women were excluded from D-dimer validation studies (RCOG and SOGC Grade D; ATS weak recommendation).4,7,8 The American College of Obstetricians and Gynecologists does not have specific recommendations regarding the use of D-dimer testing during pregnancy, but has endorsed the ATS guidelines.4,9 In addition, SOGC recommends against the use of clinical prediction scores (Grade D), and RCOG states that there is no evidence to support their use (Grade C).7,8 The remaining societies do not make a recommendation for or against the use of clinical prediction scores because of the absence of high-quality evidence regarding their use in the pregnant patient population.4,5,6

 

STUDY SUMMARY

Prospective validation of a strategy to diagnose PE in pregnant women

This multicenter, multinational, prospective diagnostic study involving 395 pregnant women evaluated the accuracy of PE diagnosis across 11 centers in France and Switzerland from August 2008 through July 2016.1 Patients with clinically suspected PE were evaluated in emergency departments. Patients were tested according to a diagnostic algorithm that included pretest clinical probability using the revised Geneva Score for Pulmonary Embolism (www.mdcalc.com/geneva-score-revised-pulmonary-­embolism), a clinical prediction tool that uses patient history, presenting symptoms, and clinical signs to classify patients as being at low (0-3/25), intermediate (4-10/25), or high (≥ 11/25) risk;10 high-sensitivity D-dimer testing; bilateral lower limb compression ultrasonography (CUS); computed tomography pulmonary angiography (CTPA); and a ventilation-perfusion (V/Q) scan.

PE was excluded in patients who had a low or intermediate pretest clinical probability score and a negative D-dimer test result (< 500 mcg/L). Patients with a high pretest probability score or positive D-dimer test result underwent CUS, and, if negative, subsequent CTPA. A V/Q scan was performed if the CTPA was inconclusive. If the work-up was negative, PE was excluded.

Untreated pregnant women had clinical follow-up at 3 months. Any cases of suspected VTE were evaluated by a 3-member independent adjudication committee blinded to the initial diagnostic work-up. The primary outcome was the rate of adjudicated VTE events during the 3-month follow-up period. PE was diagnosed in 28 patients (7.1%) and excluded in 367 (clinical probability score and negative D-dimer test result [n = 46], negative CTPA result [n = 290], normal or low-probability V/Q scan [n = 17], and other reason [n = 14]). Twenty-two women received anticoagulation during the follow-up period for other reasons (mainly history of previous VTE disease). No symptomatic VTE events occurred in any of the women after the diagnostic work-up was negative, including among those patients who were ruled out with only the clinical prediction tool and a negative D-dimer test result (rate 0.0%; 95% confidence interval [CI], 0.0%-1%).

 

 

WHAT’S NEW

Clinical probability and D-dimer rule out PE in pregnant women

This study ruled out PE in patients with low/intermediate risk as determined by the revised Geneva score and a D-dimer test, enabling patients to avoid further diagnostic testing. This low-cost strategy can be applied easily to the pregnant population.

CAVEATS

Additional research is still needed

From the results of this study, 11.6% of patients (n = 46) had a PE ruled out utilizing the revised Geneva score in conjunction with a D-dimer test result, with avoidance of chest imaging. However, this study was powered for the entire treatment algorithm and was not specifically powered for patients with low- or intermediate-risk pretest probability scores. Since this is the first published prospective diagnostic study of VTE in pregnancy, further research is needed to confirm the findings that a clinical prediction tool and a negative D-dimer test result can safely rule out PE in pregnant women.

This strategy ruled out PE in patients with low/ intermediate risk as determined by the revised Geneva score and a D-dimer test, enabling patients to avoid further diagnostic testing.

In addition, further research is needed to determine pregnancy-adapted D-dimer cut-off values, as the researchers of this study noted that < 500 mcg/L was useful in the first and second trimester, but that levels increased as gestational age increased.

 

CHALLENGES TO IMPLEMENTATION

None to speak of

Implementing a diagnostic algorithm that incorporates sequential assessment of pretest clinical probability based on the revised Geneva score and a D-dimer measurement should be relatively easy to implement, as both methods are readily available and relatively inexpensive.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Files
References

1. Righini M, Robert-Ebadi H, Elias A, et al. Diagnosis of pulmonary embolism during pregnancy. A multicenter prospective management outcome study. Ann Intern Med. 2018;169:766-773.

2. Knight M, Kenyon S, Brocklehurst P, et al. Saving lives, improving mothers’ care: lessons learned to inform future maternity care from the UK and Ireland confidential enquiries into maternal deaths and morbidity 2009-2012. Oxford: National Perinatal Epidemiology Unit, University of Oxford; 2014.

3. Bourjeily G, Paidas M, Khalil H, et al. Pulmonary embolism in pregnancy. Lancet. 2010;375:500-512.

4. Leung AN, Bull TM, Jaeschke R, et al. An official American Thoracic Society/Society of Thoracic Radiology clinical practice guideline: evaluation of suspected pulmonary embolism in pregnancy. Am J Resp Crit Care Med. 2011;184:1200-1208.

5. Konstantinides SV, Meyer G, Becattini C, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J. 2020;41:543-603.

6. Linnemann B, Bauersachs R, Rott H, et al. Working Group in Women’s Health of the Society of Thrombosis and Haemostasis. Diagnosis of pregnancy-associated venous thromboembolism-position paper of the Working Group in Women’s Health of the Society of Thrombosis and Haemostasis (GTH). Vasa. 2016;45:87-101.

7. Royal College of Obstetricians & Gynaecologists. Thromboembolic disease in pregnancy and the puerperium: acute management. Green‐top Guideline No. 37b. April 2015.

8. Chan WS, Rey E, Kent NE, et al. Venous thromboembolism and antithrombotic therapy in pregnancy. J Obstet Gynaecol Can. 2014;36:527-553.

9. James A, Birsner M, Kaimal A, American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins‐Obstetrics. ACOG Practice Bulletin No. 196: thromboembolism in pregnancy. Obstet Gynecol. 2018;132:e1-e17.

10. Le Gal G, Righini M, Roy PM, et al. Prediction of pulmonary embolism in the emergency department: the revised Geneva score. Ann Intern Med. 2006;144:165-171.

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ILLUSTRATIVE CASE

A 28-year-old G2P1001 at 28 weeks’ gestation presents to your clinic with 1 day of dyspnea and palpitations. Her pregnancy has been otherwise uncomplicated. She reports worsening dyspnea with mild exertion but denies other symptoms, including leg swelling.

The current incidence of venous thromboembolism (VTE) in pregnant women is estimated to be a relatively low 5 to 12 events per 10,000 pregnancies, yet the condition is the leading cause of maternal mortality in developed countries.2,3,4 Currently, there are conflicting recommendations among relevant organization guidelines regarding the use of D-dimer testing to aid in the diagnosis of pulmonary embolism (PE) during pregnancy. Both the Working Group in Women’s Health of the Society of Thrombosis and Haemostasis (GTH) and the European Society of Cardiology (ESC) recommend using D-dimer testing to rule out PE in pregnant women (ESC Class IIa, level of evidence B based on small studies, retrospective studies, and observational studies; GTH provides no grade).5,6

Conversely, the Royal College of Obstetricians and Gynaecologists (RCOG), the Society of Obstetricians and Gynaecologists of Canada (SOGC), and the American Thoracic Society (ATS)/Society of Thoracic Radiology recommend against the use of D-dimer testing in pregnant women because pregnant women were excluded from D-dimer validation studies (RCOG and SOGC Grade D; ATS weak recommendation).4,7,8 The American College of Obstetricians and Gynecologists does not have specific recommendations regarding the use of D-dimer testing during pregnancy, but has endorsed the ATS guidelines.4,9 In addition, SOGC recommends against the use of clinical prediction scores (Grade D), and RCOG states that there is no evidence to support their use (Grade C).7,8 The remaining societies do not make a recommendation for or against the use of clinical prediction scores because of the absence of high-quality evidence regarding their use in the pregnant patient population.4,5,6

 

STUDY SUMMARY

Prospective validation of a strategy to diagnose PE in pregnant women

This multicenter, multinational, prospective diagnostic study involving 395 pregnant women evaluated the accuracy of PE diagnosis across 11 centers in France and Switzerland from August 2008 through July 2016.1 Patients with clinically suspected PE were evaluated in emergency departments. Patients were tested according to a diagnostic algorithm that included pretest clinical probability using the revised Geneva Score for Pulmonary Embolism (www.mdcalc.com/geneva-score-revised-pulmonary-­embolism), a clinical prediction tool that uses patient history, presenting symptoms, and clinical signs to classify patients as being at low (0-3/25), intermediate (4-10/25), or high (≥ 11/25) risk;10 high-sensitivity D-dimer testing; bilateral lower limb compression ultrasonography (CUS); computed tomography pulmonary angiography (CTPA); and a ventilation-perfusion (V/Q) scan.

PE was excluded in patients who had a low or intermediate pretest clinical probability score and a negative D-dimer test result (< 500 mcg/L). Patients with a high pretest probability score or positive D-dimer test result underwent CUS, and, if negative, subsequent CTPA. A V/Q scan was performed if the CTPA was inconclusive. If the work-up was negative, PE was excluded.

Untreated pregnant women had clinical follow-up at 3 months. Any cases of suspected VTE were evaluated by a 3-member independent adjudication committee blinded to the initial diagnostic work-up. The primary outcome was the rate of adjudicated VTE events during the 3-month follow-up period. PE was diagnosed in 28 patients (7.1%) and excluded in 367 (clinical probability score and negative D-dimer test result [n = 46], negative CTPA result [n = 290], normal or low-probability V/Q scan [n = 17], and other reason [n = 14]). Twenty-two women received anticoagulation during the follow-up period for other reasons (mainly history of previous VTE disease). No symptomatic VTE events occurred in any of the women after the diagnostic work-up was negative, including among those patients who were ruled out with only the clinical prediction tool and a negative D-dimer test result (rate 0.0%; 95% confidence interval [CI], 0.0%-1%).

 

 

WHAT’S NEW

Clinical probability and D-dimer rule out PE in pregnant women

This study ruled out PE in patients with low/intermediate risk as determined by the revised Geneva score and a D-dimer test, enabling patients to avoid further diagnostic testing. This low-cost strategy can be applied easily to the pregnant population.

CAVEATS

Additional research is still needed

From the results of this study, 11.6% of patients (n = 46) had a PE ruled out utilizing the revised Geneva score in conjunction with a D-dimer test result, with avoidance of chest imaging. However, this study was powered for the entire treatment algorithm and was not specifically powered for patients with low- or intermediate-risk pretest probability scores. Since this is the first published prospective diagnostic study of VTE in pregnancy, further research is needed to confirm the findings that a clinical prediction tool and a negative D-dimer test result can safely rule out PE in pregnant women.

This strategy ruled out PE in patients with low/ intermediate risk as determined by the revised Geneva score and a D-dimer test, enabling patients to avoid further diagnostic testing.

In addition, further research is needed to determine pregnancy-adapted D-dimer cut-off values, as the researchers of this study noted that < 500 mcg/L was useful in the first and second trimester, but that levels increased as gestational age increased.

 

CHALLENGES TO IMPLEMENTATION

None to speak of

Implementing a diagnostic algorithm that incorporates sequential assessment of pretest clinical probability based on the revised Geneva score and a D-dimer measurement should be relatively easy to implement, as both methods are readily available and relatively inexpensive.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 28-year-old G2P1001 at 28 weeks’ gestation presents to your clinic with 1 day of dyspnea and palpitations. Her pregnancy has been otherwise uncomplicated. She reports worsening dyspnea with mild exertion but denies other symptoms, including leg swelling.

The current incidence of venous thromboembolism (VTE) in pregnant women is estimated to be a relatively low 5 to 12 events per 10,000 pregnancies, yet the condition is the leading cause of maternal mortality in developed countries.2,3,4 Currently, there are conflicting recommendations among relevant organization guidelines regarding the use of D-dimer testing to aid in the diagnosis of pulmonary embolism (PE) during pregnancy. Both the Working Group in Women’s Health of the Society of Thrombosis and Haemostasis (GTH) and the European Society of Cardiology (ESC) recommend using D-dimer testing to rule out PE in pregnant women (ESC Class IIa, level of evidence B based on small studies, retrospective studies, and observational studies; GTH provides no grade).5,6

Conversely, the Royal College of Obstetricians and Gynaecologists (RCOG), the Society of Obstetricians and Gynaecologists of Canada (SOGC), and the American Thoracic Society (ATS)/Society of Thoracic Radiology recommend against the use of D-dimer testing in pregnant women because pregnant women were excluded from D-dimer validation studies (RCOG and SOGC Grade D; ATS weak recommendation).4,7,8 The American College of Obstetricians and Gynecologists does not have specific recommendations regarding the use of D-dimer testing during pregnancy, but has endorsed the ATS guidelines.4,9 In addition, SOGC recommends against the use of clinical prediction scores (Grade D), and RCOG states that there is no evidence to support their use (Grade C).7,8 The remaining societies do not make a recommendation for or against the use of clinical prediction scores because of the absence of high-quality evidence regarding their use in the pregnant patient population.4,5,6

 

STUDY SUMMARY

Prospective validation of a strategy to diagnose PE in pregnant women

This multicenter, multinational, prospective diagnostic study involving 395 pregnant women evaluated the accuracy of PE diagnosis across 11 centers in France and Switzerland from August 2008 through July 2016.1 Patients with clinically suspected PE were evaluated in emergency departments. Patients were tested according to a diagnostic algorithm that included pretest clinical probability using the revised Geneva Score for Pulmonary Embolism (www.mdcalc.com/geneva-score-revised-pulmonary-­embolism), a clinical prediction tool that uses patient history, presenting symptoms, and clinical signs to classify patients as being at low (0-3/25), intermediate (4-10/25), or high (≥ 11/25) risk;10 high-sensitivity D-dimer testing; bilateral lower limb compression ultrasonography (CUS); computed tomography pulmonary angiography (CTPA); and a ventilation-perfusion (V/Q) scan.

PE was excluded in patients who had a low or intermediate pretest clinical probability score and a negative D-dimer test result (< 500 mcg/L). Patients with a high pretest probability score or positive D-dimer test result underwent CUS, and, if negative, subsequent CTPA. A V/Q scan was performed if the CTPA was inconclusive. If the work-up was negative, PE was excluded.

Untreated pregnant women had clinical follow-up at 3 months. Any cases of suspected VTE were evaluated by a 3-member independent adjudication committee blinded to the initial diagnostic work-up. The primary outcome was the rate of adjudicated VTE events during the 3-month follow-up period. PE was diagnosed in 28 patients (7.1%) and excluded in 367 (clinical probability score and negative D-dimer test result [n = 46], negative CTPA result [n = 290], normal or low-probability V/Q scan [n = 17], and other reason [n = 14]). Twenty-two women received anticoagulation during the follow-up period for other reasons (mainly history of previous VTE disease). No symptomatic VTE events occurred in any of the women after the diagnostic work-up was negative, including among those patients who were ruled out with only the clinical prediction tool and a negative D-dimer test result (rate 0.0%; 95% confidence interval [CI], 0.0%-1%).

 

 

WHAT’S NEW

Clinical probability and D-dimer rule out PE in pregnant women

This study ruled out PE in patients with low/intermediate risk as determined by the revised Geneva score and a D-dimer test, enabling patients to avoid further diagnostic testing. This low-cost strategy can be applied easily to the pregnant population.

CAVEATS

Additional research is still needed

From the results of this study, 11.6% of patients (n = 46) had a PE ruled out utilizing the revised Geneva score in conjunction with a D-dimer test result, with avoidance of chest imaging. However, this study was powered for the entire treatment algorithm and was not specifically powered for patients with low- or intermediate-risk pretest probability scores. Since this is the first published prospective diagnostic study of VTE in pregnancy, further research is needed to confirm the findings that a clinical prediction tool and a negative D-dimer test result can safely rule out PE in pregnant women.

This strategy ruled out PE in patients with low/ intermediate risk as determined by the revised Geneva score and a D-dimer test, enabling patients to avoid further diagnostic testing.

In addition, further research is needed to determine pregnancy-adapted D-dimer cut-off values, as the researchers of this study noted that < 500 mcg/L was useful in the first and second trimester, but that levels increased as gestational age increased.

 

CHALLENGES TO IMPLEMENTATION

None to speak of

Implementing a diagnostic algorithm that incorporates sequential assessment of pretest clinical probability based on the revised Geneva score and a D-dimer measurement should be relatively easy to implement, as both methods are readily available and relatively inexpensive.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

References

1. Righini M, Robert-Ebadi H, Elias A, et al. Diagnosis of pulmonary embolism during pregnancy. A multicenter prospective management outcome study. Ann Intern Med. 2018;169:766-773.

2. Knight M, Kenyon S, Brocklehurst P, et al. Saving lives, improving mothers’ care: lessons learned to inform future maternity care from the UK and Ireland confidential enquiries into maternal deaths and morbidity 2009-2012. Oxford: National Perinatal Epidemiology Unit, University of Oxford; 2014.

3. Bourjeily G, Paidas M, Khalil H, et al. Pulmonary embolism in pregnancy. Lancet. 2010;375:500-512.

4. Leung AN, Bull TM, Jaeschke R, et al. An official American Thoracic Society/Society of Thoracic Radiology clinical practice guideline: evaluation of suspected pulmonary embolism in pregnancy. Am J Resp Crit Care Med. 2011;184:1200-1208.

5. Konstantinides SV, Meyer G, Becattini C, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J. 2020;41:543-603.

6. Linnemann B, Bauersachs R, Rott H, et al. Working Group in Women’s Health of the Society of Thrombosis and Haemostasis. Diagnosis of pregnancy-associated venous thromboembolism-position paper of the Working Group in Women’s Health of the Society of Thrombosis and Haemostasis (GTH). Vasa. 2016;45:87-101.

7. Royal College of Obstetricians & Gynaecologists. Thromboembolic disease in pregnancy and the puerperium: acute management. Green‐top Guideline No. 37b. April 2015.

8. Chan WS, Rey E, Kent NE, et al. Venous thromboembolism and antithrombotic therapy in pregnancy. J Obstet Gynaecol Can. 2014;36:527-553.

9. James A, Birsner M, Kaimal A, American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins‐Obstetrics. ACOG Practice Bulletin No. 196: thromboembolism in pregnancy. Obstet Gynecol. 2018;132:e1-e17.

10. Le Gal G, Righini M, Roy PM, et al. Prediction of pulmonary embolism in the emergency department: the revised Geneva score. Ann Intern Med. 2006;144:165-171.

References

1. Righini M, Robert-Ebadi H, Elias A, et al. Diagnosis of pulmonary embolism during pregnancy. A multicenter prospective management outcome study. Ann Intern Med. 2018;169:766-773.

2. Knight M, Kenyon S, Brocklehurst P, et al. Saving lives, improving mothers’ care: lessons learned to inform future maternity care from the UK and Ireland confidential enquiries into maternal deaths and morbidity 2009-2012. Oxford: National Perinatal Epidemiology Unit, University of Oxford; 2014.

3. Bourjeily G, Paidas M, Khalil H, et al. Pulmonary embolism in pregnancy. Lancet. 2010;375:500-512.

4. Leung AN, Bull TM, Jaeschke R, et al. An official American Thoracic Society/Society of Thoracic Radiology clinical practice guideline: evaluation of suspected pulmonary embolism in pregnancy. Am J Resp Crit Care Med. 2011;184:1200-1208.

5. Konstantinides SV, Meyer G, Becattini C, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J. 2020;41:543-603.

6. Linnemann B, Bauersachs R, Rott H, et al. Working Group in Women’s Health of the Society of Thrombosis and Haemostasis. Diagnosis of pregnancy-associated venous thromboembolism-position paper of the Working Group in Women’s Health of the Society of Thrombosis and Haemostasis (GTH). Vasa. 2016;45:87-101.

7. Royal College of Obstetricians & Gynaecologists. Thromboembolic disease in pregnancy and the puerperium: acute management. Green‐top Guideline No. 37b. April 2015.

8. Chan WS, Rey E, Kent NE, et al. Venous thromboembolism and antithrombotic therapy in pregnancy. J Obstet Gynaecol Can. 2014;36:527-553.

9. James A, Birsner M, Kaimal A, American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins‐Obstetrics. ACOG Practice Bulletin No. 196: thromboembolism in pregnancy. Obstet Gynecol. 2018;132:e1-e17.

10. Le Gal G, Righini M, Roy PM, et al. Prediction of pulmonary embolism in the emergency department: the revised Geneva score. Ann Intern Med. 2006;144:165-171.

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PRACTICE CHANGER

Use a clinical probability score to identify patients at low or intermediate risk for pulmonary embolism (PE) and combine that with a high-sensitivity D-dimer test to rule out PE in pregnant women.

STRENGTH OF RECOMMENDATION

B: Prospective diagnostic management outcome study.1

Righini M, Robert-Ebadi H, Elias A, et al. Diagnosis of pulmonary embolism during pregnancy: a multicenter prospective management outcome study. Ann Intern Med. 2018;169:766-773.1

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The global burden of dementia is increasing at an alarming pace and is estimated to soon affect 81 million individuals worldwide.1 The World Health Organization and the Institute of Medicine have recommended greater dementia awareness and education.2,3 Despite this emphasis on dementia education, many general practitioners consider dementia care beyond their clinical domain and feel that specialists, such as geriatricians, geriatric psychiatrists, or neurologists should address dementia assessment and treatment. 4 Unfortunately, the geriatric health care workforce has been shrinking. The American Geriatrics Society estimates the need for 30,000 geriatricians by 2030, although there are only 7,300 board-certified geriatricians currently in the US.5 There is an urgent need for educating all medical trainees in dementia care regardless of their specialization interest. As the largest underwriter of graduate medical education in the US, the US Department of Veterans Affairs (VA) is well placed for rolling out focused dementia education. Training needs to be practical, brief, and responsive to knowledge gaps to reach the most trainees.

Despite growing emphasis on geriatric training, many medical students have limited experience with patients with dementia or their caregivers, lack exposure to interdisciplinary teams, have a poor attitude toward geriatric patients, and display specific knowledge gaps in dementia assessment and management. 6-9 Other knowledge gaps noted in medical students included assessing behavioral problems, function, safety, and caregiver burden. Medical students also had limited exposure to interdisciplinary team dementia assessment and management.

Our goal was to develop a multicomponent, experiential, brief curriculum using team-based learning to expose senior medical students to interdisciplinary assessment of dementia. The curriculum was developed with input from the interdisciplinary team to address dementia knowledge gaps while providing an opportunity to interact with caregivers. The curriculum targeted all medical students regardless of their interest in geriatrics. Particular emphasis was placed on systems-based learning and the importance of teamwork in managing complex conditions such as dementia. Students were taught that incorporating interdisciplinary input would be more effective during dementia care planning rather than developing specialized knowledge.

Methods

Our team developed a curriculum for fourthyear medical students who rotated through the VA Memory Disorders Clinic as a part of their geriatric medicine clerkship at the University of Arkansas for Medical Sciences in Little Rock. The Memory Disorders Clinic is a consultation practice at the Central Arkansas Veterans Healthcare System (CAVHS) where patients with memory problems are evaluated by a team consisting of a geriatric psychiatrist, a geriatrician, a social worker, and a neuropsychologist. Each specialist addresses specific areas of dementia assessment and management. The curriculum included didactics, clinical experience, and team-based learning.

Didactics

An hour-long didactic session lead by the team geriatrician provided a general overview of interdisciplinary assessment of dementia to groups of 2 to 3 students at a time. The geriatrician presented an overview of dementia types, comorbidities, medications that affect memory, details of the physical examination, and laboratory, cognitive, and behavioral assessments along with treatment plan development. Students also learned about the roles of the social worker, geriatrician, neuropsychologist, and geriatric psychiatrist in the clinic. Pictographs and pie charts highlighted the role of disciplines in assessing and managing aspects of dementia.

The social work evaluation included advance care planning, functional assessment, safety assessment (driving, guns, wandering behaviors, etc), home safety evaluation, support system, and financial evaluation. Each medical student received a binder with local resources to become familiar with the depth and breadth of agencies involved in dementia care. Each medical student learned how to administer the Zarit Burden Scale to assess caregiver burden.10 The details of the geriatrician assessment included reviewing medical comorbidities and medications contributing to dementia, a physical examination, including a focused neurologic examination, laboratory assessment, and judicious use of neuroimaging.

The neuropsychology assessment education included a battery of tests and assessments. The global screening instruments included the Modified Mini-Mental State examination (3MS), Montreal Cognitive Assessment (MoCA), and Saint Louis University Mental Status examination (SLUMS).11-13 Executive function is evaluated using the Trails Making Test A and Trails Making Test B, Controlled Oral Word Association Test, Semantic Fluency Test, and Repeatable Battery for the Assessment of Neuropsychological Status test. Cognitive tests were compared and age- , education-, and race-adjusted norms for rating scales were listed if available. Each student was expected to show proficiency in ≥ 2 cognitive screening instruments (3MS, MoCA, or SLUMS). The geriatric psychiatry assessment included clinical history, onset, and course of memory problems from patient and caregiver perspectives, the Neuropsychiatric Inventory for assessing behavioral problems, employing the clinical dementia rating scale, integrating the team data, summarizing assessment, and formulating a treatment plan.14

Clinical

Students had a single clinical exposure. Students followed 1 patient and his or her caregiver through the team assessment and observed each provider’s assessment to learn interview techniques to adapt to the patient’s sensory or cognitive impairment and become familiar with different tools and devices used in the dementia clinic, such as hearing amplifiers. Each specialist provided hands-on experience. This encounter helped the students connect with caregivers and appreciate their role in patient care.

 

 

Systems learning was an important component integrated throughout the clinical experience. Examples include using video teleconferences to communicate findings among team members and electronic health records to seamlessly obtain and integrate data. Students learned how to create worksheets to graph laboratory data such as B12, thyroid-stimulating hormone, and rapid plasma regain levels. Student gained experience in using applications to retrieve neuroimaging data, results of sleep studies, and other data. Many patients had not received the results of their sleep study, and students had the responsibility to share these reports, including the number of apneic episodes. Students used the VA Computerized Patient Record System for reviewing patient records. One particularly useful tool was Joint Legacy Viewer, a remote access tool used to retrieve data on veterans from anywhere within the US. Students were also trained on medication and consult order menus in the system.

Team-Based

Learning The objectives of the team-based learning section were to teach students basic concepts of integrating the interdisciplinary assessment and formulating a treatment plan, to provide an opportunity to present their case in a group format, to discuss the differential diagnosis, management and treatment plan with a geriatrician in the team-based learning format, and to answer questions from other students. The instructors developed a set of prepared take-home points (Table 1). The team-based learning sessions were structured so that all take-home points were covered.

Evaluations

Evaluations were performed before and immediately after the clinical experience. In preevaluation, students reported the frequency of their participation in an interdisciplinary team assessment of any condition and specifically for dementia. In pre- and postevaluation, students rated their perception of the role of interdisciplinary team members in assessing and managing dementia, their personal abilities to assess cognition, behavioral problems, caregiver burden, and their perception of the impact of behavioral problems on dementia care. A Likert scale (poor = 1; fair = 2; good = 3; very good = 4; and excellent = 5) was employed (eApendices 1 and 2 can be found at doi:10.12788/fp.0052). The only demographic information collected was the student’s gender. Semistructured interviews were conducted to assess students’ current knowledge, experience, and needs. These interviews lasted about 20 minutes and collected information regarding the students’ knowledge about cognitive and behavioral problems in general and those occurring in dementia, their experience with screening, and any problems they encountered.

Statistical Analysis

Student baseline characteristics were assessed. Pre- and postassessments were analyzed with the McNemar test for paired data, and associations with experience were evaluated using χ2 tests. Ratings were dichotomized as very good/excellent vs poor/fair/ good because our educational goal was “very good” to “excellent” experience in dementia care and to avoid expected small cell counts. Two-sided P < .05 indicated statistical significance. Data were analyzed using SAS Enterprise Guide v5.1.

Results

One hundred fourth-year medical students participated, including 54 women. Thirtysix percent reported they had not previously attended an interdisciplinary team assessment for dementia, while 18% stated that they had attended only 1 interdisciplinary team assessment for dementia.

Before the education, students rated their dementia ability as poor. Only 2% (1 of 54), of those with 0 to 1 assessment experience rated their ability for assessing dementia with an interdisciplinary team format as very good/excellent compared with 20% (9/46) of those previously attending ≥ 2 assessments (P = .03); other ratings of ability were not associated with prior experience.

There was a significant change in the students’ self-efficacy ratings pre- to postassessment (P < .05) (Table 2). Only 10% rated their ability to assess for dementia as very good/excellent in before the intervention compared with 96% in postassessment (P < .01). Students’ perception of the impact of behavioral problems on dementia care improved significantly (45% to 98%, P < .01). Similarly, student’s perception of their ability to assess behavioral problems, caregiver burden, and cognition improved significantly from 7 to 88%; 7 to 78%, and 18 to 92%, respectively (P < .01). Students perception of the role of social worker, neuropsychologist, geriatrician, and geriatric psychiatrist also improved significantly for most measures from 81 to 98% (P = .02), 87 to 98% (P = .05), 94 to 99% (P = .06), and 88 to 100% (P = .01), respectively.

The semistructured interviews revealed that awareness of behavioral problems associated with dementia varied for different behavioral problems. Although many students showed familiarity with depression, agitation, and psychosis, they were not comfortable assessing them in a patient with dementia. These students were less aware of other behavioral problems such as disinhibition, apathy, and movement disorders. Deficits were noted in the skill of administering commonly used global cognitive screens, such as the Mini-Mental State Examination (MMSE).15

 

 

In semistructured interviews, only 7% of senior medical students were comfortable assessing behavioral problems associated with dementia. Most were not aware of any validated rating scale to assess neuropsychiatric symptoms. Similarly, only 7% of students were comfortable assessing caregiver burden, and most were not aware of any validated rating scale to assess caregiver burden. Only 1 in 5 students were comfortable using 2 cognitive screens to assess cognitive deficits. Many students stated that they were not routinely expected to perform common cognitive screens, such as the MMSE during their medical training except students who had expressed an interest in psychiatry and were expected to be proficient in the MMSE. Most students were making common mistakes, such as converting the 3-command task to 3 individual single commands, helping too much with serial 7s, and giving too much positive feedback throughout the test.

Discussion

Significant knowledge gaps regarding dementia were found in our study, which is in keeping with other studies in the area. Dementia knowledge deficits among medical trainees have been identified in the United Kingdom, Australia, and the US.6-9

In our study, a brief multicomponent experiential curriculum improved senior medical students’ perception and self-efficacy in diagnosing dementia. This is in keeping with other studies, such as the PAIRS Program.7 Findings from another study indicated that education for geriatric- oriented physicians should focus on experiential learning components through observation and interaction with older adults.16

A background of direct experience with older adults is associated with more positive attitudes toward older adults and increased interest in geriatric medicine.16 In our study, the exposure was brief; therefore, the results could not be compared with other long-term exposure studies. However, even with this brief intervention most students reported being comfortable with assessing caregiver burden (78%), behavioral problems of dementia (88%), and using ≥ 2 cognitive screens (92%). Comfortable in dementia assessment increased after the intervention from 10% to 96%. This finding is encouraging because brief multicomponent dementia education can be devised easily. This finding needs to be taken with caution because we did not conduct a formal skills evaluation.

A unique component of our experience was to learn medical students’ perception about the impact of neuropsychiatric symptoms on the trajectory, outcomes, and management of dementia. These symptoms included delusions, hallucinations, agitation, depression, anxiety, euphoria, apathy, disinhibition, irritability, motor disturbance, nighttime behaviors, and appetite and eating. Less than half the students thought that neuropsychiatric symptoms had a significant impact on dementia before the experience. Through didactics, systematic assessment of neuropsychiatric symptoms and interaction with caregivers, > 98% of students learned that these symptoms have a significant impact on dementia management.

This experience also emphasized the role of several disciplines in dementia assessment and management. Students’ experience positively influenced appreciation of the role of the memory clinic team. Our hope is that students will seek input from social workers, neuropsychologists, and other team members when working with patients with dementia or their caregivers. The common reason why primary care physicians focus on an exclusive medical model is the time commitment for communicating with an interdisciplinary team. Students experienced the feasibility of the interdisciplinary team involvement and how technology could be used for synchronous and asynchronous communication among team members. Medical students also were introduced to complex billing codes used when ≥ 3 disciplines assess/manage a geriatric patient.

Limitations

This study is limited by the lack of long-term follow-up evaluations, no metrics for practice changes clinical outcomes, and implementation in a single medical school. The postexperience evaluation in this study was performed immediately after the intervention. Long-term follow-up would inform whether the changes noted are durable. Because of the brief nature of our intervention, we do not believe that it would change practice in clinical care. It will be informative to follow this cohort of students to study whether their clinical approach to dementia care changes. The intervention needs to be replicated in other medical schools and in more heterogeneous groups to generalize the results of the study.

Conclusions

Senior medical students are not routinely exposed to interdisciplinary team assessments. Dementia knowledge gaps were prevalent in this cohort of senior medical students. Providing interdisciplinary geriatric educational experience improved their perception of their ability to assess for dementia and their recognition of the roles of interdisciplinary team members. Plans are in place to continue and expand the program to other complex geriatric syndromes.

Acknowledgments
Poster presented at the 2019 annual meeting of the American Geriatrics Society. Oral presentation at the same meeting as part of the select Geriatric Education Methods and Materials Swap workshop.

References

1. Ferri CP, Prince M, Brayne C, et al. Global prevalence of dementia: a Delphi consensus study. Lancet. 2005;366(9503):2112-2117. doi:10.1016/S0140-6736(05)67889-0

2. Janca A, Aarli JA, Prilipko L, Dua T, Saxena S, Saraceno B. WHO/WFN survey of neurological services: a worldwide perspective. J Neurol Sci. 2006;247(1):29-34. doi:10.1016/j.jns.2006.03.003

3. Wilkins KM, Blazek MC, Brooks WB, Lehmann SW, Popeo D, Wagenaar D. Six things all medical students need to know about geriatric psychiatry (and how to teach them). Acad Psychiatry. 2017;41(5):693-700. doi:10.1007/s40596-017-0691-7

4. Turner S, Iliffe S, Downs M, et al. General practitioners’ knowledge, confidence and attitudes in the diagnosis and management of dementia. Age Ageing. 2004;33(5):461- 467. doi:10.1093/ageing/afh140

5. Lester PE, Dharmarajan TS, Weinstein E. The looming geriatrician shortage: ramifications and solutions. J Aging Health. 2019:898264319879325. doi:10.1177/0898264319879325

6. Struck BD, Bernard MA, Teasdale TA; Oklahoma University Geriatric Education G. Effect of a mandatory geriatric medicine clerkship on third-year students. J Am Geriatr Soc. 2005;53(11):2007-2011. doi:10.1111/j.1532-5415.2005.00473.x

7. Jefferson AL, Cantwell NG, Byerly LK, Morhardt D. Medical student education program in Alzheimer’s disease: the PAIRS Program. BMC Med Educ. 2012;12:80. doi:10.1186/1472-6920-12-80

8. Nagle BJ, Usita PM, Edland SD. United States medical students’ knowledge of Alzheimer disease. J Educ Eval Health Prof. 2013;10:4. doi:10.3352/jeehp.2013.10.4

9. Scott TL, Kugelman M, Tulloch K. How medical professional students view older people with dementia: Implications for education and practice. PLoS One. 2019;14(11):e0225329. doi:10.1371/journal.pone.0225329.

10. Zarit SH, Reever KE, Bach-Peterson J. Relatives of the impaired elderly: correlates of feelings of burden. Gerontologist. 1980;20(6):649-655. doi:10.1093/geront/20.6.649

11. McDowell I, Kristjansson B, Hill GB, Hebert R. Community screening for dementia: the Mini Mental State Exam (MMSE) and Modified Mini-Mental State Exam (3MS) compared. J Clin Epidemiol. 1997;50(4):377-383. doi:10.1016/s0895-4356(97)00060-7

12. Nasreddine ZS, Phillips NA, Bedirian V, et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Ger iatr Soc. 2005;53(4):695-699. doi:10.1111/j.1532-5415.2005.53221.x

13. Tariq SH, Tumosa N, Chibnall JT, Perry MH, 3rd, Morley JE. Comparison of the Saint Louis University mental status examination and the Mini-Mental State Examination for detecting dementia and mild neurocognitive disorder--a pilot study. Am J Geriatr Psychiatry. 2006;14(11):900-910. doi:10.1097/01.JGP.0000221510.33817.86

14. Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J. The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology. 1994;44(12):2308-2314. doi:10.1212/wnl.44.12.2308

15. Folstein MF, Folstein SE, McHugh PR. “Mini-mental state.” A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189-198. doi:10.1016/0022-3956(75)90026-6

16. Fitzgerald JT, Wray LA, Halter JB, Williams BC, Supiano MA. Relating medical students’ knowledge, attitudes, and experience to an interest in geriatric medicine. Gerontologist. 2003;43(6):849-855. doi:10.1093/geront/43.6.849

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The global burden of dementia is increasing at an alarming pace and is estimated to soon affect 81 million individuals worldwide.1 The World Health Organization and the Institute of Medicine have recommended greater dementia awareness and education.2,3 Despite this emphasis on dementia education, many general practitioners consider dementia care beyond their clinical domain and feel that specialists, such as geriatricians, geriatric psychiatrists, or neurologists should address dementia assessment and treatment. 4 Unfortunately, the geriatric health care workforce has been shrinking. The American Geriatrics Society estimates the need for 30,000 geriatricians by 2030, although there are only 7,300 board-certified geriatricians currently in the US.5 There is an urgent need for educating all medical trainees in dementia care regardless of their specialization interest. As the largest underwriter of graduate medical education in the US, the US Department of Veterans Affairs (VA) is well placed for rolling out focused dementia education. Training needs to be practical, brief, and responsive to knowledge gaps to reach the most trainees.

Despite growing emphasis on geriatric training, many medical students have limited experience with patients with dementia or their caregivers, lack exposure to interdisciplinary teams, have a poor attitude toward geriatric patients, and display specific knowledge gaps in dementia assessment and management. 6-9 Other knowledge gaps noted in medical students included assessing behavioral problems, function, safety, and caregiver burden. Medical students also had limited exposure to interdisciplinary team dementia assessment and management.

Our goal was to develop a multicomponent, experiential, brief curriculum using team-based learning to expose senior medical students to interdisciplinary assessment of dementia. The curriculum was developed with input from the interdisciplinary team to address dementia knowledge gaps while providing an opportunity to interact with caregivers. The curriculum targeted all medical students regardless of their interest in geriatrics. Particular emphasis was placed on systems-based learning and the importance of teamwork in managing complex conditions such as dementia. Students were taught that incorporating interdisciplinary input would be more effective during dementia care planning rather than developing specialized knowledge.

Methods

Our team developed a curriculum for fourthyear medical students who rotated through the VA Memory Disorders Clinic as a part of their geriatric medicine clerkship at the University of Arkansas for Medical Sciences in Little Rock. The Memory Disorders Clinic is a consultation practice at the Central Arkansas Veterans Healthcare System (CAVHS) where patients with memory problems are evaluated by a team consisting of a geriatric psychiatrist, a geriatrician, a social worker, and a neuropsychologist. Each specialist addresses specific areas of dementia assessment and management. The curriculum included didactics, clinical experience, and team-based learning.

Didactics

An hour-long didactic session lead by the team geriatrician provided a general overview of interdisciplinary assessment of dementia to groups of 2 to 3 students at a time. The geriatrician presented an overview of dementia types, comorbidities, medications that affect memory, details of the physical examination, and laboratory, cognitive, and behavioral assessments along with treatment plan development. Students also learned about the roles of the social worker, geriatrician, neuropsychologist, and geriatric psychiatrist in the clinic. Pictographs and pie charts highlighted the role of disciplines in assessing and managing aspects of dementia.

The social work evaluation included advance care planning, functional assessment, safety assessment (driving, guns, wandering behaviors, etc), home safety evaluation, support system, and financial evaluation. Each medical student received a binder with local resources to become familiar with the depth and breadth of agencies involved in dementia care. Each medical student learned how to administer the Zarit Burden Scale to assess caregiver burden.10 The details of the geriatrician assessment included reviewing medical comorbidities and medications contributing to dementia, a physical examination, including a focused neurologic examination, laboratory assessment, and judicious use of neuroimaging.

The neuropsychology assessment education included a battery of tests and assessments. The global screening instruments included the Modified Mini-Mental State examination (3MS), Montreal Cognitive Assessment (MoCA), and Saint Louis University Mental Status examination (SLUMS).11-13 Executive function is evaluated using the Trails Making Test A and Trails Making Test B, Controlled Oral Word Association Test, Semantic Fluency Test, and Repeatable Battery for the Assessment of Neuropsychological Status test. Cognitive tests were compared and age- , education-, and race-adjusted norms for rating scales were listed if available. Each student was expected to show proficiency in ≥ 2 cognitive screening instruments (3MS, MoCA, or SLUMS). The geriatric psychiatry assessment included clinical history, onset, and course of memory problems from patient and caregiver perspectives, the Neuropsychiatric Inventory for assessing behavioral problems, employing the clinical dementia rating scale, integrating the team data, summarizing assessment, and formulating a treatment plan.14

Clinical

Students had a single clinical exposure. Students followed 1 patient and his or her caregiver through the team assessment and observed each provider’s assessment to learn interview techniques to adapt to the patient’s sensory or cognitive impairment and become familiar with different tools and devices used in the dementia clinic, such as hearing amplifiers. Each specialist provided hands-on experience. This encounter helped the students connect with caregivers and appreciate their role in patient care.

 

 

Systems learning was an important component integrated throughout the clinical experience. Examples include using video teleconferences to communicate findings among team members and electronic health records to seamlessly obtain and integrate data. Students learned how to create worksheets to graph laboratory data such as B12, thyroid-stimulating hormone, and rapid plasma regain levels. Student gained experience in using applications to retrieve neuroimaging data, results of sleep studies, and other data. Many patients had not received the results of their sleep study, and students had the responsibility to share these reports, including the number of apneic episodes. Students used the VA Computerized Patient Record System for reviewing patient records. One particularly useful tool was Joint Legacy Viewer, a remote access tool used to retrieve data on veterans from anywhere within the US. Students were also trained on medication and consult order menus in the system.

Team-Based

Learning The objectives of the team-based learning section were to teach students basic concepts of integrating the interdisciplinary assessment and formulating a treatment plan, to provide an opportunity to present their case in a group format, to discuss the differential diagnosis, management and treatment plan with a geriatrician in the team-based learning format, and to answer questions from other students. The instructors developed a set of prepared take-home points (Table 1). The team-based learning sessions were structured so that all take-home points were covered.

Evaluations

Evaluations were performed before and immediately after the clinical experience. In preevaluation, students reported the frequency of their participation in an interdisciplinary team assessment of any condition and specifically for dementia. In pre- and postevaluation, students rated their perception of the role of interdisciplinary team members in assessing and managing dementia, their personal abilities to assess cognition, behavioral problems, caregiver burden, and their perception of the impact of behavioral problems on dementia care. A Likert scale (poor = 1; fair = 2; good = 3; very good = 4; and excellent = 5) was employed (eApendices 1 and 2 can be found at doi:10.12788/fp.0052). The only demographic information collected was the student’s gender. Semistructured interviews were conducted to assess students’ current knowledge, experience, and needs. These interviews lasted about 20 minutes and collected information regarding the students’ knowledge about cognitive and behavioral problems in general and those occurring in dementia, their experience with screening, and any problems they encountered.

Statistical Analysis

Student baseline characteristics were assessed. Pre- and postassessments were analyzed with the McNemar test for paired data, and associations with experience were evaluated using χ2 tests. Ratings were dichotomized as very good/excellent vs poor/fair/ good because our educational goal was “very good” to “excellent” experience in dementia care and to avoid expected small cell counts. Two-sided P < .05 indicated statistical significance. Data were analyzed using SAS Enterprise Guide v5.1.

Results

One hundred fourth-year medical students participated, including 54 women. Thirtysix percent reported they had not previously attended an interdisciplinary team assessment for dementia, while 18% stated that they had attended only 1 interdisciplinary team assessment for dementia.

Before the education, students rated their dementia ability as poor. Only 2% (1 of 54), of those with 0 to 1 assessment experience rated their ability for assessing dementia with an interdisciplinary team format as very good/excellent compared with 20% (9/46) of those previously attending ≥ 2 assessments (P = .03); other ratings of ability were not associated with prior experience.

There was a significant change in the students’ self-efficacy ratings pre- to postassessment (P < .05) (Table 2). Only 10% rated their ability to assess for dementia as very good/excellent in before the intervention compared with 96% in postassessment (P < .01). Students’ perception of the impact of behavioral problems on dementia care improved significantly (45% to 98%, P < .01). Similarly, student’s perception of their ability to assess behavioral problems, caregiver burden, and cognition improved significantly from 7 to 88%; 7 to 78%, and 18 to 92%, respectively (P < .01). Students perception of the role of social worker, neuropsychologist, geriatrician, and geriatric psychiatrist also improved significantly for most measures from 81 to 98% (P = .02), 87 to 98% (P = .05), 94 to 99% (P = .06), and 88 to 100% (P = .01), respectively.

The semistructured interviews revealed that awareness of behavioral problems associated with dementia varied for different behavioral problems. Although many students showed familiarity with depression, agitation, and psychosis, they were not comfortable assessing them in a patient with dementia. These students were less aware of other behavioral problems such as disinhibition, apathy, and movement disorders. Deficits were noted in the skill of administering commonly used global cognitive screens, such as the Mini-Mental State Examination (MMSE).15

 

 

In semistructured interviews, only 7% of senior medical students were comfortable assessing behavioral problems associated with dementia. Most were not aware of any validated rating scale to assess neuropsychiatric symptoms. Similarly, only 7% of students were comfortable assessing caregiver burden, and most were not aware of any validated rating scale to assess caregiver burden. Only 1 in 5 students were comfortable using 2 cognitive screens to assess cognitive deficits. Many students stated that they were not routinely expected to perform common cognitive screens, such as the MMSE during their medical training except students who had expressed an interest in psychiatry and were expected to be proficient in the MMSE. Most students were making common mistakes, such as converting the 3-command task to 3 individual single commands, helping too much with serial 7s, and giving too much positive feedback throughout the test.

Discussion

Significant knowledge gaps regarding dementia were found in our study, which is in keeping with other studies in the area. Dementia knowledge deficits among medical trainees have been identified in the United Kingdom, Australia, and the US.6-9

In our study, a brief multicomponent experiential curriculum improved senior medical students’ perception and self-efficacy in diagnosing dementia. This is in keeping with other studies, such as the PAIRS Program.7 Findings from another study indicated that education for geriatric- oriented physicians should focus on experiential learning components through observation and interaction with older adults.16

A background of direct experience with older adults is associated with more positive attitudes toward older adults and increased interest in geriatric medicine.16 In our study, the exposure was brief; therefore, the results could not be compared with other long-term exposure studies. However, even with this brief intervention most students reported being comfortable with assessing caregiver burden (78%), behavioral problems of dementia (88%), and using ≥ 2 cognitive screens (92%). Comfortable in dementia assessment increased after the intervention from 10% to 96%. This finding is encouraging because brief multicomponent dementia education can be devised easily. This finding needs to be taken with caution because we did not conduct a formal skills evaluation.

A unique component of our experience was to learn medical students’ perception about the impact of neuropsychiatric symptoms on the trajectory, outcomes, and management of dementia. These symptoms included delusions, hallucinations, agitation, depression, anxiety, euphoria, apathy, disinhibition, irritability, motor disturbance, nighttime behaviors, and appetite and eating. Less than half the students thought that neuropsychiatric symptoms had a significant impact on dementia before the experience. Through didactics, systematic assessment of neuropsychiatric symptoms and interaction with caregivers, > 98% of students learned that these symptoms have a significant impact on dementia management.

This experience also emphasized the role of several disciplines in dementia assessment and management. Students’ experience positively influenced appreciation of the role of the memory clinic team. Our hope is that students will seek input from social workers, neuropsychologists, and other team members when working with patients with dementia or their caregivers. The common reason why primary care physicians focus on an exclusive medical model is the time commitment for communicating with an interdisciplinary team. Students experienced the feasibility of the interdisciplinary team involvement and how technology could be used for synchronous and asynchronous communication among team members. Medical students also were introduced to complex billing codes used when ≥ 3 disciplines assess/manage a geriatric patient.

Limitations

This study is limited by the lack of long-term follow-up evaluations, no metrics for practice changes clinical outcomes, and implementation in a single medical school. The postexperience evaluation in this study was performed immediately after the intervention. Long-term follow-up would inform whether the changes noted are durable. Because of the brief nature of our intervention, we do not believe that it would change practice in clinical care. It will be informative to follow this cohort of students to study whether their clinical approach to dementia care changes. The intervention needs to be replicated in other medical schools and in more heterogeneous groups to generalize the results of the study.

Conclusions

Senior medical students are not routinely exposed to interdisciplinary team assessments. Dementia knowledge gaps were prevalent in this cohort of senior medical students. Providing interdisciplinary geriatric educational experience improved their perception of their ability to assess for dementia and their recognition of the roles of interdisciplinary team members. Plans are in place to continue and expand the program to other complex geriatric syndromes.

Acknowledgments
Poster presented at the 2019 annual meeting of the American Geriatrics Society. Oral presentation at the same meeting as part of the select Geriatric Education Methods and Materials Swap workshop.

The global burden of dementia is increasing at an alarming pace and is estimated to soon affect 81 million individuals worldwide.1 The World Health Organization and the Institute of Medicine have recommended greater dementia awareness and education.2,3 Despite this emphasis on dementia education, many general practitioners consider dementia care beyond their clinical domain and feel that specialists, such as geriatricians, geriatric psychiatrists, or neurologists should address dementia assessment and treatment. 4 Unfortunately, the geriatric health care workforce has been shrinking. The American Geriatrics Society estimates the need for 30,000 geriatricians by 2030, although there are only 7,300 board-certified geriatricians currently in the US.5 There is an urgent need for educating all medical trainees in dementia care regardless of their specialization interest. As the largest underwriter of graduate medical education in the US, the US Department of Veterans Affairs (VA) is well placed for rolling out focused dementia education. Training needs to be practical, brief, and responsive to knowledge gaps to reach the most trainees.

Despite growing emphasis on geriatric training, many medical students have limited experience with patients with dementia or their caregivers, lack exposure to interdisciplinary teams, have a poor attitude toward geriatric patients, and display specific knowledge gaps in dementia assessment and management. 6-9 Other knowledge gaps noted in medical students included assessing behavioral problems, function, safety, and caregiver burden. Medical students also had limited exposure to interdisciplinary team dementia assessment and management.

Our goal was to develop a multicomponent, experiential, brief curriculum using team-based learning to expose senior medical students to interdisciplinary assessment of dementia. The curriculum was developed with input from the interdisciplinary team to address dementia knowledge gaps while providing an opportunity to interact with caregivers. The curriculum targeted all medical students regardless of their interest in geriatrics. Particular emphasis was placed on systems-based learning and the importance of teamwork in managing complex conditions such as dementia. Students were taught that incorporating interdisciplinary input would be more effective during dementia care planning rather than developing specialized knowledge.

Methods

Our team developed a curriculum for fourthyear medical students who rotated through the VA Memory Disorders Clinic as a part of their geriatric medicine clerkship at the University of Arkansas for Medical Sciences in Little Rock. The Memory Disorders Clinic is a consultation practice at the Central Arkansas Veterans Healthcare System (CAVHS) where patients with memory problems are evaluated by a team consisting of a geriatric psychiatrist, a geriatrician, a social worker, and a neuropsychologist. Each specialist addresses specific areas of dementia assessment and management. The curriculum included didactics, clinical experience, and team-based learning.

Didactics

An hour-long didactic session lead by the team geriatrician provided a general overview of interdisciplinary assessment of dementia to groups of 2 to 3 students at a time. The geriatrician presented an overview of dementia types, comorbidities, medications that affect memory, details of the physical examination, and laboratory, cognitive, and behavioral assessments along with treatment plan development. Students also learned about the roles of the social worker, geriatrician, neuropsychologist, and geriatric psychiatrist in the clinic. Pictographs and pie charts highlighted the role of disciplines in assessing and managing aspects of dementia.

The social work evaluation included advance care planning, functional assessment, safety assessment (driving, guns, wandering behaviors, etc), home safety evaluation, support system, and financial evaluation. Each medical student received a binder with local resources to become familiar with the depth and breadth of agencies involved in dementia care. Each medical student learned how to administer the Zarit Burden Scale to assess caregiver burden.10 The details of the geriatrician assessment included reviewing medical comorbidities and medications contributing to dementia, a physical examination, including a focused neurologic examination, laboratory assessment, and judicious use of neuroimaging.

The neuropsychology assessment education included a battery of tests and assessments. The global screening instruments included the Modified Mini-Mental State examination (3MS), Montreal Cognitive Assessment (MoCA), and Saint Louis University Mental Status examination (SLUMS).11-13 Executive function is evaluated using the Trails Making Test A and Trails Making Test B, Controlled Oral Word Association Test, Semantic Fluency Test, and Repeatable Battery for the Assessment of Neuropsychological Status test. Cognitive tests were compared and age- , education-, and race-adjusted norms for rating scales were listed if available. Each student was expected to show proficiency in ≥ 2 cognitive screening instruments (3MS, MoCA, or SLUMS). The geriatric psychiatry assessment included clinical history, onset, and course of memory problems from patient and caregiver perspectives, the Neuropsychiatric Inventory for assessing behavioral problems, employing the clinical dementia rating scale, integrating the team data, summarizing assessment, and formulating a treatment plan.14

Clinical

Students had a single clinical exposure. Students followed 1 patient and his or her caregiver through the team assessment and observed each provider’s assessment to learn interview techniques to adapt to the patient’s sensory or cognitive impairment and become familiar with different tools and devices used in the dementia clinic, such as hearing amplifiers. Each specialist provided hands-on experience. This encounter helped the students connect with caregivers and appreciate their role in patient care.

 

 

Systems learning was an important component integrated throughout the clinical experience. Examples include using video teleconferences to communicate findings among team members and electronic health records to seamlessly obtain and integrate data. Students learned how to create worksheets to graph laboratory data such as B12, thyroid-stimulating hormone, and rapid plasma regain levels. Student gained experience in using applications to retrieve neuroimaging data, results of sleep studies, and other data. Many patients had not received the results of their sleep study, and students had the responsibility to share these reports, including the number of apneic episodes. Students used the VA Computerized Patient Record System for reviewing patient records. One particularly useful tool was Joint Legacy Viewer, a remote access tool used to retrieve data on veterans from anywhere within the US. Students were also trained on medication and consult order menus in the system.

Team-Based

Learning The objectives of the team-based learning section were to teach students basic concepts of integrating the interdisciplinary assessment and formulating a treatment plan, to provide an opportunity to present their case in a group format, to discuss the differential diagnosis, management and treatment plan with a geriatrician in the team-based learning format, and to answer questions from other students. The instructors developed a set of prepared take-home points (Table 1). The team-based learning sessions were structured so that all take-home points were covered.

Evaluations

Evaluations were performed before and immediately after the clinical experience. In preevaluation, students reported the frequency of their participation in an interdisciplinary team assessment of any condition and specifically for dementia. In pre- and postevaluation, students rated their perception of the role of interdisciplinary team members in assessing and managing dementia, their personal abilities to assess cognition, behavioral problems, caregiver burden, and their perception of the impact of behavioral problems on dementia care. A Likert scale (poor = 1; fair = 2; good = 3; very good = 4; and excellent = 5) was employed (eApendices 1 and 2 can be found at doi:10.12788/fp.0052). The only demographic information collected was the student’s gender. Semistructured interviews were conducted to assess students’ current knowledge, experience, and needs. These interviews lasted about 20 minutes and collected information regarding the students’ knowledge about cognitive and behavioral problems in general and those occurring in dementia, their experience with screening, and any problems they encountered.

Statistical Analysis

Student baseline characteristics were assessed. Pre- and postassessments were analyzed with the McNemar test for paired data, and associations with experience were evaluated using χ2 tests. Ratings were dichotomized as very good/excellent vs poor/fair/ good because our educational goal was “very good” to “excellent” experience in dementia care and to avoid expected small cell counts. Two-sided P < .05 indicated statistical significance. Data were analyzed using SAS Enterprise Guide v5.1.

Results

One hundred fourth-year medical students participated, including 54 women. Thirtysix percent reported they had not previously attended an interdisciplinary team assessment for dementia, while 18% stated that they had attended only 1 interdisciplinary team assessment for dementia.

Before the education, students rated their dementia ability as poor. Only 2% (1 of 54), of those with 0 to 1 assessment experience rated their ability for assessing dementia with an interdisciplinary team format as very good/excellent compared with 20% (9/46) of those previously attending ≥ 2 assessments (P = .03); other ratings of ability were not associated with prior experience.

There was a significant change in the students’ self-efficacy ratings pre- to postassessment (P < .05) (Table 2). Only 10% rated their ability to assess for dementia as very good/excellent in before the intervention compared with 96% in postassessment (P < .01). Students’ perception of the impact of behavioral problems on dementia care improved significantly (45% to 98%, P < .01). Similarly, student’s perception of their ability to assess behavioral problems, caregiver burden, and cognition improved significantly from 7 to 88%; 7 to 78%, and 18 to 92%, respectively (P < .01). Students perception of the role of social worker, neuropsychologist, geriatrician, and geriatric psychiatrist also improved significantly for most measures from 81 to 98% (P = .02), 87 to 98% (P = .05), 94 to 99% (P = .06), and 88 to 100% (P = .01), respectively.

The semistructured interviews revealed that awareness of behavioral problems associated with dementia varied for different behavioral problems. Although many students showed familiarity with depression, agitation, and psychosis, they were not comfortable assessing them in a patient with dementia. These students were less aware of other behavioral problems such as disinhibition, apathy, and movement disorders. Deficits were noted in the skill of administering commonly used global cognitive screens, such as the Mini-Mental State Examination (MMSE).15

 

 

In semistructured interviews, only 7% of senior medical students were comfortable assessing behavioral problems associated with dementia. Most were not aware of any validated rating scale to assess neuropsychiatric symptoms. Similarly, only 7% of students were comfortable assessing caregiver burden, and most were not aware of any validated rating scale to assess caregiver burden. Only 1 in 5 students were comfortable using 2 cognitive screens to assess cognitive deficits. Many students stated that they were not routinely expected to perform common cognitive screens, such as the MMSE during their medical training except students who had expressed an interest in psychiatry and were expected to be proficient in the MMSE. Most students were making common mistakes, such as converting the 3-command task to 3 individual single commands, helping too much with serial 7s, and giving too much positive feedback throughout the test.

Discussion

Significant knowledge gaps regarding dementia were found in our study, which is in keeping with other studies in the area. Dementia knowledge deficits among medical trainees have been identified in the United Kingdom, Australia, and the US.6-9

In our study, a brief multicomponent experiential curriculum improved senior medical students’ perception and self-efficacy in diagnosing dementia. This is in keeping with other studies, such as the PAIRS Program.7 Findings from another study indicated that education for geriatric- oriented physicians should focus on experiential learning components through observation and interaction with older adults.16

A background of direct experience with older adults is associated with more positive attitudes toward older adults and increased interest in geriatric medicine.16 In our study, the exposure was brief; therefore, the results could not be compared with other long-term exposure studies. However, even with this brief intervention most students reported being comfortable with assessing caregiver burden (78%), behavioral problems of dementia (88%), and using ≥ 2 cognitive screens (92%). Comfortable in dementia assessment increased after the intervention from 10% to 96%. This finding is encouraging because brief multicomponent dementia education can be devised easily. This finding needs to be taken with caution because we did not conduct a formal skills evaluation.

A unique component of our experience was to learn medical students’ perception about the impact of neuropsychiatric symptoms on the trajectory, outcomes, and management of dementia. These symptoms included delusions, hallucinations, agitation, depression, anxiety, euphoria, apathy, disinhibition, irritability, motor disturbance, nighttime behaviors, and appetite and eating. Less than half the students thought that neuropsychiatric symptoms had a significant impact on dementia before the experience. Through didactics, systematic assessment of neuropsychiatric symptoms and interaction with caregivers, > 98% of students learned that these symptoms have a significant impact on dementia management.

This experience also emphasized the role of several disciplines in dementia assessment and management. Students’ experience positively influenced appreciation of the role of the memory clinic team. Our hope is that students will seek input from social workers, neuropsychologists, and other team members when working with patients with dementia or their caregivers. The common reason why primary care physicians focus on an exclusive medical model is the time commitment for communicating with an interdisciplinary team. Students experienced the feasibility of the interdisciplinary team involvement and how technology could be used for synchronous and asynchronous communication among team members. Medical students also were introduced to complex billing codes used when ≥ 3 disciplines assess/manage a geriatric patient.

Limitations

This study is limited by the lack of long-term follow-up evaluations, no metrics for practice changes clinical outcomes, and implementation in a single medical school. The postexperience evaluation in this study was performed immediately after the intervention. Long-term follow-up would inform whether the changes noted are durable. Because of the brief nature of our intervention, we do not believe that it would change practice in clinical care. It will be informative to follow this cohort of students to study whether their clinical approach to dementia care changes. The intervention needs to be replicated in other medical schools and in more heterogeneous groups to generalize the results of the study.

Conclusions

Senior medical students are not routinely exposed to interdisciplinary team assessments. Dementia knowledge gaps were prevalent in this cohort of senior medical students. Providing interdisciplinary geriatric educational experience improved their perception of their ability to assess for dementia and their recognition of the roles of interdisciplinary team members. Plans are in place to continue and expand the program to other complex geriatric syndromes.

Acknowledgments
Poster presented at the 2019 annual meeting of the American Geriatrics Society. Oral presentation at the same meeting as part of the select Geriatric Education Methods and Materials Swap workshop.

References

1. Ferri CP, Prince M, Brayne C, et al. Global prevalence of dementia: a Delphi consensus study. Lancet. 2005;366(9503):2112-2117. doi:10.1016/S0140-6736(05)67889-0

2. Janca A, Aarli JA, Prilipko L, Dua T, Saxena S, Saraceno B. WHO/WFN survey of neurological services: a worldwide perspective. J Neurol Sci. 2006;247(1):29-34. doi:10.1016/j.jns.2006.03.003

3. Wilkins KM, Blazek MC, Brooks WB, Lehmann SW, Popeo D, Wagenaar D. Six things all medical students need to know about geriatric psychiatry (and how to teach them). Acad Psychiatry. 2017;41(5):693-700. doi:10.1007/s40596-017-0691-7

4. Turner S, Iliffe S, Downs M, et al. General practitioners’ knowledge, confidence and attitudes in the diagnosis and management of dementia. Age Ageing. 2004;33(5):461- 467. doi:10.1093/ageing/afh140

5. Lester PE, Dharmarajan TS, Weinstein E. The looming geriatrician shortage: ramifications and solutions. J Aging Health. 2019:898264319879325. doi:10.1177/0898264319879325

6. Struck BD, Bernard MA, Teasdale TA; Oklahoma University Geriatric Education G. Effect of a mandatory geriatric medicine clerkship on third-year students. J Am Geriatr Soc. 2005;53(11):2007-2011. doi:10.1111/j.1532-5415.2005.00473.x

7. Jefferson AL, Cantwell NG, Byerly LK, Morhardt D. Medical student education program in Alzheimer’s disease: the PAIRS Program. BMC Med Educ. 2012;12:80. doi:10.1186/1472-6920-12-80

8. Nagle BJ, Usita PM, Edland SD. United States medical students’ knowledge of Alzheimer disease. J Educ Eval Health Prof. 2013;10:4. doi:10.3352/jeehp.2013.10.4

9. Scott TL, Kugelman M, Tulloch K. How medical professional students view older people with dementia: Implications for education and practice. PLoS One. 2019;14(11):e0225329. doi:10.1371/journal.pone.0225329.

10. Zarit SH, Reever KE, Bach-Peterson J. Relatives of the impaired elderly: correlates of feelings of burden. Gerontologist. 1980;20(6):649-655. doi:10.1093/geront/20.6.649

11. McDowell I, Kristjansson B, Hill GB, Hebert R. Community screening for dementia: the Mini Mental State Exam (MMSE) and Modified Mini-Mental State Exam (3MS) compared. J Clin Epidemiol. 1997;50(4):377-383. doi:10.1016/s0895-4356(97)00060-7

12. Nasreddine ZS, Phillips NA, Bedirian V, et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Ger iatr Soc. 2005;53(4):695-699. doi:10.1111/j.1532-5415.2005.53221.x

13. Tariq SH, Tumosa N, Chibnall JT, Perry MH, 3rd, Morley JE. Comparison of the Saint Louis University mental status examination and the Mini-Mental State Examination for detecting dementia and mild neurocognitive disorder--a pilot study. Am J Geriatr Psychiatry. 2006;14(11):900-910. doi:10.1097/01.JGP.0000221510.33817.86

14. Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J. The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology. 1994;44(12):2308-2314. doi:10.1212/wnl.44.12.2308

15. Folstein MF, Folstein SE, McHugh PR. “Mini-mental state.” A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189-198. doi:10.1016/0022-3956(75)90026-6

16. Fitzgerald JT, Wray LA, Halter JB, Williams BC, Supiano MA. Relating medical students’ knowledge, attitudes, and experience to an interest in geriatric medicine. Gerontologist. 2003;43(6):849-855. doi:10.1093/geront/43.6.849

References

1. Ferri CP, Prince M, Brayne C, et al. Global prevalence of dementia: a Delphi consensus study. Lancet. 2005;366(9503):2112-2117. doi:10.1016/S0140-6736(05)67889-0

2. Janca A, Aarli JA, Prilipko L, Dua T, Saxena S, Saraceno B. WHO/WFN survey of neurological services: a worldwide perspective. J Neurol Sci. 2006;247(1):29-34. doi:10.1016/j.jns.2006.03.003

3. Wilkins KM, Blazek MC, Brooks WB, Lehmann SW, Popeo D, Wagenaar D. Six things all medical students need to know about geriatric psychiatry (and how to teach them). Acad Psychiatry. 2017;41(5):693-700. doi:10.1007/s40596-017-0691-7

4. Turner S, Iliffe S, Downs M, et al. General practitioners’ knowledge, confidence and attitudes in the diagnosis and management of dementia. Age Ageing. 2004;33(5):461- 467. doi:10.1093/ageing/afh140

5. Lester PE, Dharmarajan TS, Weinstein E. The looming geriatrician shortage: ramifications and solutions. J Aging Health. 2019:898264319879325. doi:10.1177/0898264319879325

6. Struck BD, Bernard MA, Teasdale TA; Oklahoma University Geriatric Education G. Effect of a mandatory geriatric medicine clerkship on third-year students. J Am Geriatr Soc. 2005;53(11):2007-2011. doi:10.1111/j.1532-5415.2005.00473.x

7. Jefferson AL, Cantwell NG, Byerly LK, Morhardt D. Medical student education program in Alzheimer’s disease: the PAIRS Program. BMC Med Educ. 2012;12:80. doi:10.1186/1472-6920-12-80

8. Nagle BJ, Usita PM, Edland SD. United States medical students’ knowledge of Alzheimer disease. J Educ Eval Health Prof. 2013;10:4. doi:10.3352/jeehp.2013.10.4

9. Scott TL, Kugelman M, Tulloch K. How medical professional students view older people with dementia: Implications for education and practice. PLoS One. 2019;14(11):e0225329. doi:10.1371/journal.pone.0225329.

10. Zarit SH, Reever KE, Bach-Peterson J. Relatives of the impaired elderly: correlates of feelings of burden. Gerontologist. 1980;20(6):649-655. doi:10.1093/geront/20.6.649

11. McDowell I, Kristjansson B, Hill GB, Hebert R. Community screening for dementia: the Mini Mental State Exam (MMSE) and Modified Mini-Mental State Exam (3MS) compared. J Clin Epidemiol. 1997;50(4):377-383. doi:10.1016/s0895-4356(97)00060-7

12. Nasreddine ZS, Phillips NA, Bedirian V, et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Ger iatr Soc. 2005;53(4):695-699. doi:10.1111/j.1532-5415.2005.53221.x

13. Tariq SH, Tumosa N, Chibnall JT, Perry MH, 3rd, Morley JE. Comparison of the Saint Louis University mental status examination and the Mini-Mental State Examination for detecting dementia and mild neurocognitive disorder--a pilot study. Am J Geriatr Psychiatry. 2006;14(11):900-910. doi:10.1097/01.JGP.0000221510.33817.86

14. Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J. The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology. 1994;44(12):2308-2314. doi:10.1212/wnl.44.12.2308

15. Folstein MF, Folstein SE, McHugh PR. “Mini-mental state.” A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189-198. doi:10.1016/0022-3956(75)90026-6

16. Fitzgerald JT, Wray LA, Halter JB, Williams BC, Supiano MA. Relating medical students’ knowledge, attitudes, and experience to an interest in geriatric medicine. Gerontologist. 2003;43(6):849-855. doi:10.1093/geront/43.6.849

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Highlights on Treatment of Progressive MS From ECTRIMS 2020

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Promising phase 3 trial results from French researchers indicate that the first-in-class oral TKI masitinib may provide a new treatment option for patients with primary progressive multiple sclerosis (PPMS) or nonactive secondary progressive MS (SPMS).

The masitinib study was noted by Dr Mark Freedman, professor of neurology at the University of Ottawa, as among the key findings on PPMS presented at ACTRIMS-ECTRIMS 2020. The French study reported that patients receiving masitinib over 96 weeks experienced significant delay in disability progression.

Dr Freedman explains how an analysis done by Mellon Center researchers may change how clinicians counsel patients about the risk for progressive multifocal leukoencephalopathy (PML) related to fingolimod treatment. Their research shows the incidence rate of PML among patients receiving fingolimod to be very low — in fact, fewer than 40 times that of patients receiving natalizumab.

Finally, Dr Freedman discuses an ad hoc analysis presented by leading MS researchers from University Hospital in Basel, Switzerland, which points to plasma glial fibrillary acidic protein (GFAP) levels as a prognostic biomarker of increased risk for worsening disability. Using data from the EXPAND trial, researchers found significant risk for increased disability among patients with nonactive SPMS who had elevated baseline GFAP.

Professor, Department of Neurology, University of Ottawa and The Ottawa Hospital Research Institute; Director, Multiple Sclerosis Research Unit, The Ottawa Hospital – General Campus, Ottawa, Ontario, Canada.

Mark S. Freedman, MSc, MD, has disclosed the following relevant financial relationships: Serve(d) on the advisory board, board of directors, or other similar groups for: Actelion (Janssen/Johnson & Johnson); Alexion; Atara Biotherapeutics; BayerHealthcare; BiogenIdec; Celgene; Clene Nanomedicine; GRI Bio; Hoffman La-Roche; Magenta Therapeutics; Merck Serono; MedDay; Novartis; Sanofi-Genzyme; Teva Canada Innovation. Serve(d) as a member of a speakers bureau for: Sanofi-Genzyme; EMD Serono. Received honoraria or consultation fees for: Actelion (Janssen/Johnson & Johnson); Alexion; BiogenIdec; Celgene (BMS); EMD Inc; Sanofi-Genzyme; Hoffman La-Roche; Merck Serono; Novartis; Teva Canada Innovation­. Received research or educational grants from: Sanofi-Genzyme Canada; Hoffman-La Roche; EMD Inc.

 
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Promising phase 3 trial results from French researchers indicate that the first-in-class oral TKI masitinib may provide a new treatment option for patients with primary progressive multiple sclerosis (PPMS) or nonactive secondary progressive MS (SPMS).

The masitinib study was noted by Dr Mark Freedman, professor of neurology at the University of Ottawa, as among the key findings on PPMS presented at ACTRIMS-ECTRIMS 2020. The French study reported that patients receiving masitinib over 96 weeks experienced significant delay in disability progression.

Dr Freedman explains how an analysis done by Mellon Center researchers may change how clinicians counsel patients about the risk for progressive multifocal leukoencephalopathy (PML) related to fingolimod treatment. Their research shows the incidence rate of PML among patients receiving fingolimod to be very low — in fact, fewer than 40 times that of patients receiving natalizumab.

Finally, Dr Freedman discuses an ad hoc analysis presented by leading MS researchers from University Hospital in Basel, Switzerland, which points to plasma glial fibrillary acidic protein (GFAP) levels as a prognostic biomarker of increased risk for worsening disability. Using data from the EXPAND trial, researchers found significant risk for increased disability among patients with nonactive SPMS who had elevated baseline GFAP.

Professor, Department of Neurology, University of Ottawa and The Ottawa Hospital Research Institute; Director, Multiple Sclerosis Research Unit, The Ottawa Hospital – General Campus, Ottawa, Ontario, Canada.

Mark S. Freedman, MSc, MD, has disclosed the following relevant financial relationships: Serve(d) on the advisory board, board of directors, or other similar groups for: Actelion (Janssen/Johnson & Johnson); Alexion; Atara Biotherapeutics; BayerHealthcare; BiogenIdec; Celgene; Clene Nanomedicine; GRI Bio; Hoffman La-Roche; Magenta Therapeutics; Merck Serono; MedDay; Novartis; Sanofi-Genzyme; Teva Canada Innovation. Serve(d) as a member of a speakers bureau for: Sanofi-Genzyme; EMD Serono. Received honoraria or consultation fees for: Actelion (Janssen/Johnson & Johnson); Alexion; BiogenIdec; Celgene (BMS); EMD Inc; Sanofi-Genzyme; Hoffman La-Roche; Merck Serono; Novartis; Teva Canada Innovation­. Received research or educational grants from: Sanofi-Genzyme Canada; Hoffman-La Roche; EMD Inc.

 

Promising phase 3 trial results from French researchers indicate that the first-in-class oral TKI masitinib may provide a new treatment option for patients with primary progressive multiple sclerosis (PPMS) or nonactive secondary progressive MS (SPMS).

The masitinib study was noted by Dr Mark Freedman, professor of neurology at the University of Ottawa, as among the key findings on PPMS presented at ACTRIMS-ECTRIMS 2020. The French study reported that patients receiving masitinib over 96 weeks experienced significant delay in disability progression.

Dr Freedman explains how an analysis done by Mellon Center researchers may change how clinicians counsel patients about the risk for progressive multifocal leukoencephalopathy (PML) related to fingolimod treatment. Their research shows the incidence rate of PML among patients receiving fingolimod to be very low — in fact, fewer than 40 times that of patients receiving natalizumab.

Finally, Dr Freedman discuses an ad hoc analysis presented by leading MS researchers from University Hospital in Basel, Switzerland, which points to plasma glial fibrillary acidic protein (GFAP) levels as a prognostic biomarker of increased risk for worsening disability. Using data from the EXPAND trial, researchers found significant risk for increased disability among patients with nonactive SPMS who had elevated baseline GFAP.

Professor, Department of Neurology, University of Ottawa and The Ottawa Hospital Research Institute; Director, Multiple Sclerosis Research Unit, The Ottawa Hospital – General Campus, Ottawa, Ontario, Canada.

Mark S. Freedman, MSc, MD, has disclosed the following relevant financial relationships: Serve(d) on the advisory board, board of directors, or other similar groups for: Actelion (Janssen/Johnson & Johnson); Alexion; Atara Biotherapeutics; BayerHealthcare; BiogenIdec; Celgene; Clene Nanomedicine; GRI Bio; Hoffman La-Roche; Magenta Therapeutics; Merck Serono; MedDay; Novartis; Sanofi-Genzyme; Teva Canada Innovation. Serve(d) as a member of a speakers bureau for: Sanofi-Genzyme; EMD Serono. Received honoraria or consultation fees for: Actelion (Janssen/Johnson & Johnson); Alexion; BiogenIdec; Celgene (BMS); EMD Inc; Sanofi-Genzyme; Hoffman La-Roche; Merck Serono; Novartis; Teva Canada Innovation­. Received research or educational grants from: Sanofi-Genzyme Canada; Hoffman-La Roche; EMD Inc.

 
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Survey explores mental health, services use in police officers

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New research shows that about a quarter of police officers in one large force report past or present mental health problems.

Responding to a survey, 26% of police officers on the Dallas police department screened positive for depression, anxiety, PTSD, or symptoms of suicide ideation or self-harm.

Mental illness rates were particularly high among female officers, those who were divorced, widowed, or separated, and those with military experience.

The study also showed that concerns over confidentiality and stigma may prevent officers with mental illness from seeking treatment.

The results underscored the need to identify police officers with psychiatric problems and to connect them to the most appropriate individualized care, author Katelyn K. Jetelina, PhD, assistant professor in the department of epidemiology, human genetics, and environmental sciences, University of Texas Health Science Center, Dallas, said in an interview.

“This is a very hard-to-reach population, and because of that, we need to be innovative in reaching them for services,” she said.

The study was published online Oct. 7 in JAMA Network Open.

Dr. Jetelina and colleagues are investigating various aspects of police officers’ well-being, including their nutritional needs and their occupational, physical, and mental health.

The current study included 434 members of the Dallas police department, the ninth largest in the United States. The mean age of the participants was 37 years, 82% were men, and about half were White. The 434 officers represented 97% of those invited to participate (n = 446) and 31% of the total patrol population of the Dallas police department (n = 1,413).

These officers completed a short survey on their smartphone that asked about lifetime diagnoses of depression, anxiety, and PTSD. They were also asked whether they experienced suicidal ideation or self-harm during the previous 2 weeks.

Overall, 12% of survey respondents reported having been diagnosed with a mental illness. This, said Jetelina, is slightly lower than the rate reported in the general population.

Study participants who had not currently been diagnosed with a mental illness completed the Patient Health Questionnaire–2 (PHQ-2), the Generalized Anxiety Disorder–2 (GAD-2), and the Primary Care–Posttraumatic Stress Disorder (PC-PTSD).

Officers were considered to have a positive result if they had a score of 3 or more (PHQ-2, sensitivity of 83% and specificity of 92%; PC-PTSD-5, sensitivity of 93% and specificity of 85%; GAD-2, sensitivity of 86% and specificity of 83%).

About 26% of respondents had a positive screening for mental illness symptoms, mainly PTSD and depression, which Dr. Jetelina noted is a higher percentage than in the general population.

This rate of mental health symptoms is “high and concerning,” but not surprising because of the work of police officers, which could include attending to sometimes violent car crashes, domestic abuse situations, and armed conflicts, said Dr. Jetelina.

“They’re constantly exposed to traumatic calls for service; they see people on their worst day, 8 hours a day, 5 days a week. That stress and exposure will have a detrimental effect on mental health, and we have to pay more attention to that,” she said.

Dr. Jetelina pointed out that the surveys were completed in January and February 2020, before COVID-19 had become a cause of stress for everyone and before the increase in calls for defunding police amid a resurgence of Black Lives Matter demonstrations.

However, she stressed that racial biases and occupational stress among police officers are “nothing new for them.” For example, in 2016, five Dallas police officers were killed during Black Lives Matter protests because of their race/ethnicity.
 

 

 

More at risk

The study showed that certain subgroups of officers were more at risk for mental illness. After adjustment for confounders, including demographic characteristics, marital status, and educational level, the odds of being diagnosed with a mental illness during the course of one’s life were significantly higher among female officers than male officers (adjusted odds ratio, 3.20; 95% confidence interval, 1.18-8.68).

Officers who were divorced, widowed, or separated and those who had more experience and held a higher rank were also at greater risk for mental illness.

As well, military veterans had greater odds of being diagnosed with a mental health disorder, compared with nonveterans (aOR, 3.25; 95% CI, 1.38-7.67).

The study also asked participants about use of mental health care services over the past 12 months. About 35% of those who had a current mental health diagnosis and 17% of those who screened positive for mental health symptoms reported using such services.

The study also asked those who screened positive about their interest in seeking such services. After adjustments, officers with suicidal ideation or self-harm were significantly more likely to be interested in getting help, compared with officers who did not report suicidal ideation or self-harm (aOR, 7.66; 95% CI, 1.70-34.48).

Dr. Jetelina was impressed that so many officers were keen to seek help, which “is a big positive,” she said. “It’s just a matter of better detecting who needs the help and better connecting them to medical services that meet their needs.”
 

Mindfulness exercise

Dr. Jetelina and colleagues are conducting a pilot test of the use by police officers of smartwatches that monitor heart rate and oxygen levels. If measurements with these devices reach a predetermined threshold, the officers are “pinged” and are instructed to perform a mindfulness exercise in the field, she said.

Results so far “are really exciting,” said Dr. Jetelina. “Officers have found this extremely helpful and feasible, and so the next step is to test if this truly impacts mental illness over time.”

Routine mental health screening of officers might be beneficial, but only if it’s conducted in a manner “respectful of the officers’ needs and wants,” said Dr. Jetelina.

She pointed out that although psychological assessments are routinely carried out following an extreme traumatic call, such as one involving an officer-involved shooting, the “in-between” calls could have a more severe cumulative impact on mental health.

It’s important to provide officers with easy-to-access services tailored for their individual needs, said Dr. Jetelina.
 

‘Numb to it’

Eighteen patrol officers also participated in a focus group, during which several themes regarding the use of mental health care services emerged. One theme was the inability of officers to identify when they’re personally experiencing a mental health problem.

Participants said they had become “numb” to the traumatic events on the job, which is “concerning,” Dr. Jetelina said. “They think that having nightmares every week is completely normal, but it’s not, and this needs to be addressed.”

Other themes that emerged from focus groups included the belief that psychologists can’t relate to police stressors; concerns about confidentiality (one sentiment that was expressed was “you’re an idiot” if you “trust this department”); and stigma for officers who seek mental health care (participants talked about “reprisal” from seeing “a shrink,” including being labeled as “a nutter” and losing their job).

Dr. Jetelina noted that some “champion” officers revealed their mental health journey during focus groups, which tended to “open a Pandora’s box” for others to discuss their experience. She said these champions could be leveraged throughout the police department to help reduce stigma.

The study included participants from only one police department, although rigorous data collection allows for generalizability to the entire patrol department, say the authors. Although the study included only brief screens of mental illness symptoms, these short versions of screening tests have high sensitivity and specificity for mental illness in primary care, they noted.

The next step for the researchers is to study how mental illness and symptoms affect job performance, said Dr. Jetelina. “Does this impact excessive use of force? Does this impact workers’ compensation? Does this impact dispatch times, the time it takes for a police officer to respond to [a] 911 call?”
 

 

 

Possible underrepresentation

Anthony T. Ng, MD, regional medical director, East Region Hartford HealthCare Behavioral Health Network in Mansfield, Conn., and member of the American Psychiatric Association’s Council on Communications, found the study “helpful.”

However, the 26% who tested positive for mental illness may be an “underrepresentation” of the true picture, inasmuch as police officers might minimize or be less than truthful about their mental health status, said Dr. Ng.

Law enforcement has “never been easy,” but stressors may have escalated recently as police forces deal with shortages of staff and jails, said Dr. Ng.

He also noted that officers might face stressors at home. “Evidence shows that domestic violence is quite high – or higher than average – among law enforcement,” he said. “All these things add up.”

Psychiatrists and other mental health professionals should be “aware of the unique challenges” that police officers face and be “proactively involved” in providing guidance and education on mitigating stress, said Dr. Ng.

“You have police officers wearing body armor, so why can’t you give them some training to learn how to have psychiatric or psychological body armor?” he said. But it’s a two-way street; police forces should be open to outreach from mental health professionals. “We have to meet halfway.”
 

Compassion fatigue

In an accompanying commentary, John M. Violanti, PhD, of the department of epidemiology and environmental health at the State University of New York at Buffalo, said the article helps bring “to the forefront” the issue of the psychological dangers of police work.

There is conjecture as to why police experience mental distress, said Dr. Violanti, who pointed to a study of New York City police suicides during the 1930s that suggested that police have a “social license” for aggressive behavior but are restrained as part of public trust, placing them in a position of “psychological strain.”

“This situation may be reflective of the same situation police find themselves today,” said Dr. Violanti.

“Compassion fatigue,” a feeling of mental exhaustion caused by the inability to care for all persons in trouble, may also be a factor, as could the constant stress that leaves police officers feeling “cynical and isolated from others,” he wrote.

“The socialization process of becoming a police officer is associated with constrictive reasoning, viewing the world as either right or wrong, which leaves no middle ground for alternatives to deal with mental distress,” Dr. Violanti said.

He noted that police officers may abuse alcohol because of stress, peer pressure, isolation, and a culture that approves of alcohol use. “Officers tend to drink together and reinforce their own values.”.

Although no prospective studies have linked police mental health problems with childhood abuse or neglect, some mental health professionals estimate that about 25% of their police clients have a history of childhood abuse or neglect, said Dr. Violanti.

He agreed that mindfulness may help manage stress and increase cognitive flexibility in dealing with trauma and crises.

A possible way to ensure confidentiality is a peer support program that allows distressed officers to first talk privately with a trained and trusted peer officer and to then seek professional help if necessary, said Dr. Violanti.

The study was funded by a grant from the National Institute of Occupational Health and Safety. Dr. Jetelina, Dr. Ng, and Dr. Violanti disclosed no relevant financial relationships.

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

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New research shows that about a quarter of police officers in one large force report past or present mental health problems.

Responding to a survey, 26% of police officers on the Dallas police department screened positive for depression, anxiety, PTSD, or symptoms of suicide ideation or self-harm.

Mental illness rates were particularly high among female officers, those who were divorced, widowed, or separated, and those with military experience.

The study also showed that concerns over confidentiality and stigma may prevent officers with mental illness from seeking treatment.

The results underscored the need to identify police officers with psychiatric problems and to connect them to the most appropriate individualized care, author Katelyn K. Jetelina, PhD, assistant professor in the department of epidemiology, human genetics, and environmental sciences, University of Texas Health Science Center, Dallas, said in an interview.

“This is a very hard-to-reach population, and because of that, we need to be innovative in reaching them for services,” she said.

The study was published online Oct. 7 in JAMA Network Open.

Dr. Jetelina and colleagues are investigating various aspects of police officers’ well-being, including their nutritional needs and their occupational, physical, and mental health.

The current study included 434 members of the Dallas police department, the ninth largest in the United States. The mean age of the participants was 37 years, 82% were men, and about half were White. The 434 officers represented 97% of those invited to participate (n = 446) and 31% of the total patrol population of the Dallas police department (n = 1,413).

These officers completed a short survey on their smartphone that asked about lifetime diagnoses of depression, anxiety, and PTSD. They were also asked whether they experienced suicidal ideation or self-harm during the previous 2 weeks.

Overall, 12% of survey respondents reported having been diagnosed with a mental illness. This, said Jetelina, is slightly lower than the rate reported in the general population.

Study participants who had not currently been diagnosed with a mental illness completed the Patient Health Questionnaire–2 (PHQ-2), the Generalized Anxiety Disorder–2 (GAD-2), and the Primary Care–Posttraumatic Stress Disorder (PC-PTSD).

Officers were considered to have a positive result if they had a score of 3 or more (PHQ-2, sensitivity of 83% and specificity of 92%; PC-PTSD-5, sensitivity of 93% and specificity of 85%; GAD-2, sensitivity of 86% and specificity of 83%).

About 26% of respondents had a positive screening for mental illness symptoms, mainly PTSD and depression, which Dr. Jetelina noted is a higher percentage than in the general population.

This rate of mental health symptoms is “high and concerning,” but not surprising because of the work of police officers, which could include attending to sometimes violent car crashes, domestic abuse situations, and armed conflicts, said Dr. Jetelina.

“They’re constantly exposed to traumatic calls for service; they see people on their worst day, 8 hours a day, 5 days a week. That stress and exposure will have a detrimental effect on mental health, and we have to pay more attention to that,” she said.

Dr. Jetelina pointed out that the surveys were completed in January and February 2020, before COVID-19 had become a cause of stress for everyone and before the increase in calls for defunding police amid a resurgence of Black Lives Matter demonstrations.

However, she stressed that racial biases and occupational stress among police officers are “nothing new for them.” For example, in 2016, five Dallas police officers were killed during Black Lives Matter protests because of their race/ethnicity.
 

 

 

More at risk

The study showed that certain subgroups of officers were more at risk for mental illness. After adjustment for confounders, including demographic characteristics, marital status, and educational level, the odds of being diagnosed with a mental illness during the course of one’s life were significantly higher among female officers than male officers (adjusted odds ratio, 3.20; 95% confidence interval, 1.18-8.68).

Officers who were divorced, widowed, or separated and those who had more experience and held a higher rank were also at greater risk for mental illness.

As well, military veterans had greater odds of being diagnosed with a mental health disorder, compared with nonveterans (aOR, 3.25; 95% CI, 1.38-7.67).

The study also asked participants about use of mental health care services over the past 12 months. About 35% of those who had a current mental health diagnosis and 17% of those who screened positive for mental health symptoms reported using such services.

The study also asked those who screened positive about their interest in seeking such services. After adjustments, officers with suicidal ideation or self-harm were significantly more likely to be interested in getting help, compared with officers who did not report suicidal ideation or self-harm (aOR, 7.66; 95% CI, 1.70-34.48).

Dr. Jetelina was impressed that so many officers were keen to seek help, which “is a big positive,” she said. “It’s just a matter of better detecting who needs the help and better connecting them to medical services that meet their needs.”
 

Mindfulness exercise

Dr. Jetelina and colleagues are conducting a pilot test of the use by police officers of smartwatches that monitor heart rate and oxygen levels. If measurements with these devices reach a predetermined threshold, the officers are “pinged” and are instructed to perform a mindfulness exercise in the field, she said.

Results so far “are really exciting,” said Dr. Jetelina. “Officers have found this extremely helpful and feasible, and so the next step is to test if this truly impacts mental illness over time.”

Routine mental health screening of officers might be beneficial, but only if it’s conducted in a manner “respectful of the officers’ needs and wants,” said Dr. Jetelina.

She pointed out that although psychological assessments are routinely carried out following an extreme traumatic call, such as one involving an officer-involved shooting, the “in-between” calls could have a more severe cumulative impact on mental health.

It’s important to provide officers with easy-to-access services tailored for their individual needs, said Dr. Jetelina.
 

‘Numb to it’

Eighteen patrol officers also participated in a focus group, during which several themes regarding the use of mental health care services emerged. One theme was the inability of officers to identify when they’re personally experiencing a mental health problem.

Participants said they had become “numb” to the traumatic events on the job, which is “concerning,” Dr. Jetelina said. “They think that having nightmares every week is completely normal, but it’s not, and this needs to be addressed.”

Other themes that emerged from focus groups included the belief that psychologists can’t relate to police stressors; concerns about confidentiality (one sentiment that was expressed was “you’re an idiot” if you “trust this department”); and stigma for officers who seek mental health care (participants talked about “reprisal” from seeing “a shrink,” including being labeled as “a nutter” and losing their job).

Dr. Jetelina noted that some “champion” officers revealed their mental health journey during focus groups, which tended to “open a Pandora’s box” for others to discuss their experience. She said these champions could be leveraged throughout the police department to help reduce stigma.

The study included participants from only one police department, although rigorous data collection allows for generalizability to the entire patrol department, say the authors. Although the study included only brief screens of mental illness symptoms, these short versions of screening tests have high sensitivity and specificity for mental illness in primary care, they noted.

The next step for the researchers is to study how mental illness and symptoms affect job performance, said Dr. Jetelina. “Does this impact excessive use of force? Does this impact workers’ compensation? Does this impact dispatch times, the time it takes for a police officer to respond to [a] 911 call?”
 

 

 

Possible underrepresentation

Anthony T. Ng, MD, regional medical director, East Region Hartford HealthCare Behavioral Health Network in Mansfield, Conn., and member of the American Psychiatric Association’s Council on Communications, found the study “helpful.”

However, the 26% who tested positive for mental illness may be an “underrepresentation” of the true picture, inasmuch as police officers might minimize or be less than truthful about their mental health status, said Dr. Ng.

Law enforcement has “never been easy,” but stressors may have escalated recently as police forces deal with shortages of staff and jails, said Dr. Ng.

He also noted that officers might face stressors at home. “Evidence shows that domestic violence is quite high – or higher than average – among law enforcement,” he said. “All these things add up.”

Psychiatrists and other mental health professionals should be “aware of the unique challenges” that police officers face and be “proactively involved” in providing guidance and education on mitigating stress, said Dr. Ng.

“You have police officers wearing body armor, so why can’t you give them some training to learn how to have psychiatric or psychological body armor?” he said. But it’s a two-way street; police forces should be open to outreach from mental health professionals. “We have to meet halfway.”
 

Compassion fatigue

In an accompanying commentary, John M. Violanti, PhD, of the department of epidemiology and environmental health at the State University of New York at Buffalo, said the article helps bring “to the forefront” the issue of the psychological dangers of police work.

There is conjecture as to why police experience mental distress, said Dr. Violanti, who pointed to a study of New York City police suicides during the 1930s that suggested that police have a “social license” for aggressive behavior but are restrained as part of public trust, placing them in a position of “psychological strain.”

“This situation may be reflective of the same situation police find themselves today,” said Dr. Violanti.

“Compassion fatigue,” a feeling of mental exhaustion caused by the inability to care for all persons in trouble, may also be a factor, as could the constant stress that leaves police officers feeling “cynical and isolated from others,” he wrote.

“The socialization process of becoming a police officer is associated with constrictive reasoning, viewing the world as either right or wrong, which leaves no middle ground for alternatives to deal with mental distress,” Dr. Violanti said.

He noted that police officers may abuse alcohol because of stress, peer pressure, isolation, and a culture that approves of alcohol use. “Officers tend to drink together and reinforce their own values.”.

Although no prospective studies have linked police mental health problems with childhood abuse or neglect, some mental health professionals estimate that about 25% of their police clients have a history of childhood abuse or neglect, said Dr. Violanti.

He agreed that mindfulness may help manage stress and increase cognitive flexibility in dealing with trauma and crises.

A possible way to ensure confidentiality is a peer support program that allows distressed officers to first talk privately with a trained and trusted peer officer and to then seek professional help if necessary, said Dr. Violanti.

The study was funded by a grant from the National Institute of Occupational Health and Safety. Dr. Jetelina, Dr. Ng, and Dr. Violanti disclosed no relevant financial relationships.

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

 

New research shows that about a quarter of police officers in one large force report past or present mental health problems.

Responding to a survey, 26% of police officers on the Dallas police department screened positive for depression, anxiety, PTSD, or symptoms of suicide ideation or self-harm.

Mental illness rates were particularly high among female officers, those who were divorced, widowed, or separated, and those with military experience.

The study also showed that concerns over confidentiality and stigma may prevent officers with mental illness from seeking treatment.

The results underscored the need to identify police officers with psychiatric problems and to connect them to the most appropriate individualized care, author Katelyn K. Jetelina, PhD, assistant professor in the department of epidemiology, human genetics, and environmental sciences, University of Texas Health Science Center, Dallas, said in an interview.

“This is a very hard-to-reach population, and because of that, we need to be innovative in reaching them for services,” she said.

The study was published online Oct. 7 in JAMA Network Open.

Dr. Jetelina and colleagues are investigating various aspects of police officers’ well-being, including their nutritional needs and their occupational, physical, and mental health.

The current study included 434 members of the Dallas police department, the ninth largest in the United States. The mean age of the participants was 37 years, 82% were men, and about half were White. The 434 officers represented 97% of those invited to participate (n = 446) and 31% of the total patrol population of the Dallas police department (n = 1,413).

These officers completed a short survey on their smartphone that asked about lifetime diagnoses of depression, anxiety, and PTSD. They were also asked whether they experienced suicidal ideation or self-harm during the previous 2 weeks.

Overall, 12% of survey respondents reported having been diagnosed with a mental illness. This, said Jetelina, is slightly lower than the rate reported in the general population.

Study participants who had not currently been diagnosed with a mental illness completed the Patient Health Questionnaire–2 (PHQ-2), the Generalized Anxiety Disorder–2 (GAD-2), and the Primary Care–Posttraumatic Stress Disorder (PC-PTSD).

Officers were considered to have a positive result if they had a score of 3 or more (PHQ-2, sensitivity of 83% and specificity of 92%; PC-PTSD-5, sensitivity of 93% and specificity of 85%; GAD-2, sensitivity of 86% and specificity of 83%).

About 26% of respondents had a positive screening for mental illness symptoms, mainly PTSD and depression, which Dr. Jetelina noted is a higher percentage than in the general population.

This rate of mental health symptoms is “high and concerning,” but not surprising because of the work of police officers, which could include attending to sometimes violent car crashes, domestic abuse situations, and armed conflicts, said Dr. Jetelina.

“They’re constantly exposed to traumatic calls for service; they see people on their worst day, 8 hours a day, 5 days a week. That stress and exposure will have a detrimental effect on mental health, and we have to pay more attention to that,” she said.

Dr. Jetelina pointed out that the surveys were completed in January and February 2020, before COVID-19 had become a cause of stress for everyone and before the increase in calls for defunding police amid a resurgence of Black Lives Matter demonstrations.

However, she stressed that racial biases and occupational stress among police officers are “nothing new for them.” For example, in 2016, five Dallas police officers were killed during Black Lives Matter protests because of their race/ethnicity.
 

 

 

More at risk

The study showed that certain subgroups of officers were more at risk for mental illness. After adjustment for confounders, including demographic characteristics, marital status, and educational level, the odds of being diagnosed with a mental illness during the course of one’s life were significantly higher among female officers than male officers (adjusted odds ratio, 3.20; 95% confidence interval, 1.18-8.68).

Officers who were divorced, widowed, or separated and those who had more experience and held a higher rank were also at greater risk for mental illness.

As well, military veterans had greater odds of being diagnosed with a mental health disorder, compared with nonveterans (aOR, 3.25; 95% CI, 1.38-7.67).

The study also asked participants about use of mental health care services over the past 12 months. About 35% of those who had a current mental health diagnosis and 17% of those who screened positive for mental health symptoms reported using such services.

The study also asked those who screened positive about their interest in seeking such services. After adjustments, officers with suicidal ideation or self-harm were significantly more likely to be interested in getting help, compared with officers who did not report suicidal ideation or self-harm (aOR, 7.66; 95% CI, 1.70-34.48).

Dr. Jetelina was impressed that so many officers were keen to seek help, which “is a big positive,” she said. “It’s just a matter of better detecting who needs the help and better connecting them to medical services that meet their needs.”
 

Mindfulness exercise

Dr. Jetelina and colleagues are conducting a pilot test of the use by police officers of smartwatches that monitor heart rate and oxygen levels. If measurements with these devices reach a predetermined threshold, the officers are “pinged” and are instructed to perform a mindfulness exercise in the field, she said.

Results so far “are really exciting,” said Dr. Jetelina. “Officers have found this extremely helpful and feasible, and so the next step is to test if this truly impacts mental illness over time.”

Routine mental health screening of officers might be beneficial, but only if it’s conducted in a manner “respectful of the officers’ needs and wants,” said Dr. Jetelina.

She pointed out that although psychological assessments are routinely carried out following an extreme traumatic call, such as one involving an officer-involved shooting, the “in-between” calls could have a more severe cumulative impact on mental health.

It’s important to provide officers with easy-to-access services tailored for their individual needs, said Dr. Jetelina.
 

‘Numb to it’

Eighteen patrol officers also participated in a focus group, during which several themes regarding the use of mental health care services emerged. One theme was the inability of officers to identify when they’re personally experiencing a mental health problem.

Participants said they had become “numb” to the traumatic events on the job, which is “concerning,” Dr. Jetelina said. “They think that having nightmares every week is completely normal, but it’s not, and this needs to be addressed.”

Other themes that emerged from focus groups included the belief that psychologists can’t relate to police stressors; concerns about confidentiality (one sentiment that was expressed was “you’re an idiot” if you “trust this department”); and stigma for officers who seek mental health care (participants talked about “reprisal” from seeing “a shrink,” including being labeled as “a nutter” and losing their job).

Dr. Jetelina noted that some “champion” officers revealed their mental health journey during focus groups, which tended to “open a Pandora’s box” for others to discuss their experience. She said these champions could be leveraged throughout the police department to help reduce stigma.

The study included participants from only one police department, although rigorous data collection allows for generalizability to the entire patrol department, say the authors. Although the study included only brief screens of mental illness symptoms, these short versions of screening tests have high sensitivity and specificity for mental illness in primary care, they noted.

The next step for the researchers is to study how mental illness and symptoms affect job performance, said Dr. Jetelina. “Does this impact excessive use of force? Does this impact workers’ compensation? Does this impact dispatch times, the time it takes for a police officer to respond to [a] 911 call?”
 

 

 

Possible underrepresentation

Anthony T. Ng, MD, regional medical director, East Region Hartford HealthCare Behavioral Health Network in Mansfield, Conn., and member of the American Psychiatric Association’s Council on Communications, found the study “helpful.”

However, the 26% who tested positive for mental illness may be an “underrepresentation” of the true picture, inasmuch as police officers might minimize or be less than truthful about their mental health status, said Dr. Ng.

Law enforcement has “never been easy,” but stressors may have escalated recently as police forces deal with shortages of staff and jails, said Dr. Ng.

He also noted that officers might face stressors at home. “Evidence shows that domestic violence is quite high – or higher than average – among law enforcement,” he said. “All these things add up.”

Psychiatrists and other mental health professionals should be “aware of the unique challenges” that police officers face and be “proactively involved” in providing guidance and education on mitigating stress, said Dr. Ng.

“You have police officers wearing body armor, so why can’t you give them some training to learn how to have psychiatric or psychological body armor?” he said. But it’s a two-way street; police forces should be open to outreach from mental health professionals. “We have to meet halfway.”
 

Compassion fatigue

In an accompanying commentary, John M. Violanti, PhD, of the department of epidemiology and environmental health at the State University of New York at Buffalo, said the article helps bring “to the forefront” the issue of the psychological dangers of police work.

There is conjecture as to why police experience mental distress, said Dr. Violanti, who pointed to a study of New York City police suicides during the 1930s that suggested that police have a “social license” for aggressive behavior but are restrained as part of public trust, placing them in a position of “psychological strain.”

“This situation may be reflective of the same situation police find themselves today,” said Dr. Violanti.

“Compassion fatigue,” a feeling of mental exhaustion caused by the inability to care for all persons in trouble, may also be a factor, as could the constant stress that leaves police officers feeling “cynical and isolated from others,” he wrote.

“The socialization process of becoming a police officer is associated with constrictive reasoning, viewing the world as either right or wrong, which leaves no middle ground for alternatives to deal with mental distress,” Dr. Violanti said.

He noted that police officers may abuse alcohol because of stress, peer pressure, isolation, and a culture that approves of alcohol use. “Officers tend to drink together and reinforce their own values.”.

Although no prospective studies have linked police mental health problems with childhood abuse or neglect, some mental health professionals estimate that about 25% of their police clients have a history of childhood abuse or neglect, said Dr. Violanti.

He agreed that mindfulness may help manage stress and increase cognitive flexibility in dealing with trauma and crises.

A possible way to ensure confidentiality is a peer support program that allows distressed officers to first talk privately with a trained and trusted peer officer and to then seek professional help if necessary, said Dr. Violanti.

The study was funded by a grant from the National Institute of Occupational Health and Safety. Dr. Jetelina, Dr. Ng, and Dr. Violanti disclosed no relevant financial relationships.

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

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Hidradenitis Suppurativa in the Military

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Wed, 01/06/2021 - 09:11
In Partnership With the Association of Military Dermatologists

 

Case Report

A 19-year-old female marine with a 10-year history of hidradenitis suppurativa (HS) presented with hyperpigmented nodules in the inguinal folds and a recurrent cyst in the right groin area of 2 to 3 weeks’ duration. She denied axillary or inframammary involvement. She underwent several incision and drainage procedures 1 year prior to her enlistment in the US Marine Corps at 18 years of age. She previously had been treated by dermatology with doxycycline 100-mg tablets twice daily, benzoyl peroxide wash 5% applied to affected areas and rinsed daily, and clindamycin solution 1% with minimal improvement. She denied smoking or alcohol intake and said she typically wore a loose-fitting uniform to work. As a marine, she was expected to participate in daily physical training and exercises with her military unit, during which she wore a standardized physical training uniform, including nylon shorts and a cotton T-shirt. She requested light duty—military duty status with physical limitations or restrictions—to avoid physical training that would cause further friction and irritation to the inguinal region.

Physical examination demonstrated a woman with Fitzpatrick skin type III and normal body mass index. There were hyperpigmented nodules and scarring in the inguinal folds, most consistent with Hurley stage 2. A single, 0.5-cm, draining lesion was visualized. No hyperhidrosis was noted. The patient was placed on light duty for 7 days, with physical training only at her own pace and discretion. Moreover, she was restricted from field training, rifle range training, and other situations where she may excessively sweat or not be able to adequately maintain personal hygiene. She was encouraged to continue clindamycin solution 1% to the affected area twice daily and was prescribed chlorhexidine solution 4% to use when washing affected areas in the shower. The patient also was referred to the dermatology department at the Naval Hospital Camp Pendleton (Oceanside, California), where she was treated with laser hair removal in the inguinal region, thus avoiding waxing and further aggravation of HS flares. Due to the combination of topical therapies along with laser hair removal and duty restrictions, the patient had a dramatic decrease in development of severe nodular lesions.

Comment

Presentation
Historically, the incidence of HS is estimated at 0.5% to 4% of the general population with female predominance.1 Predisposing factors include obesity, smoking, genetic predisposition to acne, apocrine duct obstruction, and secondary bacterial infection.2 During acute flares, patients generally present with tender subcutaneous nodules that drain malodorous purulent material.3,4 Acute flares are unpredictable, and patients deal with chronic, recurrent, draining wounds, leading to a poor quality of life with resulting physical, psychological, financial, social, and emotional distress.3-5 The negative impact of HS on a patient’s quality of life has been reported to be greater than other dermatologic conditions.6 Lesions can be particularly painful and can cause disfiguration to the surface of the skin.7 Lesion severity is described using the Hurley staging system. Patient quality of life is directly correlated with disease severity and Hurley stage. In stage 1, abscesses develop, but no sinus tracts or cicatrization is present. In stage 2, recurrent abscesses will form tracts and cicatrization. In stage 3, the abscesses become diffuse or near diffuse, with multiple interconnected tracts and abscesses across the entire area of the body.8,9

Severe or refractory HS within the physically active military population may require consideration of light or limited duty or even separation from service. Similarly, severe HS may pose challenges with other physically demanding occupations, such as the police force and firefighters.

Prevention Focus
Prevention of flares is key for patients with HS; secondary prevention aims to reduce impact of the disease or injury that has already occurred,10,11 which includes prevention of the infundibulofolliculitis from becoming a deep folliculitis, nodule, or fistula, as well as Hurley stage progression. Prompt diagnosis with appropriate treatment can decrease the severity of lesions, pain, and scarring. Globally, HS patients continue to experience considerable diagnostic delays of 8 to 12 years after onset of initial symptoms.11,12 Earlier accurate diagnosis and initiation of treatment from the primary care provider or general medical officer is imperative. Initial accurate management may help keep symptoms from progressing to more severe painful lesions. Similarly, patients should be educated on how to prevent HS flares. Patients should avoid known triggers, including smoking, obesity, sweating, mechanical irritation, stress, and poor hygiene.11



Shaving for hair reduction creates ingrown hair shafts, which may lead to folliculitis in mechanically stressed areas in skin folds, thus initiating the inflammatory cascade of HS.11,13 Therefore, shaving along with any other mechanical stress should be avoided in patients with HS. Laser hair removal has been shown to be quite helpful in both the prevention and treatment of HS. In one study, 22 patients with Hurley stage 2 to 3 disease were treated with an Nd:YAG laser once monthly. Results demonstrated a 65% decrease in disease severity after 3 monthly treatments.11 Similarly, other lasers have been used with success in several small case series; an 800-nm diode laser, intense pulsed light therapy, and a ruby laser have each demonstrated efficacy.14 Given these results, hair removal should be recommended to patients with HS. Military servicemembers (SMs) with certain conditions, such as polycystic ovary syndrome, pseudofolliculitis barbae, and HS, are eligible for laser hair removal when available at local military treatment facilities. Primary care providers for military SMs must have a working understanding of the disease process of HS and awareness of what resources are available for treatment, which allows for more streamlined care and improved outcomes.

 

 



Treatment Options
Treatment options are diverse and depend on the severity of HS. Typically, treatment begins with medical therapy followed by escalation to surgical intervention. Medical therapies often include antibiotics, acne treatments, antiandrogen therapy, immunosuppressive agents, and biologic therapy.15,16 If first-line medical interventions fail to control HS, surgical interventions should be considered. Surgical intervention in conjunction with medical therapy decreases the chance for recurrence.3,15,16



Although HS is internationally recognized as an inflammatory disease and not an infectious process, topical antibiotics can help to prevent and improve formation of abscesses, nodules, and pustules.11 Agents such as clindamycin and chlorhexidine wash have proven effective in preventing flares.11,16 Other antibiotics used alone or in combination also are efficacious. Tetracyclines are recommended as monotherapy for mild stages of HS.17-19 Doxycycline is the most commonly used tetracycline in HS patients and has been demonstrated to penetrate Staphylococcus aureus biofilm in high enough concentrations to maintain its antibacterial activity.20 Moreover, doxycycline, as with other tetracyclines, has a multitude of anti-inflammatory and immunomodulatory properties21 and can reduce the production of IL-1, IL-6, tumor necrosis factor α, and IL-8; downregulate chemotaxis; and promote lipo-oxygenase, matrix metalloproteinase, and nuclear factor κB (NF-κB) signaling inhibition.17

Clindamycin is the only known agent that has been studied for topical treatment and utilization in milder cases of HS.17,22 Systemic combination of clindamycin and rifampicin is the most studied, with well-established efficacy in managing HS.17,23,24 Clindamycin has bacteriostatic activity toward both aerobic and anaerobic gram-positive bacteria by binding irreversibly to the 50S ribosomal subunit, thereby inhibiting bacterial protein synthesis. Rifampicin binds to the beta subunit of DNA-dependent RNA polymerase, inhibiting bacterial DNA-dependent RNA synthesis. Rifampicin has broad-spectrum activity, mostly against gram-positive as well as some gram-negative bacteria. Moreover, rifampicin has anti-inflammatory and immunomodulatory properties, including evidence that it inhibits excessive helper T cell (TH17) responses by reducing inducible nitric oxide synthase transcription and NF-κB activity.25,26

Metronidazole, moxifloxacin, and rifampicin as triple combination therapy has been shown to be effective in reducing HS activity in moderate to severe cases that were refractory to other treatments.27 Research suggests that moxifloxacin has anti-inflammatory properties, mainly by reducing IL-1β, IL-8, and tumor necrosis factor α; stabilizing IXb protein; suppressing NF-κB signaling; and reducing IL-17A.28,29

Ertapenem can be utilized as a single 6-week antibiotic course during surgical planning or rescue therapy.18 Moreover, ertapenem can be used to treat complicated skin and soft tissue infections and has been shown to substantially improve clinical aspects of severe HS.17,27



Disease-modifying antirheumatic drugs are effective in the treatment of moderate to severe HS.17-19 In 2 phase 3 trials (PIONEER I and II), adalimumab was used as monotherapy or in conjunction with antibiotics in patients with moderate to severe HS compared to placebo.30 Results demonstrated a disease burden reduction of greater than 50%. Antibiotic dual therapy was not noted to significantly affect disease burden.30 Of note, use of immunosuppressants in the military affects an SM’s availability for worldwide deployment and duty station assignment.

 

 



Antiandrogen therapies have demonstrated some reduction in HS flares. Although recommendations for use in HS is based on limited evidence, one randomized controlled trial compared ethinyl estradiol–norgestrel to ethinyl estradiol and cyproterone acetate. Both therapies resulted in similar efficacy, with 12 of 24 (50%) patients reporting HS symptoms improving or completely resolved.31 In another retrospective study of women treated with antiandrogen therapies, including ethinyl estriol, cyproterone acetate, and spironolactone, 16 of 29 (55%) patients reported improvement.32 In another study, daily doses of 100 to 150 mg of spironolactone resulted in improvement in 17 of 20 (85%) patients, including complete remission in 11 of 20 (55%) patients. Of the 3 patients with severe HS, none had complete clearing of disease burden.33 Patients with polycystic ovary syndrome or HS flares that occur around menstruation are more likely to benefit from treatment with spironolactone.18,32,34



Retinoids frequently have been utilized in the management of HS. In some retrospective studies and other prospective studies with 5 or more patients, isotretinoin monotherapy was utilized for a 4- to 10-month period.18,35-38 In the Alikhan et al18 study, 85 of 207 patients demonstrated improvement of HS symptoms, with more remarkable improvements in milder cases. Isotretinoin for management of patients with HS who have concomitant nodulocystic acne would have two-fold benefits.18

Wound Care
Given the purulent nodular formation in HS, adequate wound care management is vital. There is an abundance of HS wound care management strategies utilized by clinicians and patients. When selecting the appropriate dressing, consideration for the type of HS wound, cost, ease of application, patient comfort, absorbency, and odor management is important.3 However, living arrangements for military SMs can create difficulties applying and maintaining HS dressings, especially if deployed or in a field setting. Active-duty SMs often find themselves in austere living conditions in the field, aboard ships, or in other scenarios where they may or may not have running water or showers. Maintaining adequate hygiene may be difficult, and additional education about how to keep wounds clean must be imparted. Ideal dressings for HS should be highly absorbent, comfortable when applied to the anatomic locations of the HS lesions, and easily self-applied. Ideally, dressings would have atraumatic adhesion and antimicrobial properties.3 Cost-effective dressing options that have good absorption capability include sanitary napkins, adult briefs, infant diapers, and gauze.3 These dressings help to wick moisture, thus protecting the wound from maceration, which is a common patient concern. Although gauze dressings are easier to obtain, they are not as absorbent. Abdominal pads can be utilized, but they are moderately absorbent, bulky, and more challenging to obtain over-the-counter. Hydrofiber and calcium alginate dressings with silver are not accessible to the common consumer and are more expensive than the aforementioned dressings, but they do have some antimicrobial activity. Silver-impregnated foam dressings are moldable to intertriginous areas, easy to self-apply, and have moderate-heavy absorption abilities.

Final Thoughts

Hidradenitis suppurativa poses cumbersome and uncomfortable symptoms for all patients and may pose additional hardships for military SMs or those with physically demanding occupations who work in austere environments. Severe HS can restrict a military SM from certain duty stations, positions, or deployments. Early identification of HS can help reduce HS flares, disfigurement, and placement on limited duty status, therefore rendering the SM more able to engage in his/her operational responsibilities. Hidradenitis suppurativa should be discussed with the patient, with the goal to prevent flares for SMs that will be in the field, placed in austere environments, or be deployed. Use of immunosuppressants in active-duty SMs may affect their deployability, duty assignment, and retention.

For a military SM with HS, all aspects of prevention and treatment need to be balanced with his/her ability to remain deployable and complete his/her daily duties. Military SMs are not guaranteed the ideal scenario for treatment and prevention of HS. Unsanitary environments and occlusive uniforms undoubtedly contribute to disease process and make treatment more challenging. If a military SM is in a field setting or deployed, frequent daily dressing changes should still be attempted.

References
  1. Dufour DN, Emtestam L, Jemec GB. Hidradenitis suppurativa: a common and burdensome, yet under-recognised, inflammatory skin disease. Postgrad Med J. 2014;90:216-221.
  2. Beshara MA. Hidradenitis suppurativa: a clinician’s tool for early diagnosis and treatment. Nurse Pract. 2010;35:24-28.
  3. Kazemi A, Carnaggio K, Clark M, et al. Optimal wound care management in hidradenitis suppurativa. J Dermatolog Treat. 2017;29:165-167.
  4. Tosti A, Piraccini BM, Pazzaglia M, et al. Clobetasol propionate 0.05% under occlusion in the treatment of alopecia totalis/universalis. J Am Acad Dermatol. 2003:49:96-98.
  5. Blattner C, Polley DC, Ferrito F, et al. Central centrifugal cicatricial alopecia. Indian Dermatol Online J. 2013:4:50.
  6. Wolkenstein P, Loundou A, Barrau K, et al. Quality of life impairment in hidradenitis suppurativa: a study of 61 cases. J Am Acad Dermatol. 2007;56:621-623.
  7. Smith HS, Chao JD, Teitelbaum J. Painful hidradenitis suppurativa. Clin J Pain. 2010;26:435-444.
  8. Alavi A, Anooshirvani N, Kim WB, et al. Quality-of-life impairment in patients with hidradenitis suppurativa: a Canadian study. Am J Clin Dermatol. 2015;16:61-65.
  9. Hurley HJ. Axillary hyperhidrosis, apocrine bromhidrosis, hidradenitis suppurativa and familial benign pemphigus: surgical approach. In: Roenigk RK, Roenigk HH Jr, eds. Dermatologic Surgery: Principles and Practice. 2nd ed. New York, NY: Marcel Dekker; 1996:623-645.
  10. Kligman AM. Welcome letter. 2nd International Conference on the Sebaceous Gland, Acne, Rosacea and Related Disorders; September 13-16, 2008; Rome Italy.
  11. Kurzen H, Kurzen M. Secondary prevention of hidradenitis suppurativa. Dermatol Reports. 2019;11:8243.
  12. Sabat R, Tsaousi A, Rossbacher J, et al. Acne inversa/hidradenitis suppurativa: an update [in German]. Hautarzt. 2017;68:999-1006.
  13. Boer J, Nazary M, Riis PT. The role of mechanical stress in hidradenitis suppurativa. Dermatol Clin. 2016;34:37-43.
  14. Hamzavi IH, Griffith JL, Riyaz F, et al. Laser and light-based treatment options for hidradenitis suppurativa. J Am Acad Dermatol. 2015;73(5 suppl 1):S78-S81.
  15. Saunte DML, Jemec GBE. Hidradenitis suppurativa: advances in diagnosis and treatment. JAMA. 2017;318:2019-2032.
  16. Michel C, DiBianco JM, Sabarwal V, et al. The treatment of genitoperineal hidradenitis suppurativa: a review of the literature. Urology. 2019;124:1-5.
  17. Constantinou CA, Fragoulis GE, Nikiphorou E. Hidradenitis suppurativa: infection, autoimmunity, or both [published online December 30, 2019]? Ther Adv Musculoskelet Dis. doi:10.1177/1759720x19895488.
  18. Alikhan A, Sayed C, Alavi A, et al. North American clinical management guidelines for hidradenitis suppurativa: a publication from the United States and Canadian Hidradenitis Suppurativa Foundations: part II: topical, intralesional, and systemic medical management. J Am Acad Dermatol. 2019;81:91-101.
  19. Zouboulis CC, Desai N, Emtestam, et al. European S1 guideline for the treatment of hidradenitis suppurativa/acne inversa. J Eur Acad Dermatol Venereol. 2015;29:619-644.
  20. Mandell JB, Orr S, Koch J, et al. Large variations in clinical antibiotic activity against Staphylococcus aureus biofilms of periprosthetic joint infection isolates. J Orthop Res. 2019;37:1604-1609.
  21. Sun J, Shigemi H, Tanaka Y, et al. Tetracyclines downregulate the production of LPS-induced cytokines and chemokines in THP-1 cells via ERK, p38, and nuclear factor-κB signaling pathways. Biochem Biophys Rep. 2015;4:397-404.
  22. Clemmensen OJ. Topical treatment of hidradenitis suppurativa with clindamycin. Int J Dermatol. 1983;22:325-328.
  23. Gener G, Canoui-Poitrine F, Revuz JE, et al. Combination therapy with clindamycin and rifampicin for hidradenitis suppurativa: a series of 116 consecutive patients. Dermatology. 2009;219:148-154.
  24. Mendonça CO, Griffiths CEM. Clindamycin and rifampicin combination therapy for hidradenitis suppurativa. Br J Dermatol. 2006;154:977-978.
  25. Ma K, Chen X, Chen J-C, et al. Rifampicin attenuates experimental autoimmune encephalomyelitis by inhibiting pathogenic Th17 cells responses. J Neurochem. 2016;139:1151-1162.
  26. Yuhas Y, Berent E, Ovadiah H, et al. Rifampin augments cytokine-induced nitric oxide production in human alveolar epithelial cells. Antimicrob Agents Chemother. 2006;50:396-398.
  27. Join-Lambert O, Coignard H, Jais J-P, et al. Efficacy of rifampin-moxifloxacin-metronidazole combination therapy in hidradenitis suppurativa. Dermatology. 2011;222:49-58.
  28. Choi J-H, Song M-J, Kim S-H, et al. Effect of moxifloxacin on production of proinflammatory cytokines from human peripheral blood mononuclear cells. Antimicrob Agents Chemother. 2003;47:3704-3707.
  29. Weiss T, Shalit I, Blau H, et al. Anti-inflammatory effects of moxifloxacin on activated human monocytic cells: inhibition of NF-kappaB and mitogen-activated protein kinase activation and of synthesis of proinflammatory cytokines.” Antimicrob Agents Chemother. 2004;48:1974-1982.
  30. Kimball AB, Okun MM, Williams DA, et al. Two phase 3 trials of adalimumab for hidradenitis suppurativa. N Engl J Med. 2016;375:422-434.
  31. Mortimer PS, Dawber RP, Gales MA, et al. A double-blind controlled cross-over trial of cyproterone acetate in females with hidradenitis suppurativa. Br J Dermatol. 1986;115:263-268.
  32. Kraft JN, Searles GE. Hidradenitis suppurativa in 64 female patients: retrospective study comparing oral antibiotics and antiandrogen therapy. J Cutan Med Surg. 2007;11:125-131.
  33. Lee A, Fischer G. A case series of 20 women with hidradenitis suppurativa treated with spironolactone. Australas J Dermatol. 2015;56:192-196.
  34. Khandalavala BN, Do MV. Finasteride in hidradenitis suppurativa: a “male” therapy for a predominantly “female” disease. J Clin Aesthet Dermatol. 2016;9:44-50.
  35. Dicken CH, Powell ST, Spear KL. Evaluation of isotretinoin treatment of hidradenitis suppurativa. J Am Acad Dermatol. 1984;11:500-502.
  36. Huang CM, Kirchof MG. A new perspective on isotretinoin treatment of hidradenitis suppurativa: a retrospective chart review of patient outcomes. Dermatology. 2017;233:120-125.
  37. Norris JF, Cunliffe WJ. Failure of treatment of familial widespread hidradenitis suppurativa with isotretinoin. Clin Exp Dermatol. 1986;11:579-583.
  38. Soria A, Canoui-Poitrine F, Wolkenstein P, et al. Absence of efficacy of oral isotretinoin in hidradenitis suppurativa: a retrospective study based on patients’ outcome assessment. Dermatology. 2009;218:134-135.
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Author and Disclosure Information

Dr. Godiwalla is from the Naval Hospital Camp Pendleton, 1st Marine Expeditionary Force, Oceanside, California. Dr. Storie is from the Department of Dermatology, Naval Hospital Camp Pendleton. Dr. Winn is from the Department of Dermatology, Naval Medical Center San Diego, California.

The authors report no conflict of interest.

The views expressed in this case report are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, or the US Government.

Correspondence: Roxana Y. Godiwalla, DO, Camp Pendleton, 20250 Vandegrift Blvd, Oceanside, CA 92058 ([email protected]).

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Author and Disclosure Information

Dr. Godiwalla is from the Naval Hospital Camp Pendleton, 1st Marine Expeditionary Force, Oceanside, California. Dr. Storie is from the Department of Dermatology, Naval Hospital Camp Pendleton. Dr. Winn is from the Department of Dermatology, Naval Medical Center San Diego, California.

The authors report no conflict of interest.

The views expressed in this case report are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, or the US Government.

Correspondence: Roxana Y. Godiwalla, DO, Camp Pendleton, 20250 Vandegrift Blvd, Oceanside, CA 92058 ([email protected]).

Author and Disclosure Information

Dr. Godiwalla is from the Naval Hospital Camp Pendleton, 1st Marine Expeditionary Force, Oceanside, California. Dr. Storie is from the Department of Dermatology, Naval Hospital Camp Pendleton. Dr. Winn is from the Department of Dermatology, Naval Medical Center San Diego, California.

The authors report no conflict of interest.

The views expressed in this case report are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, or the US Government.

Correspondence: Roxana Y. Godiwalla, DO, Camp Pendleton, 20250 Vandegrift Blvd, Oceanside, CA 92058 ([email protected]).

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In Partnership With the Association of Military Dermatologists
In Partnership With the Association of Military Dermatologists

 

Case Report

A 19-year-old female marine with a 10-year history of hidradenitis suppurativa (HS) presented with hyperpigmented nodules in the inguinal folds and a recurrent cyst in the right groin area of 2 to 3 weeks’ duration. She denied axillary or inframammary involvement. She underwent several incision and drainage procedures 1 year prior to her enlistment in the US Marine Corps at 18 years of age. She previously had been treated by dermatology with doxycycline 100-mg tablets twice daily, benzoyl peroxide wash 5% applied to affected areas and rinsed daily, and clindamycin solution 1% with minimal improvement. She denied smoking or alcohol intake and said she typically wore a loose-fitting uniform to work. As a marine, she was expected to participate in daily physical training and exercises with her military unit, during which she wore a standardized physical training uniform, including nylon shorts and a cotton T-shirt. She requested light duty—military duty status with physical limitations or restrictions—to avoid physical training that would cause further friction and irritation to the inguinal region.

Physical examination demonstrated a woman with Fitzpatrick skin type III and normal body mass index. There were hyperpigmented nodules and scarring in the inguinal folds, most consistent with Hurley stage 2. A single, 0.5-cm, draining lesion was visualized. No hyperhidrosis was noted. The patient was placed on light duty for 7 days, with physical training only at her own pace and discretion. Moreover, she was restricted from field training, rifle range training, and other situations where she may excessively sweat or not be able to adequately maintain personal hygiene. She was encouraged to continue clindamycin solution 1% to the affected area twice daily and was prescribed chlorhexidine solution 4% to use when washing affected areas in the shower. The patient also was referred to the dermatology department at the Naval Hospital Camp Pendleton (Oceanside, California), where she was treated with laser hair removal in the inguinal region, thus avoiding waxing and further aggravation of HS flares. Due to the combination of topical therapies along with laser hair removal and duty restrictions, the patient had a dramatic decrease in development of severe nodular lesions.

Comment

Presentation
Historically, the incidence of HS is estimated at 0.5% to 4% of the general population with female predominance.1 Predisposing factors include obesity, smoking, genetic predisposition to acne, apocrine duct obstruction, and secondary bacterial infection.2 During acute flares, patients generally present with tender subcutaneous nodules that drain malodorous purulent material.3,4 Acute flares are unpredictable, and patients deal with chronic, recurrent, draining wounds, leading to a poor quality of life with resulting physical, psychological, financial, social, and emotional distress.3-5 The negative impact of HS on a patient’s quality of life has been reported to be greater than other dermatologic conditions.6 Lesions can be particularly painful and can cause disfiguration to the surface of the skin.7 Lesion severity is described using the Hurley staging system. Patient quality of life is directly correlated with disease severity and Hurley stage. In stage 1, abscesses develop, but no sinus tracts or cicatrization is present. In stage 2, recurrent abscesses will form tracts and cicatrization. In stage 3, the abscesses become diffuse or near diffuse, with multiple interconnected tracts and abscesses across the entire area of the body.8,9

Severe or refractory HS within the physically active military population may require consideration of light or limited duty or even separation from service. Similarly, severe HS may pose challenges with other physically demanding occupations, such as the police force and firefighters.

Prevention Focus
Prevention of flares is key for patients with HS; secondary prevention aims to reduce impact of the disease or injury that has already occurred,10,11 which includes prevention of the infundibulofolliculitis from becoming a deep folliculitis, nodule, or fistula, as well as Hurley stage progression. Prompt diagnosis with appropriate treatment can decrease the severity of lesions, pain, and scarring. Globally, HS patients continue to experience considerable diagnostic delays of 8 to 12 years after onset of initial symptoms.11,12 Earlier accurate diagnosis and initiation of treatment from the primary care provider or general medical officer is imperative. Initial accurate management may help keep symptoms from progressing to more severe painful lesions. Similarly, patients should be educated on how to prevent HS flares. Patients should avoid known triggers, including smoking, obesity, sweating, mechanical irritation, stress, and poor hygiene.11



Shaving for hair reduction creates ingrown hair shafts, which may lead to folliculitis in mechanically stressed areas in skin folds, thus initiating the inflammatory cascade of HS.11,13 Therefore, shaving along with any other mechanical stress should be avoided in patients with HS. Laser hair removal has been shown to be quite helpful in both the prevention and treatment of HS. In one study, 22 patients with Hurley stage 2 to 3 disease were treated with an Nd:YAG laser once monthly. Results demonstrated a 65% decrease in disease severity after 3 monthly treatments.11 Similarly, other lasers have been used with success in several small case series; an 800-nm diode laser, intense pulsed light therapy, and a ruby laser have each demonstrated efficacy.14 Given these results, hair removal should be recommended to patients with HS. Military servicemembers (SMs) with certain conditions, such as polycystic ovary syndrome, pseudofolliculitis barbae, and HS, are eligible for laser hair removal when available at local military treatment facilities. Primary care providers for military SMs must have a working understanding of the disease process of HS and awareness of what resources are available for treatment, which allows for more streamlined care and improved outcomes.

 

 



Treatment Options
Treatment options are diverse and depend on the severity of HS. Typically, treatment begins with medical therapy followed by escalation to surgical intervention. Medical therapies often include antibiotics, acne treatments, antiandrogen therapy, immunosuppressive agents, and biologic therapy.15,16 If first-line medical interventions fail to control HS, surgical interventions should be considered. Surgical intervention in conjunction with medical therapy decreases the chance for recurrence.3,15,16



Although HS is internationally recognized as an inflammatory disease and not an infectious process, topical antibiotics can help to prevent and improve formation of abscesses, nodules, and pustules.11 Agents such as clindamycin and chlorhexidine wash have proven effective in preventing flares.11,16 Other antibiotics used alone or in combination also are efficacious. Tetracyclines are recommended as monotherapy for mild stages of HS.17-19 Doxycycline is the most commonly used tetracycline in HS patients and has been demonstrated to penetrate Staphylococcus aureus biofilm in high enough concentrations to maintain its antibacterial activity.20 Moreover, doxycycline, as with other tetracyclines, has a multitude of anti-inflammatory and immunomodulatory properties21 and can reduce the production of IL-1, IL-6, tumor necrosis factor α, and IL-8; downregulate chemotaxis; and promote lipo-oxygenase, matrix metalloproteinase, and nuclear factor κB (NF-κB) signaling inhibition.17

Clindamycin is the only known agent that has been studied for topical treatment and utilization in milder cases of HS.17,22 Systemic combination of clindamycin and rifampicin is the most studied, with well-established efficacy in managing HS.17,23,24 Clindamycin has bacteriostatic activity toward both aerobic and anaerobic gram-positive bacteria by binding irreversibly to the 50S ribosomal subunit, thereby inhibiting bacterial protein synthesis. Rifampicin binds to the beta subunit of DNA-dependent RNA polymerase, inhibiting bacterial DNA-dependent RNA synthesis. Rifampicin has broad-spectrum activity, mostly against gram-positive as well as some gram-negative bacteria. Moreover, rifampicin has anti-inflammatory and immunomodulatory properties, including evidence that it inhibits excessive helper T cell (TH17) responses by reducing inducible nitric oxide synthase transcription and NF-κB activity.25,26

Metronidazole, moxifloxacin, and rifampicin as triple combination therapy has been shown to be effective in reducing HS activity in moderate to severe cases that were refractory to other treatments.27 Research suggests that moxifloxacin has anti-inflammatory properties, mainly by reducing IL-1β, IL-8, and tumor necrosis factor α; stabilizing IXb protein; suppressing NF-κB signaling; and reducing IL-17A.28,29

Ertapenem can be utilized as a single 6-week antibiotic course during surgical planning or rescue therapy.18 Moreover, ertapenem can be used to treat complicated skin and soft tissue infections and has been shown to substantially improve clinical aspects of severe HS.17,27



Disease-modifying antirheumatic drugs are effective in the treatment of moderate to severe HS.17-19 In 2 phase 3 trials (PIONEER I and II), adalimumab was used as monotherapy or in conjunction with antibiotics in patients with moderate to severe HS compared to placebo.30 Results demonstrated a disease burden reduction of greater than 50%. Antibiotic dual therapy was not noted to significantly affect disease burden.30 Of note, use of immunosuppressants in the military affects an SM’s availability for worldwide deployment and duty station assignment.

 

 



Antiandrogen therapies have demonstrated some reduction in HS flares. Although recommendations for use in HS is based on limited evidence, one randomized controlled trial compared ethinyl estradiol–norgestrel to ethinyl estradiol and cyproterone acetate. Both therapies resulted in similar efficacy, with 12 of 24 (50%) patients reporting HS symptoms improving or completely resolved.31 In another retrospective study of women treated with antiandrogen therapies, including ethinyl estriol, cyproterone acetate, and spironolactone, 16 of 29 (55%) patients reported improvement.32 In another study, daily doses of 100 to 150 mg of spironolactone resulted in improvement in 17 of 20 (85%) patients, including complete remission in 11 of 20 (55%) patients. Of the 3 patients with severe HS, none had complete clearing of disease burden.33 Patients with polycystic ovary syndrome or HS flares that occur around menstruation are more likely to benefit from treatment with spironolactone.18,32,34



Retinoids frequently have been utilized in the management of HS. In some retrospective studies and other prospective studies with 5 or more patients, isotretinoin monotherapy was utilized for a 4- to 10-month period.18,35-38 In the Alikhan et al18 study, 85 of 207 patients demonstrated improvement of HS symptoms, with more remarkable improvements in milder cases. Isotretinoin for management of patients with HS who have concomitant nodulocystic acne would have two-fold benefits.18

Wound Care
Given the purulent nodular formation in HS, adequate wound care management is vital. There is an abundance of HS wound care management strategies utilized by clinicians and patients. When selecting the appropriate dressing, consideration for the type of HS wound, cost, ease of application, patient comfort, absorbency, and odor management is important.3 However, living arrangements for military SMs can create difficulties applying and maintaining HS dressings, especially if deployed or in a field setting. Active-duty SMs often find themselves in austere living conditions in the field, aboard ships, or in other scenarios where they may or may not have running water or showers. Maintaining adequate hygiene may be difficult, and additional education about how to keep wounds clean must be imparted. Ideal dressings for HS should be highly absorbent, comfortable when applied to the anatomic locations of the HS lesions, and easily self-applied. Ideally, dressings would have atraumatic adhesion and antimicrobial properties.3 Cost-effective dressing options that have good absorption capability include sanitary napkins, adult briefs, infant diapers, and gauze.3 These dressings help to wick moisture, thus protecting the wound from maceration, which is a common patient concern. Although gauze dressings are easier to obtain, they are not as absorbent. Abdominal pads can be utilized, but they are moderately absorbent, bulky, and more challenging to obtain over-the-counter. Hydrofiber and calcium alginate dressings with silver are not accessible to the common consumer and are more expensive than the aforementioned dressings, but they do have some antimicrobial activity. Silver-impregnated foam dressings are moldable to intertriginous areas, easy to self-apply, and have moderate-heavy absorption abilities.

Final Thoughts

Hidradenitis suppurativa poses cumbersome and uncomfortable symptoms for all patients and may pose additional hardships for military SMs or those with physically demanding occupations who work in austere environments. Severe HS can restrict a military SM from certain duty stations, positions, or deployments. Early identification of HS can help reduce HS flares, disfigurement, and placement on limited duty status, therefore rendering the SM more able to engage in his/her operational responsibilities. Hidradenitis suppurativa should be discussed with the patient, with the goal to prevent flares for SMs that will be in the field, placed in austere environments, or be deployed. Use of immunosuppressants in active-duty SMs may affect their deployability, duty assignment, and retention.

For a military SM with HS, all aspects of prevention and treatment need to be balanced with his/her ability to remain deployable and complete his/her daily duties. Military SMs are not guaranteed the ideal scenario for treatment and prevention of HS. Unsanitary environments and occlusive uniforms undoubtedly contribute to disease process and make treatment more challenging. If a military SM is in a field setting or deployed, frequent daily dressing changes should still be attempted.

 

Case Report

A 19-year-old female marine with a 10-year history of hidradenitis suppurativa (HS) presented with hyperpigmented nodules in the inguinal folds and a recurrent cyst in the right groin area of 2 to 3 weeks’ duration. She denied axillary or inframammary involvement. She underwent several incision and drainage procedures 1 year prior to her enlistment in the US Marine Corps at 18 years of age. She previously had been treated by dermatology with doxycycline 100-mg tablets twice daily, benzoyl peroxide wash 5% applied to affected areas and rinsed daily, and clindamycin solution 1% with minimal improvement. She denied smoking or alcohol intake and said she typically wore a loose-fitting uniform to work. As a marine, she was expected to participate in daily physical training and exercises with her military unit, during which she wore a standardized physical training uniform, including nylon shorts and a cotton T-shirt. She requested light duty—military duty status with physical limitations or restrictions—to avoid physical training that would cause further friction and irritation to the inguinal region.

Physical examination demonstrated a woman with Fitzpatrick skin type III and normal body mass index. There were hyperpigmented nodules and scarring in the inguinal folds, most consistent with Hurley stage 2. A single, 0.5-cm, draining lesion was visualized. No hyperhidrosis was noted. The patient was placed on light duty for 7 days, with physical training only at her own pace and discretion. Moreover, she was restricted from field training, rifle range training, and other situations where she may excessively sweat or not be able to adequately maintain personal hygiene. She was encouraged to continue clindamycin solution 1% to the affected area twice daily and was prescribed chlorhexidine solution 4% to use when washing affected areas in the shower. The patient also was referred to the dermatology department at the Naval Hospital Camp Pendleton (Oceanside, California), where she was treated with laser hair removal in the inguinal region, thus avoiding waxing and further aggravation of HS flares. Due to the combination of topical therapies along with laser hair removal and duty restrictions, the patient had a dramatic decrease in development of severe nodular lesions.

Comment

Presentation
Historically, the incidence of HS is estimated at 0.5% to 4% of the general population with female predominance.1 Predisposing factors include obesity, smoking, genetic predisposition to acne, apocrine duct obstruction, and secondary bacterial infection.2 During acute flares, patients generally present with tender subcutaneous nodules that drain malodorous purulent material.3,4 Acute flares are unpredictable, and patients deal with chronic, recurrent, draining wounds, leading to a poor quality of life with resulting physical, psychological, financial, social, and emotional distress.3-5 The negative impact of HS on a patient’s quality of life has been reported to be greater than other dermatologic conditions.6 Lesions can be particularly painful and can cause disfiguration to the surface of the skin.7 Lesion severity is described using the Hurley staging system. Patient quality of life is directly correlated with disease severity and Hurley stage. In stage 1, abscesses develop, but no sinus tracts or cicatrization is present. In stage 2, recurrent abscesses will form tracts and cicatrization. In stage 3, the abscesses become diffuse or near diffuse, with multiple interconnected tracts and abscesses across the entire area of the body.8,9

Severe or refractory HS within the physically active military population may require consideration of light or limited duty or even separation from service. Similarly, severe HS may pose challenges with other physically demanding occupations, such as the police force and firefighters.

Prevention Focus
Prevention of flares is key for patients with HS; secondary prevention aims to reduce impact of the disease or injury that has already occurred,10,11 which includes prevention of the infundibulofolliculitis from becoming a deep folliculitis, nodule, or fistula, as well as Hurley stage progression. Prompt diagnosis with appropriate treatment can decrease the severity of lesions, pain, and scarring. Globally, HS patients continue to experience considerable diagnostic delays of 8 to 12 years after onset of initial symptoms.11,12 Earlier accurate diagnosis and initiation of treatment from the primary care provider or general medical officer is imperative. Initial accurate management may help keep symptoms from progressing to more severe painful lesions. Similarly, patients should be educated on how to prevent HS flares. Patients should avoid known triggers, including smoking, obesity, sweating, mechanical irritation, stress, and poor hygiene.11



Shaving for hair reduction creates ingrown hair shafts, which may lead to folliculitis in mechanically stressed areas in skin folds, thus initiating the inflammatory cascade of HS.11,13 Therefore, shaving along with any other mechanical stress should be avoided in patients with HS. Laser hair removal has been shown to be quite helpful in both the prevention and treatment of HS. In one study, 22 patients with Hurley stage 2 to 3 disease were treated with an Nd:YAG laser once monthly. Results demonstrated a 65% decrease in disease severity after 3 monthly treatments.11 Similarly, other lasers have been used with success in several small case series; an 800-nm diode laser, intense pulsed light therapy, and a ruby laser have each demonstrated efficacy.14 Given these results, hair removal should be recommended to patients with HS. Military servicemembers (SMs) with certain conditions, such as polycystic ovary syndrome, pseudofolliculitis barbae, and HS, are eligible for laser hair removal when available at local military treatment facilities. Primary care providers for military SMs must have a working understanding of the disease process of HS and awareness of what resources are available for treatment, which allows for more streamlined care and improved outcomes.

 

 



Treatment Options
Treatment options are diverse and depend on the severity of HS. Typically, treatment begins with medical therapy followed by escalation to surgical intervention. Medical therapies often include antibiotics, acne treatments, antiandrogen therapy, immunosuppressive agents, and biologic therapy.15,16 If first-line medical interventions fail to control HS, surgical interventions should be considered. Surgical intervention in conjunction with medical therapy decreases the chance for recurrence.3,15,16



Although HS is internationally recognized as an inflammatory disease and not an infectious process, topical antibiotics can help to prevent and improve formation of abscesses, nodules, and pustules.11 Agents such as clindamycin and chlorhexidine wash have proven effective in preventing flares.11,16 Other antibiotics used alone or in combination also are efficacious. Tetracyclines are recommended as monotherapy for mild stages of HS.17-19 Doxycycline is the most commonly used tetracycline in HS patients and has been demonstrated to penetrate Staphylococcus aureus biofilm in high enough concentrations to maintain its antibacterial activity.20 Moreover, doxycycline, as with other tetracyclines, has a multitude of anti-inflammatory and immunomodulatory properties21 and can reduce the production of IL-1, IL-6, tumor necrosis factor α, and IL-8; downregulate chemotaxis; and promote lipo-oxygenase, matrix metalloproteinase, and nuclear factor κB (NF-κB) signaling inhibition.17

Clindamycin is the only known agent that has been studied for topical treatment and utilization in milder cases of HS.17,22 Systemic combination of clindamycin and rifampicin is the most studied, with well-established efficacy in managing HS.17,23,24 Clindamycin has bacteriostatic activity toward both aerobic and anaerobic gram-positive bacteria by binding irreversibly to the 50S ribosomal subunit, thereby inhibiting bacterial protein synthesis. Rifampicin binds to the beta subunit of DNA-dependent RNA polymerase, inhibiting bacterial DNA-dependent RNA synthesis. Rifampicin has broad-spectrum activity, mostly against gram-positive as well as some gram-negative bacteria. Moreover, rifampicin has anti-inflammatory and immunomodulatory properties, including evidence that it inhibits excessive helper T cell (TH17) responses by reducing inducible nitric oxide synthase transcription and NF-κB activity.25,26

Metronidazole, moxifloxacin, and rifampicin as triple combination therapy has been shown to be effective in reducing HS activity in moderate to severe cases that were refractory to other treatments.27 Research suggests that moxifloxacin has anti-inflammatory properties, mainly by reducing IL-1β, IL-8, and tumor necrosis factor α; stabilizing IXb protein; suppressing NF-κB signaling; and reducing IL-17A.28,29

Ertapenem can be utilized as a single 6-week antibiotic course during surgical planning or rescue therapy.18 Moreover, ertapenem can be used to treat complicated skin and soft tissue infections and has been shown to substantially improve clinical aspects of severe HS.17,27



Disease-modifying antirheumatic drugs are effective in the treatment of moderate to severe HS.17-19 In 2 phase 3 trials (PIONEER I and II), adalimumab was used as monotherapy or in conjunction with antibiotics in patients with moderate to severe HS compared to placebo.30 Results demonstrated a disease burden reduction of greater than 50%. Antibiotic dual therapy was not noted to significantly affect disease burden.30 Of note, use of immunosuppressants in the military affects an SM’s availability for worldwide deployment and duty station assignment.

 

 



Antiandrogen therapies have demonstrated some reduction in HS flares. Although recommendations for use in HS is based on limited evidence, one randomized controlled trial compared ethinyl estradiol–norgestrel to ethinyl estradiol and cyproterone acetate. Both therapies resulted in similar efficacy, with 12 of 24 (50%) patients reporting HS symptoms improving or completely resolved.31 In another retrospective study of women treated with antiandrogen therapies, including ethinyl estriol, cyproterone acetate, and spironolactone, 16 of 29 (55%) patients reported improvement.32 In another study, daily doses of 100 to 150 mg of spironolactone resulted in improvement in 17 of 20 (85%) patients, including complete remission in 11 of 20 (55%) patients. Of the 3 patients with severe HS, none had complete clearing of disease burden.33 Patients with polycystic ovary syndrome or HS flares that occur around menstruation are more likely to benefit from treatment with spironolactone.18,32,34



Retinoids frequently have been utilized in the management of HS. In some retrospective studies and other prospective studies with 5 or more patients, isotretinoin monotherapy was utilized for a 4- to 10-month period.18,35-38 In the Alikhan et al18 study, 85 of 207 patients demonstrated improvement of HS symptoms, with more remarkable improvements in milder cases. Isotretinoin for management of patients with HS who have concomitant nodulocystic acne would have two-fold benefits.18

Wound Care
Given the purulent nodular formation in HS, adequate wound care management is vital. There is an abundance of HS wound care management strategies utilized by clinicians and patients. When selecting the appropriate dressing, consideration for the type of HS wound, cost, ease of application, patient comfort, absorbency, and odor management is important.3 However, living arrangements for military SMs can create difficulties applying and maintaining HS dressings, especially if deployed or in a field setting. Active-duty SMs often find themselves in austere living conditions in the field, aboard ships, or in other scenarios where they may or may not have running water or showers. Maintaining adequate hygiene may be difficult, and additional education about how to keep wounds clean must be imparted. Ideal dressings for HS should be highly absorbent, comfortable when applied to the anatomic locations of the HS lesions, and easily self-applied. Ideally, dressings would have atraumatic adhesion and antimicrobial properties.3 Cost-effective dressing options that have good absorption capability include sanitary napkins, adult briefs, infant diapers, and gauze.3 These dressings help to wick moisture, thus protecting the wound from maceration, which is a common patient concern. Although gauze dressings are easier to obtain, they are not as absorbent. Abdominal pads can be utilized, but they are moderately absorbent, bulky, and more challenging to obtain over-the-counter. Hydrofiber and calcium alginate dressings with silver are not accessible to the common consumer and are more expensive than the aforementioned dressings, but they do have some antimicrobial activity. Silver-impregnated foam dressings are moldable to intertriginous areas, easy to self-apply, and have moderate-heavy absorption abilities.

Final Thoughts

Hidradenitis suppurativa poses cumbersome and uncomfortable symptoms for all patients and may pose additional hardships for military SMs or those with physically demanding occupations who work in austere environments. Severe HS can restrict a military SM from certain duty stations, positions, or deployments. Early identification of HS can help reduce HS flares, disfigurement, and placement on limited duty status, therefore rendering the SM more able to engage in his/her operational responsibilities. Hidradenitis suppurativa should be discussed with the patient, with the goal to prevent flares for SMs that will be in the field, placed in austere environments, or be deployed. Use of immunosuppressants in active-duty SMs may affect their deployability, duty assignment, and retention.

For a military SM with HS, all aspects of prevention and treatment need to be balanced with his/her ability to remain deployable and complete his/her daily duties. Military SMs are not guaranteed the ideal scenario for treatment and prevention of HS. Unsanitary environments and occlusive uniforms undoubtedly contribute to disease process and make treatment more challenging. If a military SM is in a field setting or deployed, frequent daily dressing changes should still be attempted.

References
  1. Dufour DN, Emtestam L, Jemec GB. Hidradenitis suppurativa: a common and burdensome, yet under-recognised, inflammatory skin disease. Postgrad Med J. 2014;90:216-221.
  2. Beshara MA. Hidradenitis suppurativa: a clinician’s tool for early diagnosis and treatment. Nurse Pract. 2010;35:24-28.
  3. Kazemi A, Carnaggio K, Clark M, et al. Optimal wound care management in hidradenitis suppurativa. J Dermatolog Treat. 2017;29:165-167.
  4. Tosti A, Piraccini BM, Pazzaglia M, et al. Clobetasol propionate 0.05% under occlusion in the treatment of alopecia totalis/universalis. J Am Acad Dermatol. 2003:49:96-98.
  5. Blattner C, Polley DC, Ferrito F, et al. Central centrifugal cicatricial alopecia. Indian Dermatol Online J. 2013:4:50.
  6. Wolkenstein P, Loundou A, Barrau K, et al. Quality of life impairment in hidradenitis suppurativa: a study of 61 cases. J Am Acad Dermatol. 2007;56:621-623.
  7. Smith HS, Chao JD, Teitelbaum J. Painful hidradenitis suppurativa. Clin J Pain. 2010;26:435-444.
  8. Alavi A, Anooshirvani N, Kim WB, et al. Quality-of-life impairment in patients with hidradenitis suppurativa: a Canadian study. Am J Clin Dermatol. 2015;16:61-65.
  9. Hurley HJ. Axillary hyperhidrosis, apocrine bromhidrosis, hidradenitis suppurativa and familial benign pemphigus: surgical approach. In: Roenigk RK, Roenigk HH Jr, eds. Dermatologic Surgery: Principles and Practice. 2nd ed. New York, NY: Marcel Dekker; 1996:623-645.
  10. Kligman AM. Welcome letter. 2nd International Conference on the Sebaceous Gland, Acne, Rosacea and Related Disorders; September 13-16, 2008; Rome Italy.
  11. Kurzen H, Kurzen M. Secondary prevention of hidradenitis suppurativa. Dermatol Reports. 2019;11:8243.
  12. Sabat R, Tsaousi A, Rossbacher J, et al. Acne inversa/hidradenitis suppurativa: an update [in German]. Hautarzt. 2017;68:999-1006.
  13. Boer J, Nazary M, Riis PT. The role of mechanical stress in hidradenitis suppurativa. Dermatol Clin. 2016;34:37-43.
  14. Hamzavi IH, Griffith JL, Riyaz F, et al. Laser and light-based treatment options for hidradenitis suppurativa. J Am Acad Dermatol. 2015;73(5 suppl 1):S78-S81.
  15. Saunte DML, Jemec GBE. Hidradenitis suppurativa: advances in diagnosis and treatment. JAMA. 2017;318:2019-2032.
  16. Michel C, DiBianco JM, Sabarwal V, et al. The treatment of genitoperineal hidradenitis suppurativa: a review of the literature. Urology. 2019;124:1-5.
  17. Constantinou CA, Fragoulis GE, Nikiphorou E. Hidradenitis suppurativa: infection, autoimmunity, or both [published online December 30, 2019]? Ther Adv Musculoskelet Dis. doi:10.1177/1759720x19895488.
  18. Alikhan A, Sayed C, Alavi A, et al. North American clinical management guidelines for hidradenitis suppurativa: a publication from the United States and Canadian Hidradenitis Suppurativa Foundations: part II: topical, intralesional, and systemic medical management. J Am Acad Dermatol. 2019;81:91-101.
  19. Zouboulis CC, Desai N, Emtestam, et al. European S1 guideline for the treatment of hidradenitis suppurativa/acne inversa. J Eur Acad Dermatol Venereol. 2015;29:619-644.
  20. Mandell JB, Orr S, Koch J, et al. Large variations in clinical antibiotic activity against Staphylococcus aureus biofilms of periprosthetic joint infection isolates. J Orthop Res. 2019;37:1604-1609.
  21. Sun J, Shigemi H, Tanaka Y, et al. Tetracyclines downregulate the production of LPS-induced cytokines and chemokines in THP-1 cells via ERK, p38, and nuclear factor-κB signaling pathways. Biochem Biophys Rep. 2015;4:397-404.
  22. Clemmensen OJ. Topical treatment of hidradenitis suppurativa with clindamycin. Int J Dermatol. 1983;22:325-328.
  23. Gener G, Canoui-Poitrine F, Revuz JE, et al. Combination therapy with clindamycin and rifampicin for hidradenitis suppurativa: a series of 116 consecutive patients. Dermatology. 2009;219:148-154.
  24. Mendonça CO, Griffiths CEM. Clindamycin and rifampicin combination therapy for hidradenitis suppurativa. Br J Dermatol. 2006;154:977-978.
  25. Ma K, Chen X, Chen J-C, et al. Rifampicin attenuates experimental autoimmune encephalomyelitis by inhibiting pathogenic Th17 cells responses. J Neurochem. 2016;139:1151-1162.
  26. Yuhas Y, Berent E, Ovadiah H, et al. Rifampin augments cytokine-induced nitric oxide production in human alveolar epithelial cells. Antimicrob Agents Chemother. 2006;50:396-398.
  27. Join-Lambert O, Coignard H, Jais J-P, et al. Efficacy of rifampin-moxifloxacin-metronidazole combination therapy in hidradenitis suppurativa. Dermatology. 2011;222:49-58.
  28. Choi J-H, Song M-J, Kim S-H, et al. Effect of moxifloxacin on production of proinflammatory cytokines from human peripheral blood mononuclear cells. Antimicrob Agents Chemother. 2003;47:3704-3707.
  29. Weiss T, Shalit I, Blau H, et al. Anti-inflammatory effects of moxifloxacin on activated human monocytic cells: inhibition of NF-kappaB and mitogen-activated protein kinase activation and of synthesis of proinflammatory cytokines.” Antimicrob Agents Chemother. 2004;48:1974-1982.
  30. Kimball AB, Okun MM, Williams DA, et al. Two phase 3 trials of adalimumab for hidradenitis suppurativa. N Engl J Med. 2016;375:422-434.
  31. Mortimer PS, Dawber RP, Gales MA, et al. A double-blind controlled cross-over trial of cyproterone acetate in females with hidradenitis suppurativa. Br J Dermatol. 1986;115:263-268.
  32. Kraft JN, Searles GE. Hidradenitis suppurativa in 64 female patients: retrospective study comparing oral antibiotics and antiandrogen therapy. J Cutan Med Surg. 2007;11:125-131.
  33. Lee A, Fischer G. A case series of 20 women with hidradenitis suppurativa treated with spironolactone. Australas J Dermatol. 2015;56:192-196.
  34. Khandalavala BN, Do MV. Finasteride in hidradenitis suppurativa: a “male” therapy for a predominantly “female” disease. J Clin Aesthet Dermatol. 2016;9:44-50.
  35. Dicken CH, Powell ST, Spear KL. Evaluation of isotretinoin treatment of hidradenitis suppurativa. J Am Acad Dermatol. 1984;11:500-502.
  36. Huang CM, Kirchof MG. A new perspective on isotretinoin treatment of hidradenitis suppurativa: a retrospective chart review of patient outcomes. Dermatology. 2017;233:120-125.
  37. Norris JF, Cunliffe WJ. Failure of treatment of familial widespread hidradenitis suppurativa with isotretinoin. Clin Exp Dermatol. 1986;11:579-583.
  38. Soria A, Canoui-Poitrine F, Wolkenstein P, et al. Absence of efficacy of oral isotretinoin in hidradenitis suppurativa: a retrospective study based on patients’ outcome assessment. Dermatology. 2009;218:134-135.
References
  1. Dufour DN, Emtestam L, Jemec GB. Hidradenitis suppurativa: a common and burdensome, yet under-recognised, inflammatory skin disease. Postgrad Med J. 2014;90:216-221.
  2. Beshara MA. Hidradenitis suppurativa: a clinician’s tool for early diagnosis and treatment. Nurse Pract. 2010;35:24-28.
  3. Kazemi A, Carnaggio K, Clark M, et al. Optimal wound care management in hidradenitis suppurativa. J Dermatolog Treat. 2017;29:165-167.
  4. Tosti A, Piraccini BM, Pazzaglia M, et al. Clobetasol propionate 0.05% under occlusion in the treatment of alopecia totalis/universalis. J Am Acad Dermatol. 2003:49:96-98.
  5. Blattner C, Polley DC, Ferrito F, et al. Central centrifugal cicatricial alopecia. Indian Dermatol Online J. 2013:4:50.
  6. Wolkenstein P, Loundou A, Barrau K, et al. Quality of life impairment in hidradenitis suppurativa: a study of 61 cases. J Am Acad Dermatol. 2007;56:621-623.
  7. Smith HS, Chao JD, Teitelbaum J. Painful hidradenitis suppurativa. Clin J Pain. 2010;26:435-444.
  8. Alavi A, Anooshirvani N, Kim WB, et al. Quality-of-life impairment in patients with hidradenitis suppurativa: a Canadian study. Am J Clin Dermatol. 2015;16:61-65.
  9. Hurley HJ. Axillary hyperhidrosis, apocrine bromhidrosis, hidradenitis suppurativa and familial benign pemphigus: surgical approach. In: Roenigk RK, Roenigk HH Jr, eds. Dermatologic Surgery: Principles and Practice. 2nd ed. New York, NY: Marcel Dekker; 1996:623-645.
  10. Kligman AM. Welcome letter. 2nd International Conference on the Sebaceous Gland, Acne, Rosacea and Related Disorders; September 13-16, 2008; Rome Italy.
  11. Kurzen H, Kurzen M. Secondary prevention of hidradenitis suppurativa. Dermatol Reports. 2019;11:8243.
  12. Sabat R, Tsaousi A, Rossbacher J, et al. Acne inversa/hidradenitis suppurativa: an update [in German]. Hautarzt. 2017;68:999-1006.
  13. Boer J, Nazary M, Riis PT. The role of mechanical stress in hidradenitis suppurativa. Dermatol Clin. 2016;34:37-43.
  14. Hamzavi IH, Griffith JL, Riyaz F, et al. Laser and light-based treatment options for hidradenitis suppurativa. J Am Acad Dermatol. 2015;73(5 suppl 1):S78-S81.
  15. Saunte DML, Jemec GBE. Hidradenitis suppurativa: advances in diagnosis and treatment. JAMA. 2017;318:2019-2032.
  16. Michel C, DiBianco JM, Sabarwal V, et al. The treatment of genitoperineal hidradenitis suppurativa: a review of the literature. Urology. 2019;124:1-5.
  17. Constantinou CA, Fragoulis GE, Nikiphorou E. Hidradenitis suppurativa: infection, autoimmunity, or both [published online December 30, 2019]? Ther Adv Musculoskelet Dis. doi:10.1177/1759720x19895488.
  18. Alikhan A, Sayed C, Alavi A, et al. North American clinical management guidelines for hidradenitis suppurativa: a publication from the United States and Canadian Hidradenitis Suppurativa Foundations: part II: topical, intralesional, and systemic medical management. J Am Acad Dermatol. 2019;81:91-101.
  19. Zouboulis CC, Desai N, Emtestam, et al. European S1 guideline for the treatment of hidradenitis suppurativa/acne inversa. J Eur Acad Dermatol Venereol. 2015;29:619-644.
  20. Mandell JB, Orr S, Koch J, et al. Large variations in clinical antibiotic activity against Staphylococcus aureus biofilms of periprosthetic joint infection isolates. J Orthop Res. 2019;37:1604-1609.
  21. Sun J, Shigemi H, Tanaka Y, et al. Tetracyclines downregulate the production of LPS-induced cytokines and chemokines in THP-1 cells via ERK, p38, and nuclear factor-κB signaling pathways. Biochem Biophys Rep. 2015;4:397-404.
  22. Clemmensen OJ. Topical treatment of hidradenitis suppurativa with clindamycin. Int J Dermatol. 1983;22:325-328.
  23. Gener G, Canoui-Poitrine F, Revuz JE, et al. Combination therapy with clindamycin and rifampicin for hidradenitis suppurativa: a series of 116 consecutive patients. Dermatology. 2009;219:148-154.
  24. Mendonça CO, Griffiths CEM. Clindamycin and rifampicin combination therapy for hidradenitis suppurativa. Br J Dermatol. 2006;154:977-978.
  25. Ma K, Chen X, Chen J-C, et al. Rifampicin attenuates experimental autoimmune encephalomyelitis by inhibiting pathogenic Th17 cells responses. J Neurochem. 2016;139:1151-1162.
  26. Yuhas Y, Berent E, Ovadiah H, et al. Rifampin augments cytokine-induced nitric oxide production in human alveolar epithelial cells. Antimicrob Agents Chemother. 2006;50:396-398.
  27. Join-Lambert O, Coignard H, Jais J-P, et al. Efficacy of rifampin-moxifloxacin-metronidazole combination therapy in hidradenitis suppurativa. Dermatology. 2011;222:49-58.
  28. Choi J-H, Song M-J, Kim S-H, et al. Effect of moxifloxacin on production of proinflammatory cytokines from human peripheral blood mononuclear cells. Antimicrob Agents Chemother. 2003;47:3704-3707.
  29. Weiss T, Shalit I, Blau H, et al. Anti-inflammatory effects of moxifloxacin on activated human monocytic cells: inhibition of NF-kappaB and mitogen-activated protein kinase activation and of synthesis of proinflammatory cytokines.” Antimicrob Agents Chemother. 2004;48:1974-1982.
  30. Kimball AB, Okun MM, Williams DA, et al. Two phase 3 trials of adalimumab for hidradenitis suppurativa. N Engl J Med. 2016;375:422-434.
  31. Mortimer PS, Dawber RP, Gales MA, et al. A double-blind controlled cross-over trial of cyproterone acetate in females with hidradenitis suppurativa. Br J Dermatol. 1986;115:263-268.
  32. Kraft JN, Searles GE. Hidradenitis suppurativa in 64 female patients: retrospective study comparing oral antibiotics and antiandrogen therapy. J Cutan Med Surg. 2007;11:125-131.
  33. Lee A, Fischer G. A case series of 20 women with hidradenitis suppurativa treated with spironolactone. Australas J Dermatol. 2015;56:192-196.
  34. Khandalavala BN, Do MV. Finasteride in hidradenitis suppurativa: a “male” therapy for a predominantly “female” disease. J Clin Aesthet Dermatol. 2016;9:44-50.
  35. Dicken CH, Powell ST, Spear KL. Evaluation of isotretinoin treatment of hidradenitis suppurativa. J Am Acad Dermatol. 1984;11:500-502.
  36. Huang CM, Kirchof MG. A new perspective on isotretinoin treatment of hidradenitis suppurativa: a retrospective chart review of patient outcomes. Dermatology. 2017;233:120-125.
  37. Norris JF, Cunliffe WJ. Failure of treatment of familial widespread hidradenitis suppurativa with isotretinoin. Clin Exp Dermatol. 1986;11:579-583.
  38. Soria A, Canoui-Poitrine F, Wolkenstein P, et al. Absence of efficacy of oral isotretinoin in hidradenitis suppurativa: a retrospective study based on patients’ outcome assessment. Dermatology. 2009;218:134-135.
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Practice Points

  • Hidradenitis suppurativa (HS) can be more difficult to treat in physically active military servicemembers (SMs).
  • Patient education and primary care physician awareness of HS is critical to initial diagnosis and long-term management.
  • Primary care physician knowledge of HS as well as an understanding of the capabilities at local military medical facilities is important for optimal treatment of HS in military SMs.
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Human Papillomavirus Vaccination in LGBTQ Patients: The Need for Dermatologists on the Front Lines

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Human papillomavirus (HPV) is one of the most common sexually transmitted infections in the United States. It is the causative agent of genital warts, as well as cervical, anal, penile, vulvar, vaginal, and some head and neck cancers.1 Development of the HPV vaccine and its introduction into the scheduled vaccine series recommended by the Centers for Disease Control and Prevention (CDC) represented a major public health milestone. The CDC recommends the HPV vaccine for all children beginning at 11 or 12 years of age, even as early as 9 years, regardless of gender identity or sexuality. As of late 2016, the 9-valent formulation (Gardasil 9 [Merck]) is the only HPV vaccine distributed in the United States, and the vaccination schedule depends specifically on age. The Advisory Committee on Immunization Practices (ACIP) of the CDC revised its recommendations in 2019 to include “shared clinical decision-making regarding HPV vaccination . . . for some adults aged 27 through 45 years.”2 This change in policy has notable implications for sexual and gender minority populations, such as lesbian, gay, bisexual, transgender, and queer or questioning (LGBTQ) patients, especially in the context of dermatologic care. Herein, we discuss HPV-related conditions for LGBTQ patients, barriers to vaccine administration, and the role of dermatologists in promoting an increased vaccination rate in the LGBTQ community.

HPV-Related Conditions

A 2019 review of dermatologic care for LGBTQ patients identified many specific health disparities of HPV.3 Specifically, men who have sex with men (MSM) are more likely than heterosexual men to have oral, anal, and penile HPV infections, including high-risk HPV types.3 From 2011 to 2014, 18% and 13% of MSM had oral HPV infection and high-risk oral HPV infection, respectively, compared to only 11% and 7%, respectively, of men who reported never having had a same-sex sexual partner.4

Similarly, despite the CDC’s position that patients with perianal warts might benefit from digital anal examination or referral for standard or high-resolution anoscopy to detect intra-anal warts, improvements in morbidity have not yet been realized. In 2017, anal cancer incidence was 45.9 cases for every 100,000 person-years among human immunodeficiency (HIV)–positive MSM and 5.1 cases for every 100,000 person-years among HIV-negative MSM vs only 1.5 cases for every 100,000 person-years among men in the United States overall.3 Yet the CDC states that there is insufficient evidence to recommend routine anal cancer screening among MSM, even when a patient is HIV positive. Therefore, current screening practices and treatments are insufficient as MSM continue to have a disproportionately higher rate of HPV-associated disease compared to other populations.

Barriers to HPV Vaccine Administration

The HPV vaccination rate among MSM in adolescent populations varies across reports.5-7 Interestingly, a 2016 survey study found that MSM had approximately 2-times greater odds of initiating the HPV vaccine than heterosexual men.8 However, a study specifically sampling young gay and bisexual men (N=428) found that only 13% had received any doses of the HPV vaccine.6

Regardless, HPV vaccination is much less common among all males than it is among all females, and the low rate of vaccination among sexual minority men has a disproportionate impact, given their higher risk for HPV infection.4 Although the HPV vaccination rate increased from 2014 to 2017, the HPV vaccination rate in MSM overall is less than half of the Healthy People 2020 goal of 80%.9 A 2018 review determined that HPV vaccination is a cost-effective strategy for preventing anal cancer in MSM10; yet male patients might still view the HPV vaccine as a “women’s issue” and are less likely to be vaccinated if they are not prompted by health care providers. Additionally, HPV vaccination is remarkably less likely in MSM when patients are older, uninsured, of lower socioeconomic status, or have not disclosed their sexual identity to their health care provider.9 Dermatologists should be mindful of these barriers to promote HPV vaccination in MSM before, or soon after, sexual debut.



Other members of the LGBTQ community, such as women who have sex with women, face notable HPV-related health disparities and would benefit from increased vaccination efforts by dermatologists. Adolescent and young adult women who have sex with women are less likely than heterosexual adolescent and young adult women to receive routine Papanicolaou tests and initiate HPV vaccination, despite having a higher number of lifetime sexual partners and a higher risk for HPV exposure.11 A 2015 survey study (N=3253) found that after adjusting for covariates, only 8.5% of lesbians and 33.2% of bisexual women and girls who had heard of the HPV vaccine had initiated vaccination compared to 28.4% of their heterosexual counterparts.11 The HPV vaccine is an effective public health tool for the prevention of cervical cancer in these populations. A study of women aged 15 to 19 years in the HPV vaccination era (2007-2014) found significant (P<.05) observed population-level decreases in cervical intraepithelial neoplasia incidence across all grades.12

Transgender women also face a high rate of HPV infection, HIV infection, and other structural and financial disparities, such as low insurance coverage, that can limit their access to vaccination. Transgender men have a higher rate of HPV infection than cisgender men, and those with female internal reproductive organs are less likely to receive routine Papanicolaou tests. A 2018 survey study found that approximately one-third of transgender men and women reported initiating the HPV vaccination series,13 but further investigation is required to make balanced comparisons to cisgender patients.

The Role of the Dermatologist

Collectively, these disparities emphasize the need for increased involvement by dermatologists in HPV vaccination efforts for all LGBTQ patients. Adult patients may have concerns about ties of the HPV vaccine to drug manufacturers and the general safety of vaccination. For pediatric patients, parents/guardians also may be concerned about an assumed but not evidence-based increase in sexual promiscuity following HPV vaccination.14 These topics can be challenging to discuss, but dermatologists have the duty to be proactive and initiate conversation about HPV vaccination, as opposed to waiting for patients to express interest. Dermatologists should stress the safety of the vaccine as well as its potential to protect against multiple, even life-threatening diseases. Providers also can explain that the ACIP recommends catch-up vaccination for all individuals through 26 years of age, regardless of sexual orientation or gender identity.

With the ACIP having recently expanded the appropriate age range for HPV vaccination, we encourage dermatologists to engage in education and shared decision-making to ensure that adult patients with specific risk factors receive the HPV vaccine. Because the expanded ACIP recommendations are aimed at vaccination before HPV exposure, vaccination might not be appropriate for all LGBTQ patients. However, eliciting a sexual history with routine patient intake forms or during the clinical encounter ensures equal access to the HPV vaccine.

Greater awareness of HPV-related disparities and barriers to vaccination in LGBTQ populations has the potential to notably decrease HPV-associated mortality and morbidity. Increased involvement by dermatologists contributes to the efforts of other specialties in universal HPV vaccination, regardless of sexual orientation or gender identity—ideally in younger age groups, such that patients receive the vaccine prior to coitarche.



There are many ways that dermatologists can advocate for HPV vaccination. Those in a multispecialty or academic practice can readily refer patients to an associated internist, primary care physician, or vaccination clinic in the same building or institution. Dermatologists in private practice might be able to administer the HPV vaccine themselves or can advocate for patients to receive the vaccine at a local facility of the Department of Health or at a nonprofit organization, such as a Planned Parenthood center. Although pediatricians and family physicians remain front-line providers of these services, dermatologists represent an additional member of a patient’s care team, capable of advocating for this important intervention.

References
  1. Brianti P, De Flammineis E, Mercuri SR. Review of HPV-related diseases and cancers. New Microbiol. 2017;40:80-85.
  2. Meites E, Szilagyi PG, Chesson HW, et al. Human papillomavirus vaccination for adults: updated recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2019;68:698-702.
  3. Yeung H, Luk KM, Chen SC, et al. Dermatologic care for lesbian, gay, bisexual, and transgender persons: epidemiology, screening, and disease prevention. J Am Acad Dermatol. 2019;80:591-602.
  4. Sonawane K, Suk R, Chiao EY, et al. Oral human papillomavirus infection: differences in prevalence between sexes and concordance with genital human papillomavirus infection, NHANES 2011 to 2014. Ann Intern Med. 2017;167:714-724.
  5. Kosche C, Mansh M, Luskus M, et al. Dermatologic care of sexual and gender minority/LGBTQIA youth, part 2: recognition and management of the unique dermatologic needs of SGM adolescents. Pediatr Dermatol. 2019;35:587-593.
  6. Reiter PL, McRee A-L, Katz ML, et al. Human papillomavirus vaccination among young adult gay and bisexual men in the United States. Am J Public Health. 2015;105:96-102.
  7. Charlton BM, Reisner SL, Agénor M, et al. Sexual orientation disparities in human papillomavirus vaccination in a longitudinal cohort of U.S. males and females. LGBT Health. 2017;4:202-209.
  8. Agénor M, Peitzmeier SM, Gordon AR, et al. Sexual orientation identity disparities in human papillomavirus vaccination initiation and completion among young adult US women and men. Cancer Causes Control. 2016;27:1187-1196.
  9. Loretan C, Chamberlain AT, Sanchez T, et al. Trends and characteristics associated with human papillomavirus vaccination uptake among men who have sex with men in the United States, 2014-2017. Sex Transm Dis. 2019;46:465-473.
  10. Setiawan D, Wondimu A, Ong K, et al. Cost effectiveness of human papillomavirus vaccination for men who have sex with men; reviewing the available evidence. Pharmacoeconomics. 2018;36:929-939.
  11. Agénor M, Peitzmeier S, Gordon AR, et al. Sexual orientation identity disparities in awareness and initiation of the human papillomavirus vaccine among U.S. women and girls: a national survey. Ann Intern Med. 2015;163:99-106.
  12. Benard VB, Castle PE, Jenison SA, et al. Population-based incidence rates of cervical intraepithelial neoplasia in the human papillomavirus vaccine era. JAMA Oncol. 2017;3:833-837.
  13. McRee A-L, Gower AL, Reiter PL. Preventive healthcare services use among transgender young adults. Int J Transgend. 2018;19:417-423.
  14. Trinidad J. Policy focus: promoting human papilloma virus vaccine to prevent genital warts and cancer. Boston, MA: The Fenway Institute; 2012. https://fenwayhealth.org/documents/the-fenway-institute/policy-briefs/PolicyFocus_HPV_v4_10.09.12.pdf. Accessed September 15, 2020.
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Mr. Cartron is from the Department of Dermatology, University of Maryland School of Medicine, Baltimore. Dr. Trinidad is from the Division of Dermatology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus.

The authors report no conflict of interest.

Correspondence: Alexander M. Cartron, BS, Department of Dermatology, University of Maryland School of Medicine, 419 W Redwood St, Ste 235, Baltimore, MD 21201 ([email protected]).

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Mr. Cartron is from the Department of Dermatology, University of Maryland School of Medicine, Baltimore. Dr. Trinidad is from the Division of Dermatology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus.

The authors report no conflict of interest.

Correspondence: Alexander M. Cartron, BS, Department of Dermatology, University of Maryland School of Medicine, 419 W Redwood St, Ste 235, Baltimore, MD 21201 ([email protected]).

Author and Disclosure Information

Mr. Cartron is from the Department of Dermatology, University of Maryland School of Medicine, Baltimore. Dr. Trinidad is from the Division of Dermatology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus.

The authors report no conflict of interest.

Correspondence: Alexander M. Cartron, BS, Department of Dermatology, University of Maryland School of Medicine, 419 W Redwood St, Ste 235, Baltimore, MD 21201 ([email protected]).

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Human papillomavirus (HPV) is one of the most common sexually transmitted infections in the United States. It is the causative agent of genital warts, as well as cervical, anal, penile, vulvar, vaginal, and some head and neck cancers.1 Development of the HPV vaccine and its introduction into the scheduled vaccine series recommended by the Centers for Disease Control and Prevention (CDC) represented a major public health milestone. The CDC recommends the HPV vaccine for all children beginning at 11 or 12 years of age, even as early as 9 years, regardless of gender identity or sexuality. As of late 2016, the 9-valent formulation (Gardasil 9 [Merck]) is the only HPV vaccine distributed in the United States, and the vaccination schedule depends specifically on age. The Advisory Committee on Immunization Practices (ACIP) of the CDC revised its recommendations in 2019 to include “shared clinical decision-making regarding HPV vaccination . . . for some adults aged 27 through 45 years.”2 This change in policy has notable implications for sexual and gender minority populations, such as lesbian, gay, bisexual, transgender, and queer or questioning (LGBTQ) patients, especially in the context of dermatologic care. Herein, we discuss HPV-related conditions for LGBTQ patients, barriers to vaccine administration, and the role of dermatologists in promoting an increased vaccination rate in the LGBTQ community.

HPV-Related Conditions

A 2019 review of dermatologic care for LGBTQ patients identified many specific health disparities of HPV.3 Specifically, men who have sex with men (MSM) are more likely than heterosexual men to have oral, anal, and penile HPV infections, including high-risk HPV types.3 From 2011 to 2014, 18% and 13% of MSM had oral HPV infection and high-risk oral HPV infection, respectively, compared to only 11% and 7%, respectively, of men who reported never having had a same-sex sexual partner.4

Similarly, despite the CDC’s position that patients with perianal warts might benefit from digital anal examination or referral for standard or high-resolution anoscopy to detect intra-anal warts, improvements in morbidity have not yet been realized. In 2017, anal cancer incidence was 45.9 cases for every 100,000 person-years among human immunodeficiency (HIV)–positive MSM and 5.1 cases for every 100,000 person-years among HIV-negative MSM vs only 1.5 cases for every 100,000 person-years among men in the United States overall.3 Yet the CDC states that there is insufficient evidence to recommend routine anal cancer screening among MSM, even when a patient is HIV positive. Therefore, current screening practices and treatments are insufficient as MSM continue to have a disproportionately higher rate of HPV-associated disease compared to other populations.

Barriers to HPV Vaccine Administration

The HPV vaccination rate among MSM in adolescent populations varies across reports.5-7 Interestingly, a 2016 survey study found that MSM had approximately 2-times greater odds of initiating the HPV vaccine than heterosexual men.8 However, a study specifically sampling young gay and bisexual men (N=428) found that only 13% had received any doses of the HPV vaccine.6

Regardless, HPV vaccination is much less common among all males than it is among all females, and the low rate of vaccination among sexual minority men has a disproportionate impact, given their higher risk for HPV infection.4 Although the HPV vaccination rate increased from 2014 to 2017, the HPV vaccination rate in MSM overall is less than half of the Healthy People 2020 goal of 80%.9 A 2018 review determined that HPV vaccination is a cost-effective strategy for preventing anal cancer in MSM10; yet male patients might still view the HPV vaccine as a “women’s issue” and are less likely to be vaccinated if they are not prompted by health care providers. Additionally, HPV vaccination is remarkably less likely in MSM when patients are older, uninsured, of lower socioeconomic status, or have not disclosed their sexual identity to their health care provider.9 Dermatologists should be mindful of these barriers to promote HPV vaccination in MSM before, or soon after, sexual debut.



Other members of the LGBTQ community, such as women who have sex with women, face notable HPV-related health disparities and would benefit from increased vaccination efforts by dermatologists. Adolescent and young adult women who have sex with women are less likely than heterosexual adolescent and young adult women to receive routine Papanicolaou tests and initiate HPV vaccination, despite having a higher number of lifetime sexual partners and a higher risk for HPV exposure.11 A 2015 survey study (N=3253) found that after adjusting for covariates, only 8.5% of lesbians and 33.2% of bisexual women and girls who had heard of the HPV vaccine had initiated vaccination compared to 28.4% of their heterosexual counterparts.11 The HPV vaccine is an effective public health tool for the prevention of cervical cancer in these populations. A study of women aged 15 to 19 years in the HPV vaccination era (2007-2014) found significant (P<.05) observed population-level decreases in cervical intraepithelial neoplasia incidence across all grades.12

Transgender women also face a high rate of HPV infection, HIV infection, and other structural and financial disparities, such as low insurance coverage, that can limit their access to vaccination. Transgender men have a higher rate of HPV infection than cisgender men, and those with female internal reproductive organs are less likely to receive routine Papanicolaou tests. A 2018 survey study found that approximately one-third of transgender men and women reported initiating the HPV vaccination series,13 but further investigation is required to make balanced comparisons to cisgender patients.

The Role of the Dermatologist

Collectively, these disparities emphasize the need for increased involvement by dermatologists in HPV vaccination efforts for all LGBTQ patients. Adult patients may have concerns about ties of the HPV vaccine to drug manufacturers and the general safety of vaccination. For pediatric patients, parents/guardians also may be concerned about an assumed but not evidence-based increase in sexual promiscuity following HPV vaccination.14 These topics can be challenging to discuss, but dermatologists have the duty to be proactive and initiate conversation about HPV vaccination, as opposed to waiting for patients to express interest. Dermatologists should stress the safety of the vaccine as well as its potential to protect against multiple, even life-threatening diseases. Providers also can explain that the ACIP recommends catch-up vaccination for all individuals through 26 years of age, regardless of sexual orientation or gender identity.

With the ACIP having recently expanded the appropriate age range for HPV vaccination, we encourage dermatologists to engage in education and shared decision-making to ensure that adult patients with specific risk factors receive the HPV vaccine. Because the expanded ACIP recommendations are aimed at vaccination before HPV exposure, vaccination might not be appropriate for all LGBTQ patients. However, eliciting a sexual history with routine patient intake forms or during the clinical encounter ensures equal access to the HPV vaccine.

Greater awareness of HPV-related disparities and barriers to vaccination in LGBTQ populations has the potential to notably decrease HPV-associated mortality and morbidity. Increased involvement by dermatologists contributes to the efforts of other specialties in universal HPV vaccination, regardless of sexual orientation or gender identity—ideally in younger age groups, such that patients receive the vaccine prior to coitarche.



There are many ways that dermatologists can advocate for HPV vaccination. Those in a multispecialty or academic practice can readily refer patients to an associated internist, primary care physician, or vaccination clinic in the same building or institution. Dermatologists in private practice might be able to administer the HPV vaccine themselves or can advocate for patients to receive the vaccine at a local facility of the Department of Health or at a nonprofit organization, such as a Planned Parenthood center. Although pediatricians and family physicians remain front-line providers of these services, dermatologists represent an additional member of a patient’s care team, capable of advocating for this important intervention.

 

Human papillomavirus (HPV) is one of the most common sexually transmitted infections in the United States. It is the causative agent of genital warts, as well as cervical, anal, penile, vulvar, vaginal, and some head and neck cancers.1 Development of the HPV vaccine and its introduction into the scheduled vaccine series recommended by the Centers for Disease Control and Prevention (CDC) represented a major public health milestone. The CDC recommends the HPV vaccine for all children beginning at 11 or 12 years of age, even as early as 9 years, regardless of gender identity or sexuality. As of late 2016, the 9-valent formulation (Gardasil 9 [Merck]) is the only HPV vaccine distributed in the United States, and the vaccination schedule depends specifically on age. The Advisory Committee on Immunization Practices (ACIP) of the CDC revised its recommendations in 2019 to include “shared clinical decision-making regarding HPV vaccination . . . for some adults aged 27 through 45 years.”2 This change in policy has notable implications for sexual and gender minority populations, such as lesbian, gay, bisexual, transgender, and queer or questioning (LGBTQ) patients, especially in the context of dermatologic care. Herein, we discuss HPV-related conditions for LGBTQ patients, barriers to vaccine administration, and the role of dermatologists in promoting an increased vaccination rate in the LGBTQ community.

HPV-Related Conditions

A 2019 review of dermatologic care for LGBTQ patients identified many specific health disparities of HPV.3 Specifically, men who have sex with men (MSM) are more likely than heterosexual men to have oral, anal, and penile HPV infections, including high-risk HPV types.3 From 2011 to 2014, 18% and 13% of MSM had oral HPV infection and high-risk oral HPV infection, respectively, compared to only 11% and 7%, respectively, of men who reported never having had a same-sex sexual partner.4

Similarly, despite the CDC’s position that patients with perianal warts might benefit from digital anal examination or referral for standard or high-resolution anoscopy to detect intra-anal warts, improvements in morbidity have not yet been realized. In 2017, anal cancer incidence was 45.9 cases for every 100,000 person-years among human immunodeficiency (HIV)–positive MSM and 5.1 cases for every 100,000 person-years among HIV-negative MSM vs only 1.5 cases for every 100,000 person-years among men in the United States overall.3 Yet the CDC states that there is insufficient evidence to recommend routine anal cancer screening among MSM, even when a patient is HIV positive. Therefore, current screening practices and treatments are insufficient as MSM continue to have a disproportionately higher rate of HPV-associated disease compared to other populations.

Barriers to HPV Vaccine Administration

The HPV vaccination rate among MSM in adolescent populations varies across reports.5-7 Interestingly, a 2016 survey study found that MSM had approximately 2-times greater odds of initiating the HPV vaccine than heterosexual men.8 However, a study specifically sampling young gay and bisexual men (N=428) found that only 13% had received any doses of the HPV vaccine.6

Regardless, HPV vaccination is much less common among all males than it is among all females, and the low rate of vaccination among sexual minority men has a disproportionate impact, given their higher risk for HPV infection.4 Although the HPV vaccination rate increased from 2014 to 2017, the HPV vaccination rate in MSM overall is less than half of the Healthy People 2020 goal of 80%.9 A 2018 review determined that HPV vaccination is a cost-effective strategy for preventing anal cancer in MSM10; yet male patients might still view the HPV vaccine as a “women’s issue” and are less likely to be vaccinated if they are not prompted by health care providers. Additionally, HPV vaccination is remarkably less likely in MSM when patients are older, uninsured, of lower socioeconomic status, or have not disclosed their sexual identity to their health care provider.9 Dermatologists should be mindful of these barriers to promote HPV vaccination in MSM before, or soon after, sexual debut.



Other members of the LGBTQ community, such as women who have sex with women, face notable HPV-related health disparities and would benefit from increased vaccination efforts by dermatologists. Adolescent and young adult women who have sex with women are less likely than heterosexual adolescent and young adult women to receive routine Papanicolaou tests and initiate HPV vaccination, despite having a higher number of lifetime sexual partners and a higher risk for HPV exposure.11 A 2015 survey study (N=3253) found that after adjusting for covariates, only 8.5% of lesbians and 33.2% of bisexual women and girls who had heard of the HPV vaccine had initiated vaccination compared to 28.4% of their heterosexual counterparts.11 The HPV vaccine is an effective public health tool for the prevention of cervical cancer in these populations. A study of women aged 15 to 19 years in the HPV vaccination era (2007-2014) found significant (P<.05) observed population-level decreases in cervical intraepithelial neoplasia incidence across all grades.12

Transgender women also face a high rate of HPV infection, HIV infection, and other structural and financial disparities, such as low insurance coverage, that can limit their access to vaccination. Transgender men have a higher rate of HPV infection than cisgender men, and those with female internal reproductive organs are less likely to receive routine Papanicolaou tests. A 2018 survey study found that approximately one-third of transgender men and women reported initiating the HPV vaccination series,13 but further investigation is required to make balanced comparisons to cisgender patients.

The Role of the Dermatologist

Collectively, these disparities emphasize the need for increased involvement by dermatologists in HPV vaccination efforts for all LGBTQ patients. Adult patients may have concerns about ties of the HPV vaccine to drug manufacturers and the general safety of vaccination. For pediatric patients, parents/guardians also may be concerned about an assumed but not evidence-based increase in sexual promiscuity following HPV vaccination.14 These topics can be challenging to discuss, but dermatologists have the duty to be proactive and initiate conversation about HPV vaccination, as opposed to waiting for patients to express interest. Dermatologists should stress the safety of the vaccine as well as its potential to protect against multiple, even life-threatening diseases. Providers also can explain that the ACIP recommends catch-up vaccination for all individuals through 26 years of age, regardless of sexual orientation or gender identity.

With the ACIP having recently expanded the appropriate age range for HPV vaccination, we encourage dermatologists to engage in education and shared decision-making to ensure that adult patients with specific risk factors receive the HPV vaccine. Because the expanded ACIP recommendations are aimed at vaccination before HPV exposure, vaccination might not be appropriate for all LGBTQ patients. However, eliciting a sexual history with routine patient intake forms or during the clinical encounter ensures equal access to the HPV vaccine.

Greater awareness of HPV-related disparities and barriers to vaccination in LGBTQ populations has the potential to notably decrease HPV-associated mortality and morbidity. Increased involvement by dermatologists contributes to the efforts of other specialties in universal HPV vaccination, regardless of sexual orientation or gender identity—ideally in younger age groups, such that patients receive the vaccine prior to coitarche.



There are many ways that dermatologists can advocate for HPV vaccination. Those in a multispecialty or academic practice can readily refer patients to an associated internist, primary care physician, or vaccination clinic in the same building or institution. Dermatologists in private practice might be able to administer the HPV vaccine themselves or can advocate for patients to receive the vaccine at a local facility of the Department of Health or at a nonprofit organization, such as a Planned Parenthood center. Although pediatricians and family physicians remain front-line providers of these services, dermatologists represent an additional member of a patient’s care team, capable of advocating for this important intervention.

References
  1. Brianti P, De Flammineis E, Mercuri SR. Review of HPV-related diseases and cancers. New Microbiol. 2017;40:80-85.
  2. Meites E, Szilagyi PG, Chesson HW, et al. Human papillomavirus vaccination for adults: updated recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2019;68:698-702.
  3. Yeung H, Luk KM, Chen SC, et al. Dermatologic care for lesbian, gay, bisexual, and transgender persons: epidemiology, screening, and disease prevention. J Am Acad Dermatol. 2019;80:591-602.
  4. Sonawane K, Suk R, Chiao EY, et al. Oral human papillomavirus infection: differences in prevalence between sexes and concordance with genital human papillomavirus infection, NHANES 2011 to 2014. Ann Intern Med. 2017;167:714-724.
  5. Kosche C, Mansh M, Luskus M, et al. Dermatologic care of sexual and gender minority/LGBTQIA youth, part 2: recognition and management of the unique dermatologic needs of SGM adolescents. Pediatr Dermatol. 2019;35:587-593.
  6. Reiter PL, McRee A-L, Katz ML, et al. Human papillomavirus vaccination among young adult gay and bisexual men in the United States. Am J Public Health. 2015;105:96-102.
  7. Charlton BM, Reisner SL, Agénor M, et al. Sexual orientation disparities in human papillomavirus vaccination in a longitudinal cohort of U.S. males and females. LGBT Health. 2017;4:202-209.
  8. Agénor M, Peitzmeier SM, Gordon AR, et al. Sexual orientation identity disparities in human papillomavirus vaccination initiation and completion among young adult US women and men. Cancer Causes Control. 2016;27:1187-1196.
  9. Loretan C, Chamberlain AT, Sanchez T, et al. Trends and characteristics associated with human papillomavirus vaccination uptake among men who have sex with men in the United States, 2014-2017. Sex Transm Dis. 2019;46:465-473.
  10. Setiawan D, Wondimu A, Ong K, et al. Cost effectiveness of human papillomavirus vaccination for men who have sex with men; reviewing the available evidence. Pharmacoeconomics. 2018;36:929-939.
  11. Agénor M, Peitzmeier S, Gordon AR, et al. Sexual orientation identity disparities in awareness and initiation of the human papillomavirus vaccine among U.S. women and girls: a national survey. Ann Intern Med. 2015;163:99-106.
  12. Benard VB, Castle PE, Jenison SA, et al. Population-based incidence rates of cervical intraepithelial neoplasia in the human papillomavirus vaccine era. JAMA Oncol. 2017;3:833-837.
  13. McRee A-L, Gower AL, Reiter PL. Preventive healthcare services use among transgender young adults. Int J Transgend. 2018;19:417-423.
  14. Trinidad J. Policy focus: promoting human papilloma virus vaccine to prevent genital warts and cancer. Boston, MA: The Fenway Institute; 2012. https://fenwayhealth.org/documents/the-fenway-institute/policy-briefs/PolicyFocus_HPV_v4_10.09.12.pdf. Accessed September 15, 2020.
References
  1. Brianti P, De Flammineis E, Mercuri SR. Review of HPV-related diseases and cancers. New Microbiol. 2017;40:80-85.
  2. Meites E, Szilagyi PG, Chesson HW, et al. Human papillomavirus vaccination for adults: updated recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2019;68:698-702.
  3. Yeung H, Luk KM, Chen SC, et al. Dermatologic care for lesbian, gay, bisexual, and transgender persons: epidemiology, screening, and disease prevention. J Am Acad Dermatol. 2019;80:591-602.
  4. Sonawane K, Suk R, Chiao EY, et al. Oral human papillomavirus infection: differences in prevalence between sexes and concordance with genital human papillomavirus infection, NHANES 2011 to 2014. Ann Intern Med. 2017;167:714-724.
  5. Kosche C, Mansh M, Luskus M, et al. Dermatologic care of sexual and gender minority/LGBTQIA youth, part 2: recognition and management of the unique dermatologic needs of SGM adolescents. Pediatr Dermatol. 2019;35:587-593.
  6. Reiter PL, McRee A-L, Katz ML, et al. Human papillomavirus vaccination among young adult gay and bisexual men in the United States. Am J Public Health. 2015;105:96-102.
  7. Charlton BM, Reisner SL, Agénor M, et al. Sexual orientation disparities in human papillomavirus vaccination in a longitudinal cohort of U.S. males and females. LGBT Health. 2017;4:202-209.
  8. Agénor M, Peitzmeier SM, Gordon AR, et al. Sexual orientation identity disparities in human papillomavirus vaccination initiation and completion among young adult US women and men. Cancer Causes Control. 2016;27:1187-1196.
  9. Loretan C, Chamberlain AT, Sanchez T, et al. Trends and characteristics associated with human papillomavirus vaccination uptake among men who have sex with men in the United States, 2014-2017. Sex Transm Dis. 2019;46:465-473.
  10. Setiawan D, Wondimu A, Ong K, et al. Cost effectiveness of human papillomavirus vaccination for men who have sex with men; reviewing the available evidence. Pharmacoeconomics. 2018;36:929-939.
  11. Agénor M, Peitzmeier S, Gordon AR, et al. Sexual orientation identity disparities in awareness and initiation of the human papillomavirus vaccine among U.S. women and girls: a national survey. Ann Intern Med. 2015;163:99-106.
  12. Benard VB, Castle PE, Jenison SA, et al. Population-based incidence rates of cervical intraepithelial neoplasia in the human papillomavirus vaccine era. JAMA Oncol. 2017;3:833-837.
  13. McRee A-L, Gower AL, Reiter PL. Preventive healthcare services use among transgender young adults. Int J Transgend. 2018;19:417-423.
  14. Trinidad J. Policy focus: promoting human papilloma virus vaccine to prevent genital warts and cancer. Boston, MA: The Fenway Institute; 2012. https://fenwayhealth.org/documents/the-fenway-institute/policy-briefs/PolicyFocus_HPV_v4_10.09.12.pdf. Accessed September 15, 2020.
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An Unusual Skin Infection With Achromobacter xylosoxidans

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An Unusual Skin Infection With Achromobacter xylosoxidans

 

Case Report

A 50-year-old woman presented with a sore, tender, red lump on the right superior buttock of 5 months’ duration. Five months prior to presentation the patient used this area to attach the infusion set for an insulin pump, which was left in place for 7 days as opposed to the 2 or 3 days recommended by the device manufacturer. A firm, slightly tender lump formed, similar to prior scars that had developed from use of the insulin pump. However, the lump began to grow and get softer. It was intermittently warm and red. Although the area was sore and tender, she never had any major pain. She also denied any fever, malaise, or other systemic symptoms.

The patient indicated a medical history of type 1 diabetes mellitus diagnosed at 9 years of age; hypertension; asthma; gastroesophageal reflux disease; allergic rhinitis; migraine headaches; depression; hidradenitis suppurativa that resolved after surgical excision; and recurrent vaginal yeast infections, especially when taking antibiotics. She had a surgical history of hidradenitis suppurativa excision at the inguinal folds, bilateral carpal tunnel release, tubal ligation, abdominoplasty, and cholecystectomy. The patient’s current medications included insulin aspart, mometasone furoate, inhaled fluticasone, pantoprazole, cetirizine, spironolactone, duloxetine, sumatriptan, fluconazole, topiramate, and enalapril.

Physical examination revealed normal vital signs and the patient was afebrile. She had no swollen or tender lymph nodes. There was a 5.5×7.0-cm, soft, tender, erythematous subcutaneous mass with no visible punctum or overlying epidermal change on the right superior buttock (Figure 1). Based on the history and physical examination, the differential diagnosis included subcutaneous fat necrosis, epidermal inclusion cyst, and an abscess.

Figure 1. A soft, tender, erythematous subcutaneous mass on the right superior buttock.


The patient was scheduled for excision of the mass the day after presenting to the clinic. During excision, 10 mL of thick purulent liquid was drained. A sample of the liquid was sent for Gram stain, aerobic and anaerobic culture, and antibiotic sensitivities. Necrotic-appearing adipose and fibrotic tissues were dissected and extirpated through an elliptical incision and submitted for pathologic evaluation.

Histopathology showed a subcutaneous defect with palisaded granulomatous inflammation and sclerosis (Figure 2). There was no detection of microorganisms with Grocott-Gomori methenamine-silver, tissue Gram, or acid-fast stains. There was a focus of acellular material embedded within the inflammation (Figure 3). The Gram stain of the purulent material showed few white blood cells and rare gram-negative bacilli. Culture grew moderate Achromobacter xylosoxidans resistant to cefepime, cefotaxime, and gentamicin. The culture was susceptible to ceftazidime, imipenem, levofloxacin, piperacillin, and trimethoprim-sulfamethoxazole (TMP-SMX).

Figure 2. Palisaded granulomatous inflammation (H&E, original magnification ×20).

Figure 3. Focus of acellular material, possibly representing a small piece of partially biodegraded plastic from the insulin pump catheter (H&E, original magnification ×10).

The patient was prescribed oral TMP-SMX (160 mg of TMP and 800 mg of SMX) twice daily for 10 days. The patient tolerated the procedure and the subsequent antibiotics well. The patient had normal levels of IgA, IgG, and IgM, as well as a negative screening test for human immunodeficiency virus. She healed well from the surgical procedure and has had no recurrence of symptoms.

Comment

Achromobacter xylosoxidans is a nonfermentative, non–spore-forming, motile, gram-negative, aerobic, catalase-positive and oxidase-positive flagellate bacterium. It is an emerging pathogen that was first isolated in 1971 from patients with chronic otitis media.1 Since its recognition, it has been documented to cause a variety of infections, including pneumonia, meningitis, osteomyelitis, endocarditis, and bacteremia, as well as abdominal, urinary tract, ocular, and skin and soft tissue infections.2,3 Those affected usually are immunocompromised, have hematologic disorders, or have indwelling catheters.4 Strains of A xylosoxidans have shown resistance to multiple antibiotics including penicillins, cephalosporins, carbapenems, aminoglycosides, macrolides, fluoroquinolones, and TMP-SMX. Achromobacter xylosoxidans has been documented to form biofilms on plastics, including on contact lenses, urinary and intravenous catheters, and reusable tissue dispensers treated with disinfectant solution.4-6 One study demonstrated that A xylosoxidans is even capable of biodegradation of plastic, using the plastic as its sole source of carbon.7

Our case illustrates an indolent infection with A xylosoxidans forming a granulomatous abscess at the site of an insulin pump that was left in place for 7 days in an immunocompetent patient. Although infections with A xylosoxidans in patients with urinary or intravenous catheters have been reported,4 our case is unique, as the insulin pump was the source of such an infection. It is possible that the subcutaneous focus of acellular material described on the pathology report represented a partially biodegraded piece of the insulin pump catheter that broke off and was serving as a nidus of infection for A xylosoxidans. Although multidrug resistance is common, the culture grown from our patient was susceptible to TMP-SMX, among other antibiotics. Our patient was treated successfully with surgical excision, drainage, and a 10-day course of TMP-SMX.

Conclusion

Health care providers should recognize A xylosoxidans as an emerging pathogen that is capable of forming biofilms on “disinfected” surfaces and medical products, especially plastics. Achromobacter xylosoxidans may be resistant to multiple antibiotics and can cause infections with various presentations.

References
  1. Yabuuchi E, Oyama A. Achromobacter xylosoxidans  n. sp. from human ear discharge. Jpn J Microbiol. 1971;15:477-481.
  2. Rodrigues CG, Rays J, Kanegae MY. Native-valve endocarditis caused by Achromobacter xylosoxidans: a case report and review of literature. Autops Case Rep. 2017;7:50-55.
  3. Tena D, Martínez NM, Losa C, et al. Skin and soft tissue infection caused by Achromobacter xylosoxidans: report of 14 cases. Scand J Infect Dis. 2014;46:130-135.
  4. Pérez Barragán E, Sandino Pérez J, Corbella L, et al. Achromobacter xylosoxidans bacteremia: clinical and microbiological features in a 10-year case series. Rev Esp Quimioter. 2018;31:268-273.
  5. Konstantinović  N,  Ćirković I, Đukić S, et al. Biofilm formation of Achromobacter xylosoxidans on contact lens. Acta Microbiol Immunol Hung. 2017;64:293-300.
  6. Günther F, Merle U, Frank U, et al. Pseudobacteremia outbreak of biofilm-forming Achromobacter xylosoxidans—environmental transmission. BMC Infect Dis. 2016;16:584.
  7. Kowalczyk A, Chyc M, Ryszka P, et al. Achromobacter xylosoxidans as a new microorganism strain colonizing high-density polyethylene as a key step to its biodegradation. Environ Sci Pollut Res Int. 2016;23:11349-11356.
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The authors report no conflict of interest.

Correspondence: Matthew S. Crosby, DO, 1916 Paseo San Luis, Sierra Vista, AZ 85635 ([email protected]).

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Drs. Crosby and Mackey are from Advanced Desert Dermatology/Midwestern University, Glendale, Arizona. Dr. Petropolis is from the Section of Dermatology, Sierra Vista Community Health Center, Arizona. Dr. Culpepper is from Dermpath Diagnostics, Tucson, Arizona.

The authors report no conflict of interest.

Correspondence: Matthew S. Crosby, DO, 1916 Paseo San Luis, Sierra Vista, AZ 85635 ([email protected]).

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Drs. Crosby and Mackey are from Advanced Desert Dermatology/Midwestern University, Glendale, Arizona. Dr. Petropolis is from the Section of Dermatology, Sierra Vista Community Health Center, Arizona. Dr. Culpepper is from Dermpath Diagnostics, Tucson, Arizona.

The authors report no conflict of interest.

Correspondence: Matthew S. Crosby, DO, 1916 Paseo San Luis, Sierra Vista, AZ 85635 ([email protected]).

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Case Report

A 50-year-old woman presented with a sore, tender, red lump on the right superior buttock of 5 months’ duration. Five months prior to presentation the patient used this area to attach the infusion set for an insulin pump, which was left in place for 7 days as opposed to the 2 or 3 days recommended by the device manufacturer. A firm, slightly tender lump formed, similar to prior scars that had developed from use of the insulin pump. However, the lump began to grow and get softer. It was intermittently warm and red. Although the area was sore and tender, she never had any major pain. She also denied any fever, malaise, or other systemic symptoms.

The patient indicated a medical history of type 1 diabetes mellitus diagnosed at 9 years of age; hypertension; asthma; gastroesophageal reflux disease; allergic rhinitis; migraine headaches; depression; hidradenitis suppurativa that resolved after surgical excision; and recurrent vaginal yeast infections, especially when taking antibiotics. She had a surgical history of hidradenitis suppurativa excision at the inguinal folds, bilateral carpal tunnel release, tubal ligation, abdominoplasty, and cholecystectomy. The patient’s current medications included insulin aspart, mometasone furoate, inhaled fluticasone, pantoprazole, cetirizine, spironolactone, duloxetine, sumatriptan, fluconazole, topiramate, and enalapril.

Physical examination revealed normal vital signs and the patient was afebrile. She had no swollen or tender lymph nodes. There was a 5.5×7.0-cm, soft, tender, erythematous subcutaneous mass with no visible punctum or overlying epidermal change on the right superior buttock (Figure 1). Based on the history and physical examination, the differential diagnosis included subcutaneous fat necrosis, epidermal inclusion cyst, and an abscess.

Figure 1. A soft, tender, erythematous subcutaneous mass on the right superior buttock.


The patient was scheduled for excision of the mass the day after presenting to the clinic. During excision, 10 mL of thick purulent liquid was drained. A sample of the liquid was sent for Gram stain, aerobic and anaerobic culture, and antibiotic sensitivities. Necrotic-appearing adipose and fibrotic tissues were dissected and extirpated through an elliptical incision and submitted for pathologic evaluation.

Histopathology showed a subcutaneous defect with palisaded granulomatous inflammation and sclerosis (Figure 2). There was no detection of microorganisms with Grocott-Gomori methenamine-silver, tissue Gram, or acid-fast stains. There was a focus of acellular material embedded within the inflammation (Figure 3). The Gram stain of the purulent material showed few white blood cells and rare gram-negative bacilli. Culture grew moderate Achromobacter xylosoxidans resistant to cefepime, cefotaxime, and gentamicin. The culture was susceptible to ceftazidime, imipenem, levofloxacin, piperacillin, and trimethoprim-sulfamethoxazole (TMP-SMX).

Figure 2. Palisaded granulomatous inflammation (H&E, original magnification ×20).

Figure 3. Focus of acellular material, possibly representing a small piece of partially biodegraded plastic from the insulin pump catheter (H&E, original magnification ×10).

The patient was prescribed oral TMP-SMX (160 mg of TMP and 800 mg of SMX) twice daily for 10 days. The patient tolerated the procedure and the subsequent antibiotics well. The patient had normal levels of IgA, IgG, and IgM, as well as a negative screening test for human immunodeficiency virus. She healed well from the surgical procedure and has had no recurrence of symptoms.

Comment

Achromobacter xylosoxidans is a nonfermentative, non–spore-forming, motile, gram-negative, aerobic, catalase-positive and oxidase-positive flagellate bacterium. It is an emerging pathogen that was first isolated in 1971 from patients with chronic otitis media.1 Since its recognition, it has been documented to cause a variety of infections, including pneumonia, meningitis, osteomyelitis, endocarditis, and bacteremia, as well as abdominal, urinary tract, ocular, and skin and soft tissue infections.2,3 Those affected usually are immunocompromised, have hematologic disorders, or have indwelling catheters.4 Strains of A xylosoxidans have shown resistance to multiple antibiotics including penicillins, cephalosporins, carbapenems, aminoglycosides, macrolides, fluoroquinolones, and TMP-SMX. Achromobacter xylosoxidans has been documented to form biofilms on plastics, including on contact lenses, urinary and intravenous catheters, and reusable tissue dispensers treated with disinfectant solution.4-6 One study demonstrated that A xylosoxidans is even capable of biodegradation of plastic, using the plastic as its sole source of carbon.7

Our case illustrates an indolent infection with A xylosoxidans forming a granulomatous abscess at the site of an insulin pump that was left in place for 7 days in an immunocompetent patient. Although infections with A xylosoxidans in patients with urinary or intravenous catheters have been reported,4 our case is unique, as the insulin pump was the source of such an infection. It is possible that the subcutaneous focus of acellular material described on the pathology report represented a partially biodegraded piece of the insulin pump catheter that broke off and was serving as a nidus of infection for A xylosoxidans. Although multidrug resistance is common, the culture grown from our patient was susceptible to TMP-SMX, among other antibiotics. Our patient was treated successfully with surgical excision, drainage, and a 10-day course of TMP-SMX.

Conclusion

Health care providers should recognize A xylosoxidans as an emerging pathogen that is capable of forming biofilms on “disinfected” surfaces and medical products, especially plastics. Achromobacter xylosoxidans may be resistant to multiple antibiotics and can cause infections with various presentations.

 

Case Report

A 50-year-old woman presented with a sore, tender, red lump on the right superior buttock of 5 months’ duration. Five months prior to presentation the patient used this area to attach the infusion set for an insulin pump, which was left in place for 7 days as opposed to the 2 or 3 days recommended by the device manufacturer. A firm, slightly tender lump formed, similar to prior scars that had developed from use of the insulin pump. However, the lump began to grow and get softer. It was intermittently warm and red. Although the area was sore and tender, she never had any major pain. She also denied any fever, malaise, or other systemic symptoms.

The patient indicated a medical history of type 1 diabetes mellitus diagnosed at 9 years of age; hypertension; asthma; gastroesophageal reflux disease; allergic rhinitis; migraine headaches; depression; hidradenitis suppurativa that resolved after surgical excision; and recurrent vaginal yeast infections, especially when taking antibiotics. She had a surgical history of hidradenitis suppurativa excision at the inguinal folds, bilateral carpal tunnel release, tubal ligation, abdominoplasty, and cholecystectomy. The patient’s current medications included insulin aspart, mometasone furoate, inhaled fluticasone, pantoprazole, cetirizine, spironolactone, duloxetine, sumatriptan, fluconazole, topiramate, and enalapril.

Physical examination revealed normal vital signs and the patient was afebrile. She had no swollen or tender lymph nodes. There was a 5.5×7.0-cm, soft, tender, erythematous subcutaneous mass with no visible punctum or overlying epidermal change on the right superior buttock (Figure 1). Based on the history and physical examination, the differential diagnosis included subcutaneous fat necrosis, epidermal inclusion cyst, and an abscess.

Figure 1. A soft, tender, erythematous subcutaneous mass on the right superior buttock.


The patient was scheduled for excision of the mass the day after presenting to the clinic. During excision, 10 mL of thick purulent liquid was drained. A sample of the liquid was sent for Gram stain, aerobic and anaerobic culture, and antibiotic sensitivities. Necrotic-appearing adipose and fibrotic tissues were dissected and extirpated through an elliptical incision and submitted for pathologic evaluation.

Histopathology showed a subcutaneous defect with palisaded granulomatous inflammation and sclerosis (Figure 2). There was no detection of microorganisms with Grocott-Gomori methenamine-silver, tissue Gram, or acid-fast stains. There was a focus of acellular material embedded within the inflammation (Figure 3). The Gram stain of the purulent material showed few white blood cells and rare gram-negative bacilli. Culture grew moderate Achromobacter xylosoxidans resistant to cefepime, cefotaxime, and gentamicin. The culture was susceptible to ceftazidime, imipenem, levofloxacin, piperacillin, and trimethoprim-sulfamethoxazole (TMP-SMX).

Figure 2. Palisaded granulomatous inflammation (H&E, original magnification ×20).

Figure 3. Focus of acellular material, possibly representing a small piece of partially biodegraded plastic from the insulin pump catheter (H&E, original magnification ×10).

The patient was prescribed oral TMP-SMX (160 mg of TMP and 800 mg of SMX) twice daily for 10 days. The patient tolerated the procedure and the subsequent antibiotics well. The patient had normal levels of IgA, IgG, and IgM, as well as a negative screening test for human immunodeficiency virus. She healed well from the surgical procedure and has had no recurrence of symptoms.

Comment

Achromobacter xylosoxidans is a nonfermentative, non–spore-forming, motile, gram-negative, aerobic, catalase-positive and oxidase-positive flagellate bacterium. It is an emerging pathogen that was first isolated in 1971 from patients with chronic otitis media.1 Since its recognition, it has been documented to cause a variety of infections, including pneumonia, meningitis, osteomyelitis, endocarditis, and bacteremia, as well as abdominal, urinary tract, ocular, and skin and soft tissue infections.2,3 Those affected usually are immunocompromised, have hematologic disorders, or have indwelling catheters.4 Strains of A xylosoxidans have shown resistance to multiple antibiotics including penicillins, cephalosporins, carbapenems, aminoglycosides, macrolides, fluoroquinolones, and TMP-SMX. Achromobacter xylosoxidans has been documented to form biofilms on plastics, including on contact lenses, urinary and intravenous catheters, and reusable tissue dispensers treated with disinfectant solution.4-6 One study demonstrated that A xylosoxidans is even capable of biodegradation of plastic, using the plastic as its sole source of carbon.7

Our case illustrates an indolent infection with A xylosoxidans forming a granulomatous abscess at the site of an insulin pump that was left in place for 7 days in an immunocompetent patient. Although infections with A xylosoxidans in patients with urinary or intravenous catheters have been reported,4 our case is unique, as the insulin pump was the source of such an infection. It is possible that the subcutaneous focus of acellular material described on the pathology report represented a partially biodegraded piece of the insulin pump catheter that broke off and was serving as a nidus of infection for A xylosoxidans. Although multidrug resistance is common, the culture grown from our patient was susceptible to TMP-SMX, among other antibiotics. Our patient was treated successfully with surgical excision, drainage, and a 10-day course of TMP-SMX.

Conclusion

Health care providers should recognize A xylosoxidans as an emerging pathogen that is capable of forming biofilms on “disinfected” surfaces and medical products, especially plastics. Achromobacter xylosoxidans may be resistant to multiple antibiotics and can cause infections with various presentations.

References
  1. Yabuuchi E, Oyama A. Achromobacter xylosoxidans  n. sp. from human ear discharge. Jpn J Microbiol. 1971;15:477-481.
  2. Rodrigues CG, Rays J, Kanegae MY. Native-valve endocarditis caused by Achromobacter xylosoxidans: a case report and review of literature. Autops Case Rep. 2017;7:50-55.
  3. Tena D, Martínez NM, Losa C, et al. Skin and soft tissue infection caused by Achromobacter xylosoxidans: report of 14 cases. Scand J Infect Dis. 2014;46:130-135.
  4. Pérez Barragán E, Sandino Pérez J, Corbella L, et al. Achromobacter xylosoxidans bacteremia: clinical and microbiological features in a 10-year case series. Rev Esp Quimioter. 2018;31:268-273.
  5. Konstantinović  N,  Ćirković I, Đukić S, et al. Biofilm formation of Achromobacter xylosoxidans on contact lens. Acta Microbiol Immunol Hung. 2017;64:293-300.
  6. Günther F, Merle U, Frank U, et al. Pseudobacteremia outbreak of biofilm-forming Achromobacter xylosoxidans—environmental transmission. BMC Infect Dis. 2016;16:584.
  7. Kowalczyk A, Chyc M, Ryszka P, et al. Achromobacter xylosoxidans as a new microorganism strain colonizing high-density polyethylene as a key step to its biodegradation. Environ Sci Pollut Res Int. 2016;23:11349-11356.
References
  1. Yabuuchi E, Oyama A. Achromobacter xylosoxidans  n. sp. from human ear discharge. Jpn J Microbiol. 1971;15:477-481.
  2. Rodrigues CG, Rays J, Kanegae MY. Native-valve endocarditis caused by Achromobacter xylosoxidans: a case report and review of literature. Autops Case Rep. 2017;7:50-55.
  3. Tena D, Martínez NM, Losa C, et al. Skin and soft tissue infection caused by Achromobacter xylosoxidans: report of 14 cases. Scand J Infect Dis. 2014;46:130-135.
  4. Pérez Barragán E, Sandino Pérez J, Corbella L, et al. Achromobacter xylosoxidans bacteremia: clinical and microbiological features in a 10-year case series. Rev Esp Quimioter. 2018;31:268-273.
  5. Konstantinović  N,  Ćirković I, Đukić S, et al. Biofilm formation of Achromobacter xylosoxidans on contact lens. Acta Microbiol Immunol Hung. 2017;64:293-300.
  6. Günther F, Merle U, Frank U, et al. Pseudobacteremia outbreak of biofilm-forming Achromobacter xylosoxidans—environmental transmission. BMC Infect Dis. 2016;16:584.
  7. Kowalczyk A, Chyc M, Ryszka P, et al. Achromobacter xylosoxidans as a new microorganism strain colonizing high-density polyethylene as a key step to its biodegradation. Environ Sci Pollut Res Int. 2016;23:11349-11356.
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  • Achromobacter xylosoxidans is an emerging pathogen primarily in the immunocompromised patient.
  • Achromobacter xylosoxidans can form biofilms on plastics treated with disinfectant solution, including medical products.
  • Strains of A xylosoxidans have shown multiantibiotic resistance.
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Cutaneous Leishmaniasis Successfully Treated With Miltefosine

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Leishmaniasis is a neglected parasitic disease with an estimated annual incidence of 1.3 million cases, the majority of which manifest as cutaneous leishmaniasis.1 The cutaneous and mucosal forms demonstrate substantial global burden with morbidity and socioeconomic repercussions, while the visceral form is responsible for up to 30,000 deaths annually.2 Despite increasing prevalence in the United States, awareness and diagnosis remain relatively low.3 We describe 2 cases of cutaneous leishmaniasis in New England, United States, in travelers returning from Central America, both successfully treated with miltefosine. We also review prevention, diagnosis, and treatment options.

Case Reports

Patient 1
A 47-year-old woman presented with an enlarging, 2-cm, erythematous, ulcerated nodule on the right dorsal hand of 2 weeks’ duration with accompanying right epitrochlear lymphadenopathy (Figure 1A). She noticed the lesion 10 weeks after returning from Panama, where she had been photographing the jungle. Prior to the initial presentation to dermatology, salicylic acid wart remover, intramuscular ceftriaxone, and oral trimethoprim had failed to alleviate the lesion. Her laboratory results were notable for an elevated C-reactive protein level of 5.4 mg/L (reference range, ≤4.9 mg/L). A punch biopsy demonstrated pseudoepitheliomatous hyperplasia with diffuse dermal lymphohistiocytic inflammation and small intracytoplasmic structures within histiocytes consistent with leishmaniasis (Figure 2). Immunohistochemistry was consistent with leishmaniasis (Figure 3), and polymerase chain reaction performed by the Centers for Disease Control and Prevention (CDC) identified the pathogen as Leishmania braziliensis.

Figure 1. A and B, An erythematous ulcerated nodule on the right dorsal hand in patient 1 at presentation and after almost 3 months of miltefosine treatment, respectively.

Figure 2. Diffuse dermal mixed infiltrate and intracytoplasmic amastigotes demonstrating a marquee sign in patient 1 (H&E, original magnification ×40). 

Figure 3. Positive immunohistochemistry with polyclonal anti-CAIN antibodies to leishmaniasis in patient 1 (original magnification ×40).

Patient 2
An 18-year-old man presented with an enlarging, well-delineated, tender ulcer of 6 weeks’ duration measuring 2.5×2 cm with an erythematous and edematous border on the right medial forearm with associated epitrochlear lymphadenopathy (Figure 4). Nine weeks prior to initial presentation, he had returned from a 3-month outdoor adventure trip to the Florida Keys, Costa Rica, and Panama. He had used bug repellent intermittently, slept under a bug net, and did not recall any trauma or bite at the ulcer site. Biopsy and tissue culture were obtained, and histopathology demonstrated an ulcer with a dense dermal lymphogranulomatous infiltrate and intracytoplasmic organisms consistent with leishmaniasis. Polymerase chain reaction by the CDC identified the pathogen as Leishmania panamensis.

Figure  4. A and B, A well-demarcated tender ulcer on the right medial forearm in patient 2 at presentation and after 2 months of miltefosine treatment, respectively.


Treatment
Both patients were prescribed oral miltefosine 50 mg twice daily for 28 days. Patient 1 initiated treatment 1 month after lesion onset, and patient 2 initiated treatment 2.5 months after initial presentation. Both patients had noticeable clinical improvement within 21 days of starting treatment, with lesions diminishing in size and lymphadenopathy resolving. Within 2 months of treatment, patient 1’s ulcer completely resolved with only postinflammatory hyperpigmentation (Figure 1B), while patient 2’s ulcer was noticeably smaller and shallower compared with its peak size of 4.2×2.4 cm (Figure 4B). Miltefosine was well tolerated by both patients; emesis resolved with ondansetron in patient 1 and spontaneously in patient 2, who had asymptomatic temporary hyperkalemia of 5.2 mmol/L (reference range, 3.5–5.0 mmol/L).

Comment

Epidemiology and Prevention
Risk factors for leishmaniasis include weak immunity, poverty, poor housing, poor sanitation, malnutrition, urbanization, climate change, and human migration.4 Our patients were most directly affected by travel to locations where leishmaniasis is endemic. Despite an increasing prevalence of endemic leishmaniasis and new animal hosts in the southern United States, most patients diagnosed in the United States are infected abroad by Leishmania mexicana and L braziliensis, both cutaneous New World species.3 Our patients were infected by species within the New World subgenus Viannia that have potential for mucocutaneous spread.4

Because there is no chemoprophylaxis or acquired active immunity such as vaccines that can mitigate the risk for leishmaniasis, public health efforts focus on preventive measures. Although difficult to achieve, avoidance of the phlebotomine sand fly species that transmit the obligate intracellular Leishmania parasite is a most effective measure.4 Travelers entering geographic regions with higher risk for leishmaniasis should be aware of the inherent risk and determine which methods of prevention, such as N,N-diethyl-meta-toluamide (DEET) insecticides or permethrin-treated protective clothing, are most feasible. Although higher concentrations of DEET provide longer protection, the effectiveness tends to plateau at approximately 50%.5

 

 



Presentation and Prognosis
For patients who develop leishmaniasis, the disease course and prognosis depend greatly on the species and manifestation. The most common form of leishmaniasis is localized cutaneous leishmaniasis, which has an annual incidence of up to 1 million cases. It initially presents as macules, usually at the site of inoculation within several months to years of infection.6 The macules expand into papules and plaques that reach maximum size over at least 1 week4 and then progress into crusted ulcers up to 5 cm in diameter with raised edges. Although usually painless and self-limited, these lesions can take years to spontaneously heal, with the risk for atrophic scarring and altered pigmentation. Lymphatic involvement manifests as lymphadenitis or regional lymphadenopathy and is common with lesions caused by the subgenus Viannia.6



Leishmania braziliensis and L panamensis, the species that infected our patients, can uniquely cause cutaneous leishmaniasis that metastasizes into mucocutaneous leishmaniasis, which always affects the nasal mucosa. Risk factors for transformation include a primary lesion site above the waist, multiple or large primary lesions, and delayed healing of primary cutaneous leishmaniasis. Mucocutaneous leishmaniasis can result in notable morbidity and even mortality from invasion and destruction of nasal and oropharyngeal mucosa, as well as intercurrent pneumonia, especially if treatment is insufficient or delayed.4

Diagnosis
Prompt treatment relies on accurate and timely diagnosis, which is complicated by the relative unfamiliarity with leishmaniasis in the United States. The differential diagnosis for cutaneous leishmaniasis is broad, including deep fungal infection, Mycobacterium infection, cutaneous granulomatous conditions, nonmelanoma cutaneous neoplasms, and trauma. Taking a thorough patient history, including potential exposures and travels; having high clinical suspicion; and being aware of classic presentation allows for identification of leishmaniasis and subsequent stratification by manifestation.7

Diagnosis is made by detecting Leishmania organisms or DNA using light microscopy and staining to visualize the kinetoplast in an amastigote, molecular methods, or specialized culturing.7 The CDC is a valuable diagnostic partner for confirmation and speciation. Specific instructions for specimen collection and transportation can be found by contacting the CDC or reading their guide.8 To provide prompt care and reassurance to patients, it is important to be aware of the coordination effort that may be needed to send samples, receive results, and otherwise correspond with a separate institution.

Treatment
Treatment of cutaneous leishmaniasis is indicated to decrease the risk for mucosal dissemination and clinical reactivation of lesions, accelerate healing of lesions, decrease local morbidity caused by large or persistent lesions, and decrease the reservoir of infection in places where infected humans serve as reservoir hosts. Oral treatments include ketoconazole, itraconazole, and fluconazole, recommended at doses ranging from 200 to 600 mg daily for at least 28 days. For severe, refractory, or visceral leishmaniasis, parenteral choices include pentavalent antimonials, amphotericin B deoxycholate, and pentamidine isethionate, each with known toxicity or limited data on efficacy.6 Pentavalent antimonials can cause life-threatening cardiotoxicity and are more difficult to administer.9 Furthermore, they are not approved by the US Food and Drug Administration or commercially available in the United States, with only sodium stibogluconate available through the CDC.6



Miltefosine is becoming a more common treatment of leishmaniasis because of its oral route, tolerability in nonpregnant patients, and commercial availability. It was approved by the US Food and Drug Administration in 2014 for cutaneous leishmaniasis due to L braziliensis, L panamensis, and Leishmania guyanensis; mucosal leishmaniasis due to L braziliensis; and visceral leishmaniasis due to Leishmania donovani in patients at least 12 years of age. For cutaneous leishmaniasis, the standard dosage of 50 mg twice daily (for patients weighing 30–44 kg) or 3 times daily (for patients weighing 45 kg or more) for 28 consecutive days has cure rates of 48% to 85% by 6 months after therapy ends. Cure is defined as epithelialization of lesions, no enlargement greater than 50% in lesions, no appearance of new lesions, and/or negative parasitology. The antileishmanial mechanism of action is unknown and likely involves interaction with lipids, inhibition of cytochrome c oxidase, and apoptosislike cell death. Miltefosine is contraindicated in pregnancy. The most common adverse reactions in patients include nausea (35.9%–41.7%), motion sickness (29.2%), headache (28.1%), and emesis (4.5%–27.5%). With the exception of headache, these adverse reactions can decrease with administration of food, fluids, and antiemetics. Potentially more serious but rarer adverse reactions include elevated serum creatinine (5%–25%) and transaminases (5%). Although our patients had mild hyperkalemia, it is not an established adverse reaction. However, renal injury has been reported.10

Conclusion

Cutaneous leishmaniasis is increasing in prevalence in the United States due to increased foreign travel. Providers should be familiar with the cutaneous presentation of leishmaniasis, even in areas of low prevalence, to limit the risk for mucocutaneous dissemination from infection with the subgenus Viannia. Prompt treatment is vital to ensuring the best prognosis, and first-line treatment with miltefosine should be strongly considered given its efficacy and tolerability.

References
  1. Babuadze G, Alvar J, Argaw D, et al. Epidemiology of visceral leishmaniasis in Georgia. PLoS Negl Trop Dis. 2014;8:e2725.
  2. Leishmaniasis. World Health Organization website. https://www.afro.who.int/health-topics/Leishmaniasis. Accessed September 15, 2020.
  3. McIlwee BE, Weis SE, Hosler GA. Incidence of endemic human cutaneous leishmaniasis in the United States. JAMA Dermatol. 2018;154:1032-1039.
  4. Leishmaniasis. World Health Organization website. https://www.who.int/news-room/fact-sheets/detail/leishmaniasis. Update March 2, 2020. Accessed September 15, 2020.
  5. Centers for Disease Control and Prevention. Guidelines for DEET insect repellent use. https://www.cdc.gov/malaria/toolkit/DEET.pdf. Accessed September 20, 2020.
  6. Buescher MD, Rutledge LC, Wirtz RA, et al. The dose-persistence relationship of DEET against Aedes aegypti. Mosq News. 1983;43:364-366.
  7. Aronson N, Herwaldt BL, Libman M, et al. Diagnosis and treatment of leishmaniasis: clinical practice guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH). Clin Infect Dis. 2016;63:e202-e264.
  8. US Department of Health and Human Services. Practical guide for specimen collection and reference diagnosis of leishmaniasis. Centers for Disease Control and Prevention website. https://www.cdc.gov/parasites/leishmaniasis/resources/pdf/cdc_diagnosis_guide_leishmaniasis_2016.pdf. Accessed September 15, 2020.
  9. Visceral leishmaniasis. Drugs for Neglected Diseases Initiative website. https://www.dndi.org/diseases-projects/leishmaniasis/. Accessed September 15, 2020.
  10. Impavido Medication Guide. Food and Drug Administration Web site. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/204684s000lbl.pdf. Revised March 2014. Accessed May 18, 2020.
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Ms. Chan is from Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire. Drs. Simmons, Call, Yan, Glass, and Chapman are from Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire. Drs. Simmons, Call, Glass, and Chapman are from the Department of Dermatology, and Dr. Yan is from the Department of Pathology and Laboratory Medicine.

The authors report no conflict of interest.

Correspondence: M. Shane Chapman, MD, 1 Medical Center Dr, Lebanon, NH 03756 ([email protected]).

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Ms. Chan is from Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire. Drs. Simmons, Call, Yan, Glass, and Chapman are from Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire. Drs. Simmons, Call, Glass, and Chapman are from the Department of Dermatology, and Dr. Yan is from the Department of Pathology and Laboratory Medicine.

The authors report no conflict of interest.

Correspondence: M. Shane Chapman, MD, 1 Medical Center Dr, Lebanon, NH 03756 ([email protected]).

Author and Disclosure Information

Ms. Chan is from Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire. Drs. Simmons, Call, Yan, Glass, and Chapman are from Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire. Drs. Simmons, Call, Glass, and Chapman are from the Department of Dermatology, and Dr. Yan is from the Department of Pathology and Laboratory Medicine.

The authors report no conflict of interest.

Correspondence: M. Shane Chapman, MD, 1 Medical Center Dr, Lebanon, NH 03756 ([email protected]).

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Leishmaniasis is a neglected parasitic disease with an estimated annual incidence of 1.3 million cases, the majority of which manifest as cutaneous leishmaniasis.1 The cutaneous and mucosal forms demonstrate substantial global burden with morbidity and socioeconomic repercussions, while the visceral form is responsible for up to 30,000 deaths annually.2 Despite increasing prevalence in the United States, awareness and diagnosis remain relatively low.3 We describe 2 cases of cutaneous leishmaniasis in New England, United States, in travelers returning from Central America, both successfully treated with miltefosine. We also review prevention, diagnosis, and treatment options.

Case Reports

Patient 1
A 47-year-old woman presented with an enlarging, 2-cm, erythematous, ulcerated nodule on the right dorsal hand of 2 weeks’ duration with accompanying right epitrochlear lymphadenopathy (Figure 1A). She noticed the lesion 10 weeks after returning from Panama, where she had been photographing the jungle. Prior to the initial presentation to dermatology, salicylic acid wart remover, intramuscular ceftriaxone, and oral trimethoprim had failed to alleviate the lesion. Her laboratory results were notable for an elevated C-reactive protein level of 5.4 mg/L (reference range, ≤4.9 mg/L). A punch biopsy demonstrated pseudoepitheliomatous hyperplasia with diffuse dermal lymphohistiocytic inflammation and small intracytoplasmic structures within histiocytes consistent with leishmaniasis (Figure 2). Immunohistochemistry was consistent with leishmaniasis (Figure 3), and polymerase chain reaction performed by the Centers for Disease Control and Prevention (CDC) identified the pathogen as Leishmania braziliensis.

Figure 1. A and B, An erythematous ulcerated nodule on the right dorsal hand in patient 1 at presentation and after almost 3 months of miltefosine treatment, respectively.

Figure 2. Diffuse dermal mixed infiltrate and intracytoplasmic amastigotes demonstrating a marquee sign in patient 1 (H&E, original magnification ×40). 

Figure 3. Positive immunohistochemistry with polyclonal anti-CAIN antibodies to leishmaniasis in patient 1 (original magnification ×40).

Patient 2
An 18-year-old man presented with an enlarging, well-delineated, tender ulcer of 6 weeks’ duration measuring 2.5×2 cm with an erythematous and edematous border on the right medial forearm with associated epitrochlear lymphadenopathy (Figure 4). Nine weeks prior to initial presentation, he had returned from a 3-month outdoor adventure trip to the Florida Keys, Costa Rica, and Panama. He had used bug repellent intermittently, slept under a bug net, and did not recall any trauma or bite at the ulcer site. Biopsy and tissue culture were obtained, and histopathology demonstrated an ulcer with a dense dermal lymphogranulomatous infiltrate and intracytoplasmic organisms consistent with leishmaniasis. Polymerase chain reaction by the CDC identified the pathogen as Leishmania panamensis.

Figure  4. A and B, A well-demarcated tender ulcer on the right medial forearm in patient 2 at presentation and after 2 months of miltefosine treatment, respectively.


Treatment
Both patients were prescribed oral miltefosine 50 mg twice daily for 28 days. Patient 1 initiated treatment 1 month after lesion onset, and patient 2 initiated treatment 2.5 months after initial presentation. Both patients had noticeable clinical improvement within 21 days of starting treatment, with lesions diminishing in size and lymphadenopathy resolving. Within 2 months of treatment, patient 1’s ulcer completely resolved with only postinflammatory hyperpigmentation (Figure 1B), while patient 2’s ulcer was noticeably smaller and shallower compared with its peak size of 4.2×2.4 cm (Figure 4B). Miltefosine was well tolerated by both patients; emesis resolved with ondansetron in patient 1 and spontaneously in patient 2, who had asymptomatic temporary hyperkalemia of 5.2 mmol/L (reference range, 3.5–5.0 mmol/L).

Comment

Epidemiology and Prevention
Risk factors for leishmaniasis include weak immunity, poverty, poor housing, poor sanitation, malnutrition, urbanization, climate change, and human migration.4 Our patients were most directly affected by travel to locations where leishmaniasis is endemic. Despite an increasing prevalence of endemic leishmaniasis and new animal hosts in the southern United States, most patients diagnosed in the United States are infected abroad by Leishmania mexicana and L braziliensis, both cutaneous New World species.3 Our patients were infected by species within the New World subgenus Viannia that have potential for mucocutaneous spread.4

Because there is no chemoprophylaxis or acquired active immunity such as vaccines that can mitigate the risk for leishmaniasis, public health efforts focus on preventive measures. Although difficult to achieve, avoidance of the phlebotomine sand fly species that transmit the obligate intracellular Leishmania parasite is a most effective measure.4 Travelers entering geographic regions with higher risk for leishmaniasis should be aware of the inherent risk and determine which methods of prevention, such as N,N-diethyl-meta-toluamide (DEET) insecticides or permethrin-treated protective clothing, are most feasible. Although higher concentrations of DEET provide longer protection, the effectiveness tends to plateau at approximately 50%.5

 

 



Presentation and Prognosis
For patients who develop leishmaniasis, the disease course and prognosis depend greatly on the species and manifestation. The most common form of leishmaniasis is localized cutaneous leishmaniasis, which has an annual incidence of up to 1 million cases. It initially presents as macules, usually at the site of inoculation within several months to years of infection.6 The macules expand into papules and plaques that reach maximum size over at least 1 week4 and then progress into crusted ulcers up to 5 cm in diameter with raised edges. Although usually painless and self-limited, these lesions can take years to spontaneously heal, with the risk for atrophic scarring and altered pigmentation. Lymphatic involvement manifests as lymphadenitis or regional lymphadenopathy and is common with lesions caused by the subgenus Viannia.6



Leishmania braziliensis and L panamensis, the species that infected our patients, can uniquely cause cutaneous leishmaniasis that metastasizes into mucocutaneous leishmaniasis, which always affects the nasal mucosa. Risk factors for transformation include a primary lesion site above the waist, multiple or large primary lesions, and delayed healing of primary cutaneous leishmaniasis. Mucocutaneous leishmaniasis can result in notable morbidity and even mortality from invasion and destruction of nasal and oropharyngeal mucosa, as well as intercurrent pneumonia, especially if treatment is insufficient or delayed.4

Diagnosis
Prompt treatment relies on accurate and timely diagnosis, which is complicated by the relative unfamiliarity with leishmaniasis in the United States. The differential diagnosis for cutaneous leishmaniasis is broad, including deep fungal infection, Mycobacterium infection, cutaneous granulomatous conditions, nonmelanoma cutaneous neoplasms, and trauma. Taking a thorough patient history, including potential exposures and travels; having high clinical suspicion; and being aware of classic presentation allows for identification of leishmaniasis and subsequent stratification by manifestation.7

Diagnosis is made by detecting Leishmania organisms or DNA using light microscopy and staining to visualize the kinetoplast in an amastigote, molecular methods, or specialized culturing.7 The CDC is a valuable diagnostic partner for confirmation and speciation. Specific instructions for specimen collection and transportation can be found by contacting the CDC or reading their guide.8 To provide prompt care and reassurance to patients, it is important to be aware of the coordination effort that may be needed to send samples, receive results, and otherwise correspond with a separate institution.

Treatment
Treatment of cutaneous leishmaniasis is indicated to decrease the risk for mucosal dissemination and clinical reactivation of lesions, accelerate healing of lesions, decrease local morbidity caused by large or persistent lesions, and decrease the reservoir of infection in places where infected humans serve as reservoir hosts. Oral treatments include ketoconazole, itraconazole, and fluconazole, recommended at doses ranging from 200 to 600 mg daily for at least 28 days. For severe, refractory, or visceral leishmaniasis, parenteral choices include pentavalent antimonials, amphotericin B deoxycholate, and pentamidine isethionate, each with known toxicity or limited data on efficacy.6 Pentavalent antimonials can cause life-threatening cardiotoxicity and are more difficult to administer.9 Furthermore, they are not approved by the US Food and Drug Administration or commercially available in the United States, with only sodium stibogluconate available through the CDC.6



Miltefosine is becoming a more common treatment of leishmaniasis because of its oral route, tolerability in nonpregnant patients, and commercial availability. It was approved by the US Food and Drug Administration in 2014 for cutaneous leishmaniasis due to L braziliensis, L panamensis, and Leishmania guyanensis; mucosal leishmaniasis due to L braziliensis; and visceral leishmaniasis due to Leishmania donovani in patients at least 12 years of age. For cutaneous leishmaniasis, the standard dosage of 50 mg twice daily (for patients weighing 30–44 kg) or 3 times daily (for patients weighing 45 kg or more) for 28 consecutive days has cure rates of 48% to 85% by 6 months after therapy ends. Cure is defined as epithelialization of lesions, no enlargement greater than 50% in lesions, no appearance of new lesions, and/or negative parasitology. The antileishmanial mechanism of action is unknown and likely involves interaction with lipids, inhibition of cytochrome c oxidase, and apoptosislike cell death. Miltefosine is contraindicated in pregnancy. The most common adverse reactions in patients include nausea (35.9%–41.7%), motion sickness (29.2%), headache (28.1%), and emesis (4.5%–27.5%). With the exception of headache, these adverse reactions can decrease with administration of food, fluids, and antiemetics. Potentially more serious but rarer adverse reactions include elevated serum creatinine (5%–25%) and transaminases (5%). Although our patients had mild hyperkalemia, it is not an established adverse reaction. However, renal injury has been reported.10

Conclusion

Cutaneous leishmaniasis is increasing in prevalence in the United States due to increased foreign travel. Providers should be familiar with the cutaneous presentation of leishmaniasis, even in areas of low prevalence, to limit the risk for mucocutaneous dissemination from infection with the subgenus Viannia. Prompt treatment is vital to ensuring the best prognosis, and first-line treatment with miltefosine should be strongly considered given its efficacy and tolerability.

Leishmaniasis is a neglected parasitic disease with an estimated annual incidence of 1.3 million cases, the majority of which manifest as cutaneous leishmaniasis.1 The cutaneous and mucosal forms demonstrate substantial global burden with morbidity and socioeconomic repercussions, while the visceral form is responsible for up to 30,000 deaths annually.2 Despite increasing prevalence in the United States, awareness and diagnosis remain relatively low.3 We describe 2 cases of cutaneous leishmaniasis in New England, United States, in travelers returning from Central America, both successfully treated with miltefosine. We also review prevention, diagnosis, and treatment options.

Case Reports

Patient 1
A 47-year-old woman presented with an enlarging, 2-cm, erythematous, ulcerated nodule on the right dorsal hand of 2 weeks’ duration with accompanying right epitrochlear lymphadenopathy (Figure 1A). She noticed the lesion 10 weeks after returning from Panama, where she had been photographing the jungle. Prior to the initial presentation to dermatology, salicylic acid wart remover, intramuscular ceftriaxone, and oral trimethoprim had failed to alleviate the lesion. Her laboratory results were notable for an elevated C-reactive protein level of 5.4 mg/L (reference range, ≤4.9 mg/L). A punch biopsy demonstrated pseudoepitheliomatous hyperplasia with diffuse dermal lymphohistiocytic inflammation and small intracytoplasmic structures within histiocytes consistent with leishmaniasis (Figure 2). Immunohistochemistry was consistent with leishmaniasis (Figure 3), and polymerase chain reaction performed by the Centers for Disease Control and Prevention (CDC) identified the pathogen as Leishmania braziliensis.

Figure 1. A and B, An erythematous ulcerated nodule on the right dorsal hand in patient 1 at presentation and after almost 3 months of miltefosine treatment, respectively.

Figure 2. Diffuse dermal mixed infiltrate and intracytoplasmic amastigotes demonstrating a marquee sign in patient 1 (H&E, original magnification ×40). 

Figure 3. Positive immunohistochemistry with polyclonal anti-CAIN antibodies to leishmaniasis in patient 1 (original magnification ×40).

Patient 2
An 18-year-old man presented with an enlarging, well-delineated, tender ulcer of 6 weeks’ duration measuring 2.5×2 cm with an erythematous and edematous border on the right medial forearm with associated epitrochlear lymphadenopathy (Figure 4). Nine weeks prior to initial presentation, he had returned from a 3-month outdoor adventure trip to the Florida Keys, Costa Rica, and Panama. He had used bug repellent intermittently, slept under a bug net, and did not recall any trauma or bite at the ulcer site. Biopsy and tissue culture were obtained, and histopathology demonstrated an ulcer with a dense dermal lymphogranulomatous infiltrate and intracytoplasmic organisms consistent with leishmaniasis. Polymerase chain reaction by the CDC identified the pathogen as Leishmania panamensis.

Figure  4. A and B, A well-demarcated tender ulcer on the right medial forearm in patient 2 at presentation and after 2 months of miltefosine treatment, respectively.


Treatment
Both patients were prescribed oral miltefosine 50 mg twice daily for 28 days. Patient 1 initiated treatment 1 month after lesion onset, and patient 2 initiated treatment 2.5 months after initial presentation. Both patients had noticeable clinical improvement within 21 days of starting treatment, with lesions diminishing in size and lymphadenopathy resolving. Within 2 months of treatment, patient 1’s ulcer completely resolved with only postinflammatory hyperpigmentation (Figure 1B), while patient 2’s ulcer was noticeably smaller and shallower compared with its peak size of 4.2×2.4 cm (Figure 4B). Miltefosine was well tolerated by both patients; emesis resolved with ondansetron in patient 1 and spontaneously in patient 2, who had asymptomatic temporary hyperkalemia of 5.2 mmol/L (reference range, 3.5–5.0 mmol/L).

Comment

Epidemiology and Prevention
Risk factors for leishmaniasis include weak immunity, poverty, poor housing, poor sanitation, malnutrition, urbanization, climate change, and human migration.4 Our patients were most directly affected by travel to locations where leishmaniasis is endemic. Despite an increasing prevalence of endemic leishmaniasis and new animal hosts in the southern United States, most patients diagnosed in the United States are infected abroad by Leishmania mexicana and L braziliensis, both cutaneous New World species.3 Our patients were infected by species within the New World subgenus Viannia that have potential for mucocutaneous spread.4

Because there is no chemoprophylaxis or acquired active immunity such as vaccines that can mitigate the risk for leishmaniasis, public health efforts focus on preventive measures. Although difficult to achieve, avoidance of the phlebotomine sand fly species that transmit the obligate intracellular Leishmania parasite is a most effective measure.4 Travelers entering geographic regions with higher risk for leishmaniasis should be aware of the inherent risk and determine which methods of prevention, such as N,N-diethyl-meta-toluamide (DEET) insecticides or permethrin-treated protective clothing, are most feasible. Although higher concentrations of DEET provide longer protection, the effectiveness tends to plateau at approximately 50%.5

 

 



Presentation and Prognosis
For patients who develop leishmaniasis, the disease course and prognosis depend greatly on the species and manifestation. The most common form of leishmaniasis is localized cutaneous leishmaniasis, which has an annual incidence of up to 1 million cases. It initially presents as macules, usually at the site of inoculation within several months to years of infection.6 The macules expand into papules and plaques that reach maximum size over at least 1 week4 and then progress into crusted ulcers up to 5 cm in diameter with raised edges. Although usually painless and self-limited, these lesions can take years to spontaneously heal, with the risk for atrophic scarring and altered pigmentation. Lymphatic involvement manifests as lymphadenitis or regional lymphadenopathy and is common with lesions caused by the subgenus Viannia.6



Leishmania braziliensis and L panamensis, the species that infected our patients, can uniquely cause cutaneous leishmaniasis that metastasizes into mucocutaneous leishmaniasis, which always affects the nasal mucosa. Risk factors for transformation include a primary lesion site above the waist, multiple or large primary lesions, and delayed healing of primary cutaneous leishmaniasis. Mucocutaneous leishmaniasis can result in notable morbidity and even mortality from invasion and destruction of nasal and oropharyngeal mucosa, as well as intercurrent pneumonia, especially if treatment is insufficient or delayed.4

Diagnosis
Prompt treatment relies on accurate and timely diagnosis, which is complicated by the relative unfamiliarity with leishmaniasis in the United States. The differential diagnosis for cutaneous leishmaniasis is broad, including deep fungal infection, Mycobacterium infection, cutaneous granulomatous conditions, nonmelanoma cutaneous neoplasms, and trauma. Taking a thorough patient history, including potential exposures and travels; having high clinical suspicion; and being aware of classic presentation allows for identification of leishmaniasis and subsequent stratification by manifestation.7

Diagnosis is made by detecting Leishmania organisms or DNA using light microscopy and staining to visualize the kinetoplast in an amastigote, molecular methods, or specialized culturing.7 The CDC is a valuable diagnostic partner for confirmation and speciation. Specific instructions for specimen collection and transportation can be found by contacting the CDC or reading their guide.8 To provide prompt care and reassurance to patients, it is important to be aware of the coordination effort that may be needed to send samples, receive results, and otherwise correspond with a separate institution.

Treatment
Treatment of cutaneous leishmaniasis is indicated to decrease the risk for mucosal dissemination and clinical reactivation of lesions, accelerate healing of lesions, decrease local morbidity caused by large or persistent lesions, and decrease the reservoir of infection in places where infected humans serve as reservoir hosts. Oral treatments include ketoconazole, itraconazole, and fluconazole, recommended at doses ranging from 200 to 600 mg daily for at least 28 days. For severe, refractory, or visceral leishmaniasis, parenteral choices include pentavalent antimonials, amphotericin B deoxycholate, and pentamidine isethionate, each with known toxicity or limited data on efficacy.6 Pentavalent antimonials can cause life-threatening cardiotoxicity and are more difficult to administer.9 Furthermore, they are not approved by the US Food and Drug Administration or commercially available in the United States, with only sodium stibogluconate available through the CDC.6



Miltefosine is becoming a more common treatment of leishmaniasis because of its oral route, tolerability in nonpregnant patients, and commercial availability. It was approved by the US Food and Drug Administration in 2014 for cutaneous leishmaniasis due to L braziliensis, L panamensis, and Leishmania guyanensis; mucosal leishmaniasis due to L braziliensis; and visceral leishmaniasis due to Leishmania donovani in patients at least 12 years of age. For cutaneous leishmaniasis, the standard dosage of 50 mg twice daily (for patients weighing 30–44 kg) or 3 times daily (for patients weighing 45 kg or more) for 28 consecutive days has cure rates of 48% to 85% by 6 months after therapy ends. Cure is defined as epithelialization of lesions, no enlargement greater than 50% in lesions, no appearance of new lesions, and/or negative parasitology. The antileishmanial mechanism of action is unknown and likely involves interaction with lipids, inhibition of cytochrome c oxidase, and apoptosislike cell death. Miltefosine is contraindicated in pregnancy. The most common adverse reactions in patients include nausea (35.9%–41.7%), motion sickness (29.2%), headache (28.1%), and emesis (4.5%–27.5%). With the exception of headache, these adverse reactions can decrease with administration of food, fluids, and antiemetics. Potentially more serious but rarer adverse reactions include elevated serum creatinine (5%–25%) and transaminases (5%). Although our patients had mild hyperkalemia, it is not an established adverse reaction. However, renal injury has been reported.10

Conclusion

Cutaneous leishmaniasis is increasing in prevalence in the United States due to increased foreign travel. Providers should be familiar with the cutaneous presentation of leishmaniasis, even in areas of low prevalence, to limit the risk for mucocutaneous dissemination from infection with the subgenus Viannia. Prompt treatment is vital to ensuring the best prognosis, and first-line treatment with miltefosine should be strongly considered given its efficacy and tolerability.

References
  1. Babuadze G, Alvar J, Argaw D, et al. Epidemiology of visceral leishmaniasis in Georgia. PLoS Negl Trop Dis. 2014;8:e2725.
  2. Leishmaniasis. World Health Organization website. https://www.afro.who.int/health-topics/Leishmaniasis. Accessed September 15, 2020.
  3. McIlwee BE, Weis SE, Hosler GA. Incidence of endemic human cutaneous leishmaniasis in the United States. JAMA Dermatol. 2018;154:1032-1039.
  4. Leishmaniasis. World Health Organization website. https://www.who.int/news-room/fact-sheets/detail/leishmaniasis. Update March 2, 2020. Accessed September 15, 2020.
  5. Centers for Disease Control and Prevention. Guidelines for DEET insect repellent use. https://www.cdc.gov/malaria/toolkit/DEET.pdf. Accessed September 20, 2020.
  6. Buescher MD, Rutledge LC, Wirtz RA, et al. The dose-persistence relationship of DEET against Aedes aegypti. Mosq News. 1983;43:364-366.
  7. Aronson N, Herwaldt BL, Libman M, et al. Diagnosis and treatment of leishmaniasis: clinical practice guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH). Clin Infect Dis. 2016;63:e202-e264.
  8. US Department of Health and Human Services. Practical guide for specimen collection and reference diagnosis of leishmaniasis. Centers for Disease Control and Prevention website. https://www.cdc.gov/parasites/leishmaniasis/resources/pdf/cdc_diagnosis_guide_leishmaniasis_2016.pdf. Accessed September 15, 2020.
  9. Visceral leishmaniasis. Drugs for Neglected Diseases Initiative website. https://www.dndi.org/diseases-projects/leishmaniasis/. Accessed September 15, 2020.
  10. Impavido Medication Guide. Food and Drug Administration Web site. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/204684s000lbl.pdf. Revised March 2014. Accessed May 18, 2020.
References
  1. Babuadze G, Alvar J, Argaw D, et al. Epidemiology of visceral leishmaniasis in Georgia. PLoS Negl Trop Dis. 2014;8:e2725.
  2. Leishmaniasis. World Health Organization website. https://www.afro.who.int/health-topics/Leishmaniasis. Accessed September 15, 2020.
  3. McIlwee BE, Weis SE, Hosler GA. Incidence of endemic human cutaneous leishmaniasis in the United States. JAMA Dermatol. 2018;154:1032-1039.
  4. Leishmaniasis. World Health Organization website. https://www.who.int/news-room/fact-sheets/detail/leishmaniasis. Update March 2, 2020. Accessed September 15, 2020.
  5. Centers for Disease Control and Prevention. Guidelines for DEET insect repellent use. https://www.cdc.gov/malaria/toolkit/DEET.pdf. Accessed September 20, 2020.
  6. Buescher MD, Rutledge LC, Wirtz RA, et al. The dose-persistence relationship of DEET against Aedes aegypti. Mosq News. 1983;43:364-366.
  7. Aronson N, Herwaldt BL, Libman M, et al. Diagnosis and treatment of leishmaniasis: clinical practice guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH). Clin Infect Dis. 2016;63:e202-e264.
  8. US Department of Health and Human Services. Practical guide for specimen collection and reference diagnosis of leishmaniasis. Centers for Disease Control and Prevention website. https://www.cdc.gov/parasites/leishmaniasis/resources/pdf/cdc_diagnosis_guide_leishmaniasis_2016.pdf. Accessed September 15, 2020.
  9. Visceral leishmaniasis. Drugs for Neglected Diseases Initiative website. https://www.dndi.org/diseases-projects/leishmaniasis/. Accessed September 15, 2020.
  10. Impavido Medication Guide. Food and Drug Administration Web site. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/204684s000lbl.pdf. Revised March 2014. Accessed May 18, 2020.
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Practice Points

  • Avoiding phlebotomine sand fly vector bites is the most effective way to prevent leishmaniasis.
  • Prompt diagnosis and treatment of cutaneous leishmaniasis caused by Leishmania species that have potential for mucocutaneous spread are key to limiting morbidity and mortality.
  • Partnering with the Centers for Disease Control and Prevention is critical for timely diagnosis.
  • Miltefosine should be considered as a first-line agent for cutaneous leishmaniasis given its efficacy, tolerability, and ease of administration.
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