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Serum brodalumab levels linked with treatment outcomes in patients with psoriasis

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Monitoring serum brodalumab levels may help doctors treat some patients with psoriasis more effectively, the authors of a small Danish case series report.

In a study of patients with psoriasis who had previously failed treatment with interleukin-17 receptor A inhibitor therapy, “all patients with quantifiable levels of brodalumab after 12 weeks of therapy experienced PASI reductions” and subquantifiable brodalumab levels were associated with a lack of response after 12 weeks, they wrote in JAMA Dermatology.

Lead study author Christian Enevold, PhD, a researcher at the Institute for Inflammation Research at Copenhagen University Hospital, and colleagues monitored patients with plaque psoriasis who had not improved with previous IL-17A inhibitor therapy, to evaluate whether trough levels and antidrug antibodies were associated with clinical response in this group of patients.

The 20 consecutive adult patients were treated at two academic hospital dermatology clinics between 2018 and 2020 and ranged in age from 19 to 66 years; 13 were male. At baseline, their weight ranged from 59 to 182 kg (median, 103 kg), their body mass index (BMI) ranged from 20 to 50 (median, 32), and their Psoriasis Area and Severity Index (PASI) scores ranged from 7 to 26 (median, 13). All had failed treatment with at least one IL-17A inhibitor, and 90% had failed treatment with at least one tumor necrosis factor–alpha or IL-12/-23 inhibitor.

Patients stopped taking systemic psoriasis therapies for 4 weeks before entering the study, then received subcutaneous injections of 210 mg of the IL-17A inhibitor brodalumab (Siliq) at weeks 0, 1, 2, and every 2 weeks thereafter. Patients whose PASI scores did not improve at least 75% from baseline (PASI 75) after 12 weeks of brodalumab discontinued treatment and left the study, while those who maintained PASI 75 were monitored for up to 52 weeks.



The researchers used assays to compare decreases in PASI score with brodalumab levels as well as with antibrodalumab antibodies at 12 weeks, and determined the following:

  • Participants with quantifiable brodalumab levels (≥ 0.05 mcg/mL) showed a greater drop in PASI scores (median, 93%; range, 61%-100%) than those without quantifiable brodalumab levels (median, −3; range, −49% to 94%) (P = .006).
  • Four of 5 patients (80%) who did not achieve a PASI 75, compared with 3 of 14 PASI 75 responders (21%), had drug levels too low to be measured (< 0.05 mcg/mL).
  • The eight patients who did not have obesity (BMI < 30) had PASI reductions of at least 77%, and seven of the eight patients (88%) had quantifiable brodalumab levels.
  • Six of the 12 patients with obesity (BMI ≥ 30) had brodalumab levels too low to be measured. Of those, four had increased PASI after 12 weeks of treatment. For all patients with obesity with quantifiable brodalumab levels, PASI scores dropped by at least 61% after 12 weeks.
  • Five of the 12 (42%) patients with obesity versus 7 of the 8 (88%) patients without obesity had quantifiable brodalumab levels.
  • None of the seven patients (35%) with subquantifiable drug levels after 12 weeks remained PASI responders.
  • No antibrodalumab antibodies were detected in any serum samples.
 

 

The authors acknowledged that there were limitations of the study, including its retrospective design and restriction to the few available participants with a history of treatment failure.

Dr. Han
Dr. George Han

George Han, MD, PhD, associate professor of dermatology at Hofstra University, Hempstead, N.Y., said in an interview that he found the study interesting. “The authors did an admirable job looking at many factors to try to understand response to treatment in a challenging population of patients who had failed at least one, and in many cases, numerous, biologics from different classes.”

“The most interesting finding is that patients with higher BMIs had much higher rates of low-to-undetectable drug concentration,” said Dr. Han, who was not involved in the study. “This very practical finding could help patient care immediately. While it’s impractical to start performing assays of drug concentration in clinical practice, this finding certainly would guide my conversations with my heavier-set patients who have had multiple failures on previous biologics.

“I’m looking forward to further studies that explore this issue and provide better evidence-based guidance for treating patients who have experienced multi-biologic failure,” he added.

UC San Diego Health Sciences
Dr. Robert A. Dorschner

Robert A. Dorschner, MD, assistant professor of dermatology at the UC San Diego Health System, also welcomed the study’s results.

“Current psoriasis treatment is based on trial-and-error application of various biologics targeting different pathways, with initial selection frequently based on insurance preference, not patient characteristics,” he said in an interview.

“Studies like this help clinicians make more informed decisions about whether a patient may benefit from a different dose or may require a different drug, and make those decisions earlier in therapy,” he said. “This can improve patient care and decrease costs associated with prolonged treatments with ineffective drugs.”

But Dr. Dorschner, who also was not involved in the study, cautions clinicians to not draw conclusions about dose adjustments from these results. “These findings need to be verified in a larger cohort,” he advised, “and they should drive future studies with larger cohorts and prospective designs.”

“The last couple of decades have seen an explosion in the availability of biologics targeting different cytokines, with significant benefits to patients,” Dr. Dorschner explained. “However, there is a dearth of information on how to choose the right biologic for a particular patient and how to assess the benefit of dose alteration versus changing the drug target. Medicine needs more studies like this one.”

Several authors of the study report financial relationships with LEO Pharma and other pharmaceutical companies. Most authors, including Dr. Enevold, reported no relevant financial relationships. Dr. Dorschner reported no relevant financial relationships. Dr. Han reported financial relationships with pharmaceutical companies not involved in the study. The study was funded by LEO Pharma and the Danish Biotechnology Program.
 

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Monitoring serum brodalumab levels may help doctors treat some patients with psoriasis more effectively, the authors of a small Danish case series report.

In a study of patients with psoriasis who had previously failed treatment with interleukin-17 receptor A inhibitor therapy, “all patients with quantifiable levels of brodalumab after 12 weeks of therapy experienced PASI reductions” and subquantifiable brodalumab levels were associated with a lack of response after 12 weeks, they wrote in JAMA Dermatology.

Lead study author Christian Enevold, PhD, a researcher at the Institute for Inflammation Research at Copenhagen University Hospital, and colleagues monitored patients with plaque psoriasis who had not improved with previous IL-17A inhibitor therapy, to evaluate whether trough levels and antidrug antibodies were associated with clinical response in this group of patients.

The 20 consecutive adult patients were treated at two academic hospital dermatology clinics between 2018 and 2020 and ranged in age from 19 to 66 years; 13 were male. At baseline, their weight ranged from 59 to 182 kg (median, 103 kg), their body mass index (BMI) ranged from 20 to 50 (median, 32), and their Psoriasis Area and Severity Index (PASI) scores ranged from 7 to 26 (median, 13). All had failed treatment with at least one IL-17A inhibitor, and 90% had failed treatment with at least one tumor necrosis factor–alpha or IL-12/-23 inhibitor.

Patients stopped taking systemic psoriasis therapies for 4 weeks before entering the study, then received subcutaneous injections of 210 mg of the IL-17A inhibitor brodalumab (Siliq) at weeks 0, 1, 2, and every 2 weeks thereafter. Patients whose PASI scores did not improve at least 75% from baseline (PASI 75) after 12 weeks of brodalumab discontinued treatment and left the study, while those who maintained PASI 75 were monitored for up to 52 weeks.



The researchers used assays to compare decreases in PASI score with brodalumab levels as well as with antibrodalumab antibodies at 12 weeks, and determined the following:

  • Participants with quantifiable brodalumab levels (≥ 0.05 mcg/mL) showed a greater drop in PASI scores (median, 93%; range, 61%-100%) than those without quantifiable brodalumab levels (median, −3; range, −49% to 94%) (P = .006).
  • Four of 5 patients (80%) who did not achieve a PASI 75, compared with 3 of 14 PASI 75 responders (21%), had drug levels too low to be measured (< 0.05 mcg/mL).
  • The eight patients who did not have obesity (BMI < 30) had PASI reductions of at least 77%, and seven of the eight patients (88%) had quantifiable brodalumab levels.
  • Six of the 12 patients with obesity (BMI ≥ 30) had brodalumab levels too low to be measured. Of those, four had increased PASI after 12 weeks of treatment. For all patients with obesity with quantifiable brodalumab levels, PASI scores dropped by at least 61% after 12 weeks.
  • Five of the 12 (42%) patients with obesity versus 7 of the 8 (88%) patients without obesity had quantifiable brodalumab levels.
  • None of the seven patients (35%) with subquantifiable drug levels after 12 weeks remained PASI responders.
  • No antibrodalumab antibodies were detected in any serum samples.
 

 

The authors acknowledged that there were limitations of the study, including its retrospective design and restriction to the few available participants with a history of treatment failure.

Dr. Han
Dr. George Han

George Han, MD, PhD, associate professor of dermatology at Hofstra University, Hempstead, N.Y., said in an interview that he found the study interesting. “The authors did an admirable job looking at many factors to try to understand response to treatment in a challenging population of patients who had failed at least one, and in many cases, numerous, biologics from different classes.”

“The most interesting finding is that patients with higher BMIs had much higher rates of low-to-undetectable drug concentration,” said Dr. Han, who was not involved in the study. “This very practical finding could help patient care immediately. While it’s impractical to start performing assays of drug concentration in clinical practice, this finding certainly would guide my conversations with my heavier-set patients who have had multiple failures on previous biologics.

“I’m looking forward to further studies that explore this issue and provide better evidence-based guidance for treating patients who have experienced multi-biologic failure,” he added.

UC San Diego Health Sciences
Dr. Robert A. Dorschner

Robert A. Dorschner, MD, assistant professor of dermatology at the UC San Diego Health System, also welcomed the study’s results.

“Current psoriasis treatment is based on trial-and-error application of various biologics targeting different pathways, with initial selection frequently based on insurance preference, not patient characteristics,” he said in an interview.

“Studies like this help clinicians make more informed decisions about whether a patient may benefit from a different dose or may require a different drug, and make those decisions earlier in therapy,” he said. “This can improve patient care and decrease costs associated with prolonged treatments with ineffective drugs.”

But Dr. Dorschner, who also was not involved in the study, cautions clinicians to not draw conclusions about dose adjustments from these results. “These findings need to be verified in a larger cohort,” he advised, “and they should drive future studies with larger cohorts and prospective designs.”

“The last couple of decades have seen an explosion in the availability of biologics targeting different cytokines, with significant benefits to patients,” Dr. Dorschner explained. “However, there is a dearth of information on how to choose the right biologic for a particular patient and how to assess the benefit of dose alteration versus changing the drug target. Medicine needs more studies like this one.”

Several authors of the study report financial relationships with LEO Pharma and other pharmaceutical companies. Most authors, including Dr. Enevold, reported no relevant financial relationships. Dr. Dorschner reported no relevant financial relationships. Dr. Han reported financial relationships with pharmaceutical companies not involved in the study. The study was funded by LEO Pharma and the Danish Biotechnology Program.
 

Monitoring serum brodalumab levels may help doctors treat some patients with psoriasis more effectively, the authors of a small Danish case series report.

In a study of patients with psoriasis who had previously failed treatment with interleukin-17 receptor A inhibitor therapy, “all patients with quantifiable levels of brodalumab after 12 weeks of therapy experienced PASI reductions” and subquantifiable brodalumab levels were associated with a lack of response after 12 weeks, they wrote in JAMA Dermatology.

Lead study author Christian Enevold, PhD, a researcher at the Institute for Inflammation Research at Copenhagen University Hospital, and colleagues monitored patients with plaque psoriasis who had not improved with previous IL-17A inhibitor therapy, to evaluate whether trough levels and antidrug antibodies were associated with clinical response in this group of patients.

The 20 consecutive adult patients were treated at two academic hospital dermatology clinics between 2018 and 2020 and ranged in age from 19 to 66 years; 13 were male. At baseline, their weight ranged from 59 to 182 kg (median, 103 kg), their body mass index (BMI) ranged from 20 to 50 (median, 32), and their Psoriasis Area and Severity Index (PASI) scores ranged from 7 to 26 (median, 13). All had failed treatment with at least one IL-17A inhibitor, and 90% had failed treatment with at least one tumor necrosis factor–alpha or IL-12/-23 inhibitor.

Patients stopped taking systemic psoriasis therapies for 4 weeks before entering the study, then received subcutaneous injections of 210 mg of the IL-17A inhibitor brodalumab (Siliq) at weeks 0, 1, 2, and every 2 weeks thereafter. Patients whose PASI scores did not improve at least 75% from baseline (PASI 75) after 12 weeks of brodalumab discontinued treatment and left the study, while those who maintained PASI 75 were monitored for up to 52 weeks.



The researchers used assays to compare decreases in PASI score with brodalumab levels as well as with antibrodalumab antibodies at 12 weeks, and determined the following:

  • Participants with quantifiable brodalumab levels (≥ 0.05 mcg/mL) showed a greater drop in PASI scores (median, 93%; range, 61%-100%) than those without quantifiable brodalumab levels (median, −3; range, −49% to 94%) (P = .006).
  • Four of 5 patients (80%) who did not achieve a PASI 75, compared with 3 of 14 PASI 75 responders (21%), had drug levels too low to be measured (< 0.05 mcg/mL).
  • The eight patients who did not have obesity (BMI < 30) had PASI reductions of at least 77%, and seven of the eight patients (88%) had quantifiable brodalumab levels.
  • Six of the 12 patients with obesity (BMI ≥ 30) had brodalumab levels too low to be measured. Of those, four had increased PASI after 12 weeks of treatment. For all patients with obesity with quantifiable brodalumab levels, PASI scores dropped by at least 61% after 12 weeks.
  • Five of the 12 (42%) patients with obesity versus 7 of the 8 (88%) patients without obesity had quantifiable brodalumab levels.
  • None of the seven patients (35%) with subquantifiable drug levels after 12 weeks remained PASI responders.
  • No antibrodalumab antibodies were detected in any serum samples.
 

 

The authors acknowledged that there were limitations of the study, including its retrospective design and restriction to the few available participants with a history of treatment failure.

Dr. Han
Dr. George Han

George Han, MD, PhD, associate professor of dermatology at Hofstra University, Hempstead, N.Y., said in an interview that he found the study interesting. “The authors did an admirable job looking at many factors to try to understand response to treatment in a challenging population of patients who had failed at least one, and in many cases, numerous, biologics from different classes.”

“The most interesting finding is that patients with higher BMIs had much higher rates of low-to-undetectable drug concentration,” said Dr. Han, who was not involved in the study. “This very practical finding could help patient care immediately. While it’s impractical to start performing assays of drug concentration in clinical practice, this finding certainly would guide my conversations with my heavier-set patients who have had multiple failures on previous biologics.

“I’m looking forward to further studies that explore this issue and provide better evidence-based guidance for treating patients who have experienced multi-biologic failure,” he added.

UC San Diego Health Sciences
Dr. Robert A. Dorschner

Robert A. Dorschner, MD, assistant professor of dermatology at the UC San Diego Health System, also welcomed the study’s results.

“Current psoriasis treatment is based on trial-and-error application of various biologics targeting different pathways, with initial selection frequently based on insurance preference, not patient characteristics,” he said in an interview.

“Studies like this help clinicians make more informed decisions about whether a patient may benefit from a different dose or may require a different drug, and make those decisions earlier in therapy,” he said. “This can improve patient care and decrease costs associated with prolonged treatments with ineffective drugs.”

But Dr. Dorschner, who also was not involved in the study, cautions clinicians to not draw conclusions about dose adjustments from these results. “These findings need to be verified in a larger cohort,” he advised, “and they should drive future studies with larger cohorts and prospective designs.”

“The last couple of decades have seen an explosion in the availability of biologics targeting different cytokines, with significant benefits to patients,” Dr. Dorschner explained. “However, there is a dearth of information on how to choose the right biologic for a particular patient and how to assess the benefit of dose alteration versus changing the drug target. Medicine needs more studies like this one.”

Several authors of the study report financial relationships with LEO Pharma and other pharmaceutical companies. Most authors, including Dr. Enevold, reported no relevant financial relationships. Dr. Dorschner reported no relevant financial relationships. Dr. Han reported financial relationships with pharmaceutical companies not involved in the study. The study was funded by LEO Pharma and the Danish Biotechnology Program.
 

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Today’s medical oxymoron: Healthy overconfidence

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Thu, 06/02/2022 - 09:33

 

Doctor, doctor, gimme the news. I got a bad case of knowing better than you

Stop us if you’ve heard this before. One of your parents (let’s be honest, probably your ornery father) refuses to go to the doctor. You tell him it’s for the best, but in his words, “Doctors don’t know nothin’. I’m fine.” How many TV shows with grumpy fathers feature this exact plot in an episode as the frustrated child attempts increasingly convoluted traps to encourage the stubborn parent to get himself to the doctor?

rudall30/iStockphoto.com

As is so often the case, wacky sitcoms reflect reality, according to a new study from the Journal of the Economics of Aging. In a massive survey of 80,000 Europeans aged 50 years and older, the researchers found that individuals who were overconfident and rated their health as better than it actually was visited their doctor 17% less often than did those who correctly judge their own health. Fewer medical visits leaves them more vulnerable to chronic disease, since they’re not getting the preventive care they need to catch illnesses early.

Perhaps unsurprisingly, the inverse is also true: People who underestimate their health status visit the doctor 21% more often. On the one hand, regular visits to the doctor are a good thing, as is awareness of how healthy one really is. On the other hand, though, extra visits cost money and time, especially relevant in an aging society with high public health costs.

Nobody likes visiting the doctor, but it is kind of important, especially as we age and our bodies start to let us down. Confidence is fine, but don’t be overly confident. And if you do go, don’t be like a certain former president of the United States. Don’t pay a sycophant to look in your general direction and then declare that you are in very good (great!) condition on Twitter. That’s not how medicine is meant to work.
 

Your liver stays toddler age

Rapid cell regeneration might seem like something straight out of a sci-fi novel, but it happens to your liver all the time. So much so that the human liver is never a day over 3 years old.

Peter Gridley/Getty Images

How’s that possible? The liver deals with a lot of toxic substances in its job as the Brita filter of the human body, so it has a unique capacity among organs to regenerate itself after damage.

Dr. Olaf Bergmann and his team at Technical University Dresden’s (Germany) Center for Regenerative Therapies used retrospective radiocarbon birth dating to determine the age of the livers of a group of people who died at the ages of 20-84 years. The results were the same regardless of age.

This information could be a complete game changer for understanding cell regeneration. It’s important in determining cancer cell formation in the liver but also if new heart muscle cells can be generated in people with cardiovascular disease, which the researchers are looking into.

So sure, your liver may be totally capable of filtering those drinks at happy hour, but as old as it is, a juice box might be more appropriate.
 

 

 

To bee, or not to bee? That is the vacation

Sleeping is pretty important for humans, no doubt about that, so anything that improves sleep is worth considering, right? But how far would you go for a good night’s sleep? Would you be willing to travel to Italy to experience the ultimate white-noise generator?

Airbnb

For more on this exciting, yet also sleep-inducing, news story, let’s go to the village of Grottole in southern Italy, where we meet bee keeper and Airbnb host Rocco Filomeno. ”This is the first place in the world where you can sleep immersed in the distinctive sound and aroma of the bees, experiencing ‘bee-therapy’ in the most authentic and natural way,” he said in a written statement for Airbnb.

Mr. Filomeno worked with local NGO Wonder Grottole and a self-build specialist to take the next step in tiny-house evolution. The resulting structure cost just $17,000 – crowdfunded, of course, and built by 25 local bee-lievers (aka volunteers) – and consists of a single room surrounded by nine apiaries, which contain a combined total of 1 million working bees. It is now available to book on Airbnb, and guests “will receive their first lesson on bees and how to live with them,” Airbnb said.

The immersion in bee sound/scent is fully realized through the building’s most prominent interior feature, a screened box in the ceiling with a working hive that allows guests to see the bees and fall asleep to the “gently humming sound,” Airbnb explained. The sound from the hive is said to have a soothing effect that “acts as salve to day-to-day stressors,” according to the BBC.

This is just the start of a trend and we want in on it. Should our tiny house feature the sights/smells/sounds of angry rattlesnakes or a swarm of locusts?
 

Joysticks can make the world a better place

Someday, it might be possible for surgeons to treat a stroke or aneurysm during the “golden hour,” even if they’re not in the same hospital as the patient. MIT engineers have created a robotic system that can be controlled remotely with a modified joystick, so the patient can go to a closer, smaller hospital and be treated by a surgeon at a larger facility through live imaging.

Xuanhe Zhao et al/MIT

Endovascular surgery seems difficult enough with the patient and doctor in the same hospital, “but having a robot twist with the same level of sophistication [as a surgeon] is challenging,” Yoonho Kim, lead author of a study in Science Robotics, said in a written statement. “Our system is based on a fundamentally different mechanism.”

It involves “a medical-grade robotic arm with a magnet attached to its wrist. With a joystick and live imaging, an operator can adjust the magnet’s orientation and manipulate the arm to guide a soft and thin magnetic wire through arteries and vessels,” MIT explained in the statement.

The system was tested using life-like models, and it took each surgeon about an hour of training to learn how to use the new joystick and other equipment. Another perk: No exposure to radiation from x-ray imaging.

If someone you know is obsessed with video games, stop thinking “slacker” and start thinking “neurosurgeon.”

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Doctor, doctor, gimme the news. I got a bad case of knowing better than you

Stop us if you’ve heard this before. One of your parents (let’s be honest, probably your ornery father) refuses to go to the doctor. You tell him it’s for the best, but in his words, “Doctors don’t know nothin’. I’m fine.” How many TV shows with grumpy fathers feature this exact plot in an episode as the frustrated child attempts increasingly convoluted traps to encourage the stubborn parent to get himself to the doctor?

rudall30/iStockphoto.com

As is so often the case, wacky sitcoms reflect reality, according to a new study from the Journal of the Economics of Aging. In a massive survey of 80,000 Europeans aged 50 years and older, the researchers found that individuals who were overconfident and rated their health as better than it actually was visited their doctor 17% less often than did those who correctly judge their own health. Fewer medical visits leaves them more vulnerable to chronic disease, since they’re not getting the preventive care they need to catch illnesses early.

Perhaps unsurprisingly, the inverse is also true: People who underestimate their health status visit the doctor 21% more often. On the one hand, regular visits to the doctor are a good thing, as is awareness of how healthy one really is. On the other hand, though, extra visits cost money and time, especially relevant in an aging society with high public health costs.

Nobody likes visiting the doctor, but it is kind of important, especially as we age and our bodies start to let us down. Confidence is fine, but don’t be overly confident. And if you do go, don’t be like a certain former president of the United States. Don’t pay a sycophant to look in your general direction and then declare that you are in very good (great!) condition on Twitter. That’s not how medicine is meant to work.
 

Your liver stays toddler age

Rapid cell regeneration might seem like something straight out of a sci-fi novel, but it happens to your liver all the time. So much so that the human liver is never a day over 3 years old.

Peter Gridley/Getty Images

How’s that possible? The liver deals with a lot of toxic substances in its job as the Brita filter of the human body, so it has a unique capacity among organs to regenerate itself after damage.

Dr. Olaf Bergmann and his team at Technical University Dresden’s (Germany) Center for Regenerative Therapies used retrospective radiocarbon birth dating to determine the age of the livers of a group of people who died at the ages of 20-84 years. The results were the same regardless of age.

This information could be a complete game changer for understanding cell regeneration. It’s important in determining cancer cell formation in the liver but also if new heart muscle cells can be generated in people with cardiovascular disease, which the researchers are looking into.

So sure, your liver may be totally capable of filtering those drinks at happy hour, but as old as it is, a juice box might be more appropriate.
 

 

 

To bee, or not to bee? That is the vacation

Sleeping is pretty important for humans, no doubt about that, so anything that improves sleep is worth considering, right? But how far would you go for a good night’s sleep? Would you be willing to travel to Italy to experience the ultimate white-noise generator?

Airbnb

For more on this exciting, yet also sleep-inducing, news story, let’s go to the village of Grottole in southern Italy, where we meet bee keeper and Airbnb host Rocco Filomeno. ”This is the first place in the world where you can sleep immersed in the distinctive sound and aroma of the bees, experiencing ‘bee-therapy’ in the most authentic and natural way,” he said in a written statement for Airbnb.

Mr. Filomeno worked with local NGO Wonder Grottole and a self-build specialist to take the next step in tiny-house evolution. The resulting structure cost just $17,000 – crowdfunded, of course, and built by 25 local bee-lievers (aka volunteers) – and consists of a single room surrounded by nine apiaries, which contain a combined total of 1 million working bees. It is now available to book on Airbnb, and guests “will receive their first lesson on bees and how to live with them,” Airbnb said.

The immersion in bee sound/scent is fully realized through the building’s most prominent interior feature, a screened box in the ceiling with a working hive that allows guests to see the bees and fall asleep to the “gently humming sound,” Airbnb explained. The sound from the hive is said to have a soothing effect that “acts as salve to day-to-day stressors,” according to the BBC.

This is just the start of a trend and we want in on it. Should our tiny house feature the sights/smells/sounds of angry rattlesnakes or a swarm of locusts?
 

Joysticks can make the world a better place

Someday, it might be possible for surgeons to treat a stroke or aneurysm during the “golden hour,” even if they’re not in the same hospital as the patient. MIT engineers have created a robotic system that can be controlled remotely with a modified joystick, so the patient can go to a closer, smaller hospital and be treated by a surgeon at a larger facility through live imaging.

Xuanhe Zhao et al/MIT

Endovascular surgery seems difficult enough with the patient and doctor in the same hospital, “but having a robot twist with the same level of sophistication [as a surgeon] is challenging,” Yoonho Kim, lead author of a study in Science Robotics, said in a written statement. “Our system is based on a fundamentally different mechanism.”

It involves “a medical-grade robotic arm with a magnet attached to its wrist. With a joystick and live imaging, an operator can adjust the magnet’s orientation and manipulate the arm to guide a soft and thin magnetic wire through arteries and vessels,” MIT explained in the statement.

The system was tested using life-like models, and it took each surgeon about an hour of training to learn how to use the new joystick and other equipment. Another perk: No exposure to radiation from x-ray imaging.

If someone you know is obsessed with video games, stop thinking “slacker” and start thinking “neurosurgeon.”

 

Doctor, doctor, gimme the news. I got a bad case of knowing better than you

Stop us if you’ve heard this before. One of your parents (let’s be honest, probably your ornery father) refuses to go to the doctor. You tell him it’s for the best, but in his words, “Doctors don’t know nothin’. I’m fine.” How many TV shows with grumpy fathers feature this exact plot in an episode as the frustrated child attempts increasingly convoluted traps to encourage the stubborn parent to get himself to the doctor?

rudall30/iStockphoto.com

As is so often the case, wacky sitcoms reflect reality, according to a new study from the Journal of the Economics of Aging. In a massive survey of 80,000 Europeans aged 50 years and older, the researchers found that individuals who were overconfident and rated their health as better than it actually was visited their doctor 17% less often than did those who correctly judge their own health. Fewer medical visits leaves them more vulnerable to chronic disease, since they’re not getting the preventive care they need to catch illnesses early.

Perhaps unsurprisingly, the inverse is also true: People who underestimate their health status visit the doctor 21% more often. On the one hand, regular visits to the doctor are a good thing, as is awareness of how healthy one really is. On the other hand, though, extra visits cost money and time, especially relevant in an aging society with high public health costs.

Nobody likes visiting the doctor, but it is kind of important, especially as we age and our bodies start to let us down. Confidence is fine, but don’t be overly confident. And if you do go, don’t be like a certain former president of the United States. Don’t pay a sycophant to look in your general direction and then declare that you are in very good (great!) condition on Twitter. That’s not how medicine is meant to work.
 

Your liver stays toddler age

Rapid cell regeneration might seem like something straight out of a sci-fi novel, but it happens to your liver all the time. So much so that the human liver is never a day over 3 years old.

Peter Gridley/Getty Images

How’s that possible? The liver deals with a lot of toxic substances in its job as the Brita filter of the human body, so it has a unique capacity among organs to regenerate itself after damage.

Dr. Olaf Bergmann and his team at Technical University Dresden’s (Germany) Center for Regenerative Therapies used retrospective radiocarbon birth dating to determine the age of the livers of a group of people who died at the ages of 20-84 years. The results were the same regardless of age.

This information could be a complete game changer for understanding cell regeneration. It’s important in determining cancer cell formation in the liver but also if new heart muscle cells can be generated in people with cardiovascular disease, which the researchers are looking into.

So sure, your liver may be totally capable of filtering those drinks at happy hour, but as old as it is, a juice box might be more appropriate.
 

 

 

To bee, or not to bee? That is the vacation

Sleeping is pretty important for humans, no doubt about that, so anything that improves sleep is worth considering, right? But how far would you go for a good night’s sleep? Would you be willing to travel to Italy to experience the ultimate white-noise generator?

Airbnb

For more on this exciting, yet also sleep-inducing, news story, let’s go to the village of Grottole in southern Italy, where we meet bee keeper and Airbnb host Rocco Filomeno. ”This is the first place in the world where you can sleep immersed in the distinctive sound and aroma of the bees, experiencing ‘bee-therapy’ in the most authentic and natural way,” he said in a written statement for Airbnb.

Mr. Filomeno worked with local NGO Wonder Grottole and a self-build specialist to take the next step in tiny-house evolution. The resulting structure cost just $17,000 – crowdfunded, of course, and built by 25 local bee-lievers (aka volunteers) – and consists of a single room surrounded by nine apiaries, which contain a combined total of 1 million working bees. It is now available to book on Airbnb, and guests “will receive their first lesson on bees and how to live with them,” Airbnb said.

The immersion in bee sound/scent is fully realized through the building’s most prominent interior feature, a screened box in the ceiling with a working hive that allows guests to see the bees and fall asleep to the “gently humming sound,” Airbnb explained. The sound from the hive is said to have a soothing effect that “acts as salve to day-to-day stressors,” according to the BBC.

This is just the start of a trend and we want in on it. Should our tiny house feature the sights/smells/sounds of angry rattlesnakes or a swarm of locusts?
 

Joysticks can make the world a better place

Someday, it might be possible for surgeons to treat a stroke or aneurysm during the “golden hour,” even if they’re not in the same hospital as the patient. MIT engineers have created a robotic system that can be controlled remotely with a modified joystick, so the patient can go to a closer, smaller hospital and be treated by a surgeon at a larger facility through live imaging.

Xuanhe Zhao et al/MIT

Endovascular surgery seems difficult enough with the patient and doctor in the same hospital, “but having a robot twist with the same level of sophistication [as a surgeon] is challenging,” Yoonho Kim, lead author of a study in Science Robotics, said in a written statement. “Our system is based on a fundamentally different mechanism.”

It involves “a medical-grade robotic arm with a magnet attached to its wrist. With a joystick and live imaging, an operator can adjust the magnet’s orientation and manipulate the arm to guide a soft and thin magnetic wire through arteries and vessels,” MIT explained in the statement.

The system was tested using life-like models, and it took each surgeon about an hour of training to learn how to use the new joystick and other equipment. Another perk: No exposure to radiation from x-ray imaging.

If someone you know is obsessed with video games, stop thinking “slacker” and start thinking “neurosurgeon.”

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Adjunctive confocal microscopy found to reduce unnecessary skin excisions

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Wed, 06/01/2022 - 11:15

Using adjunctive reflectance confocal microscopy (RCM) for examining suspect skin lesions reduced the number of unnecessary skin excisions by 43%, results from a large randomized clinical trial showed.

“Skin cancer management exerts a sizable burden on health systems,” researchers led by Giovanni Pellacani, MD, wrote in an article published in JAMA Dermatology. “The systematic application of RCM in the triage of high-risk patients should improve diagnostic accuracy and reduce unnecessary excisions for histopathological diagnostic confirmation, thereby reducing costs, surgical waiting lists, and delayed diagnoses.”

Dr. Giovanni Pellacani

However, they added, “the clinical application of RCM has mainly been limited to retrospective and prospective observational studies producing hypothetical estimates of clinical applicability without intention to affect clinical and therapeutic patient pathways.”

For the current study, Dr. Pellacani, who chairs the department of dermatology at Sapienza University, Rome, and colleagues hypothesized that RCM would reduce unnecessary excisions by more than 30% and would identify all melanoma lesions 0.5 mm or thinner at baseline. They enrolled 3,165 patients with suspect lesions from three dermatology referral centers between January 2017 and December 2019, with a mean follow-up of 9.6 months in the study. Participants were randomly assigned 1:1 to standard therapeutic care, which consisted of clinical and dermoscopy evaluation with or without adjunctive RCM, a novel noninvasive technology that provides in vivo imaging of the skin, with a high diagnostic accuracy.

Histopathologic examination of all excised lesions was performed at the pathology department of the referral center. Resulting information guided prospective clinical decision-making (excision or follow-up). The mean age of patients was 49 years, 49% were women, 21% had a personal history of melanoma, and 51% had Fitzpatrick phototype 2 skin.



When compared with standard therapeutic care only, adjunctive RCM was associated with a higher positive predictive value (18.9 vs. 33.3, respectively), lower benign to malignant ratio (3.7:1.0 vs. 1.8:1.0), and a reduction in the number needed to excise of 43.4% (5.3 vs. 3.0). In addition, all 15 lesions with delayed melanoma diagnoses were thinner than 0.5 mm. Of these, eight were diagnosed as melanoma in situ.

Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Conn., who was asked to comment on the study, said that a strength of the analysis was its follow-up and histopathologic evaluation, “which are both essentially forms of feedback. Good, relevant feedback is necessary for all of us to improve.”

She pointed out that, while RCM does appear to reduce the number of benign lesions unnecessarily removed and increase the number of skin cancers appropriately excised, the authors acknowledged that they had at least 4 years of experience with RCM. “The study also does not address the time factor (the procedure takes about 7 minutes per lesion) and the financial cost of reflectance confocal microscopy, as compared to the cost of standard follow-up alone with an increased number of excisions.”

She added that the findings “are not yet applicable to general dermatology across the world, as the authors comment, given that reflectance confocal microscopy is not yet widely available.”

The Italian Ministry of Health supported the study. Neither the researchers nor Dr. Ko reported having relevant financial conflicts.

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Using adjunctive reflectance confocal microscopy (RCM) for examining suspect skin lesions reduced the number of unnecessary skin excisions by 43%, results from a large randomized clinical trial showed.

“Skin cancer management exerts a sizable burden on health systems,” researchers led by Giovanni Pellacani, MD, wrote in an article published in JAMA Dermatology. “The systematic application of RCM in the triage of high-risk patients should improve diagnostic accuracy and reduce unnecessary excisions for histopathological diagnostic confirmation, thereby reducing costs, surgical waiting lists, and delayed diagnoses.”

Dr. Giovanni Pellacani

However, they added, “the clinical application of RCM has mainly been limited to retrospective and prospective observational studies producing hypothetical estimates of clinical applicability without intention to affect clinical and therapeutic patient pathways.”

For the current study, Dr. Pellacani, who chairs the department of dermatology at Sapienza University, Rome, and colleagues hypothesized that RCM would reduce unnecessary excisions by more than 30% and would identify all melanoma lesions 0.5 mm or thinner at baseline. They enrolled 3,165 patients with suspect lesions from three dermatology referral centers between January 2017 and December 2019, with a mean follow-up of 9.6 months in the study. Participants were randomly assigned 1:1 to standard therapeutic care, which consisted of clinical and dermoscopy evaluation with or without adjunctive RCM, a novel noninvasive technology that provides in vivo imaging of the skin, with a high diagnostic accuracy.

Histopathologic examination of all excised lesions was performed at the pathology department of the referral center. Resulting information guided prospective clinical decision-making (excision or follow-up). The mean age of patients was 49 years, 49% were women, 21% had a personal history of melanoma, and 51% had Fitzpatrick phototype 2 skin.



When compared with standard therapeutic care only, adjunctive RCM was associated with a higher positive predictive value (18.9 vs. 33.3, respectively), lower benign to malignant ratio (3.7:1.0 vs. 1.8:1.0), and a reduction in the number needed to excise of 43.4% (5.3 vs. 3.0). In addition, all 15 lesions with delayed melanoma diagnoses were thinner than 0.5 mm. Of these, eight were diagnosed as melanoma in situ.

Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Conn., who was asked to comment on the study, said that a strength of the analysis was its follow-up and histopathologic evaluation, “which are both essentially forms of feedback. Good, relevant feedback is necessary for all of us to improve.”

She pointed out that, while RCM does appear to reduce the number of benign lesions unnecessarily removed and increase the number of skin cancers appropriately excised, the authors acknowledged that they had at least 4 years of experience with RCM. “The study also does not address the time factor (the procedure takes about 7 minutes per lesion) and the financial cost of reflectance confocal microscopy, as compared to the cost of standard follow-up alone with an increased number of excisions.”

She added that the findings “are not yet applicable to general dermatology across the world, as the authors comment, given that reflectance confocal microscopy is not yet widely available.”

The Italian Ministry of Health supported the study. Neither the researchers nor Dr. Ko reported having relevant financial conflicts.

Using adjunctive reflectance confocal microscopy (RCM) for examining suspect skin lesions reduced the number of unnecessary skin excisions by 43%, results from a large randomized clinical trial showed.

“Skin cancer management exerts a sizable burden on health systems,” researchers led by Giovanni Pellacani, MD, wrote in an article published in JAMA Dermatology. “The systematic application of RCM in the triage of high-risk patients should improve diagnostic accuracy and reduce unnecessary excisions for histopathological diagnostic confirmation, thereby reducing costs, surgical waiting lists, and delayed diagnoses.”

Dr. Giovanni Pellacani

However, they added, “the clinical application of RCM has mainly been limited to retrospective and prospective observational studies producing hypothetical estimates of clinical applicability without intention to affect clinical and therapeutic patient pathways.”

For the current study, Dr. Pellacani, who chairs the department of dermatology at Sapienza University, Rome, and colleagues hypothesized that RCM would reduce unnecessary excisions by more than 30% and would identify all melanoma lesions 0.5 mm or thinner at baseline. They enrolled 3,165 patients with suspect lesions from three dermatology referral centers between January 2017 and December 2019, with a mean follow-up of 9.6 months in the study. Participants were randomly assigned 1:1 to standard therapeutic care, which consisted of clinical and dermoscopy evaluation with or without adjunctive RCM, a novel noninvasive technology that provides in vivo imaging of the skin, with a high diagnostic accuracy.

Histopathologic examination of all excised lesions was performed at the pathology department of the referral center. Resulting information guided prospective clinical decision-making (excision or follow-up). The mean age of patients was 49 years, 49% were women, 21% had a personal history of melanoma, and 51% had Fitzpatrick phototype 2 skin.



When compared with standard therapeutic care only, adjunctive RCM was associated with a higher positive predictive value (18.9 vs. 33.3, respectively), lower benign to malignant ratio (3.7:1.0 vs. 1.8:1.0), and a reduction in the number needed to excise of 43.4% (5.3 vs. 3.0). In addition, all 15 lesions with delayed melanoma diagnoses were thinner than 0.5 mm. Of these, eight were diagnosed as melanoma in situ.

Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Conn., who was asked to comment on the study, said that a strength of the analysis was its follow-up and histopathologic evaluation, “which are both essentially forms of feedback. Good, relevant feedback is necessary for all of us to improve.”

She pointed out that, while RCM does appear to reduce the number of benign lesions unnecessarily removed and increase the number of skin cancers appropriately excised, the authors acknowledged that they had at least 4 years of experience with RCM. “The study also does not address the time factor (the procedure takes about 7 minutes per lesion) and the financial cost of reflectance confocal microscopy, as compared to the cost of standard follow-up alone with an increased number of excisions.”

She added that the findings “are not yet applicable to general dermatology across the world, as the authors comment, given that reflectance confocal microscopy is not yet widely available.”

The Italian Ministry of Health supported the study. Neither the researchers nor Dr. Ko reported having relevant financial conflicts.

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Vascular Plaque in a Pregnant Patient With a History of Breast Cancer

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Display Headline
Vascular Plaque in a Pregnant Patient With a History of Breast Cancer

The Diagnosis: Tufted Angioma

Histopathology revealed discrete lobules of closely packed capillaries with bland endothelial cells throughout the upper and lower dermis (Figure 1). The surrounding crescentlike vessels and lymphatics stained with D2-40 (Figure 2). These histologic findings were consistent with tufted angioma, and the patient elected for observation.

Compressed capillaries lined by bland endothelial cells with peripherally dilated crescent-shaped lymphatic channels
FIGURE 1. Compressed capillaries lined by bland endothelial cells with peripherally dilated crescent-shaped lymphatic channels (H&E, original magnification ×200).

Tufted angiomas are benign vascular lesions named for the tufted appearance of capillaries on histology.1 They commonly present in children, with a lower incidence in adults and rare cases in pregnancy.2 Tufted angiomas typically present as solitary, slowly expanding, erythematous macules, plaques, or nodules on the neck or trunk ranging in size from less than 1 to 10 cm.2-4 They can be histologically distinguished from other vascular tumors, including aggressive malignant neoplasms.1

D2-40 immunohistochemical staining of lymphatics surrounding capillary proliferations with an absence of staining of the capillary endothelial cells
FIGURE 2. D2-40 immunohistochemical staining of lymphatics surrounding capillary proliferations with an absence of staining of the capillary endothelial cells (original magnification ×200).

Tufted angiomas are identified by characteristic “cannon ball tufts” of capillaries in the dermis and subcutis at low power.3,5 Distinct cellular lobules may be found bulging into thin-walled vascular channels at the margins of the lobules in the dermis and subcutis (Figure 3).4 The lobules are formed by cells with spindle-shaped nuclei.6 Some mitotic figures may be present, but no cellular atypia is seen.2 The capillaries at the periphery appear as dilated semilunar vessels.4 Dilated lymphatics, which stain with D2-40, can be found at the periphery of the tufted capillaries and throughout the remaining dermis.3,4

Discrete collections of closely packed capillary-sized vessels throughout the upper and lower dermis
FIGURE 3. Discrete collections of closely packed capillary-sized vessels throughout the upper and lower dermis (H&E, original magnification ×40).

Tufted angiomas may arise independently in adults but also have been associated with conditions such as pregnancy. Omori et al7 identified an acquired tufted angioma in pregnancy that was positive for estrogen and progesterone receptors. Reports of tufted angiomas in pregnancy vary; some are multiple lesions, some regress postpartum, and some undergo successful surgical treatment.3,5

Vascular lesions such as tufted angiomas specifically may appear in pregnancy due to a high-volume state with vasodilation and increased vascular proliferation. Although tumor angiogenesis has been linked to specific growth factors and cytokines, it has been hypothesized that the systemic hormones of pregnancy such as human chorionic gonadotropin, estradiol, and progesterone also shift the body to a more angiogenic state.8 In a study of cutaneous changes in pregnant women (N=905), 41% developed a vascular skin change, including spider veins, varicosities, hemangiomas, and granulomas.9 The most common vascular tumor in pregnancy is pyogenic granuloma. Pyogenic granulomas are small, solitary, friable papules that commonly are found on the hands, forearms, face, or in the mouth; histologically they demonstrate dilated capillaries in lobular structures accompanied by larger thick-walled vessels.3,10,11

Tufted angiomas may mimic a variety of other conditions. Epithelioid hemangioma, considered by some to be on the same morphologic spectrum as angiolymphoid hyperplasia with eosinophilia, classically occurs in young adults on the head and in the neck region. It histologically demonstrates a lobular appearance at low power; however, these lobules are made up of vessels with histiocytoid to epithelioid endothelial cells surrounded by a prominent inflammatory infiltrate consisting of lymphocytes and eosinophils.12

Kaposi sarcoma may appear on the neck but most often presents as macules and patches on the extremities that may form nodules with a rubbery consistency. In tufted angiomas, the cellular nodules with dilated channels at the margins bear a resemblance to Kaposi sarcoma or kaposiform hemangioendothelioma; however, in tufted angiomas the lobules are composed of bland spindle cells and slitlike vessels at the periphery.3,13,14 Tufted angiomas are negative for human herpesvirus 8 and typically do not have an associated inflammatory infiltrate with plasma cells.11,15

Moreover, it is important to differentiate tufted angioma from a cutaneous manifestation of an underlying malignancy, which has been described previously in cases of breast cancer.16,17 Our case illustrates a rare vascular tumor arising in the novel context of a pregnant patient with breast cancer. Distinguishing tufted angioma from other benign or malignant vascular tumors is necessary to avoid inappropriate therapeutic interventions.

References
  1. Jones EW, Orkin M. Tufted angioma (angioblastoma). a benign progressive angioma, not to be confused with Kaposi’s sarcoma or low-grade angiosarcoma. J Am Acad Dermatol. 1989;20(2 pt 1):214-225.
  2. Lee B, Chiu M, Soriano T, et al. Adult-onset tufted angioma: a case report and review of the literature. Cutis. 2006;78:341-345.
  3. Kim YK, Kim HJ, Lee KG. Acquired tufted angioma associated with pregnancy. Clin Exp Dermatol. 1992;17:458-459.
  4. Feito-Rodriguez M, Sanchez-Orta A, De Lucas R, et al. Congenital tufted angioma: a multicenter retrospective study of 30 cases. Pediatr Dermatol. 2018;35:808-816.
  5. Pietroletti R, Leardi S, Simi M. Perianal acquired tufted angioma associated with pregnancy: case report. Tech Coloproctol. 2002;6:117-119.
  6. Osio A, Fraitag S, Hadj-Rabia S, et al. Clinical spectrum of tufted angiomas in childhood: a report of 13 cases and a review of the literature. Arch Dermatol. 2010;146:758-763.
  7. Omori M, Bito T, Nishigori C. Acquired tufted angioma in pregnancy showing expression of estrogen and progesterone receptors. Eur J Dermatol. 2013;23:898-899.
  8. Boeldt DS, Bird IM. Vascular adaptation in pregnancy and endothelial dysfunction in preeclampsia. J Endocrinol. 2017;232:R27-R44.
  9. Fernandes LB, Amaral W. Clinical study of skin changes in low and high risk pregnant women. An Bras Dermatol. 2015;90:822-826.
  10. Walker JL, Wang AR, Kroumpouzos G, et al. Cutaneous tumors in pregnancy. Clin Dermatol. 2016;34:359-367.
  11. Sarwal P, Lapumnuaypol K. Pyogenic granuloma. In: StatPearls. StatPearls Publishing; 2021.
  12. Ortins-Pina A, Llamas-Velasco M, Turpin S, et al. FOSB immunoreactivity in endothelia of epithelioid hemangioma (angiolymphoid hyperplasia with eosinophilia). J Cutan Pathol. 2018;45:395-402.
  13. Arai E, Kuramochi A, Tsuchida T, et al. Usefulness of D2-40 immunohistochemistry for differentiation between kaposiform hemangioendothelioma and tufted angioma. J Cutan Pathol. 2006;33:492-497.
  14. Grassi S, Carugno A, Vignini M, et al. Adult-onset tufted angiomas associated with an arteriovenous malformation in a renal transplant recipient: case report and review of the literature. Am J Dermatopathol. 2015;37:162-165.
  15. Lyons LL, North PE, Mac-Moune Lai F, et al. Kaposiform hemangioendothelioma: a study of 33 cases emphasizing its pathologic, immunophenotypic, and biologic uniqueness from juvenile hemangioma. Am J Surg Pathol. 2004;28:559-568.
  16. Putra HP, Djawad K, Nurdin AR. Cutaneous lesions as the first manifestation of breast cancer: a rare case. Pan Afr Med J. 2020;37:383.
  17. Thiers BH, Sahn RE, Callen JP. Cutaneous manifestations of internal malignancy. CA Cancer J Clin. 2009;59:73-98.
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From the Medical University of South Carolina, Charleston. Ms. Barker is from the College of Medicine, and Dr. Scribner is from the Department of Dermatology and Dermatologic Surgery.

The authors report no conflict of interest.

Correspondence: Catherine S. Barker, BS, Department of Dermatology and Dermatologic Surgery, 135 Rutledge Ave, MSC 578, Charleston, SC 29425 ([email protected]).

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The authors report no conflict of interest.

Correspondence: Catherine S. Barker, BS, Department of Dermatology and Dermatologic Surgery, 135 Rutledge Ave, MSC 578, Charleston, SC 29425 ([email protected]).

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From the Medical University of South Carolina, Charleston. Ms. Barker is from the College of Medicine, and Dr. Scribner is from the Department of Dermatology and Dermatologic Surgery.

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Correspondence: Catherine S. Barker, BS, Department of Dermatology and Dermatologic Surgery, 135 Rutledge Ave, MSC 578, Charleston, SC 29425 ([email protected]).

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The Diagnosis: Tufted Angioma

Histopathology revealed discrete lobules of closely packed capillaries with bland endothelial cells throughout the upper and lower dermis (Figure 1). The surrounding crescentlike vessels and lymphatics stained with D2-40 (Figure 2). These histologic findings were consistent with tufted angioma, and the patient elected for observation.

Compressed capillaries lined by bland endothelial cells with peripherally dilated crescent-shaped lymphatic channels
FIGURE 1. Compressed capillaries lined by bland endothelial cells with peripherally dilated crescent-shaped lymphatic channels (H&E, original magnification ×200).

Tufted angiomas are benign vascular lesions named for the tufted appearance of capillaries on histology.1 They commonly present in children, with a lower incidence in adults and rare cases in pregnancy.2 Tufted angiomas typically present as solitary, slowly expanding, erythematous macules, plaques, or nodules on the neck or trunk ranging in size from less than 1 to 10 cm.2-4 They can be histologically distinguished from other vascular tumors, including aggressive malignant neoplasms.1

D2-40 immunohistochemical staining of lymphatics surrounding capillary proliferations with an absence of staining of the capillary endothelial cells
FIGURE 2. D2-40 immunohistochemical staining of lymphatics surrounding capillary proliferations with an absence of staining of the capillary endothelial cells (original magnification ×200).

Tufted angiomas are identified by characteristic “cannon ball tufts” of capillaries in the dermis and subcutis at low power.3,5 Distinct cellular lobules may be found bulging into thin-walled vascular channels at the margins of the lobules in the dermis and subcutis (Figure 3).4 The lobules are formed by cells with spindle-shaped nuclei.6 Some mitotic figures may be present, but no cellular atypia is seen.2 The capillaries at the periphery appear as dilated semilunar vessels.4 Dilated lymphatics, which stain with D2-40, can be found at the periphery of the tufted capillaries and throughout the remaining dermis.3,4

Discrete collections of closely packed capillary-sized vessels throughout the upper and lower dermis
FIGURE 3. Discrete collections of closely packed capillary-sized vessels throughout the upper and lower dermis (H&E, original magnification ×40).

Tufted angiomas may arise independently in adults but also have been associated with conditions such as pregnancy. Omori et al7 identified an acquired tufted angioma in pregnancy that was positive for estrogen and progesterone receptors. Reports of tufted angiomas in pregnancy vary; some are multiple lesions, some regress postpartum, and some undergo successful surgical treatment.3,5

Vascular lesions such as tufted angiomas specifically may appear in pregnancy due to a high-volume state with vasodilation and increased vascular proliferation. Although tumor angiogenesis has been linked to specific growth factors and cytokines, it has been hypothesized that the systemic hormones of pregnancy such as human chorionic gonadotropin, estradiol, and progesterone also shift the body to a more angiogenic state.8 In a study of cutaneous changes in pregnant women (N=905), 41% developed a vascular skin change, including spider veins, varicosities, hemangiomas, and granulomas.9 The most common vascular tumor in pregnancy is pyogenic granuloma. Pyogenic granulomas are small, solitary, friable papules that commonly are found on the hands, forearms, face, or in the mouth; histologically they demonstrate dilated capillaries in lobular structures accompanied by larger thick-walled vessels.3,10,11

Tufted angiomas may mimic a variety of other conditions. Epithelioid hemangioma, considered by some to be on the same morphologic spectrum as angiolymphoid hyperplasia with eosinophilia, classically occurs in young adults on the head and in the neck region. It histologically demonstrates a lobular appearance at low power; however, these lobules are made up of vessels with histiocytoid to epithelioid endothelial cells surrounded by a prominent inflammatory infiltrate consisting of lymphocytes and eosinophils.12

Kaposi sarcoma may appear on the neck but most often presents as macules and patches on the extremities that may form nodules with a rubbery consistency. In tufted angiomas, the cellular nodules with dilated channels at the margins bear a resemblance to Kaposi sarcoma or kaposiform hemangioendothelioma; however, in tufted angiomas the lobules are composed of bland spindle cells and slitlike vessels at the periphery.3,13,14 Tufted angiomas are negative for human herpesvirus 8 and typically do not have an associated inflammatory infiltrate with plasma cells.11,15

Moreover, it is important to differentiate tufted angioma from a cutaneous manifestation of an underlying malignancy, which has been described previously in cases of breast cancer.16,17 Our case illustrates a rare vascular tumor arising in the novel context of a pregnant patient with breast cancer. Distinguishing tufted angioma from other benign or malignant vascular tumors is necessary to avoid inappropriate therapeutic interventions.

The Diagnosis: Tufted Angioma

Histopathology revealed discrete lobules of closely packed capillaries with bland endothelial cells throughout the upper and lower dermis (Figure 1). The surrounding crescentlike vessels and lymphatics stained with D2-40 (Figure 2). These histologic findings were consistent with tufted angioma, and the patient elected for observation.

Compressed capillaries lined by bland endothelial cells with peripherally dilated crescent-shaped lymphatic channels
FIGURE 1. Compressed capillaries lined by bland endothelial cells with peripherally dilated crescent-shaped lymphatic channels (H&E, original magnification ×200).

Tufted angiomas are benign vascular lesions named for the tufted appearance of capillaries on histology.1 They commonly present in children, with a lower incidence in adults and rare cases in pregnancy.2 Tufted angiomas typically present as solitary, slowly expanding, erythematous macules, plaques, or nodules on the neck or trunk ranging in size from less than 1 to 10 cm.2-4 They can be histologically distinguished from other vascular tumors, including aggressive malignant neoplasms.1

D2-40 immunohistochemical staining of lymphatics surrounding capillary proliferations with an absence of staining of the capillary endothelial cells
FIGURE 2. D2-40 immunohistochemical staining of lymphatics surrounding capillary proliferations with an absence of staining of the capillary endothelial cells (original magnification ×200).

Tufted angiomas are identified by characteristic “cannon ball tufts” of capillaries in the dermis and subcutis at low power.3,5 Distinct cellular lobules may be found bulging into thin-walled vascular channels at the margins of the lobules in the dermis and subcutis (Figure 3).4 The lobules are formed by cells with spindle-shaped nuclei.6 Some mitotic figures may be present, but no cellular atypia is seen.2 The capillaries at the periphery appear as dilated semilunar vessels.4 Dilated lymphatics, which stain with D2-40, can be found at the periphery of the tufted capillaries and throughout the remaining dermis.3,4

Discrete collections of closely packed capillary-sized vessels throughout the upper and lower dermis
FIGURE 3. Discrete collections of closely packed capillary-sized vessels throughout the upper and lower dermis (H&E, original magnification ×40).

Tufted angiomas may arise independently in adults but also have been associated with conditions such as pregnancy. Omori et al7 identified an acquired tufted angioma in pregnancy that was positive for estrogen and progesterone receptors. Reports of tufted angiomas in pregnancy vary; some are multiple lesions, some regress postpartum, and some undergo successful surgical treatment.3,5

Vascular lesions such as tufted angiomas specifically may appear in pregnancy due to a high-volume state with vasodilation and increased vascular proliferation. Although tumor angiogenesis has been linked to specific growth factors and cytokines, it has been hypothesized that the systemic hormones of pregnancy such as human chorionic gonadotropin, estradiol, and progesterone also shift the body to a more angiogenic state.8 In a study of cutaneous changes in pregnant women (N=905), 41% developed a vascular skin change, including spider veins, varicosities, hemangiomas, and granulomas.9 The most common vascular tumor in pregnancy is pyogenic granuloma. Pyogenic granulomas are small, solitary, friable papules that commonly are found on the hands, forearms, face, or in the mouth; histologically they demonstrate dilated capillaries in lobular structures accompanied by larger thick-walled vessels.3,10,11

Tufted angiomas may mimic a variety of other conditions. Epithelioid hemangioma, considered by some to be on the same morphologic spectrum as angiolymphoid hyperplasia with eosinophilia, classically occurs in young adults on the head and in the neck region. It histologically demonstrates a lobular appearance at low power; however, these lobules are made up of vessels with histiocytoid to epithelioid endothelial cells surrounded by a prominent inflammatory infiltrate consisting of lymphocytes and eosinophils.12

Kaposi sarcoma may appear on the neck but most often presents as macules and patches on the extremities that may form nodules with a rubbery consistency. In tufted angiomas, the cellular nodules with dilated channels at the margins bear a resemblance to Kaposi sarcoma or kaposiform hemangioendothelioma; however, in tufted angiomas the lobules are composed of bland spindle cells and slitlike vessels at the periphery.3,13,14 Tufted angiomas are negative for human herpesvirus 8 and typically do not have an associated inflammatory infiltrate with plasma cells.11,15

Moreover, it is important to differentiate tufted angioma from a cutaneous manifestation of an underlying malignancy, which has been described previously in cases of breast cancer.16,17 Our case illustrates a rare vascular tumor arising in the novel context of a pregnant patient with breast cancer. Distinguishing tufted angioma from other benign or malignant vascular tumors is necessary to avoid inappropriate therapeutic interventions.

References
  1. Jones EW, Orkin M. Tufted angioma (angioblastoma). a benign progressive angioma, not to be confused with Kaposi’s sarcoma or low-grade angiosarcoma. J Am Acad Dermatol. 1989;20(2 pt 1):214-225.
  2. Lee B, Chiu M, Soriano T, et al. Adult-onset tufted angioma: a case report and review of the literature. Cutis. 2006;78:341-345.
  3. Kim YK, Kim HJ, Lee KG. Acquired tufted angioma associated with pregnancy. Clin Exp Dermatol. 1992;17:458-459.
  4. Feito-Rodriguez M, Sanchez-Orta A, De Lucas R, et al. Congenital tufted angioma: a multicenter retrospective study of 30 cases. Pediatr Dermatol. 2018;35:808-816.
  5. Pietroletti R, Leardi S, Simi M. Perianal acquired tufted angioma associated with pregnancy: case report. Tech Coloproctol. 2002;6:117-119.
  6. Osio A, Fraitag S, Hadj-Rabia S, et al. Clinical spectrum of tufted angiomas in childhood: a report of 13 cases and a review of the literature. Arch Dermatol. 2010;146:758-763.
  7. Omori M, Bito T, Nishigori C. Acquired tufted angioma in pregnancy showing expression of estrogen and progesterone receptors. Eur J Dermatol. 2013;23:898-899.
  8. Boeldt DS, Bird IM. Vascular adaptation in pregnancy and endothelial dysfunction in preeclampsia. J Endocrinol. 2017;232:R27-R44.
  9. Fernandes LB, Amaral W. Clinical study of skin changes in low and high risk pregnant women. An Bras Dermatol. 2015;90:822-826.
  10. Walker JL, Wang AR, Kroumpouzos G, et al. Cutaneous tumors in pregnancy. Clin Dermatol. 2016;34:359-367.
  11. Sarwal P, Lapumnuaypol K. Pyogenic granuloma. In: StatPearls. StatPearls Publishing; 2021.
  12. Ortins-Pina A, Llamas-Velasco M, Turpin S, et al. FOSB immunoreactivity in endothelia of epithelioid hemangioma (angiolymphoid hyperplasia with eosinophilia). J Cutan Pathol. 2018;45:395-402.
  13. Arai E, Kuramochi A, Tsuchida T, et al. Usefulness of D2-40 immunohistochemistry for differentiation between kaposiform hemangioendothelioma and tufted angioma. J Cutan Pathol. 2006;33:492-497.
  14. Grassi S, Carugno A, Vignini M, et al. Adult-onset tufted angiomas associated with an arteriovenous malformation in a renal transplant recipient: case report and review of the literature. Am J Dermatopathol. 2015;37:162-165.
  15. Lyons LL, North PE, Mac-Moune Lai F, et al. Kaposiform hemangioendothelioma: a study of 33 cases emphasizing its pathologic, immunophenotypic, and biologic uniqueness from juvenile hemangioma. Am J Surg Pathol. 2004;28:559-568.
  16. Putra HP, Djawad K, Nurdin AR. Cutaneous lesions as the first manifestation of breast cancer: a rare case. Pan Afr Med J. 2020;37:383.
  17. Thiers BH, Sahn RE, Callen JP. Cutaneous manifestations of internal malignancy. CA Cancer J Clin. 2009;59:73-98.
References
  1. Jones EW, Orkin M. Tufted angioma (angioblastoma). a benign progressive angioma, not to be confused with Kaposi’s sarcoma or low-grade angiosarcoma. J Am Acad Dermatol. 1989;20(2 pt 1):214-225.
  2. Lee B, Chiu M, Soriano T, et al. Adult-onset tufted angioma: a case report and review of the literature. Cutis. 2006;78:341-345.
  3. Kim YK, Kim HJ, Lee KG. Acquired tufted angioma associated with pregnancy. Clin Exp Dermatol. 1992;17:458-459.
  4. Feito-Rodriguez M, Sanchez-Orta A, De Lucas R, et al. Congenital tufted angioma: a multicenter retrospective study of 30 cases. Pediatr Dermatol. 2018;35:808-816.
  5. Pietroletti R, Leardi S, Simi M. Perianal acquired tufted angioma associated with pregnancy: case report. Tech Coloproctol. 2002;6:117-119.
  6. Osio A, Fraitag S, Hadj-Rabia S, et al. Clinical spectrum of tufted angiomas in childhood: a report of 13 cases and a review of the literature. Arch Dermatol. 2010;146:758-763.
  7. Omori M, Bito T, Nishigori C. Acquired tufted angioma in pregnancy showing expression of estrogen and progesterone receptors. Eur J Dermatol. 2013;23:898-899.
  8. Boeldt DS, Bird IM. Vascular adaptation in pregnancy and endothelial dysfunction in preeclampsia. J Endocrinol. 2017;232:R27-R44.
  9. Fernandes LB, Amaral W. Clinical study of skin changes in low and high risk pregnant women. An Bras Dermatol. 2015;90:822-826.
  10. Walker JL, Wang AR, Kroumpouzos G, et al. Cutaneous tumors in pregnancy. Clin Dermatol. 2016;34:359-367.
  11. Sarwal P, Lapumnuaypol K. Pyogenic granuloma. In: StatPearls. StatPearls Publishing; 2021.
  12. Ortins-Pina A, Llamas-Velasco M, Turpin S, et al. FOSB immunoreactivity in endothelia of epithelioid hemangioma (angiolymphoid hyperplasia with eosinophilia). J Cutan Pathol. 2018;45:395-402.
  13. Arai E, Kuramochi A, Tsuchida T, et al. Usefulness of D2-40 immunohistochemistry for differentiation between kaposiform hemangioendothelioma and tufted angioma. J Cutan Pathol. 2006;33:492-497.
  14. Grassi S, Carugno A, Vignini M, et al. Adult-onset tufted angiomas associated with an arteriovenous malformation in a renal transplant recipient: case report and review of the literature. Am J Dermatopathol. 2015;37:162-165.
  15. Lyons LL, North PE, Mac-Moune Lai F, et al. Kaposiform hemangioendothelioma: a study of 33 cases emphasizing its pathologic, immunophenotypic, and biologic uniqueness from juvenile hemangioma. Am J Surg Pathol. 2004;28:559-568.
  16. Putra HP, Djawad K, Nurdin AR. Cutaneous lesions as the first manifestation of breast cancer: a rare case. Pan Afr Med J. 2020;37:383.
  17. Thiers BH, Sahn RE, Callen JP. Cutaneous manifestations of internal malignancy. CA Cancer J Clin. 2009;59:73-98.
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A 31-year-old woman at 34 weeks’ gestation presented with skin discoloration of the anterior neck of 7 months’ duration. Her pregnancy had been complicated by a diagnosis of invasive papillary carcinoma of the breast with unilateral complete mastectomy and negative sentinel lymph node biopsy in the first trimester. The lesion was tender, darkening, and rapidly enlarging. Physical examination demonstrated a linear, violaceous, vascular, and indurated plaque with microvesiculation that was 3.5 cm in width. She had no history of blistering sunburns, frequent UV exposure, or skin cancer.

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Studies address ibrutinib bleeding risk in patients with CLL receiving Mohs surgery

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Patients receiving treatment with ibrutinib for chronic lymphocytic leukemia (CLL) show significant increases in the risk for bleeding when undergoing Mohs micrographic surgery for skin cancer, indicating the need for temporary treatment interruptions, new research shows.

“Our cohort of CLL patients on ibrutinib had a two-times greater risk of bleeding complications relative to those on anticoagulants and a nearly 40-times greater risk of bleeding complications relative to those patients on no anticoagulants or CLL therapy,” Kelsey E. Hirotsu, MD, first author of one of two studies on the issue presented at the American College of Mohs Surgery annual meeting, told this news organization.

Dr. Kelsey E. Hirotsu

“It was definitely surprising to see this doubled risk with ibrutinib relative to anticoagulants, and certainly highlights the clinically relevant increased bleeding risk in patients on ibrutinib,” said Dr. Hirotsu, a Mohs micrographic surgery fellow in the department of dermatology, University of California, San Diego (UCSD).

With CLL associated with an increased risk for aggressive skin cancers, particularly squamous cell carcinoma, Mohs surgeons may commonly find themselves treating patients with these unique considerations. Surgical treatment of those cancers can be complicated not only because of potential underlying thrombocytopenia, which occurs in about 5% of untreated CLL patients, but also because of the increased risk for bleeding that is associated with the use of the Bruton tyrosine kinase inhibitor ibrutinib, commonly used for CLL.

While the nature of the increased bleeding-related complications among patients with CLL undergoing Mohs surgery has been documented in some case reports, evidence from larger studies has been lacking.

In one of the studies presented at the ACMS meeting, Dr. Hirotsu and her colleagues evaluated data on patients with CLL who underwent at least one Mohs surgery procedure at UCSD Dermatologic Surgery over 10 years. Of the 362 Mohs cases among 98 patients with CLL, 32 cases had at least one complication. Patients on anticoagulants, including antiplatelet agents, Coumadin, and direct oral anticoagulants (DOACs), not surprisingly, had higher rates of complications, particularly bleeding.

However, those treated with ibrutinib had the highest rates of complications among all of the patients (40.6%), with all of their complications involving bleeding-related events. In comparison, the complication rates, for instance, of patients treated with antiplatelets were 21.9%; Coumadin, 6.2%; and DOACs, 15.6%.

The incidence of bleeding-related complications among the cases in the ibrutinib-treated patients was 30.2% compared with 13.2% among those on blood thinners and no CLL therapy (relative risk [RR], 2.08; 95% confidence interval [CI], 0.85-5.11; P = .11). “Although not statistically significant, these results could trend toward significance with larger sample sizes,” Dr. Hirotsu said.

The risk for bleeding among patients on ibrutinib compared with patients on no medications, however, was significant, with a relative risk of 39.0 (95% CI, 2.35-646; P = .011).



Of note, among 12 patients on ibrutinib who experienced bleeding complications, 7 had previously undergone Mohs surgeries when they were not taking ibrutinib and no bleeding complications had occurred in those procedures. “This may further implicate ibrutinib as a cause of the bleeding-related complications,” Dr. Hirotsu said.

In investigating the role of thrombocytopenia at the time of Mohs surgery, the authors found that, among ibrutinib-treated patients who had no complications, 30% had thrombocytopenia, compared with 70% of those who did have bleeding while on ibrutinib at the time of surgery.

“It was interesting that thrombocytopenia is more common in ibrutinib patients with bleeding-related complications, but further research needs to be done to determine the clinical relevance and possible management implications,” Dr. Hirotsu said.

In a separate study presented at the meeting, 37 patients treated with ibrutinib for CLL while undergoing cutaneous surgery that included Mohs surgery and excisions had a significantly increased bleeding complication rate compared with a control group of 64 age- and sex-matched patients with CLL undergoing cutaneous surgery: 6 of 75 procedures (8%) versus 1 of 115 procedures (0.9%; P = .02).

Those with bleeding complications while on ibrutinib were all male, older (mean age, 82.7 vs. 73.0; P = .01), and had lower mean platelet counts (104 K/mcL vs. 150.5 K/mcL; P = .03).

There were no significant differences between the case and control groups in terms of anatomic site, type of procedure (Mohs versus excision), tumor diagnosis, lesion size, or type of reconstruction, while the control group was more likely to be on aspirin or other anticoagulants (P < .0001).

In an interview, senior author Nahid Y. Vidal, MD, a Mohs surgeon and dermatologic oncologist at the Mayo Clinic, Rochester, Minn., said that “the take-home message is that patients on ibrutinib should be considered higher risk for bleeding events, regardless of whether they are having a simpler surgery [excision] or more involved skin surgery procedure [Mohs with flap].”

Dr. Nahid Y. Vidal

 

Holding treatment

To offset the bleeding risk, Dr. Vidal notes that holding the treatment is considered safe and that the manufacturer recommends holding ibrutinib for at least 3-7 days pre- and post surgery, “depending on type of surgery and risk of bleeding.”

“In our institution, with the hematologist/oncologist’s input, we hold ibrutinib for 5 days preop and 3 days post op, and have not had bleed complications in these patients,” she said, noting that there were no bleeding events in the patients in the study when ibrutinib was held.

Likewise, Dr. Hirotsu noted that at her center at UCSD, patients on ibrutinib are asked during the preop call to hold treatment for 3 days before and after Mohs surgery – but are advised to discuss the decision with their hematologist/oncologist for approval.

The measure isn’t always successful in preventing bleeding, however, as seen in a case study describing two patients who experienced bleeding complications following Mohs surgery despite being taken off ibrutinib 3 days prior to the procedure.

The senior author of that study, Kira Minkis, MD, PhD, department of dermatology, Weill Cornell/New York Presbyterian, New York, told this news organization that her team concluded that in those cases ibrutinib perhaps should have been held longer than 3 days.

“In some cases, especially if the Mohs surgery is a large procedure with a more advanced reconstruction, such as a large flap, it might be more prudent to continue it longer than 3 days,” Dr. Minkis said. She noted that the high bleeding risk observed in the studies at ACMS was notable – but not unexpected.

“I’m not that surprised because if you look at the hematologic literature, the risk is indeed pretty significant, so it makes sense that it would also occur with Mohs surgeries,” she said.

She underscored that a 3-day hold of ibrutinib should be considered the minimum, “and in some cases, it should be held up to 7 days prior to surgery, depending on the specific surgery,” with the important caveat of consulting with the patient’s hematology team.

“Multidisciplinary decision-making is necessary for these cases, and the interruption of therapy should always be discussed with their hematology team,” she added. That said, Dr. Minkis noted that “I’ve never had a hematologist who had any concerns for withholding ibrutinib even for a week around the time of a surgery.”

Dr. Hirotsu, Dr. Vidal, and Dr. Minkis reported no relevant financial relationships.

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

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Patients receiving treatment with ibrutinib for chronic lymphocytic leukemia (CLL) show significant increases in the risk for bleeding when undergoing Mohs micrographic surgery for skin cancer, indicating the need for temporary treatment interruptions, new research shows.

“Our cohort of CLL patients on ibrutinib had a two-times greater risk of bleeding complications relative to those on anticoagulants and a nearly 40-times greater risk of bleeding complications relative to those patients on no anticoagulants or CLL therapy,” Kelsey E. Hirotsu, MD, first author of one of two studies on the issue presented at the American College of Mohs Surgery annual meeting, told this news organization.

Dr. Kelsey E. Hirotsu

“It was definitely surprising to see this doubled risk with ibrutinib relative to anticoagulants, and certainly highlights the clinically relevant increased bleeding risk in patients on ibrutinib,” said Dr. Hirotsu, a Mohs micrographic surgery fellow in the department of dermatology, University of California, San Diego (UCSD).

With CLL associated with an increased risk for aggressive skin cancers, particularly squamous cell carcinoma, Mohs surgeons may commonly find themselves treating patients with these unique considerations. Surgical treatment of those cancers can be complicated not only because of potential underlying thrombocytopenia, which occurs in about 5% of untreated CLL patients, but also because of the increased risk for bleeding that is associated with the use of the Bruton tyrosine kinase inhibitor ibrutinib, commonly used for CLL.

While the nature of the increased bleeding-related complications among patients with CLL undergoing Mohs surgery has been documented in some case reports, evidence from larger studies has been lacking.

In one of the studies presented at the ACMS meeting, Dr. Hirotsu and her colleagues evaluated data on patients with CLL who underwent at least one Mohs surgery procedure at UCSD Dermatologic Surgery over 10 years. Of the 362 Mohs cases among 98 patients with CLL, 32 cases had at least one complication. Patients on anticoagulants, including antiplatelet agents, Coumadin, and direct oral anticoagulants (DOACs), not surprisingly, had higher rates of complications, particularly bleeding.

However, those treated with ibrutinib had the highest rates of complications among all of the patients (40.6%), with all of their complications involving bleeding-related events. In comparison, the complication rates, for instance, of patients treated with antiplatelets were 21.9%; Coumadin, 6.2%; and DOACs, 15.6%.

The incidence of bleeding-related complications among the cases in the ibrutinib-treated patients was 30.2% compared with 13.2% among those on blood thinners and no CLL therapy (relative risk [RR], 2.08; 95% confidence interval [CI], 0.85-5.11; P = .11). “Although not statistically significant, these results could trend toward significance with larger sample sizes,” Dr. Hirotsu said.

The risk for bleeding among patients on ibrutinib compared with patients on no medications, however, was significant, with a relative risk of 39.0 (95% CI, 2.35-646; P = .011).



Of note, among 12 patients on ibrutinib who experienced bleeding complications, 7 had previously undergone Mohs surgeries when they were not taking ibrutinib and no bleeding complications had occurred in those procedures. “This may further implicate ibrutinib as a cause of the bleeding-related complications,” Dr. Hirotsu said.

In investigating the role of thrombocytopenia at the time of Mohs surgery, the authors found that, among ibrutinib-treated patients who had no complications, 30% had thrombocytopenia, compared with 70% of those who did have bleeding while on ibrutinib at the time of surgery.

“It was interesting that thrombocytopenia is more common in ibrutinib patients with bleeding-related complications, but further research needs to be done to determine the clinical relevance and possible management implications,” Dr. Hirotsu said.

In a separate study presented at the meeting, 37 patients treated with ibrutinib for CLL while undergoing cutaneous surgery that included Mohs surgery and excisions had a significantly increased bleeding complication rate compared with a control group of 64 age- and sex-matched patients with CLL undergoing cutaneous surgery: 6 of 75 procedures (8%) versus 1 of 115 procedures (0.9%; P = .02).

Those with bleeding complications while on ibrutinib were all male, older (mean age, 82.7 vs. 73.0; P = .01), and had lower mean platelet counts (104 K/mcL vs. 150.5 K/mcL; P = .03).

There were no significant differences between the case and control groups in terms of anatomic site, type of procedure (Mohs versus excision), tumor diagnosis, lesion size, or type of reconstruction, while the control group was more likely to be on aspirin or other anticoagulants (P < .0001).

In an interview, senior author Nahid Y. Vidal, MD, a Mohs surgeon and dermatologic oncologist at the Mayo Clinic, Rochester, Minn., said that “the take-home message is that patients on ibrutinib should be considered higher risk for bleeding events, regardless of whether they are having a simpler surgery [excision] or more involved skin surgery procedure [Mohs with flap].”

Dr. Nahid Y. Vidal

 

Holding treatment

To offset the bleeding risk, Dr. Vidal notes that holding the treatment is considered safe and that the manufacturer recommends holding ibrutinib for at least 3-7 days pre- and post surgery, “depending on type of surgery and risk of bleeding.”

“In our institution, with the hematologist/oncologist’s input, we hold ibrutinib for 5 days preop and 3 days post op, and have not had bleed complications in these patients,” she said, noting that there were no bleeding events in the patients in the study when ibrutinib was held.

Likewise, Dr. Hirotsu noted that at her center at UCSD, patients on ibrutinib are asked during the preop call to hold treatment for 3 days before and after Mohs surgery – but are advised to discuss the decision with their hematologist/oncologist for approval.

The measure isn’t always successful in preventing bleeding, however, as seen in a case study describing two patients who experienced bleeding complications following Mohs surgery despite being taken off ibrutinib 3 days prior to the procedure.

The senior author of that study, Kira Minkis, MD, PhD, department of dermatology, Weill Cornell/New York Presbyterian, New York, told this news organization that her team concluded that in those cases ibrutinib perhaps should have been held longer than 3 days.

“In some cases, especially if the Mohs surgery is a large procedure with a more advanced reconstruction, such as a large flap, it might be more prudent to continue it longer than 3 days,” Dr. Minkis said. She noted that the high bleeding risk observed in the studies at ACMS was notable – but not unexpected.

“I’m not that surprised because if you look at the hematologic literature, the risk is indeed pretty significant, so it makes sense that it would also occur with Mohs surgeries,” she said.

She underscored that a 3-day hold of ibrutinib should be considered the minimum, “and in some cases, it should be held up to 7 days prior to surgery, depending on the specific surgery,” with the important caveat of consulting with the patient’s hematology team.

“Multidisciplinary decision-making is necessary for these cases, and the interruption of therapy should always be discussed with their hematology team,” she added. That said, Dr. Minkis noted that “I’ve never had a hematologist who had any concerns for withholding ibrutinib even for a week around the time of a surgery.”

Dr. Hirotsu, Dr. Vidal, and Dr. Minkis reported no relevant financial relationships.

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

Patients receiving treatment with ibrutinib for chronic lymphocytic leukemia (CLL) show significant increases in the risk for bleeding when undergoing Mohs micrographic surgery for skin cancer, indicating the need for temporary treatment interruptions, new research shows.

“Our cohort of CLL patients on ibrutinib had a two-times greater risk of bleeding complications relative to those on anticoagulants and a nearly 40-times greater risk of bleeding complications relative to those patients on no anticoagulants or CLL therapy,” Kelsey E. Hirotsu, MD, first author of one of two studies on the issue presented at the American College of Mohs Surgery annual meeting, told this news organization.

Dr. Kelsey E. Hirotsu

“It was definitely surprising to see this doubled risk with ibrutinib relative to anticoagulants, and certainly highlights the clinically relevant increased bleeding risk in patients on ibrutinib,” said Dr. Hirotsu, a Mohs micrographic surgery fellow in the department of dermatology, University of California, San Diego (UCSD).

With CLL associated with an increased risk for aggressive skin cancers, particularly squamous cell carcinoma, Mohs surgeons may commonly find themselves treating patients with these unique considerations. Surgical treatment of those cancers can be complicated not only because of potential underlying thrombocytopenia, which occurs in about 5% of untreated CLL patients, but also because of the increased risk for bleeding that is associated with the use of the Bruton tyrosine kinase inhibitor ibrutinib, commonly used for CLL.

While the nature of the increased bleeding-related complications among patients with CLL undergoing Mohs surgery has been documented in some case reports, evidence from larger studies has been lacking.

In one of the studies presented at the ACMS meeting, Dr. Hirotsu and her colleagues evaluated data on patients with CLL who underwent at least one Mohs surgery procedure at UCSD Dermatologic Surgery over 10 years. Of the 362 Mohs cases among 98 patients with CLL, 32 cases had at least one complication. Patients on anticoagulants, including antiplatelet agents, Coumadin, and direct oral anticoagulants (DOACs), not surprisingly, had higher rates of complications, particularly bleeding.

However, those treated with ibrutinib had the highest rates of complications among all of the patients (40.6%), with all of their complications involving bleeding-related events. In comparison, the complication rates, for instance, of patients treated with antiplatelets were 21.9%; Coumadin, 6.2%; and DOACs, 15.6%.

The incidence of bleeding-related complications among the cases in the ibrutinib-treated patients was 30.2% compared with 13.2% among those on blood thinners and no CLL therapy (relative risk [RR], 2.08; 95% confidence interval [CI], 0.85-5.11; P = .11). “Although not statistically significant, these results could trend toward significance with larger sample sizes,” Dr. Hirotsu said.

The risk for bleeding among patients on ibrutinib compared with patients on no medications, however, was significant, with a relative risk of 39.0 (95% CI, 2.35-646; P = .011).



Of note, among 12 patients on ibrutinib who experienced bleeding complications, 7 had previously undergone Mohs surgeries when they were not taking ibrutinib and no bleeding complications had occurred in those procedures. “This may further implicate ibrutinib as a cause of the bleeding-related complications,” Dr. Hirotsu said.

In investigating the role of thrombocytopenia at the time of Mohs surgery, the authors found that, among ibrutinib-treated patients who had no complications, 30% had thrombocytopenia, compared with 70% of those who did have bleeding while on ibrutinib at the time of surgery.

“It was interesting that thrombocytopenia is more common in ibrutinib patients with bleeding-related complications, but further research needs to be done to determine the clinical relevance and possible management implications,” Dr. Hirotsu said.

In a separate study presented at the meeting, 37 patients treated with ibrutinib for CLL while undergoing cutaneous surgery that included Mohs surgery and excisions had a significantly increased bleeding complication rate compared with a control group of 64 age- and sex-matched patients with CLL undergoing cutaneous surgery: 6 of 75 procedures (8%) versus 1 of 115 procedures (0.9%; P = .02).

Those with bleeding complications while on ibrutinib were all male, older (mean age, 82.7 vs. 73.0; P = .01), and had lower mean platelet counts (104 K/mcL vs. 150.5 K/mcL; P = .03).

There were no significant differences between the case and control groups in terms of anatomic site, type of procedure (Mohs versus excision), tumor diagnosis, lesion size, or type of reconstruction, while the control group was more likely to be on aspirin or other anticoagulants (P < .0001).

In an interview, senior author Nahid Y. Vidal, MD, a Mohs surgeon and dermatologic oncologist at the Mayo Clinic, Rochester, Minn., said that “the take-home message is that patients on ibrutinib should be considered higher risk for bleeding events, regardless of whether they are having a simpler surgery [excision] or more involved skin surgery procedure [Mohs with flap].”

Dr. Nahid Y. Vidal

 

Holding treatment

To offset the bleeding risk, Dr. Vidal notes that holding the treatment is considered safe and that the manufacturer recommends holding ibrutinib for at least 3-7 days pre- and post surgery, “depending on type of surgery and risk of bleeding.”

“In our institution, with the hematologist/oncologist’s input, we hold ibrutinib for 5 days preop and 3 days post op, and have not had bleed complications in these patients,” she said, noting that there were no bleeding events in the patients in the study when ibrutinib was held.

Likewise, Dr. Hirotsu noted that at her center at UCSD, patients on ibrutinib are asked during the preop call to hold treatment for 3 days before and after Mohs surgery – but are advised to discuss the decision with their hematologist/oncologist for approval.

The measure isn’t always successful in preventing bleeding, however, as seen in a case study describing two patients who experienced bleeding complications following Mohs surgery despite being taken off ibrutinib 3 days prior to the procedure.

The senior author of that study, Kira Minkis, MD, PhD, department of dermatology, Weill Cornell/New York Presbyterian, New York, told this news organization that her team concluded that in those cases ibrutinib perhaps should have been held longer than 3 days.

“In some cases, especially if the Mohs surgery is a large procedure with a more advanced reconstruction, such as a large flap, it might be more prudent to continue it longer than 3 days,” Dr. Minkis said. She noted that the high bleeding risk observed in the studies at ACMS was notable – but not unexpected.

“I’m not that surprised because if you look at the hematologic literature, the risk is indeed pretty significant, so it makes sense that it would also occur with Mohs surgeries,” she said.

She underscored that a 3-day hold of ibrutinib should be considered the minimum, “and in some cases, it should be held up to 7 days prior to surgery, depending on the specific surgery,” with the important caveat of consulting with the patient’s hematology team.

“Multidisciplinary decision-making is necessary for these cases, and the interruption of therapy should always be discussed with their hematology team,” she added. That said, Dr. Minkis noted that “I’ve never had a hematologist who had any concerns for withholding ibrutinib even for a week around the time of a surgery.”

Dr. Hirotsu, Dr. Vidal, and Dr. Minkis reported no relevant financial relationships.

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

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Pilonidal disease, other conditions may benefit from laser treatment

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– Pilonidal disease – a chronic inflammatory condition that can trigger the formation of cysts and sinuses in the superior portion of the intragluteal cleft or the sacrococcygeal area – remains challenging to manage, but mounting evidence supports the use of lasers to enhance treatment success.

“Draining sinuses or acute abscesses are usually associated with an underlying cyst and associated granulation tissue, fibrosis, and tufts of hair,” Catherine M. DiGiorgio, MD, said at the annual conference of the American Society for Laser Medicine and Surgery. “This is why laser hair removal can help with the treatment of these patients.”

Dr. Catherine M. DiGiorgio

The suspected etiology is a foreign body reaction to the entrapped hairs, which are found in the sinuses in about 75% of cases. “The treatment for that is surgery,” said Dr. DiGiorgio, a laser and cosmetic dermatologist in Boston. Laser hair reduction decreases the recurrence of cyst formation and drainage, and is usually covered by insurance, she noted.
 

Supportive evidence

In a comparative study, French researchers retrospectively reviewed the efficacy of laser hair removal after surgery in reducing recurrence rate of pilonidal cysts, versus surgery alone. Of the 41 study participants, 12 had laser hair removal plus surgery and 29 had surgery alone. The rate of cyst recurrence was significantly lower in the laser hair removal plus surgery group, compared with the surgery only group (8.3% vs. 51.7%, respectively; P < .001).

In another study, researchers from the United Kingdom and The Johns Hopkins Hospital, Baltimore, evaluated the use of the long-pulsed Alexandrite laser in 19 patients with recurrent pilonidal disease who had undergone multiple surgeries.They were treated with the laser for hair removal in the sinus area, requiring 4-12 sessions. The researchers found that 84.2% of patients had a reduction of hair density to less than 5 hairs/cm2, while 15.8% had a reduction of hair density to 5-10 hairs/cm2. They also noted a statistically significant increase in disease-free time in the laser-treated group compared with those treated with surgical management only (P < .01).
 

Lasers for pseudofolliculitis barbae, HS

Lasers also play a significant role in the treatment of pseudofolliculitis barbae, a chronic, inflammatory disease that primarily affects the bearded area of men with thick hairs, usually those with a darker Fitzpatrick skin type. This can also occur in women, particularly those with polycystic ovary syndrome, Dr. DiGiorgio said.

In people with pseudofolliculitis barbae, the hair follicle is positioned at an acute angle to the skin surface and the sharp end of shaved hair reenters the skin, which results in the formation of pustules, papules, secondary infection, and keloids. Treatment involves a variety of medical therapies including retinoids, benzoyl peroxide, antibiotics, and keratolytics, “but laser hair removal is the best way to get rid of this issue, and results in permanent reduction,” she said. “When treating male patients with laser hair removal in the bearded area, you have to tell them that they won’t be able to grow a beard going forward. Most of them are okay with that.”

A 2002 study, led by E. Victor Ross, MD, of the Naval Medical Center, San Diego, evaluated treatment of pseudofolliculitis barbae in patients with skin types IV, V, and VI with a long-pulsed Nd:YAG laser. For the first phase of the study, the investigators tested epidermal tolerance on the thighs of 37 patients and determined that the laser was safe and effective. For the second phase 2 weeks later, they treated a 15x15-mm submental area with the highest fluence tolerated in phase 1 of the trial and used an adjacent site as the control.

After 90 days, the mean papule count was 6.95 for the control site compared with 1 for the laser-treated site. The researchers observed that miniaturization and elimination of hair shafts resulted in decreased inflamed papules. “We know that this works,” Dr. DiGiorgio said.

In another study from investigators at the Naval Medical Center, San Diego, 22 patients with skin types IV, V, and VI who had pseudofolliculitis barbae underwent 5 weekly treatments with a 1,064 nm Nd:YAG laser. Topical anesthesia was not used, and 10 evaluators used a Global Assessment Scale (GAS) to assess treatment success from photos taken at baseline and at 4 weeks. At 4 weeks, 11 patients demonstrated 83% improvement on the GAS (P < .01), the investigators reported.

Laser and energy-based treatments can also be used to treat hidradenitis suppurativa (HS), a chronic condition that affects apocrine gland–bearing skin. “The hypothesized pathogenesis is that it’s an inflammatory disorder of the hair follicle, where the follicle rupture introduces its contents into the surrounding dermis,” Dr. DiGiorgio said. “The skin reacts with a chemotactic response and abscess formation. This results in inflammatory nodules and sterile abscesses, which can lead to sinus tracts and hypertrophic scars and chronic drainage, which can be foul-smelling. This frequently leads to depression and psychological distress for the patients.”



Possible laser and energy-based treatments for HS include follicular destruction with the Nd:YAG laser, the diode laser, the Alexandrite laser, microwave technology, or intense pulsed light, she said. Microwave technology or radiofrequency can be used for sweat gland destruction, while CO2 lasers can be used to debulk tissue, and the ablative fractional CO2 laser can be used to reduce scarring and improve range of motion.

In a prospective, randomized, intraindividual comparative trial conducted at eight centers in France, researchers evaluated the use of a long-pulsed Nd:YAG laser to treat 36 patients with mild to moderate HS; 27 had inguinal disease and 9 had axillary disease. They received four laser treatments at 6-week intervals; laser settings varied depending on the patient skin type.

At 1 month, there was a significant reduction in the number of inflammatory lesions on the areas treated with lasers, compared to the untreated areas, but the difference was not significant at 3 months. There was no significant difference in the number of flares between the treated and untreated sites at 1 or 3 months.

In a separate study, researchers found that the Nd:YAG laser in combination with topical benzoyl peroxide and clindamycin was significantly more effective than topical benzoyl peroxide and clindamycin alone for the treatment of HS in 22 patients with Hurley stage II disease. The patients received monthly treatments for 4 months and were followed up 2 months after the last treatment; the Hidradenitis Suppurativa Area and Severity Index was used to measure treatment response.

Statistically significant improvements were observed in the inguinal and axillary areas but not in the inframammary areas. Most patients (90%) reported less frequent breakouts while 10% reported no change. “In addition, 92% of subjects felt that the use of laser was more effective than other treatments they had tried but 8% stated it was equal to the other treatments they had tried,” said Dr. DiGiorgio, who was not affiliated with the study. “The researchers noted continued improvement with subsequent laser sessions,” she added.

According to 2019 guidelines from the United States and Canadian HS Foundations on the management of HS – in the section on light, laser, and energy sources – an Nd:YAG laser is recommended in patients with Hurley stage II or III disease on the basis of randomized, controlled trials and case series data, and in patients with Hurley stage I disease based on expert consensus. “Other wavelengths that are used for follicular destruction are recommended on the basis of lower-quality evidence,” the recommendations state.

The guidelines also state that CO2 laser excision “is recommended in patients with Hurley stage II or III disease with fibrotic sinus tracts” while “external beam radiation and PDT have a limited role in the management of patients with HS.”

Dr. DiGiorgio reported having no relevant disclosures.

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– Pilonidal disease – a chronic inflammatory condition that can trigger the formation of cysts and sinuses in the superior portion of the intragluteal cleft or the sacrococcygeal area – remains challenging to manage, but mounting evidence supports the use of lasers to enhance treatment success.

“Draining sinuses or acute abscesses are usually associated with an underlying cyst and associated granulation tissue, fibrosis, and tufts of hair,” Catherine M. DiGiorgio, MD, said at the annual conference of the American Society for Laser Medicine and Surgery. “This is why laser hair removal can help with the treatment of these patients.”

Dr. Catherine M. DiGiorgio

The suspected etiology is a foreign body reaction to the entrapped hairs, which are found in the sinuses in about 75% of cases. “The treatment for that is surgery,” said Dr. DiGiorgio, a laser and cosmetic dermatologist in Boston. Laser hair reduction decreases the recurrence of cyst formation and drainage, and is usually covered by insurance, she noted.
 

Supportive evidence

In a comparative study, French researchers retrospectively reviewed the efficacy of laser hair removal after surgery in reducing recurrence rate of pilonidal cysts, versus surgery alone. Of the 41 study participants, 12 had laser hair removal plus surgery and 29 had surgery alone. The rate of cyst recurrence was significantly lower in the laser hair removal plus surgery group, compared with the surgery only group (8.3% vs. 51.7%, respectively; P < .001).

In another study, researchers from the United Kingdom and The Johns Hopkins Hospital, Baltimore, evaluated the use of the long-pulsed Alexandrite laser in 19 patients with recurrent pilonidal disease who had undergone multiple surgeries.They were treated with the laser for hair removal in the sinus area, requiring 4-12 sessions. The researchers found that 84.2% of patients had a reduction of hair density to less than 5 hairs/cm2, while 15.8% had a reduction of hair density to 5-10 hairs/cm2. They also noted a statistically significant increase in disease-free time in the laser-treated group compared with those treated with surgical management only (P < .01).
 

Lasers for pseudofolliculitis barbae, HS

Lasers also play a significant role in the treatment of pseudofolliculitis barbae, a chronic, inflammatory disease that primarily affects the bearded area of men with thick hairs, usually those with a darker Fitzpatrick skin type. This can also occur in women, particularly those with polycystic ovary syndrome, Dr. DiGiorgio said.

In people with pseudofolliculitis barbae, the hair follicle is positioned at an acute angle to the skin surface and the sharp end of shaved hair reenters the skin, which results in the formation of pustules, papules, secondary infection, and keloids. Treatment involves a variety of medical therapies including retinoids, benzoyl peroxide, antibiotics, and keratolytics, “but laser hair removal is the best way to get rid of this issue, and results in permanent reduction,” she said. “When treating male patients with laser hair removal in the bearded area, you have to tell them that they won’t be able to grow a beard going forward. Most of them are okay with that.”

A 2002 study, led by E. Victor Ross, MD, of the Naval Medical Center, San Diego, evaluated treatment of pseudofolliculitis barbae in patients with skin types IV, V, and VI with a long-pulsed Nd:YAG laser. For the first phase of the study, the investigators tested epidermal tolerance on the thighs of 37 patients and determined that the laser was safe and effective. For the second phase 2 weeks later, they treated a 15x15-mm submental area with the highest fluence tolerated in phase 1 of the trial and used an adjacent site as the control.

After 90 days, the mean papule count was 6.95 for the control site compared with 1 for the laser-treated site. The researchers observed that miniaturization and elimination of hair shafts resulted in decreased inflamed papules. “We know that this works,” Dr. DiGiorgio said.

In another study from investigators at the Naval Medical Center, San Diego, 22 patients with skin types IV, V, and VI who had pseudofolliculitis barbae underwent 5 weekly treatments with a 1,064 nm Nd:YAG laser. Topical anesthesia was not used, and 10 evaluators used a Global Assessment Scale (GAS) to assess treatment success from photos taken at baseline and at 4 weeks. At 4 weeks, 11 patients demonstrated 83% improvement on the GAS (P < .01), the investigators reported.

Laser and energy-based treatments can also be used to treat hidradenitis suppurativa (HS), a chronic condition that affects apocrine gland–bearing skin. “The hypothesized pathogenesis is that it’s an inflammatory disorder of the hair follicle, where the follicle rupture introduces its contents into the surrounding dermis,” Dr. DiGiorgio said. “The skin reacts with a chemotactic response and abscess formation. This results in inflammatory nodules and sterile abscesses, which can lead to sinus tracts and hypertrophic scars and chronic drainage, which can be foul-smelling. This frequently leads to depression and psychological distress for the patients.”



Possible laser and energy-based treatments for HS include follicular destruction with the Nd:YAG laser, the diode laser, the Alexandrite laser, microwave technology, or intense pulsed light, she said. Microwave technology or radiofrequency can be used for sweat gland destruction, while CO2 lasers can be used to debulk tissue, and the ablative fractional CO2 laser can be used to reduce scarring and improve range of motion.

In a prospective, randomized, intraindividual comparative trial conducted at eight centers in France, researchers evaluated the use of a long-pulsed Nd:YAG laser to treat 36 patients with mild to moderate HS; 27 had inguinal disease and 9 had axillary disease. They received four laser treatments at 6-week intervals; laser settings varied depending on the patient skin type.

At 1 month, there was a significant reduction in the number of inflammatory lesions on the areas treated with lasers, compared to the untreated areas, but the difference was not significant at 3 months. There was no significant difference in the number of flares between the treated and untreated sites at 1 or 3 months.

In a separate study, researchers found that the Nd:YAG laser in combination with topical benzoyl peroxide and clindamycin was significantly more effective than topical benzoyl peroxide and clindamycin alone for the treatment of HS in 22 patients with Hurley stage II disease. The patients received monthly treatments for 4 months and were followed up 2 months after the last treatment; the Hidradenitis Suppurativa Area and Severity Index was used to measure treatment response.

Statistically significant improvements were observed in the inguinal and axillary areas but not in the inframammary areas. Most patients (90%) reported less frequent breakouts while 10% reported no change. “In addition, 92% of subjects felt that the use of laser was more effective than other treatments they had tried but 8% stated it was equal to the other treatments they had tried,” said Dr. DiGiorgio, who was not affiliated with the study. “The researchers noted continued improvement with subsequent laser sessions,” she added.

According to 2019 guidelines from the United States and Canadian HS Foundations on the management of HS – in the section on light, laser, and energy sources – an Nd:YAG laser is recommended in patients with Hurley stage II or III disease on the basis of randomized, controlled trials and case series data, and in patients with Hurley stage I disease based on expert consensus. “Other wavelengths that are used for follicular destruction are recommended on the basis of lower-quality evidence,” the recommendations state.

The guidelines also state that CO2 laser excision “is recommended in patients with Hurley stage II or III disease with fibrotic sinus tracts” while “external beam radiation and PDT have a limited role in the management of patients with HS.”

Dr. DiGiorgio reported having no relevant disclosures.

– Pilonidal disease – a chronic inflammatory condition that can trigger the formation of cysts and sinuses in the superior portion of the intragluteal cleft or the sacrococcygeal area – remains challenging to manage, but mounting evidence supports the use of lasers to enhance treatment success.

“Draining sinuses or acute abscesses are usually associated with an underlying cyst and associated granulation tissue, fibrosis, and tufts of hair,” Catherine M. DiGiorgio, MD, said at the annual conference of the American Society for Laser Medicine and Surgery. “This is why laser hair removal can help with the treatment of these patients.”

Dr. Catherine M. DiGiorgio

The suspected etiology is a foreign body reaction to the entrapped hairs, which are found in the sinuses in about 75% of cases. “The treatment for that is surgery,” said Dr. DiGiorgio, a laser and cosmetic dermatologist in Boston. Laser hair reduction decreases the recurrence of cyst formation and drainage, and is usually covered by insurance, she noted.
 

Supportive evidence

In a comparative study, French researchers retrospectively reviewed the efficacy of laser hair removal after surgery in reducing recurrence rate of pilonidal cysts, versus surgery alone. Of the 41 study participants, 12 had laser hair removal plus surgery and 29 had surgery alone. The rate of cyst recurrence was significantly lower in the laser hair removal plus surgery group, compared with the surgery only group (8.3% vs. 51.7%, respectively; P < .001).

In another study, researchers from the United Kingdom and The Johns Hopkins Hospital, Baltimore, evaluated the use of the long-pulsed Alexandrite laser in 19 patients with recurrent pilonidal disease who had undergone multiple surgeries.They were treated with the laser for hair removal in the sinus area, requiring 4-12 sessions. The researchers found that 84.2% of patients had a reduction of hair density to less than 5 hairs/cm2, while 15.8% had a reduction of hair density to 5-10 hairs/cm2. They also noted a statistically significant increase in disease-free time in the laser-treated group compared with those treated with surgical management only (P < .01).
 

Lasers for pseudofolliculitis barbae, HS

Lasers also play a significant role in the treatment of pseudofolliculitis barbae, a chronic, inflammatory disease that primarily affects the bearded area of men with thick hairs, usually those with a darker Fitzpatrick skin type. This can also occur in women, particularly those with polycystic ovary syndrome, Dr. DiGiorgio said.

In people with pseudofolliculitis barbae, the hair follicle is positioned at an acute angle to the skin surface and the sharp end of shaved hair reenters the skin, which results in the formation of pustules, papules, secondary infection, and keloids. Treatment involves a variety of medical therapies including retinoids, benzoyl peroxide, antibiotics, and keratolytics, “but laser hair removal is the best way to get rid of this issue, and results in permanent reduction,” she said. “When treating male patients with laser hair removal in the bearded area, you have to tell them that they won’t be able to grow a beard going forward. Most of them are okay with that.”

A 2002 study, led by E. Victor Ross, MD, of the Naval Medical Center, San Diego, evaluated treatment of pseudofolliculitis barbae in patients with skin types IV, V, and VI with a long-pulsed Nd:YAG laser. For the first phase of the study, the investigators tested epidermal tolerance on the thighs of 37 patients and determined that the laser was safe and effective. For the second phase 2 weeks later, they treated a 15x15-mm submental area with the highest fluence tolerated in phase 1 of the trial and used an adjacent site as the control.

After 90 days, the mean papule count was 6.95 for the control site compared with 1 for the laser-treated site. The researchers observed that miniaturization and elimination of hair shafts resulted in decreased inflamed papules. “We know that this works,” Dr. DiGiorgio said.

In another study from investigators at the Naval Medical Center, San Diego, 22 patients with skin types IV, V, and VI who had pseudofolliculitis barbae underwent 5 weekly treatments with a 1,064 nm Nd:YAG laser. Topical anesthesia was not used, and 10 evaluators used a Global Assessment Scale (GAS) to assess treatment success from photos taken at baseline and at 4 weeks. At 4 weeks, 11 patients demonstrated 83% improvement on the GAS (P < .01), the investigators reported.

Laser and energy-based treatments can also be used to treat hidradenitis suppurativa (HS), a chronic condition that affects apocrine gland–bearing skin. “The hypothesized pathogenesis is that it’s an inflammatory disorder of the hair follicle, where the follicle rupture introduces its contents into the surrounding dermis,” Dr. DiGiorgio said. “The skin reacts with a chemotactic response and abscess formation. This results in inflammatory nodules and sterile abscesses, which can lead to sinus tracts and hypertrophic scars and chronic drainage, which can be foul-smelling. This frequently leads to depression and psychological distress for the patients.”



Possible laser and energy-based treatments for HS include follicular destruction with the Nd:YAG laser, the diode laser, the Alexandrite laser, microwave technology, or intense pulsed light, she said. Microwave technology or radiofrequency can be used for sweat gland destruction, while CO2 lasers can be used to debulk tissue, and the ablative fractional CO2 laser can be used to reduce scarring and improve range of motion.

In a prospective, randomized, intraindividual comparative trial conducted at eight centers in France, researchers evaluated the use of a long-pulsed Nd:YAG laser to treat 36 patients with mild to moderate HS; 27 had inguinal disease and 9 had axillary disease. They received four laser treatments at 6-week intervals; laser settings varied depending on the patient skin type.

At 1 month, there was a significant reduction in the number of inflammatory lesions on the areas treated with lasers, compared to the untreated areas, but the difference was not significant at 3 months. There was no significant difference in the number of flares between the treated and untreated sites at 1 or 3 months.

In a separate study, researchers found that the Nd:YAG laser in combination with topical benzoyl peroxide and clindamycin was significantly more effective than topical benzoyl peroxide and clindamycin alone for the treatment of HS in 22 patients with Hurley stage II disease. The patients received monthly treatments for 4 months and were followed up 2 months after the last treatment; the Hidradenitis Suppurativa Area and Severity Index was used to measure treatment response.

Statistically significant improvements were observed in the inguinal and axillary areas but not in the inframammary areas. Most patients (90%) reported less frequent breakouts while 10% reported no change. “In addition, 92% of subjects felt that the use of laser was more effective than other treatments they had tried but 8% stated it was equal to the other treatments they had tried,” said Dr. DiGiorgio, who was not affiliated with the study. “The researchers noted continued improvement with subsequent laser sessions,” she added.

According to 2019 guidelines from the United States and Canadian HS Foundations on the management of HS – in the section on light, laser, and energy sources – an Nd:YAG laser is recommended in patients with Hurley stage II or III disease on the basis of randomized, controlled trials and case series data, and in patients with Hurley stage I disease based on expert consensus. “Other wavelengths that are used for follicular destruction are recommended on the basis of lower-quality evidence,” the recommendations state.

The guidelines also state that CO2 laser excision “is recommended in patients with Hurley stage II or III disease with fibrotic sinus tracts” while “external beam radiation and PDT have a limited role in the management of patients with HS.”

Dr. DiGiorgio reported having no relevant disclosures.

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Fractional lasers appear to treat more than a fraction of skin, expert says

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– Using the ablative fractional laser and other wounding therapies to destroy actinic keratoses (AKs) as a way to prevent skin cancer appears to spark other beneficial effects on skin biology, according to Molly Wanner, MD, MBA.

As a case in point, Dr. Wanner discussed the results of a trial of 48 people over aged 60 years with actinic damage, who received ablative fractional laser treatment on one arm and no treatment on the other arm, which served as the control. At 24 months, only two nonmelanoma skin cancers (NMSCs) developed on the treated arms, compared with 26 on the treated arms.

“What I find interesting is that the treated arm did not develop basal cell carcinoma, only squamous cell carcinoma,” she said at the annual meeting of the American Society for Laser Medicine and Surgery. “It appears that this is working through more than just treatment of the AK precursor lesions, for which fractional lasers are cleared for use. It appears to impact both types of NMSCs.”

The ablative fractional laser and other wounding therapies can modulate a response to UV light – a process that naturally diminishes with age, according to Dr. Wanner, a dermatologist at Massachusetts General Hospital’s Dermatology Laser and Cosmetic Center in Boston. “This ability to repair DNA is actually modulated by insulin-like growth factor 1,” she said. “IGF-1 is produced by papillary dermal fibroblasts and communicates with keratinocytes. If keratinocytes are exposed to UV light and there is no IGF-1 around, you get a mutated cell, and that keeps spreading, and you could potentially get a skin cancer.”

On the other hand, she continued, if IGF-1 is injected around the keratinocytes, they are able to respond. “Keratinocytes, which are the most superficial layer of the skin, are really active,” noted Dr. Wanner, who is also an assistant professor of dermatology at Harvard Medical School, Boston. “They’re dividing and replicating, whereas fibroblasts are more non-proliferative and more long-lived. They stick around for a long time. I think of them as the adults in the room, giving these new keratinocytes direction.”



In a review of wounding therapies for the prevention of photocarcinogenesis, she and her coauthors noted that IGF-1 increases nucleotide excision repair of damaged DNA, promotes checkpoint signaling and suppression of DNA synthesis, favors specialized polymerases that are better able to repair DNA damage, and enhances p53-dependent transcriptional responses to DNA damage.

“Older fibroblasts produce less IGF-1 and lead to a situation where keratinocytes can grow unchecked,” she said. “We can use fractional laser to help with this. Fractional laser increases fibroblast production and decreases senescent fibroblasts.”

In a 2017 review on the impact of age and IGF-1 on DNA damage responses in UV-irradiated skin, the authors noted the high levels of IGF-1 in the skin of younger individuals and lower levels in the skin of their older counterparts.

“But once older skin has been treated with either dermabrasion or fractional laser, the levels of IGF-1 are restored to that of a young adult,” Dr. Wanner said. “The restoration of IGF-1 then restores that level of appropriate response to UV light. So, what’s interesting is that fractional lasers treat more than a fraction [of skin]. Fractional lasers were developed to have an easier way to improve wound healing by leaving the skin intact around these columns [of treated skin]. It turns out that treatment of these columns of skin does not just impact the cells in that area. There is a true global effect that’s allowing us to almost normalize skin.”

Dr. Wanner now thinks of fractional lasers as stimulating a laser-cell biology interaction, not just a laser-tissue interaction. “It’s incredible that we can use these photons to not only impact the tissue itself but how the cells actually respond,” she said. “What’s going to be interesting for us in the next few years is to look at how lasers impact our cellular biology. How can we harness it to help our patients?”

She and her colleagues are conducting a trial of different wounding modalities to assess their impact on IGF-1. “Does depth matter? Does density matter? Does the wavelength matter?” she asked. “The bottom line is, it turns out that when the skin looks healthier, it is healthier. Cosmetic treatments can impact medical outcomes.”

Dr. Wanner disclosed that she is a consultant and advisor to Nu Skin. She has also received research funding and equipment from Solta.

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– Using the ablative fractional laser and other wounding therapies to destroy actinic keratoses (AKs) as a way to prevent skin cancer appears to spark other beneficial effects on skin biology, according to Molly Wanner, MD, MBA.

As a case in point, Dr. Wanner discussed the results of a trial of 48 people over aged 60 years with actinic damage, who received ablative fractional laser treatment on one arm and no treatment on the other arm, which served as the control. At 24 months, only two nonmelanoma skin cancers (NMSCs) developed on the treated arms, compared with 26 on the treated arms.

“What I find interesting is that the treated arm did not develop basal cell carcinoma, only squamous cell carcinoma,” she said at the annual meeting of the American Society for Laser Medicine and Surgery. “It appears that this is working through more than just treatment of the AK precursor lesions, for which fractional lasers are cleared for use. It appears to impact both types of NMSCs.”

The ablative fractional laser and other wounding therapies can modulate a response to UV light – a process that naturally diminishes with age, according to Dr. Wanner, a dermatologist at Massachusetts General Hospital’s Dermatology Laser and Cosmetic Center in Boston. “This ability to repair DNA is actually modulated by insulin-like growth factor 1,” she said. “IGF-1 is produced by papillary dermal fibroblasts and communicates with keratinocytes. If keratinocytes are exposed to UV light and there is no IGF-1 around, you get a mutated cell, and that keeps spreading, and you could potentially get a skin cancer.”

On the other hand, she continued, if IGF-1 is injected around the keratinocytes, they are able to respond. “Keratinocytes, which are the most superficial layer of the skin, are really active,” noted Dr. Wanner, who is also an assistant professor of dermatology at Harvard Medical School, Boston. “They’re dividing and replicating, whereas fibroblasts are more non-proliferative and more long-lived. They stick around for a long time. I think of them as the adults in the room, giving these new keratinocytes direction.”



In a review of wounding therapies for the prevention of photocarcinogenesis, she and her coauthors noted that IGF-1 increases nucleotide excision repair of damaged DNA, promotes checkpoint signaling and suppression of DNA synthesis, favors specialized polymerases that are better able to repair DNA damage, and enhances p53-dependent transcriptional responses to DNA damage.

“Older fibroblasts produce less IGF-1 and lead to a situation where keratinocytes can grow unchecked,” she said. “We can use fractional laser to help with this. Fractional laser increases fibroblast production and decreases senescent fibroblasts.”

In a 2017 review on the impact of age and IGF-1 on DNA damage responses in UV-irradiated skin, the authors noted the high levels of IGF-1 in the skin of younger individuals and lower levels in the skin of their older counterparts.

“But once older skin has been treated with either dermabrasion or fractional laser, the levels of IGF-1 are restored to that of a young adult,” Dr. Wanner said. “The restoration of IGF-1 then restores that level of appropriate response to UV light. So, what’s interesting is that fractional lasers treat more than a fraction [of skin]. Fractional lasers were developed to have an easier way to improve wound healing by leaving the skin intact around these columns [of treated skin]. It turns out that treatment of these columns of skin does not just impact the cells in that area. There is a true global effect that’s allowing us to almost normalize skin.”

Dr. Wanner now thinks of fractional lasers as stimulating a laser-cell biology interaction, not just a laser-tissue interaction. “It’s incredible that we can use these photons to not only impact the tissue itself but how the cells actually respond,” she said. “What’s going to be interesting for us in the next few years is to look at how lasers impact our cellular biology. How can we harness it to help our patients?”

She and her colleagues are conducting a trial of different wounding modalities to assess their impact on IGF-1. “Does depth matter? Does density matter? Does the wavelength matter?” she asked. “The bottom line is, it turns out that when the skin looks healthier, it is healthier. Cosmetic treatments can impact medical outcomes.”

Dr. Wanner disclosed that she is a consultant and advisor to Nu Skin. She has also received research funding and equipment from Solta.

– Using the ablative fractional laser and other wounding therapies to destroy actinic keratoses (AKs) as a way to prevent skin cancer appears to spark other beneficial effects on skin biology, according to Molly Wanner, MD, MBA.

As a case in point, Dr. Wanner discussed the results of a trial of 48 people over aged 60 years with actinic damage, who received ablative fractional laser treatment on one arm and no treatment on the other arm, which served as the control. At 24 months, only two nonmelanoma skin cancers (NMSCs) developed on the treated arms, compared with 26 on the treated arms.

“What I find interesting is that the treated arm did not develop basal cell carcinoma, only squamous cell carcinoma,” she said at the annual meeting of the American Society for Laser Medicine and Surgery. “It appears that this is working through more than just treatment of the AK precursor lesions, for which fractional lasers are cleared for use. It appears to impact both types of NMSCs.”

The ablative fractional laser and other wounding therapies can modulate a response to UV light – a process that naturally diminishes with age, according to Dr. Wanner, a dermatologist at Massachusetts General Hospital’s Dermatology Laser and Cosmetic Center in Boston. “This ability to repair DNA is actually modulated by insulin-like growth factor 1,” she said. “IGF-1 is produced by papillary dermal fibroblasts and communicates with keratinocytes. If keratinocytes are exposed to UV light and there is no IGF-1 around, you get a mutated cell, and that keeps spreading, and you could potentially get a skin cancer.”

On the other hand, she continued, if IGF-1 is injected around the keratinocytes, they are able to respond. “Keratinocytes, which are the most superficial layer of the skin, are really active,” noted Dr. Wanner, who is also an assistant professor of dermatology at Harvard Medical School, Boston. “They’re dividing and replicating, whereas fibroblasts are more non-proliferative and more long-lived. They stick around for a long time. I think of them as the adults in the room, giving these new keratinocytes direction.”



In a review of wounding therapies for the prevention of photocarcinogenesis, she and her coauthors noted that IGF-1 increases nucleotide excision repair of damaged DNA, promotes checkpoint signaling and suppression of DNA synthesis, favors specialized polymerases that are better able to repair DNA damage, and enhances p53-dependent transcriptional responses to DNA damage.

“Older fibroblasts produce less IGF-1 and lead to a situation where keratinocytes can grow unchecked,” she said. “We can use fractional laser to help with this. Fractional laser increases fibroblast production and decreases senescent fibroblasts.”

In a 2017 review on the impact of age and IGF-1 on DNA damage responses in UV-irradiated skin, the authors noted the high levels of IGF-1 in the skin of younger individuals and lower levels in the skin of their older counterparts.

“But once older skin has been treated with either dermabrasion or fractional laser, the levels of IGF-1 are restored to that of a young adult,” Dr. Wanner said. “The restoration of IGF-1 then restores that level of appropriate response to UV light. So, what’s interesting is that fractional lasers treat more than a fraction [of skin]. Fractional lasers were developed to have an easier way to improve wound healing by leaving the skin intact around these columns [of treated skin]. It turns out that treatment of these columns of skin does not just impact the cells in that area. There is a true global effect that’s allowing us to almost normalize skin.”

Dr. Wanner now thinks of fractional lasers as stimulating a laser-cell biology interaction, not just a laser-tissue interaction. “It’s incredible that we can use these photons to not only impact the tissue itself but how the cells actually respond,” she said. “What’s going to be interesting for us in the next few years is to look at how lasers impact our cellular biology. How can we harness it to help our patients?”

She and her colleagues are conducting a trial of different wounding modalities to assess their impact on IGF-1. “Does depth matter? Does density matter? Does the wavelength matter?” she asked. “The bottom line is, it turns out that when the skin looks healthier, it is healthier. Cosmetic treatments can impact medical outcomes.”

Dr. Wanner disclosed that she is a consultant and advisor to Nu Skin. She has also received research funding and equipment from Solta.

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Abortion debate may affect Rx decisions for pregnant women

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Tue, 02/07/2023 - 16:40

Obstetrician Beverly Gray, MD, is already seeing the effects of the Roe v. Wade abortion debate in her North Carolina practice.

Dr. Beverly Gray

The state allows abortion but requires that women get counseling with a qualified health professional 72 hours before the procedure. “Aside from that, we still have patients asking for more efficacious contraceptive methods just in case,” said Dr. Gray, residency director and division director for women’s community and population health and associate professor for obstetrics and gynecology at Duke University, Durham, N.C.

Patients and staff in her clinic have also been approaching her about tubal ligation. “They’re asking about additional birth control methods because they’re concerned about what’s going to happen” with the challenge to the historic Roe v. Wade decision in the Supreme Court and subsequent actions in the states to restrict or ban abortion, she said.

This has implications not just for abortion but for medications known to affect pregnancy. “What I’m really worried about is physicians will be withholding medicine because they’re concerned about teratogenic effects,” said Dr. Gray.

With more states issuing restrictions on abortion, doctors are worried that patients needing certain drugs to maintain their lupus flares, cancer, or other diseases may decide not to take them in the event they accidentally become pregnant. If the drug is known to affect the fetus, the fear is a patient who lives in a state with abortion restrictions will no longer have the option to terminate a pregnancy.

zoranm/Getty Images


Instead, a scenario may arise in which the patient – and their physician – may opt not to treat at all with an otherwise lifesaving medication, experts told this news organization.
 

The U.S. landscape on abortion restrictions

A leaked draft of a U.S. Supreme Court opinion on Mississippi’s 15-week abortion ban has sent the medical community into a tailspin. The case, Dobbs v. Jackson Women’s Health Organization, challenges the 1973 Roe v. Wade decision that affirms the constitutional right to abortion. It’s anticipated the high court will decide on the case in June.

Although the upcoming decision is subject to change, the draft indicated the high court would uphold the Mississippi ban. This would essentially overturn the 1973 ruling. An earlier Supreme Court decision allowing a Texas law banning abortion at 6 weeks suggests the court may already be heading in this direction. At the state level, legislatures have been moving on divergent paths – some taking steps to preserve abortion rights, others initiating restrictions.

More than 100 abortion restrictions in 19 states took effect in 2021, according to the Guttmacher Institute, which tracks such metrics. In 2022, “two key themes are anti-abortion policymakers’ continued pursuit of various types of abortion bans and restrictions on medication abortion,” the institute reported.

Forty-six states and the District of Columbia have introduced 2,025 restrictions or proactive measures on sexual and reproductive health and rights so far this year. The latest tally from Guttmacher, updated in late May, revealed that 11 states so far have enacted 42 abortion restrictions. A total of 6 states (Arizona, Florida, Idaho, Kentucky, Oklahoma, and Wyoming) have issued nine bans on abortion.

Comparatively, 11 states have enacted 19 protective abortion measures.

Twenty-two states have introduced 117 restrictions on medication abortions, which account for 54% of U.S. abortions. This includes seven measures that would ban medication abortion outright, according to Guttmacher. Kentucky and South Dakota collectively have enacted 14 restrictions on medication abortion, as well as provisions that ban mailing of abortion pills.
 

 

 

Chilling effect on prescribing

Some physicians anticipate that drugs such as the “morning-after” pill (levonorgestrel) will become less available as restrictions go into effect, since these are medications designed to prevent pregnancy.*

However, the ongoing effort to put a lid on abortion measures has prompted concerns about a trickle-down effect on other medications that are otherwise life-changing or lifesaving to patients but pose a risk to the fetus.

Several drugs are well documented to affect fetal growth and development of the fetus, ranging from mild, transitory effects to severe, permanent birth defects, said Ronald G. Grifka, MD, chief medical officer of University of Michigan Health-West and clinical professor of pediatrics at the University of Michigan Medical School, Ann Arbor. “As new medications are developed, we will need heightened attention to make sure they are safe for the fetus,” he added.

Dr. Ronald G. Grifka


Certain teratogenic medications are associated with a high risk of abortion even though this isn’t their primary use, noted Christina Chambers, PhD, MPH, co-director of the Center for Better Beginnings and associate director with the Altman Clinical & Translational Research Institute at the University of California, San Diego.

Christina Chambers
Dr. Christina Chambers


“I don’t think anyone would intentionally take these drugs to induce spontaneous abortion. But if the drugs pose a risk for it, I can see how the laws might be stretched” to include them, said Dr. Chambers.

Methotrexate, a medication for autoimmune disorders, has a high risk of spontaneous abortion. So do acne medications such as isotretinoin.

Patients are usually told they’re not supposed to get pregnant on these drugs because there’s a high risk of pregnancy loss and risk of malformations and potential learning problems in the fetus. But many pregnancies aren’t planned, said Dr. Chambers. “Patients may forget about the side effects or think their birth control will protect them. And the next time they refill the medication, they may not hear about the warnings again.”

With a restrictive abortion law or ban in effect, a woman might think: “I won’t take this drug because if there’s any potential that I might get pregnant, I won’t have the option to abort an at-risk pregnancy.” Women and their doctors, for that matter, don’t want to put themselves in this position, said Dr. Chambers.

Rheumatologist Megan Clowse, MD, who prescribes several medications that potentially cause major birth defects and pregnancy loss, worries about the ramifications of these accumulating bans.

Dr. Megan Clowse


“Methotrexate has been a leading drug for us for decades for rheumatoid arthritis. Mycophenolate is a vital drug for lupus,” said Dr. Clowse, associate professor of medicine at Duke University’s division of rheumatology and immunology.

Both methotrexate and mycophenolate pose about a 40% risk of pregnancy loss and significantly increase the risk for birth defects. “I’m definitely concerned that there might be doctors or women who elect not to use those medications in women of reproductive age because of the potential risk for pregnancy and absence of abortion rights,” said Dr. Clowse.

These situations might force women to use contraceptives they don’t want to use, such as hormonal implants or intrauterine devices, she added. Another side effect is that women and their partners may decide to abstain from sex.
 

 

 

The iPLEDGE factor

Some rheumatology drugs like lenalidomide (Revlimid) require a valid negative pregnancy test in a lab every month. Similarly, the iPLEDGE Risk Evaluation and Mitigation Strategy seeks to reduce the teratogenicity of isotretinoin by requiring two types of birth control and regular pregnancy tests by users.

For isotretinoin specifically, abortion restrictions “could lead to increased adherence to pregnancy prevention measures which are already stringent in iPLEDGE. But on the other hand, it could lead to reduced willingness of physicians to prescribe or patients to take the medication,” said Dr. Chambers.

With programs like iPLEDGE in effect, the rate of pregnancies and abortions that occur in dermatology are relatively low, said Jenny Murase, MD, associate clinical professor of dermatology at the University of California, San Francisco.

Dr. Jenny E. Murase


Nevertheless, as a physician who regularly prescribes medications like isotretinoin in women of childbearing age, “it’s terrifying to me that a woman wouldn’t have the option to terminate the pregnancy if a teratogenic effect from the medication caused a severe birth defect,” said Dr. Murase. 

Dermatologists use other teratogenic medications such as thalidomide, mycophenolate mofetil, and methotrexate for chronic dermatologic disease like psoriasis and atopic dermatitis. 

The situation is especially tricky for dermatologists since most patients – about 80% – never discuss their pregnancy with their specialist prior to pregnancy initiation. Dr. Murase recalls when a patient with chronic plaque psoriasis on methotrexate in her late 40s became pregnant and had an abortion even before Dr. Murase became aware of the pregnancy. 

Because dermatologists routinely prescribe long-term medications for chronic diseases like acne, psoriasis, and atopic dermatitis, it is important to have a conversation regarding the risks and benefits of long-term medication should a pregnancy occur in any woman of childbearing age, she said.
 

Fewer women in clinical trials?

Abortion restrictions could possibly discourage women of reproductive age to participate in a clinical trial for a new medication, said Dr. Chambers.

A female patient with a chronic disease who’s randomized to receive a new medication may be required to use certain types of birth control because of unknown potential adverse effects the drug may have on the fetus. But in some cases, accidental pregnancies happen.

The participant in the trial may say, “I don’t know enough about the safety of this drug in pregnancy, and I’ve already taken it. I want to terminate the pregnancy,” said Dr. Chambers. Thinking ahead, a woman may decide not to do the trial to avoid the risk of getting pregnant and not having the option to terminate the pregnancy.

This could apply to new drugs such as antiviral treatments, or medications for severe chronic disease that typically have no clinical trial data in pregnancy prior to initial release into the market.

Women may start taking the drug without thinking about getting pregnant, then realize there are no safety data and become concerned about its effects on a future pregnancy.

The question is: Will abortion restrictions have a chilling effect on these new drugs as well? Patients and their doctors may decide not to try it until more data are available. “I can see where abortion restrictions would change the risk or benefit calculation in thinking about what you do or don’t prescribe or take during reproductive age,” said Dr. Chambers.
 

 

 

The upside of restrictions?

If there’s a positive side to these developments with abortion bans, it may encourage women taking new medications or joining clinical trials to think even more carefully about adherence to effective contraception, said Dr. Chambers.

Some methods are more effective than others, she emphasized. “When you have an unplanned pregnancy, it could mean that the method you used wasn’t optimal or you weren’t using it as recommended.” A goal moving forward is to encourage more thoughtful use of highly effective contraceptives, thus reducing the number of unplanned pregnancies, she added.

If patients are taking methotrexate, “the time to think about pregnancy is before getting pregnant so you can switch to a drug that’s compatible with pregnancy,” she said.

This whole thought process regarding pregnancy planning could work toward useful health goals, said Dr. Chambers. “Nobody thinks termination is the preferred method, but planning ahead should involve a discussion of what works best for the patient.”

Patients do have other choices, said Dr. Grifka. “Fortunately, there are many commonly prescribed medications which cross the placenta and have no ill effects on the fetus.”

Talking to patients about choices

Dr. Clowse, who spends a lot of time training rheumatologists, encourages them to have conversations with patients about pregnancy planning. It’s a lot to manage, getting the right drug to a female patient with chronic illness, especially in this current climate of abortion upheaval, she noted.

Her approach is to have an open and honest conversation with patients about their concerns and fears, what the realities are, and what the potential future options are for certain rheumatology drugs in the United States.

Some women who see what’s happening across the country may become so risk averse that they may choose to die rather than take a lifesaving drug that poses certain risks under new restrictions.

“I think that’s tragic,” said Dr. Clowse.

To help their patients, Dr. Gray believes physicians across specialties should better educate themselves about physiology in pregnancy and how to counsel patients on the impact of not taking medications in pregnancy.

In her view, it’s almost coercive to say to a patient, “You really need to have effective contraception if I’m going to give you this lifesaving or quality-of-life-improving medication.”

When confronting such scenarios, Dr. Gray doesn’t think physicians need to change how they counsel patients about contraception. “I don’t think we should be putting pressure on patients to consider other permanent methods just because there’s a lack of abortion options.”

Patients will eventually make those decisions for themselves, she said. “They’re going to want a more efficacious method because they’re worried about not having access to abortion if they get pregnant.”

Dr. Gray reports being a site principal investigator for a phase 3 trial for VeraCept IUD, funded by Sebela Pharmaceuticals. Dr. Clowse reports receiving research funding and doing consulting for GlaxoSmithKline.

*Correction, 6/2/2022: A previous version of this article misstated the intended use of drugs such as the “morning-after” pill (levonorgestrel). They are taken to prevent unintended pregnancy.

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

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Obstetrician Beverly Gray, MD, is already seeing the effects of the Roe v. Wade abortion debate in her North Carolina practice.

Dr. Beverly Gray

The state allows abortion but requires that women get counseling with a qualified health professional 72 hours before the procedure. “Aside from that, we still have patients asking for more efficacious contraceptive methods just in case,” said Dr. Gray, residency director and division director for women’s community and population health and associate professor for obstetrics and gynecology at Duke University, Durham, N.C.

Patients and staff in her clinic have also been approaching her about tubal ligation. “They’re asking about additional birth control methods because they’re concerned about what’s going to happen” with the challenge to the historic Roe v. Wade decision in the Supreme Court and subsequent actions in the states to restrict or ban abortion, she said.

This has implications not just for abortion but for medications known to affect pregnancy. “What I’m really worried about is physicians will be withholding medicine because they’re concerned about teratogenic effects,” said Dr. Gray.

With more states issuing restrictions on abortion, doctors are worried that patients needing certain drugs to maintain their lupus flares, cancer, or other diseases may decide not to take them in the event they accidentally become pregnant. If the drug is known to affect the fetus, the fear is a patient who lives in a state with abortion restrictions will no longer have the option to terminate a pregnancy.

zoranm/Getty Images


Instead, a scenario may arise in which the patient – and their physician – may opt not to treat at all with an otherwise lifesaving medication, experts told this news organization.
 

The U.S. landscape on abortion restrictions

A leaked draft of a U.S. Supreme Court opinion on Mississippi’s 15-week abortion ban has sent the medical community into a tailspin. The case, Dobbs v. Jackson Women’s Health Organization, challenges the 1973 Roe v. Wade decision that affirms the constitutional right to abortion. It’s anticipated the high court will decide on the case in June.

Although the upcoming decision is subject to change, the draft indicated the high court would uphold the Mississippi ban. This would essentially overturn the 1973 ruling. An earlier Supreme Court decision allowing a Texas law banning abortion at 6 weeks suggests the court may already be heading in this direction. At the state level, legislatures have been moving on divergent paths – some taking steps to preserve abortion rights, others initiating restrictions.

More than 100 abortion restrictions in 19 states took effect in 2021, according to the Guttmacher Institute, which tracks such metrics. In 2022, “two key themes are anti-abortion policymakers’ continued pursuit of various types of abortion bans and restrictions on medication abortion,” the institute reported.

Forty-six states and the District of Columbia have introduced 2,025 restrictions or proactive measures on sexual and reproductive health and rights so far this year. The latest tally from Guttmacher, updated in late May, revealed that 11 states so far have enacted 42 abortion restrictions. A total of 6 states (Arizona, Florida, Idaho, Kentucky, Oklahoma, and Wyoming) have issued nine bans on abortion.

Comparatively, 11 states have enacted 19 protective abortion measures.

Twenty-two states have introduced 117 restrictions on medication abortions, which account for 54% of U.S. abortions. This includes seven measures that would ban medication abortion outright, according to Guttmacher. Kentucky and South Dakota collectively have enacted 14 restrictions on medication abortion, as well as provisions that ban mailing of abortion pills.
 

 

 

Chilling effect on prescribing

Some physicians anticipate that drugs such as the “morning-after” pill (levonorgestrel) will become less available as restrictions go into effect, since these are medications designed to prevent pregnancy.*

However, the ongoing effort to put a lid on abortion measures has prompted concerns about a trickle-down effect on other medications that are otherwise life-changing or lifesaving to patients but pose a risk to the fetus.

Several drugs are well documented to affect fetal growth and development of the fetus, ranging from mild, transitory effects to severe, permanent birth defects, said Ronald G. Grifka, MD, chief medical officer of University of Michigan Health-West and clinical professor of pediatrics at the University of Michigan Medical School, Ann Arbor. “As new medications are developed, we will need heightened attention to make sure they are safe for the fetus,” he added.

Dr. Ronald G. Grifka


Certain teratogenic medications are associated with a high risk of abortion even though this isn’t their primary use, noted Christina Chambers, PhD, MPH, co-director of the Center for Better Beginnings and associate director with the Altman Clinical & Translational Research Institute at the University of California, San Diego.

Christina Chambers
Dr. Christina Chambers


“I don’t think anyone would intentionally take these drugs to induce spontaneous abortion. But if the drugs pose a risk for it, I can see how the laws might be stretched” to include them, said Dr. Chambers.

Methotrexate, a medication for autoimmune disorders, has a high risk of spontaneous abortion. So do acne medications such as isotretinoin.

Patients are usually told they’re not supposed to get pregnant on these drugs because there’s a high risk of pregnancy loss and risk of malformations and potential learning problems in the fetus. But many pregnancies aren’t planned, said Dr. Chambers. “Patients may forget about the side effects or think their birth control will protect them. And the next time they refill the medication, they may not hear about the warnings again.”

With a restrictive abortion law or ban in effect, a woman might think: “I won’t take this drug because if there’s any potential that I might get pregnant, I won’t have the option to abort an at-risk pregnancy.” Women and their doctors, for that matter, don’t want to put themselves in this position, said Dr. Chambers.

Rheumatologist Megan Clowse, MD, who prescribes several medications that potentially cause major birth defects and pregnancy loss, worries about the ramifications of these accumulating bans.

Dr. Megan Clowse


“Methotrexate has been a leading drug for us for decades for rheumatoid arthritis. Mycophenolate is a vital drug for lupus,” said Dr. Clowse, associate professor of medicine at Duke University’s division of rheumatology and immunology.

Both methotrexate and mycophenolate pose about a 40% risk of pregnancy loss and significantly increase the risk for birth defects. “I’m definitely concerned that there might be doctors or women who elect not to use those medications in women of reproductive age because of the potential risk for pregnancy and absence of abortion rights,” said Dr. Clowse.

These situations might force women to use contraceptives they don’t want to use, such as hormonal implants or intrauterine devices, she added. Another side effect is that women and their partners may decide to abstain from sex.
 

 

 

The iPLEDGE factor

Some rheumatology drugs like lenalidomide (Revlimid) require a valid negative pregnancy test in a lab every month. Similarly, the iPLEDGE Risk Evaluation and Mitigation Strategy seeks to reduce the teratogenicity of isotretinoin by requiring two types of birth control and regular pregnancy tests by users.

For isotretinoin specifically, abortion restrictions “could lead to increased adherence to pregnancy prevention measures which are already stringent in iPLEDGE. But on the other hand, it could lead to reduced willingness of physicians to prescribe or patients to take the medication,” said Dr. Chambers.

With programs like iPLEDGE in effect, the rate of pregnancies and abortions that occur in dermatology are relatively low, said Jenny Murase, MD, associate clinical professor of dermatology at the University of California, San Francisco.

Dr. Jenny E. Murase


Nevertheless, as a physician who regularly prescribes medications like isotretinoin in women of childbearing age, “it’s terrifying to me that a woman wouldn’t have the option to terminate the pregnancy if a teratogenic effect from the medication caused a severe birth defect,” said Dr. Murase. 

Dermatologists use other teratogenic medications such as thalidomide, mycophenolate mofetil, and methotrexate for chronic dermatologic disease like psoriasis and atopic dermatitis. 

The situation is especially tricky for dermatologists since most patients – about 80% – never discuss their pregnancy with their specialist prior to pregnancy initiation. Dr. Murase recalls when a patient with chronic plaque psoriasis on methotrexate in her late 40s became pregnant and had an abortion even before Dr. Murase became aware of the pregnancy. 

Because dermatologists routinely prescribe long-term medications for chronic diseases like acne, psoriasis, and atopic dermatitis, it is important to have a conversation regarding the risks and benefits of long-term medication should a pregnancy occur in any woman of childbearing age, she said.
 

Fewer women in clinical trials?

Abortion restrictions could possibly discourage women of reproductive age to participate in a clinical trial for a new medication, said Dr. Chambers.

A female patient with a chronic disease who’s randomized to receive a new medication may be required to use certain types of birth control because of unknown potential adverse effects the drug may have on the fetus. But in some cases, accidental pregnancies happen.

The participant in the trial may say, “I don’t know enough about the safety of this drug in pregnancy, and I’ve already taken it. I want to terminate the pregnancy,” said Dr. Chambers. Thinking ahead, a woman may decide not to do the trial to avoid the risk of getting pregnant and not having the option to terminate the pregnancy.

This could apply to new drugs such as antiviral treatments, or medications for severe chronic disease that typically have no clinical trial data in pregnancy prior to initial release into the market.

Women may start taking the drug without thinking about getting pregnant, then realize there are no safety data and become concerned about its effects on a future pregnancy.

The question is: Will abortion restrictions have a chilling effect on these new drugs as well? Patients and their doctors may decide not to try it until more data are available. “I can see where abortion restrictions would change the risk or benefit calculation in thinking about what you do or don’t prescribe or take during reproductive age,” said Dr. Chambers.
 

 

 

The upside of restrictions?

If there’s a positive side to these developments with abortion bans, it may encourage women taking new medications or joining clinical trials to think even more carefully about adherence to effective contraception, said Dr. Chambers.

Some methods are more effective than others, she emphasized. “When you have an unplanned pregnancy, it could mean that the method you used wasn’t optimal or you weren’t using it as recommended.” A goal moving forward is to encourage more thoughtful use of highly effective contraceptives, thus reducing the number of unplanned pregnancies, she added.

If patients are taking methotrexate, “the time to think about pregnancy is before getting pregnant so you can switch to a drug that’s compatible with pregnancy,” she said.

This whole thought process regarding pregnancy planning could work toward useful health goals, said Dr. Chambers. “Nobody thinks termination is the preferred method, but planning ahead should involve a discussion of what works best for the patient.”

Patients do have other choices, said Dr. Grifka. “Fortunately, there are many commonly prescribed medications which cross the placenta and have no ill effects on the fetus.”

Talking to patients about choices

Dr. Clowse, who spends a lot of time training rheumatologists, encourages them to have conversations with patients about pregnancy planning. It’s a lot to manage, getting the right drug to a female patient with chronic illness, especially in this current climate of abortion upheaval, she noted.

Her approach is to have an open and honest conversation with patients about their concerns and fears, what the realities are, and what the potential future options are for certain rheumatology drugs in the United States.

Some women who see what’s happening across the country may become so risk averse that they may choose to die rather than take a lifesaving drug that poses certain risks under new restrictions.

“I think that’s tragic,” said Dr. Clowse.

To help their patients, Dr. Gray believes physicians across specialties should better educate themselves about physiology in pregnancy and how to counsel patients on the impact of not taking medications in pregnancy.

In her view, it’s almost coercive to say to a patient, “You really need to have effective contraception if I’m going to give you this lifesaving or quality-of-life-improving medication.”

When confronting such scenarios, Dr. Gray doesn’t think physicians need to change how they counsel patients about contraception. “I don’t think we should be putting pressure on patients to consider other permanent methods just because there’s a lack of abortion options.”

Patients will eventually make those decisions for themselves, she said. “They’re going to want a more efficacious method because they’re worried about not having access to abortion if they get pregnant.”

Dr. Gray reports being a site principal investigator for a phase 3 trial for VeraCept IUD, funded by Sebela Pharmaceuticals. Dr. Clowse reports receiving research funding and doing consulting for GlaxoSmithKline.

*Correction, 6/2/2022: A previous version of this article misstated the intended use of drugs such as the “morning-after” pill (levonorgestrel). They are taken to prevent unintended pregnancy.

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

Obstetrician Beverly Gray, MD, is already seeing the effects of the Roe v. Wade abortion debate in her North Carolina practice.

Dr. Beverly Gray

The state allows abortion but requires that women get counseling with a qualified health professional 72 hours before the procedure. “Aside from that, we still have patients asking for more efficacious contraceptive methods just in case,” said Dr. Gray, residency director and division director for women’s community and population health and associate professor for obstetrics and gynecology at Duke University, Durham, N.C.

Patients and staff in her clinic have also been approaching her about tubal ligation. “They’re asking about additional birth control methods because they’re concerned about what’s going to happen” with the challenge to the historic Roe v. Wade decision in the Supreme Court and subsequent actions in the states to restrict or ban abortion, she said.

This has implications not just for abortion but for medications known to affect pregnancy. “What I’m really worried about is physicians will be withholding medicine because they’re concerned about teratogenic effects,” said Dr. Gray.

With more states issuing restrictions on abortion, doctors are worried that patients needing certain drugs to maintain their lupus flares, cancer, or other diseases may decide not to take them in the event they accidentally become pregnant. If the drug is known to affect the fetus, the fear is a patient who lives in a state with abortion restrictions will no longer have the option to terminate a pregnancy.

zoranm/Getty Images


Instead, a scenario may arise in which the patient – and their physician – may opt not to treat at all with an otherwise lifesaving medication, experts told this news organization.
 

The U.S. landscape on abortion restrictions

A leaked draft of a U.S. Supreme Court opinion on Mississippi’s 15-week abortion ban has sent the medical community into a tailspin. The case, Dobbs v. Jackson Women’s Health Organization, challenges the 1973 Roe v. Wade decision that affirms the constitutional right to abortion. It’s anticipated the high court will decide on the case in June.

Although the upcoming decision is subject to change, the draft indicated the high court would uphold the Mississippi ban. This would essentially overturn the 1973 ruling. An earlier Supreme Court decision allowing a Texas law banning abortion at 6 weeks suggests the court may already be heading in this direction. At the state level, legislatures have been moving on divergent paths – some taking steps to preserve abortion rights, others initiating restrictions.

More than 100 abortion restrictions in 19 states took effect in 2021, according to the Guttmacher Institute, which tracks such metrics. In 2022, “two key themes are anti-abortion policymakers’ continued pursuit of various types of abortion bans and restrictions on medication abortion,” the institute reported.

Forty-six states and the District of Columbia have introduced 2,025 restrictions or proactive measures on sexual and reproductive health and rights so far this year. The latest tally from Guttmacher, updated in late May, revealed that 11 states so far have enacted 42 abortion restrictions. A total of 6 states (Arizona, Florida, Idaho, Kentucky, Oklahoma, and Wyoming) have issued nine bans on abortion.

Comparatively, 11 states have enacted 19 protective abortion measures.

Twenty-two states have introduced 117 restrictions on medication abortions, which account for 54% of U.S. abortions. This includes seven measures that would ban medication abortion outright, according to Guttmacher. Kentucky and South Dakota collectively have enacted 14 restrictions on medication abortion, as well as provisions that ban mailing of abortion pills.
 

 

 

Chilling effect on prescribing

Some physicians anticipate that drugs such as the “morning-after” pill (levonorgestrel) will become less available as restrictions go into effect, since these are medications designed to prevent pregnancy.*

However, the ongoing effort to put a lid on abortion measures has prompted concerns about a trickle-down effect on other medications that are otherwise life-changing or lifesaving to patients but pose a risk to the fetus.

Several drugs are well documented to affect fetal growth and development of the fetus, ranging from mild, transitory effects to severe, permanent birth defects, said Ronald G. Grifka, MD, chief medical officer of University of Michigan Health-West and clinical professor of pediatrics at the University of Michigan Medical School, Ann Arbor. “As new medications are developed, we will need heightened attention to make sure they are safe for the fetus,” he added.

Dr. Ronald G. Grifka


Certain teratogenic medications are associated with a high risk of abortion even though this isn’t their primary use, noted Christina Chambers, PhD, MPH, co-director of the Center for Better Beginnings and associate director with the Altman Clinical & Translational Research Institute at the University of California, San Diego.

Christina Chambers
Dr. Christina Chambers


“I don’t think anyone would intentionally take these drugs to induce spontaneous abortion. But if the drugs pose a risk for it, I can see how the laws might be stretched” to include them, said Dr. Chambers.

Methotrexate, a medication for autoimmune disorders, has a high risk of spontaneous abortion. So do acne medications such as isotretinoin.

Patients are usually told they’re not supposed to get pregnant on these drugs because there’s a high risk of pregnancy loss and risk of malformations and potential learning problems in the fetus. But many pregnancies aren’t planned, said Dr. Chambers. “Patients may forget about the side effects or think their birth control will protect them. And the next time they refill the medication, they may not hear about the warnings again.”

With a restrictive abortion law or ban in effect, a woman might think: “I won’t take this drug because if there’s any potential that I might get pregnant, I won’t have the option to abort an at-risk pregnancy.” Women and their doctors, for that matter, don’t want to put themselves in this position, said Dr. Chambers.

Rheumatologist Megan Clowse, MD, who prescribes several medications that potentially cause major birth defects and pregnancy loss, worries about the ramifications of these accumulating bans.

Dr. Megan Clowse


“Methotrexate has been a leading drug for us for decades for rheumatoid arthritis. Mycophenolate is a vital drug for lupus,” said Dr. Clowse, associate professor of medicine at Duke University’s division of rheumatology and immunology.

Both methotrexate and mycophenolate pose about a 40% risk of pregnancy loss and significantly increase the risk for birth defects. “I’m definitely concerned that there might be doctors or women who elect not to use those medications in women of reproductive age because of the potential risk for pregnancy and absence of abortion rights,” said Dr. Clowse.

These situations might force women to use contraceptives they don’t want to use, such as hormonal implants or intrauterine devices, she added. Another side effect is that women and their partners may decide to abstain from sex.
 

 

 

The iPLEDGE factor

Some rheumatology drugs like lenalidomide (Revlimid) require a valid negative pregnancy test in a lab every month. Similarly, the iPLEDGE Risk Evaluation and Mitigation Strategy seeks to reduce the teratogenicity of isotretinoin by requiring two types of birth control and regular pregnancy tests by users.

For isotretinoin specifically, abortion restrictions “could lead to increased adherence to pregnancy prevention measures which are already stringent in iPLEDGE. But on the other hand, it could lead to reduced willingness of physicians to prescribe or patients to take the medication,” said Dr. Chambers.

With programs like iPLEDGE in effect, the rate of pregnancies and abortions that occur in dermatology are relatively low, said Jenny Murase, MD, associate clinical professor of dermatology at the University of California, San Francisco.

Dr. Jenny E. Murase


Nevertheless, as a physician who regularly prescribes medications like isotretinoin in women of childbearing age, “it’s terrifying to me that a woman wouldn’t have the option to terminate the pregnancy if a teratogenic effect from the medication caused a severe birth defect,” said Dr. Murase. 

Dermatologists use other teratogenic medications such as thalidomide, mycophenolate mofetil, and methotrexate for chronic dermatologic disease like psoriasis and atopic dermatitis. 

The situation is especially tricky for dermatologists since most patients – about 80% – never discuss their pregnancy with their specialist prior to pregnancy initiation. Dr. Murase recalls when a patient with chronic plaque psoriasis on methotrexate in her late 40s became pregnant and had an abortion even before Dr. Murase became aware of the pregnancy. 

Because dermatologists routinely prescribe long-term medications for chronic diseases like acne, psoriasis, and atopic dermatitis, it is important to have a conversation regarding the risks and benefits of long-term medication should a pregnancy occur in any woman of childbearing age, she said.
 

Fewer women in clinical trials?

Abortion restrictions could possibly discourage women of reproductive age to participate in a clinical trial for a new medication, said Dr. Chambers.

A female patient with a chronic disease who’s randomized to receive a new medication may be required to use certain types of birth control because of unknown potential adverse effects the drug may have on the fetus. But in some cases, accidental pregnancies happen.

The participant in the trial may say, “I don’t know enough about the safety of this drug in pregnancy, and I’ve already taken it. I want to terminate the pregnancy,” said Dr. Chambers. Thinking ahead, a woman may decide not to do the trial to avoid the risk of getting pregnant and not having the option to terminate the pregnancy.

This could apply to new drugs such as antiviral treatments, or medications for severe chronic disease that typically have no clinical trial data in pregnancy prior to initial release into the market.

Women may start taking the drug without thinking about getting pregnant, then realize there are no safety data and become concerned about its effects on a future pregnancy.

The question is: Will abortion restrictions have a chilling effect on these new drugs as well? Patients and their doctors may decide not to try it until more data are available. “I can see where abortion restrictions would change the risk or benefit calculation in thinking about what you do or don’t prescribe or take during reproductive age,” said Dr. Chambers.
 

 

 

The upside of restrictions?

If there’s a positive side to these developments with abortion bans, it may encourage women taking new medications or joining clinical trials to think even more carefully about adherence to effective contraception, said Dr. Chambers.

Some methods are more effective than others, she emphasized. “When you have an unplanned pregnancy, it could mean that the method you used wasn’t optimal or you weren’t using it as recommended.” A goal moving forward is to encourage more thoughtful use of highly effective contraceptives, thus reducing the number of unplanned pregnancies, she added.

If patients are taking methotrexate, “the time to think about pregnancy is before getting pregnant so you can switch to a drug that’s compatible with pregnancy,” she said.

This whole thought process regarding pregnancy planning could work toward useful health goals, said Dr. Chambers. “Nobody thinks termination is the preferred method, but planning ahead should involve a discussion of what works best for the patient.”

Patients do have other choices, said Dr. Grifka. “Fortunately, there are many commonly prescribed medications which cross the placenta and have no ill effects on the fetus.”

Talking to patients about choices

Dr. Clowse, who spends a lot of time training rheumatologists, encourages them to have conversations with patients about pregnancy planning. It’s a lot to manage, getting the right drug to a female patient with chronic illness, especially in this current climate of abortion upheaval, she noted.

Her approach is to have an open and honest conversation with patients about their concerns and fears, what the realities are, and what the potential future options are for certain rheumatology drugs in the United States.

Some women who see what’s happening across the country may become so risk averse that they may choose to die rather than take a lifesaving drug that poses certain risks under new restrictions.

“I think that’s tragic,” said Dr. Clowse.

To help their patients, Dr. Gray believes physicians across specialties should better educate themselves about physiology in pregnancy and how to counsel patients on the impact of not taking medications in pregnancy.

In her view, it’s almost coercive to say to a patient, “You really need to have effective contraception if I’m going to give you this lifesaving or quality-of-life-improving medication.”

When confronting such scenarios, Dr. Gray doesn’t think physicians need to change how they counsel patients about contraception. “I don’t think we should be putting pressure on patients to consider other permanent methods just because there’s a lack of abortion options.”

Patients will eventually make those decisions for themselves, she said. “They’re going to want a more efficacious method because they’re worried about not having access to abortion if they get pregnant.”

Dr. Gray reports being a site principal investigator for a phase 3 trial for VeraCept IUD, funded by Sebela Pharmaceuticals. Dr. Clowse reports receiving research funding and doing consulting for GlaxoSmithKline.

*Correction, 6/2/2022: A previous version of this article misstated the intended use of drugs such as the “morning-after” pill (levonorgestrel). They are taken to prevent unintended pregnancy.

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

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Are docs getting fed up with hearing about burnout?

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Tue, 05/31/2022 - 14:03

There is a feeling of exhaustion, being unable to shake a lingering cold, suffering from frequent headaches and gastrointestinal disturbances, sleeplessness and shortness of breath ...

That was how burnout was described by clinical psychologist Herbert Freudenberger, PhD, who first used the phrase in a paper back in 1974, after observing the emotional depletion and accompanying psychosomatic symptoms among volunteer staff of a free clinic in New York City. He called it “burnout,” a term borrowed from the slang of substance abusers.

It has now been established beyond a shadow of a doubt that burnout is a serious issue facing physicians across specialties, albeit some more intensely than others. But with the constant barrage of stories published on an almost daily basis, along with studies and surveys, it begs the question: Are physicians getting tired of hearing about burnout? In other words, are they getting “burned out” about burnout?

Some have suggested that the focus should be more on tackling burnout and instituting viable solutions rather than rehashing the problem.

There haven’t been studies or surveys on this question, but several experts have offered their opinion.

Jonathan Fisher, MD, a cardiologist and organizational well-being and resiliency leader at Novant Health, Charlotte, N.C., cautioned that he hesitates to speak about what physicians in general believe. “We are a diverse group of nearly 1 million in the United States alone,” he said.

But he noted that there is a specific phenomenon among burned-out health care providers who are “burned out on burnout.”

“Essentially, the underlying thought is ‘talk is cheap and we want action,’” said Dr. Fisher, who is chair and co-founder of the Ending Physician Burnout Global Summit that was held in 2021. “This reaction is often a reflection of disheartened physicians’ sense of hopelessness and cynicism that systemic change to improve working conditions will happen in our lifetime.”

Dr. Fisher explained that “typically, anyone suffering – physicians or nonphysicians – cares more about ending the suffering as soon as possible than learning its causes, but to alleviate suffering at its core – including the emotional suffering of burnout – we must understand the many causes.”

“To address both the organizational and individual drivers of burnout requires a keen awareness of the thoughts, fears, and dreams of physicians, health care executives, and all other stakeholders in health care,” he added.

Burnout, of course, is a very real problem. The 2022 Medscape Physician Burnout & Depression Report found that nearly half of all respondents (47%) said they are burned out, which was higher than the prior year. Perhaps not surprisingly, burnout among emergency physicians took the biggest leap, jumping from 43% in 2021 to 60% this year. More than half of critical care physicians (56%) also reported that they were burned out.

The World Health Organization’s International Classification of Diseases (ICD-11) – the official compendium of diseases – has categorized burnout as a “syndrome” that results from “chronic workplace stress that has not been successfully managed.” It is considered to be an occupational phenomenon and is not classified as a medical condition.

But whether or not physicians are burned out on hearing about burnout remains unclear. “I am not sure if physicians are tired of hearing about ‘burnout,’ but I do think that they want to hear about solutions that go beyond just telling them to take better care of themselves,” said Anne Thorndike, MD, MPH, an internal medicine physician at Massachusetts General Hospital and associate professor of medicine at Harvard Medical School, Boston. “There are major systematic factors that contribute to physicians burning out.”
 

 

 

Why talk about negative outcomes?

Jonathan Ripp, MD, MPH, however, is familiar with this sentiment. “‘Why do we keep identifying a problem without solutions’ is certainly a sentiment that is being expressed,” he said. “It’s a negative outcome, so why do we keep talking about negative outcomes?”

Dr. Ripp, who is a professor of medicine, medical education, and geriatrics and palliative medicine; the senior associate dean for well-being and resilience; and chief wellness officer at Icahn School of Medicine at Mount Sinai, New York, is also a well-known expert and researcher in burnout and physician well-being.

He noted that burnout was one of the first “tools” used as a metric to measure well-being, but it is a negative measurement. “It’s been around a long time, so it has a lot of evidence,” said Dr. Ripp. “But that said, there are other ways of measuring well-being without a negative association, and ways of measuring meaning in work – fulfillment and satisfaction, and so on. It should be balanced.”

But for the average physician not familiar with the long legacy of research, they may be frustrated by this situation. “Then they ask, ‘Why are you just showing me more of this instead of doing something about it?’ but we are actually doing something about it,” said Dr. Ripp.

There are many efforts underway, he explained, but it’s a challenging and complex issue. “There are numerous drivers impacting the well-being of any given segment within the health care workforce,” he said. “It will also vary by discipline and location, and there are also a host of individual factors that may have very little to do with the work environment. There are some very well-established efforts for an organizational approach, but it remains to be seen which is the most effective.”

But in broad strokes, he continued, it’s about tackling the system and not about making an individual more resilient. “Individuals that do engage in activities that improve resilience do better, but that’s not what this is about – it’s not going to solve the problem,” said Dr. Ripp. “Those of us like myself, who are working in this space, are trying to promote a culture of well-being – at the system level.”

The question is how to enable the workforce to do their best work in an efficient way so that the balance of their activities are not the meaningless aspects. “And instead, shoot that balance to the meaningful aspects of work,” he added. “There are enormous challenges, but even though we are working on solutions, I can see how the individual may not see that – they may say, ‘Stop telling me to be resilient, stop telling me there’s a problem,’ but we’re working on it.”
 

Moving medicine forward

James Jerzak, MD, a family physician in Green Bay, Wisc., and physician lead at Bellin Health, noted that “it seems to me that doctors aren’t burned out talking about burnout, but they are burned out hearing that the solution to burnout is simply for them to become more resilient,” he said. “In actuality, the path to dealing with this huge problem is to make meaningful systemic changes in how medicine is practiced.”

He reiterated that medical care has become increasingly complex, with the aging of the population; the increasing incidence of chronic diseases, such as diabetes; the challenges with the increasing cost of care, higher copays, and lack of health insurance for a large portion of the country; and general incivility toward health care workers that was exacerbated by the pandemic.

“This has all led to significantly increased stress levels for medical workers,” he said. “Couple all of that with the increased work involved in meeting the demands of the electronic health record, and it is clear that the current situation is unsustainable.”

In his own health care system, moving medicine forward has meant advancing team-based care, which translates to expanding teams to include adequate support for physicians. This strategy addressed problems in health care delivery, part of which is burnout.

“In many systems practicing advanced team-based care, the ancillary staff – medical assistants, LPNs, and RNs – play an enhanced role in the patient visit and perform functions such as quality care gap closure, medication review and refill pending, pending orders, and helping with documentation,” he said. “Although the current health care workforce shortages has created challenges, there are a lot of innovative approaches being tried [that are] aimed at providing solutions.”

The second key factor is for systems is to develop robust support for their providers with a broad range of team members, such as case managers, clinical pharmacists, diabetic educators, care coordinators, and others. “The day has passed where individual physicians can effectivity manage all of the complexities of care, especially since there are so many nonclinical factors affecting care,” said Dr. Jerzak.

“The recent focus on the social determinants of health and health equity underlies the fact that it truly takes a team of health care professionals working together to provide optimal care for patients,” he said.

Dr. Thorndike, who mentors premedical and medical trainees, has pointed out that burnout begins way before an individual enters the workplace as a doctor. Burnout begins in the earliest stages of medical practice, with the application process to medical school. The admissions process extends over a 12-month period, causing a great deal of “toxic stress.”

One study found that, compared with non-premedical students, premedical students had greater depression severity and emotional exhaustion.

“The current system of medical school admissions ignores the toll that the lengthy and emotionally exhausting process takes on aspiring physicians,” she said. “This is just one example of many in training and health care that requires physicians to set aside their own lives to achieve their goals and to provide the best possible care to others.”

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

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There is a feeling of exhaustion, being unable to shake a lingering cold, suffering from frequent headaches and gastrointestinal disturbances, sleeplessness and shortness of breath ...

That was how burnout was described by clinical psychologist Herbert Freudenberger, PhD, who first used the phrase in a paper back in 1974, after observing the emotional depletion and accompanying psychosomatic symptoms among volunteer staff of a free clinic in New York City. He called it “burnout,” a term borrowed from the slang of substance abusers.

It has now been established beyond a shadow of a doubt that burnout is a serious issue facing physicians across specialties, albeit some more intensely than others. But with the constant barrage of stories published on an almost daily basis, along with studies and surveys, it begs the question: Are physicians getting tired of hearing about burnout? In other words, are they getting “burned out” about burnout?

Some have suggested that the focus should be more on tackling burnout and instituting viable solutions rather than rehashing the problem.

There haven’t been studies or surveys on this question, but several experts have offered their opinion.

Jonathan Fisher, MD, a cardiologist and organizational well-being and resiliency leader at Novant Health, Charlotte, N.C., cautioned that he hesitates to speak about what physicians in general believe. “We are a diverse group of nearly 1 million in the United States alone,” he said.

But he noted that there is a specific phenomenon among burned-out health care providers who are “burned out on burnout.”

“Essentially, the underlying thought is ‘talk is cheap and we want action,’” said Dr. Fisher, who is chair and co-founder of the Ending Physician Burnout Global Summit that was held in 2021. “This reaction is often a reflection of disheartened physicians’ sense of hopelessness and cynicism that systemic change to improve working conditions will happen in our lifetime.”

Dr. Fisher explained that “typically, anyone suffering – physicians or nonphysicians – cares more about ending the suffering as soon as possible than learning its causes, but to alleviate suffering at its core – including the emotional suffering of burnout – we must understand the many causes.”

“To address both the organizational and individual drivers of burnout requires a keen awareness of the thoughts, fears, and dreams of physicians, health care executives, and all other stakeholders in health care,” he added.

Burnout, of course, is a very real problem. The 2022 Medscape Physician Burnout & Depression Report found that nearly half of all respondents (47%) said they are burned out, which was higher than the prior year. Perhaps not surprisingly, burnout among emergency physicians took the biggest leap, jumping from 43% in 2021 to 60% this year. More than half of critical care physicians (56%) also reported that they were burned out.

The World Health Organization’s International Classification of Diseases (ICD-11) – the official compendium of diseases – has categorized burnout as a “syndrome” that results from “chronic workplace stress that has not been successfully managed.” It is considered to be an occupational phenomenon and is not classified as a medical condition.

But whether or not physicians are burned out on hearing about burnout remains unclear. “I am not sure if physicians are tired of hearing about ‘burnout,’ but I do think that they want to hear about solutions that go beyond just telling them to take better care of themselves,” said Anne Thorndike, MD, MPH, an internal medicine physician at Massachusetts General Hospital and associate professor of medicine at Harvard Medical School, Boston. “There are major systematic factors that contribute to physicians burning out.”
 

 

 

Why talk about negative outcomes?

Jonathan Ripp, MD, MPH, however, is familiar with this sentiment. “‘Why do we keep identifying a problem without solutions’ is certainly a sentiment that is being expressed,” he said. “It’s a negative outcome, so why do we keep talking about negative outcomes?”

Dr. Ripp, who is a professor of medicine, medical education, and geriatrics and palliative medicine; the senior associate dean for well-being and resilience; and chief wellness officer at Icahn School of Medicine at Mount Sinai, New York, is also a well-known expert and researcher in burnout and physician well-being.

He noted that burnout was one of the first “tools” used as a metric to measure well-being, but it is a negative measurement. “It’s been around a long time, so it has a lot of evidence,” said Dr. Ripp. “But that said, there are other ways of measuring well-being without a negative association, and ways of measuring meaning in work – fulfillment and satisfaction, and so on. It should be balanced.”

But for the average physician not familiar with the long legacy of research, they may be frustrated by this situation. “Then they ask, ‘Why are you just showing me more of this instead of doing something about it?’ but we are actually doing something about it,” said Dr. Ripp.

There are many efforts underway, he explained, but it’s a challenging and complex issue. “There are numerous drivers impacting the well-being of any given segment within the health care workforce,” he said. “It will also vary by discipline and location, and there are also a host of individual factors that may have very little to do with the work environment. There are some very well-established efforts for an organizational approach, but it remains to be seen which is the most effective.”

But in broad strokes, he continued, it’s about tackling the system and not about making an individual more resilient. “Individuals that do engage in activities that improve resilience do better, but that’s not what this is about – it’s not going to solve the problem,” said Dr. Ripp. “Those of us like myself, who are working in this space, are trying to promote a culture of well-being – at the system level.”

The question is how to enable the workforce to do their best work in an efficient way so that the balance of their activities are not the meaningless aspects. “And instead, shoot that balance to the meaningful aspects of work,” he added. “There are enormous challenges, but even though we are working on solutions, I can see how the individual may not see that – they may say, ‘Stop telling me to be resilient, stop telling me there’s a problem,’ but we’re working on it.”
 

Moving medicine forward

James Jerzak, MD, a family physician in Green Bay, Wisc., and physician lead at Bellin Health, noted that “it seems to me that doctors aren’t burned out talking about burnout, but they are burned out hearing that the solution to burnout is simply for them to become more resilient,” he said. “In actuality, the path to dealing with this huge problem is to make meaningful systemic changes in how medicine is practiced.”

He reiterated that medical care has become increasingly complex, with the aging of the population; the increasing incidence of chronic diseases, such as diabetes; the challenges with the increasing cost of care, higher copays, and lack of health insurance for a large portion of the country; and general incivility toward health care workers that was exacerbated by the pandemic.

“This has all led to significantly increased stress levels for medical workers,” he said. “Couple all of that with the increased work involved in meeting the demands of the electronic health record, and it is clear that the current situation is unsustainable.”

In his own health care system, moving medicine forward has meant advancing team-based care, which translates to expanding teams to include adequate support for physicians. This strategy addressed problems in health care delivery, part of which is burnout.

“In many systems practicing advanced team-based care, the ancillary staff – medical assistants, LPNs, and RNs – play an enhanced role in the patient visit and perform functions such as quality care gap closure, medication review and refill pending, pending orders, and helping with documentation,” he said. “Although the current health care workforce shortages has created challenges, there are a lot of innovative approaches being tried [that are] aimed at providing solutions.”

The second key factor is for systems is to develop robust support for their providers with a broad range of team members, such as case managers, clinical pharmacists, diabetic educators, care coordinators, and others. “The day has passed where individual physicians can effectivity manage all of the complexities of care, especially since there are so many nonclinical factors affecting care,” said Dr. Jerzak.

“The recent focus on the social determinants of health and health equity underlies the fact that it truly takes a team of health care professionals working together to provide optimal care for patients,” he said.

Dr. Thorndike, who mentors premedical and medical trainees, has pointed out that burnout begins way before an individual enters the workplace as a doctor. Burnout begins in the earliest stages of medical practice, with the application process to medical school. The admissions process extends over a 12-month period, causing a great deal of “toxic stress.”

One study found that, compared with non-premedical students, premedical students had greater depression severity and emotional exhaustion.

“The current system of medical school admissions ignores the toll that the lengthy and emotionally exhausting process takes on aspiring physicians,” she said. “This is just one example of many in training and health care that requires physicians to set aside their own lives to achieve their goals and to provide the best possible care to others.”

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

There is a feeling of exhaustion, being unable to shake a lingering cold, suffering from frequent headaches and gastrointestinal disturbances, sleeplessness and shortness of breath ...

That was how burnout was described by clinical psychologist Herbert Freudenberger, PhD, who first used the phrase in a paper back in 1974, after observing the emotional depletion and accompanying psychosomatic symptoms among volunteer staff of a free clinic in New York City. He called it “burnout,” a term borrowed from the slang of substance abusers.

It has now been established beyond a shadow of a doubt that burnout is a serious issue facing physicians across specialties, albeit some more intensely than others. But with the constant barrage of stories published on an almost daily basis, along with studies and surveys, it begs the question: Are physicians getting tired of hearing about burnout? In other words, are they getting “burned out” about burnout?

Some have suggested that the focus should be more on tackling burnout and instituting viable solutions rather than rehashing the problem.

There haven’t been studies or surveys on this question, but several experts have offered their opinion.

Jonathan Fisher, MD, a cardiologist and organizational well-being and resiliency leader at Novant Health, Charlotte, N.C., cautioned that he hesitates to speak about what physicians in general believe. “We are a diverse group of nearly 1 million in the United States alone,” he said.

But he noted that there is a specific phenomenon among burned-out health care providers who are “burned out on burnout.”

“Essentially, the underlying thought is ‘talk is cheap and we want action,’” said Dr. Fisher, who is chair and co-founder of the Ending Physician Burnout Global Summit that was held in 2021. “This reaction is often a reflection of disheartened physicians’ sense of hopelessness and cynicism that systemic change to improve working conditions will happen in our lifetime.”

Dr. Fisher explained that “typically, anyone suffering – physicians or nonphysicians – cares more about ending the suffering as soon as possible than learning its causes, but to alleviate suffering at its core – including the emotional suffering of burnout – we must understand the many causes.”

“To address both the organizational and individual drivers of burnout requires a keen awareness of the thoughts, fears, and dreams of physicians, health care executives, and all other stakeholders in health care,” he added.

Burnout, of course, is a very real problem. The 2022 Medscape Physician Burnout & Depression Report found that nearly half of all respondents (47%) said they are burned out, which was higher than the prior year. Perhaps not surprisingly, burnout among emergency physicians took the biggest leap, jumping from 43% in 2021 to 60% this year. More than half of critical care physicians (56%) also reported that they were burned out.

The World Health Organization’s International Classification of Diseases (ICD-11) – the official compendium of diseases – has categorized burnout as a “syndrome” that results from “chronic workplace stress that has not been successfully managed.” It is considered to be an occupational phenomenon and is not classified as a medical condition.

But whether or not physicians are burned out on hearing about burnout remains unclear. “I am not sure if physicians are tired of hearing about ‘burnout,’ but I do think that they want to hear about solutions that go beyond just telling them to take better care of themselves,” said Anne Thorndike, MD, MPH, an internal medicine physician at Massachusetts General Hospital and associate professor of medicine at Harvard Medical School, Boston. “There are major systematic factors that contribute to physicians burning out.”
 

 

 

Why talk about negative outcomes?

Jonathan Ripp, MD, MPH, however, is familiar with this sentiment. “‘Why do we keep identifying a problem without solutions’ is certainly a sentiment that is being expressed,” he said. “It’s a negative outcome, so why do we keep talking about negative outcomes?”

Dr. Ripp, who is a professor of medicine, medical education, and geriatrics and palliative medicine; the senior associate dean for well-being and resilience; and chief wellness officer at Icahn School of Medicine at Mount Sinai, New York, is also a well-known expert and researcher in burnout and physician well-being.

He noted that burnout was one of the first “tools” used as a metric to measure well-being, but it is a negative measurement. “It’s been around a long time, so it has a lot of evidence,” said Dr. Ripp. “But that said, there are other ways of measuring well-being without a negative association, and ways of measuring meaning in work – fulfillment and satisfaction, and so on. It should be balanced.”

But for the average physician not familiar with the long legacy of research, they may be frustrated by this situation. “Then they ask, ‘Why are you just showing me more of this instead of doing something about it?’ but we are actually doing something about it,” said Dr. Ripp.

There are many efforts underway, he explained, but it’s a challenging and complex issue. “There are numerous drivers impacting the well-being of any given segment within the health care workforce,” he said. “It will also vary by discipline and location, and there are also a host of individual factors that may have very little to do with the work environment. There are some very well-established efforts for an organizational approach, but it remains to be seen which is the most effective.”

But in broad strokes, he continued, it’s about tackling the system and not about making an individual more resilient. “Individuals that do engage in activities that improve resilience do better, but that’s not what this is about – it’s not going to solve the problem,” said Dr. Ripp. “Those of us like myself, who are working in this space, are trying to promote a culture of well-being – at the system level.”

The question is how to enable the workforce to do their best work in an efficient way so that the balance of their activities are not the meaningless aspects. “And instead, shoot that balance to the meaningful aspects of work,” he added. “There are enormous challenges, but even though we are working on solutions, I can see how the individual may not see that – they may say, ‘Stop telling me to be resilient, stop telling me there’s a problem,’ but we’re working on it.”
 

Moving medicine forward

James Jerzak, MD, a family physician in Green Bay, Wisc., and physician lead at Bellin Health, noted that “it seems to me that doctors aren’t burned out talking about burnout, but they are burned out hearing that the solution to burnout is simply for them to become more resilient,” he said. “In actuality, the path to dealing with this huge problem is to make meaningful systemic changes in how medicine is practiced.”

He reiterated that medical care has become increasingly complex, with the aging of the population; the increasing incidence of chronic diseases, such as diabetes; the challenges with the increasing cost of care, higher copays, and lack of health insurance for a large portion of the country; and general incivility toward health care workers that was exacerbated by the pandemic.

“This has all led to significantly increased stress levels for medical workers,” he said. “Couple all of that with the increased work involved in meeting the demands of the electronic health record, and it is clear that the current situation is unsustainable.”

In his own health care system, moving medicine forward has meant advancing team-based care, which translates to expanding teams to include adequate support for physicians. This strategy addressed problems in health care delivery, part of which is burnout.

“In many systems practicing advanced team-based care, the ancillary staff – medical assistants, LPNs, and RNs – play an enhanced role in the patient visit and perform functions such as quality care gap closure, medication review and refill pending, pending orders, and helping with documentation,” he said. “Although the current health care workforce shortages has created challenges, there are a lot of innovative approaches being tried [that are] aimed at providing solutions.”

The second key factor is for systems is to develop robust support for their providers with a broad range of team members, such as case managers, clinical pharmacists, diabetic educators, care coordinators, and others. “The day has passed where individual physicians can effectivity manage all of the complexities of care, especially since there are so many nonclinical factors affecting care,” said Dr. Jerzak.

“The recent focus on the social determinants of health and health equity underlies the fact that it truly takes a team of health care professionals working together to provide optimal care for patients,” he said.

Dr. Thorndike, who mentors premedical and medical trainees, has pointed out that burnout begins way before an individual enters the workplace as a doctor. Burnout begins in the earliest stages of medical practice, with the application process to medical school. The admissions process extends over a 12-month period, causing a great deal of “toxic stress.”

One study found that, compared with non-premedical students, premedical students had greater depression severity and emotional exhaustion.

“The current system of medical school admissions ignores the toll that the lengthy and emotionally exhausting process takes on aspiring physicians,” she said. “This is just one example of many in training and health care that requires physicians to set aside their own lives to achieve their goals and to provide the best possible care to others.”

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

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Does taking isotretinoin worsen a patient’s baseline IBD symptoms?

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Tue, 05/31/2022 - 08:10

A limited association exists between the use of isotretinoin for severe acne and worsening of a patient’s baseline inflammatory bowel disease, results from a small retrospective study suggests.

“Early studies of isotretinoin for use in severe acne suggested the drug may serve as a trigger for new-onset inflammatory bowel disease (IBD),” researchers led by Christina G. Lopez, MD, of the Lewis Katz School of Medicine at Temple University, Philadelphia, wrote in an article published online , in the Journal of the American Academy of Dermatology. “While more recent studies have suggested no such causal relationship, little is known about the medication’s effect on patients with a preexisting IBD diagnosis.”

To investigate this topic further, the researchers identified 19 patients who were diagnosed with IBD and treated with isotretinoin between Jan. 1, 2006, and Jan. 1, 2020, at Mass General Brigham Hospitals, Boston. They determined severity of disease and degree of antecedent management of IBD by evaluating flaring two years prior to starting isotretinoin. The patients were considered to have a flare caused by isotretinoin if the IBD flare occurred during or up to 3 months following course completion.

The mean age of the 19 patients was 35 years, 26% were female, and 95% were White. Nearly half of the patients (42%) had ulcerative colitis, 37% had Crohn’s disease, and 21% had both. The researchers found that nine patients had flared two years before starting isotretinoin. Of these, five (56%) flared and four (44%) did not flare during treatment or within three months of completing the course of isotretinoin.

Of the 10 patients who did not flare two years before starting isotretinoin, seven (70%) did not flare during treatment and three (30%) flared during or within three months following completion of isotretinoin use. The researchers found no statistically significant association between isotretinoin use and flaring among patients with IBD (P = .76).



Dr. Lopez and her colleagues also assessed IBD maintenance therapy with respect to IBD flares in the study population. They observed no statistically significant association between the use of maintenance IBD therapy and the likelihood of having flares during isotretinoin treatment (P = .15).

“The results suggest limited association between isotretinoin and the worsening of a patient’s baseline IBD,” the authors concluded. They acknowledged certain limitations of the study, including its small sample size and retrospective design, and they called for larger and prospective studies to assess the relationship of IBD flaring in this population of patients.

Pooja Sodha, MD, director of the Center for Laser and Cosmetic Dermatology at George Washington University, Washington, who was asked to comment on the results, characterized the trial as “an important study highlighting how we continue to understand the safe use of isotretinoin in the IBD cohort.”

Isotretinoin, she added, “continues to be a highly important treatment for acne and in patients such as these where oral antibiotics are relatively contraindicated due to risk of exacerbating their bowel disease.” Such data are reassuring, “albeit future studies with larger patient pools are desirable,” she added. “Future studies could also help to elucidate if diet, smoking, sleep, exercise, and medication adherence are potential confounding factors along with whether the cumulative isotretinoin dose has any effect on IBD flares in those who are susceptible.”

Neither the researchers nor Dr. Sodha had financial conflicts. The other authors were from Brigham and Women’s Hospital, Harvard University, Boston, and the University of Massachusetts, Worcester.

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A limited association exists between the use of isotretinoin for severe acne and worsening of a patient’s baseline inflammatory bowel disease, results from a small retrospective study suggests.

“Early studies of isotretinoin for use in severe acne suggested the drug may serve as a trigger for new-onset inflammatory bowel disease (IBD),” researchers led by Christina G. Lopez, MD, of the Lewis Katz School of Medicine at Temple University, Philadelphia, wrote in an article published online , in the Journal of the American Academy of Dermatology. “While more recent studies have suggested no such causal relationship, little is known about the medication’s effect on patients with a preexisting IBD diagnosis.”

To investigate this topic further, the researchers identified 19 patients who were diagnosed with IBD and treated with isotretinoin between Jan. 1, 2006, and Jan. 1, 2020, at Mass General Brigham Hospitals, Boston. They determined severity of disease and degree of antecedent management of IBD by evaluating flaring two years prior to starting isotretinoin. The patients were considered to have a flare caused by isotretinoin if the IBD flare occurred during or up to 3 months following course completion.

The mean age of the 19 patients was 35 years, 26% were female, and 95% were White. Nearly half of the patients (42%) had ulcerative colitis, 37% had Crohn’s disease, and 21% had both. The researchers found that nine patients had flared two years before starting isotretinoin. Of these, five (56%) flared and four (44%) did not flare during treatment or within three months of completing the course of isotretinoin.

Of the 10 patients who did not flare two years before starting isotretinoin, seven (70%) did not flare during treatment and three (30%) flared during or within three months following completion of isotretinoin use. The researchers found no statistically significant association between isotretinoin use and flaring among patients with IBD (P = .76).



Dr. Lopez and her colleagues also assessed IBD maintenance therapy with respect to IBD flares in the study population. They observed no statistically significant association between the use of maintenance IBD therapy and the likelihood of having flares during isotretinoin treatment (P = .15).

“The results suggest limited association between isotretinoin and the worsening of a patient’s baseline IBD,” the authors concluded. They acknowledged certain limitations of the study, including its small sample size and retrospective design, and they called for larger and prospective studies to assess the relationship of IBD flaring in this population of patients.

Pooja Sodha, MD, director of the Center for Laser and Cosmetic Dermatology at George Washington University, Washington, who was asked to comment on the results, characterized the trial as “an important study highlighting how we continue to understand the safe use of isotretinoin in the IBD cohort.”

Isotretinoin, she added, “continues to be a highly important treatment for acne and in patients such as these where oral antibiotics are relatively contraindicated due to risk of exacerbating their bowel disease.” Such data are reassuring, “albeit future studies with larger patient pools are desirable,” she added. “Future studies could also help to elucidate if diet, smoking, sleep, exercise, and medication adherence are potential confounding factors along with whether the cumulative isotretinoin dose has any effect on IBD flares in those who are susceptible.”

Neither the researchers nor Dr. Sodha had financial conflicts. The other authors were from Brigham and Women’s Hospital, Harvard University, Boston, and the University of Massachusetts, Worcester.

A limited association exists between the use of isotretinoin for severe acne and worsening of a patient’s baseline inflammatory bowel disease, results from a small retrospective study suggests.

“Early studies of isotretinoin for use in severe acne suggested the drug may serve as a trigger for new-onset inflammatory bowel disease (IBD),” researchers led by Christina G. Lopez, MD, of the Lewis Katz School of Medicine at Temple University, Philadelphia, wrote in an article published online , in the Journal of the American Academy of Dermatology. “While more recent studies have suggested no such causal relationship, little is known about the medication’s effect on patients with a preexisting IBD diagnosis.”

To investigate this topic further, the researchers identified 19 patients who were diagnosed with IBD and treated with isotretinoin between Jan. 1, 2006, and Jan. 1, 2020, at Mass General Brigham Hospitals, Boston. They determined severity of disease and degree of antecedent management of IBD by evaluating flaring two years prior to starting isotretinoin. The patients were considered to have a flare caused by isotretinoin if the IBD flare occurred during or up to 3 months following course completion.

The mean age of the 19 patients was 35 years, 26% were female, and 95% were White. Nearly half of the patients (42%) had ulcerative colitis, 37% had Crohn’s disease, and 21% had both. The researchers found that nine patients had flared two years before starting isotretinoin. Of these, five (56%) flared and four (44%) did not flare during treatment or within three months of completing the course of isotretinoin.

Of the 10 patients who did not flare two years before starting isotretinoin, seven (70%) did not flare during treatment and three (30%) flared during or within three months following completion of isotretinoin use. The researchers found no statistically significant association between isotretinoin use and flaring among patients with IBD (P = .76).



Dr. Lopez and her colleagues also assessed IBD maintenance therapy with respect to IBD flares in the study population. They observed no statistically significant association between the use of maintenance IBD therapy and the likelihood of having flares during isotretinoin treatment (P = .15).

“The results suggest limited association between isotretinoin and the worsening of a patient’s baseline IBD,” the authors concluded. They acknowledged certain limitations of the study, including its small sample size and retrospective design, and they called for larger and prospective studies to assess the relationship of IBD flaring in this population of patients.

Pooja Sodha, MD, director of the Center for Laser and Cosmetic Dermatology at George Washington University, Washington, who was asked to comment on the results, characterized the trial as “an important study highlighting how we continue to understand the safe use of isotretinoin in the IBD cohort.”

Isotretinoin, she added, “continues to be a highly important treatment for acne and in patients such as these where oral antibiotics are relatively contraindicated due to risk of exacerbating their bowel disease.” Such data are reassuring, “albeit future studies with larger patient pools are desirable,” she added. “Future studies could also help to elucidate if diet, smoking, sleep, exercise, and medication adherence are potential confounding factors along with whether the cumulative isotretinoin dose has any effect on IBD flares in those who are susceptible.”

Neither the researchers nor Dr. Sodha had financial conflicts. The other authors were from Brigham and Women’s Hospital, Harvard University, Boston, and the University of Massachusetts, Worcester.

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FROM THE JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY

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