MDedge Dermatology

Lupus images in medical resource materials underrepresent patients with skin of color, based on data from a review of more than 1,400 images published between 2014 and 2019 in materials from a university’s online medical library.

Courtesy Dr. Catalina Matiz

Patients with skin of color who develop lupus tend to present earlier and with more severe cases, and often experience worse outcomes, compared with other populations, wrote Amaad Rana, MD, of Washington University, St. Louis, and colleagues. Medical resources in general have historically underrepresented patients of color, and the researchers reviewed lupus materials for a similar publication bias.

In a study published in Arthritis Care & Research, the investigators identified 1,417 images in rheumatology, dermatology, and internal medicine resources, including 119 medical textbooks, 15 medical journals, 2 online image libraries, and the online image collections of Google and UpToDate. An additional 24 images came from skin of color atlases.

Excluding the skin of color atlases, 56.4% of the images represented light skin, 35.1% showed medium skin, and 8.5% showed dark skin. Overall, publishers were more than twice as likely to portray light skin tones and were significantly less likely to portray dark skin tones (odds ratios, 2.59 and 0.19, respectively), compared with an equal representation of skin tones; however, the difference was not significant for portrayal of medium skin tones (OR, 1.08).

By specialty, dermatology was more inclusive of skin of color images than rheumatology or internal medicine, although the internal medicine sample size was too small for comparable analysis, the researchers noted. Dermatology textbooks were 2.42 times more likely and rheumatology textbooks were 4.87 times more likely to depict light skin tones than an equal representation of light, medium, and dark skin tones.

The researchers rated the skin color in the images using the New Immigrant Survey Skin Color Scale and categorized the images as representing light (NISSCS scores, 1-2), medium (NISSCS scores, 3-5), or dark skin (NISSCS scores, 6-10). Medical journals had the most images of dark skin, excluding skin of color atlases. In a comparison of specialties, dermatology materials included the most images of medium and darker skin tones.

The underrepresentation of skin of color patients can contribute to a limited knowledge of lupus presentation that could lead to disparate health outcomes, the researchers noted.

The study findings were limited by several factors, including the review of only the online textbooks and journals available through the medical library of a single university, the researchers noted. In addition, definitions of light, medium, and dark skin tones were variable among studies, and the researchers did not distinguish among lupus pathologies.

“Further research is needed to quantitatively assess the influence these materials have on healthcare providers’ ability to care for patients with lupus and SOC, and new material and strategies will be required to correct this disparity and promote equitable representation,” the researchers emphasized. “Ultimately, this will arm practitioners with the resources to competently treat patients with any skin color and work towards reducing disparities in health outcomes.”

The study received no outside funding. The researchers had no financial conflicts to disclose.

Lupus images in medical resource materials underrepresent patients with skin of color, based on data from a review of more than 1,400 images published between 2014 and 2019 in materials from a university’s online medical library.

Courtesy Dr. Catalina Matiz

Patients with skin of color who develop lupus tend to present earlier and with more severe cases, and often experience worse outcomes, compared with other populations, wrote Amaad Rana, MD, of Washington University, St. Louis, and colleagues. Medical resources in general have historically underrepresented patients of color, and the researchers reviewed lupus materials for a similar publication bias.

In a study published in Arthritis Care & Research, the investigators identified 1,417 images in rheumatology, dermatology, and internal medicine resources, including 119 medical textbooks, 15 medical journals, 2 online image libraries, and the online image collections of Google and UpToDate. An additional 24 images came from skin of color atlases.

Excluding the skin of color atlases, 56.4% of the images represented light skin, 35.1% showed medium skin, and 8.5% showed dark skin. Overall, publishers were more than twice as likely to portray light skin tones and were significantly less likely to portray dark skin tones (odds ratios, 2.59 and 0.19, respectively), compared with an equal representation of skin tones; however, the difference was not significant for portrayal of medium skin tones (OR, 1.08).

By specialty, dermatology was more inclusive of skin of color images than rheumatology or internal medicine, although the internal medicine sample size was too small for comparable analysis, the researchers noted. Dermatology textbooks were 2.42 times more likely and rheumatology textbooks were 4.87 times more likely to depict light skin tones than an equal representation of light, medium, and dark skin tones.

The researchers rated the skin color in the images using the New Immigrant Survey Skin Color Scale and categorized the images as representing light (NISSCS scores, 1-2), medium (NISSCS scores, 3-5), or dark skin (NISSCS scores, 6-10). Medical journals had the most images of dark skin, excluding skin of color atlases. In a comparison of specialties, dermatology materials included the most images of medium and darker skin tones.

The underrepresentation of skin of color patients can contribute to a limited knowledge of lupus presentation that could lead to disparate health outcomes, the researchers noted.

The study findings were limited by several factors, including the review of only the online textbooks and journals available through the medical library of a single university, the researchers noted. In addition, definitions of light, medium, and dark skin tones were variable among studies, and the researchers did not distinguish among lupus pathologies.

“Further research is needed to quantitatively assess the influence these materials have on healthcare providers’ ability to care for patients with lupus and SOC, and new material and strategies will be required to correct this disparity and promote equitable representation,” the researchers emphasized. “Ultimately, this will arm practitioners with the resources to competently treat patients with any skin color and work towards reducing disparities in health outcomes.”

The study received no outside funding. The researchers had no financial conflicts to disclose.

Lupus images in medical resource materials underrepresent patients with skin of color, based on data from a review of more than 1,400 images published between 2014 and 2019 in materials from a university’s online medical library.

Courtesy Dr. Catalina Matiz

Patients with skin of color who develop lupus tend to present earlier and with more severe cases, and often experience worse outcomes, compared with other populations, wrote Amaad Rana, MD, of Washington University, St. Louis, and colleagues. Medical resources in general have historically underrepresented patients of color, and the researchers reviewed lupus materials for a similar publication bias.

In a study published in Arthritis Care & Research, the investigators identified 1,417 images in rheumatology, dermatology, and internal medicine resources, including 119 medical textbooks, 15 medical journals, 2 online image libraries, and the online image collections of Google and UpToDate. An additional 24 images came from skin of color atlases.

Excluding the skin of color atlases, 56.4% of the images represented light skin, 35.1% showed medium skin, and 8.5% showed dark skin. Overall, publishers were more than twice as likely to portray light skin tones and were significantly less likely to portray dark skin tones (odds ratios, 2.59 and 0.19, respectively), compared with an equal representation of skin tones; however, the difference was not significant for portrayal of medium skin tones (OR, 1.08).

By specialty, dermatology was more inclusive of skin of color images than rheumatology or internal medicine, although the internal medicine sample size was too small for comparable analysis, the researchers noted. Dermatology textbooks were 2.42 times more likely and rheumatology textbooks were 4.87 times more likely to depict light skin tones than an equal representation of light, medium, and dark skin tones.

The researchers rated the skin color in the images using the New Immigrant Survey Skin Color Scale and categorized the images as representing light (NISSCS scores, 1-2), medium (NISSCS scores, 3-5), or dark skin (NISSCS scores, 6-10). Medical journals had the most images of dark skin, excluding skin of color atlases. In a comparison of specialties, dermatology materials included the most images of medium and darker skin tones.

The underrepresentation of skin of color patients can contribute to a limited knowledge of lupus presentation that could lead to disparate health outcomes, the researchers noted.

The study findings were limited by several factors, including the review of only the online textbooks and journals available through the medical library of a single university, the researchers noted. In addition, definitions of light, medium, and dark skin tones were variable among studies, and the researchers did not distinguish among lupus pathologies.

“Further research is needed to quantitatively assess the influence these materials have on healthcare providers’ ability to care for patients with lupus and SOC, and new material and strategies will be required to correct this disparity and promote equitable representation,” the researchers emphasized. “Ultimately, this will arm practitioners with the resources to competently treat patients with any skin color and work towards reducing disparities in health outcomes.”

The study received no outside funding. The researchers had no financial conflicts to disclose.

“It’s good to be in something from the ground floor. I came too late for that. ... But lately, I’m getting the feeling that I came in at the end. The best is over.” –Tony Soprano

If you could choose, would you rather be transported to live 25 years ago in the past or 25 years from now in the future? For me, I’m unsure. Sometimes it feels like our best days are behind us. When I was a kid, we explored life in pond water, watching water fleas and hydra swim under our Child World toy microscopes. Today, kids learn to eat Tide Pods from TikTok. Back when I was young, a doctor’s appointment was a special occasion! My brothers and I had a bath and got dressed in our Sunday best for our appointment with Dr. Bellin, a genteel, gray-haired pediatrician who worked out of his Victorian office with wooden floors and crystal door handles. Contrast that with the appointment I had with a patient the other day, done by telephone while she was in line ordering at Starbucks. I waited patiently for her to give her order.

This ache I feel for the past is called nostalgia. At one time, it was a diagnosable condition. It was first used by Dr. Johannes Hofer in the 17th century to describe Swiss soldiers fighting in foreign lands. From the Greek, it means “homecoming pain.” Although over time nostalgia has lost its clinical meaning, the feeling of yearning for the past has dramatically gained in prevalence. The word “nostalgia” appears more in print now than at any point since 1800. We are most nostalgic during times of duress, it seems. This, no doubt, is because it’s comforting to think we’d be better off back in pastoral, idyll times, back when work ended at 5 p.m. and cotton balls were soaked in alcohol and office visits ended with a lollipop on a loop.

Of course, the good old days weren’t really better. We have a selective view of history – as many things were contemptible or bad then as now. Yes, Dr. Bellin was the consummate professional, but thank goodness, I didn’t have acute lymphocytic leukemia or Haemophilus influenzae type B or even suffocate under a pile of blankets while sleeping on my stomach. Without doubt, clinically we’re much better today. Also back then, there was hardly a consideration for atrocious racial disparities in care. We’ve not come far, but we are at least better off today than a few decades ago. And what about medicine as a profession? Although he had loads of autonomy and respect, Dr. Bellin also started every day of his 50-year career at 6 a.m. rounding in the newborn nursery before seeing patients in the office 6 days a week. Not many of us would trade our practice for his.

Yet, there’s reasons to be nostalgic. Chart notes might have been barely legible, but at least they served a purpose. The problem-oriented medical record was intended to logically capture and organize data. SOAP notes were invented to help us think better, to get diagnoses correct, to succinctly see progress. Today, notes are written for administrators and payers and patients. As a result, they’re often useless to us.

And although it may have been inconvenient to sit in the waiting room reading Highlights magazine, I’m unsure it was a worse user experience, compared with a chain pharmacy “virtual” doctor visit. (Particularly because you could always drop pennies down the large hot-air iron floor grate in the corner).

The thrumming undercurrent of progress promises artificial intelligence and genomics and wearable diagnostics in our future. But the assumption is the new things will be better suited to our needs than the old. Sometimes, they are not. Sometimes technology diminishes us instead of enhancing us.

I cannot count how many times I’ve hit my head or whacked my shin because our Tesla Model X doors open by magic and of their own accord. Back when I was young, we opened car doors by pulling on the door handle. I sometimes miss those days.
 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

“It’s good to be in something from the ground floor. I came too late for that. ... But lately, I’m getting the feeling that I came in at the end. The best is over.” –Tony Soprano

If you could choose, would you rather be transported to live 25 years ago in the past or 25 years from now in the future? For me, I’m unsure. Sometimes it feels like our best days are behind us. When I was a kid, we explored life in pond water, watching water fleas and hydra swim under our Child World toy microscopes. Today, kids learn to eat Tide Pods from TikTok. Back when I was young, a doctor’s appointment was a special occasion! My brothers and I had a bath and got dressed in our Sunday best for our appointment with Dr. Bellin, a genteel, gray-haired pediatrician who worked out of his Victorian office with wooden floors and crystal door handles. Contrast that with the appointment I had with a patient the other day, done by telephone while she was in line ordering at Starbucks. I waited patiently for her to give her order.

This ache I feel for the past is called nostalgia. At one time, it was a diagnosable condition. It was first used by Dr. Johannes Hofer in the 17th century to describe Swiss soldiers fighting in foreign lands. From the Greek, it means “homecoming pain.” Although over time nostalgia has lost its clinical meaning, the feeling of yearning for the past has dramatically gained in prevalence. The word “nostalgia” appears more in print now than at any point since 1800. We are most nostalgic during times of duress, it seems. This, no doubt, is because it’s comforting to think we’d be better off back in pastoral, idyll times, back when work ended at 5 p.m. and cotton balls were soaked in alcohol and office visits ended with a lollipop on a loop.

Of course, the good old days weren’t really better. We have a selective view of history – as many things were contemptible or bad then as now. Yes, Dr. Bellin was the consummate professional, but thank goodness, I didn’t have acute lymphocytic leukemia or Haemophilus influenzae type B or even suffocate under a pile of blankets while sleeping on my stomach. Without doubt, clinically we’re much better today. Also back then, there was hardly a consideration for atrocious racial disparities in care. We’ve not come far, but we are at least better off today than a few decades ago. And what about medicine as a profession? Although he had loads of autonomy and respect, Dr. Bellin also started every day of his 50-year career at 6 a.m. rounding in the newborn nursery before seeing patients in the office 6 days a week. Not many of us would trade our practice for his.

Yet, there’s reasons to be nostalgic. Chart notes might have been barely legible, but at least they served a purpose. The problem-oriented medical record was intended to logically capture and organize data. SOAP notes were invented to help us think better, to get diagnoses correct, to succinctly see progress. Today, notes are written for administrators and payers and patients. As a result, they’re often useless to us.

And although it may have been inconvenient to sit in the waiting room reading Highlights magazine, I’m unsure it was a worse user experience, compared with a chain pharmacy “virtual” doctor visit. (Particularly because you could always drop pennies down the large hot-air iron floor grate in the corner).

The thrumming undercurrent of progress promises artificial intelligence and genomics and wearable diagnostics in our future. But the assumption is the new things will be better suited to our needs than the old. Sometimes, they are not. Sometimes technology diminishes us instead of enhancing us.

I cannot count how many times I’ve hit my head or whacked my shin because our Tesla Model X doors open by magic and of their own accord. Back when I was young, we opened car doors by pulling on the door handle. I sometimes miss those days.
 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

“It’s good to be in something from the ground floor. I came too late for that. ... But lately, I’m getting the feeling that I came in at the end. The best is over.” –Tony Soprano

If you could choose, would you rather be transported to live 25 years ago in the past or 25 years from now in the future? For me, I’m unsure. Sometimes it feels like our best days are behind us. When I was a kid, we explored life in pond water, watching water fleas and hydra swim under our Child World toy microscopes. Today, kids learn to eat Tide Pods from TikTok. Back when I was young, a doctor’s appointment was a special occasion! My brothers and I had a bath and got dressed in our Sunday best for our appointment with Dr. Bellin, a genteel, gray-haired pediatrician who worked out of his Victorian office with wooden floors and crystal door handles. Contrast that with the appointment I had with a patient the other day, done by telephone while she was in line ordering at Starbucks. I waited patiently for her to give her order.

This ache I feel for the past is called nostalgia. At one time, it was a diagnosable condition. It was first used by Dr. Johannes Hofer in the 17th century to describe Swiss soldiers fighting in foreign lands. From the Greek, it means “homecoming pain.” Although over time nostalgia has lost its clinical meaning, the feeling of yearning for the past has dramatically gained in prevalence. The word “nostalgia” appears more in print now than at any point since 1800. We are most nostalgic during times of duress, it seems. This, no doubt, is because it’s comforting to think we’d be better off back in pastoral, idyll times, back when work ended at 5 p.m. and cotton balls were soaked in alcohol and office visits ended with a lollipop on a loop.

Of course, the good old days weren’t really better. We have a selective view of history – as many things were contemptible or bad then as now. Yes, Dr. Bellin was the consummate professional, but thank goodness, I didn’t have acute lymphocytic leukemia or Haemophilus influenzae type B or even suffocate under a pile of blankets while sleeping on my stomach. Without doubt, clinically we’re much better today. Also back then, there was hardly a consideration for atrocious racial disparities in care. We’ve not come far, but we are at least better off today than a few decades ago. And what about medicine as a profession? Although he had loads of autonomy and respect, Dr. Bellin also started every day of his 50-year career at 6 a.m. rounding in the newborn nursery before seeing patients in the office 6 days a week. Not many of us would trade our practice for his.

Yet, there’s reasons to be nostalgic. Chart notes might have been barely legible, but at least they served a purpose. The problem-oriented medical record was intended to logically capture and organize data. SOAP notes were invented to help us think better, to get diagnoses correct, to succinctly see progress. Today, notes are written for administrators and payers and patients. As a result, they’re often useless to us.

And although it may have been inconvenient to sit in the waiting room reading Highlights magazine, I’m unsure it was a worse user experience, compared with a chain pharmacy “virtual” doctor visit. (Particularly because you could always drop pennies down the large hot-air iron floor grate in the corner).

The thrumming undercurrent of progress promises artificial intelligence and genomics and wearable diagnostics in our future. But the assumption is the new things will be better suited to our needs than the old. Sometimes, they are not. Sometimes technology diminishes us instead of enhancing us.

I cannot count how many times I’ve hit my head or whacked my shin because our Tesla Model X doors open by magic and of their own accord. Back when I was young, we opened car doors by pulling on the door handle. I sometimes miss those days.
 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

People may be absorbing and ingesting potentially toxic chemicals from their cosmetic products, a new study suggests.

Researchers found high fluorine levels in most of the waterproof mascara, liquid lipsticks, and foundations they tested, indicating the probable presence of what’s known as PFAS – per- and polyfluoroalkyl substances. Many of these chemicals were not included on the product labels, making it difficult for consumers to consciously avoid them.

Environmental Science & Technology

“This study is very helpful for elucidating the PFAS content of different types of cosmetics in the U.S. and Canadian markets,” said Elsie Sunderland, PhD, an environmental scientist who was not involved with the study.

“Previously, all the data had been collected in Europe, and this study shows we are dealing with similar problems in the North American marketplace,” said Dr. Sunderland, a professor of environmental chemistry at the Harvard School of Public Health, Boston.

PFAS are a class of chemicals used in a variety of consumer products, such as nonstick cookware, stain-resistant carpeting, and water-repellent clothing, according to the Centers for Disease Control and Prevention. They are added to cosmetics to make the products more durable and spreadable, researchers said in the study.

“[PFAS] are added to change the properties of surfaces, to make them nonstick or resistant to stay in water or oils,” said study coauthor Tom Bruton, PhD, senior scientist at the Green Science Policy Institute in Berkeley, Calif. “The concerning thing about cosmetics is that these are products that you’re applying to your skin and face every day, so there’s the skin absorption route that’s of concern, but also incidental ingestion of cosmetics is also a concern as well.”

The CDC says some of the potential health effects of PFAS exposure includes increased cholesterol levels, increased risk of kidney and testicular cancer, changes in liver enzymes, decreased vaccine response in children, and a higher risk of high blood pressure or preeclampsia in pregnant women.

JackF/iStock/Getty Images

“PFAS are a large class of chemicals. In humans, exposure to some of these chemicals has been associated with impaired immune function, certain cancers, increased risks of diabetes, obesity and endocrine disruption,” Dr. Sunderland said. “They appear to be harmful to every major organ system in the human body.”

For the current study, published online in Environmental Science & Technology Letters, Dr. Bruton and colleagues purchased 231 cosmetic products in the United States and Canada from retailers such as Ulta Beauty, Sephora, Target, and Bed Bath & Beyond. They then screened them for fluorine.Three-quarters of waterproof mascara samples contained high fluorine concentrations, as did nearly two-thirds of foundations and liquid lipsticks, and more than half of the eye and lip products tested.

The authors found that different categories of makeup tended to have higher or lower fluorine concentrations. “High fluorine levels were found in products commonly advertised as ‘wear-resistant’ to water and oils or ‘long-lasting,’ including foundations, liquid lipsticks, and waterproof mascaras,” Dr. Bruton and colleagues wrote.

When they further analyzed a subset of 29 products to determine what types of chemicals were present, they found that each cosmetic product contained at least 4 PFAS, with one product containing 13.The PFAS substances found included some that break down into other chemicals that are known to be highly toxic and environmentally harmful.

“It’s concerning that some of the products we tested appear to be intentionally using PFAS, but not listing those ingredients on the label,” Dr. Bruton said. “I do think that it is helpful for consumers to read labels, but beyond that, there’s not a lot of ways that consumers themselves can solve this problem. ... We think that the industry needs to be more proactive about moving away from this group of chemicals.”

Dr. Sunderland said a resource people can use when trying to avoid PFAS is the Environmental Working Group, a nonprofit organization that maintains an extensive database of cosmetics and personal care products.

“At this point, there is very little regulatory activity related to PFAS in cosmetics,” Dr. Sunderland said. “The best thing to happen now would be for consumers to indicate that they prefer products without PFAS and to demand better transparency in product ingredient lists.”

A similar study done in 2018 by the Danish Environmental Protection Agency found high levels of PFAS in nearly one-third of the cosmetics products it tested.

People can also be exposed to PFAS by eating or drinking contaminated food or water and through food packaging. Dr. Sunderland said some wild foods like seafood are known to accumulate these compounds in the environment.

“There are examples of contaminated biosolids leading to accumulation of PFAS in vegetables and milk,” Dr. Sunderland explained. “Food packaging is another concern because it can also result in PFAS accumulation in the foods we eat.”

Although it’s difficult to avoid PFAS altogether, the CDC suggests lowering exposure rates by avoiding contaminated water and food. If you’re not sure if your water is contaminated, you should ask your local or state health and environmental quality departments for fish or water advisories in your area.

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

People may be absorbing and ingesting potentially toxic chemicals from their cosmetic products, a new study suggests.

Researchers found high fluorine levels in most of the waterproof mascara, liquid lipsticks, and foundations they tested, indicating the probable presence of what’s known as PFAS – per- and polyfluoroalkyl substances. Many of these chemicals were not included on the product labels, making it difficult for consumers to consciously avoid them.

Environmental Science & Technology

“This study is very helpful for elucidating the PFAS content of different types of cosmetics in the U.S. and Canadian markets,” said Elsie Sunderland, PhD, an environmental scientist who was not involved with the study.

“Previously, all the data had been collected in Europe, and this study shows we are dealing with similar problems in the North American marketplace,” said Dr. Sunderland, a professor of environmental chemistry at the Harvard School of Public Health, Boston.

PFAS are a class of chemicals used in a variety of consumer products, such as nonstick cookware, stain-resistant carpeting, and water-repellent clothing, according to the Centers for Disease Control and Prevention. They are added to cosmetics to make the products more durable and spreadable, researchers said in the study.

“[PFAS] are added to change the properties of surfaces, to make them nonstick or resistant to stay in water or oils,” said study coauthor Tom Bruton, PhD, senior scientist at the Green Science Policy Institute in Berkeley, Calif. “The concerning thing about cosmetics is that these are products that you’re applying to your skin and face every day, so there’s the skin absorption route that’s of concern, but also incidental ingestion of cosmetics is also a concern as well.”

The CDC says some of the potential health effects of PFAS exposure includes increased cholesterol levels, increased risk of kidney and testicular cancer, changes in liver enzymes, decreased vaccine response in children, and a higher risk of high blood pressure or preeclampsia in pregnant women.

JackF/iStock/Getty Images

“PFAS are a large class of chemicals. In humans, exposure to some of these chemicals has been associated with impaired immune function, certain cancers, increased risks of diabetes, obesity and endocrine disruption,” Dr. Sunderland said. “They appear to be harmful to every major organ system in the human body.”

For the current study, published online in Environmental Science & Technology Letters, Dr. Bruton and colleagues purchased 231 cosmetic products in the United States and Canada from retailers such as Ulta Beauty, Sephora, Target, and Bed Bath & Beyond. They then screened them for fluorine.Three-quarters of waterproof mascara samples contained high fluorine concentrations, as did nearly two-thirds of foundations and liquid lipsticks, and more than half of the eye and lip products tested.

The authors found that different categories of makeup tended to have higher or lower fluorine concentrations. “High fluorine levels were found in products commonly advertised as ‘wear-resistant’ to water and oils or ‘long-lasting,’ including foundations, liquid lipsticks, and waterproof mascaras,” Dr. Bruton and colleagues wrote.

When they further analyzed a subset of 29 products to determine what types of chemicals were present, they found that each cosmetic product contained at least 4 PFAS, with one product containing 13.The PFAS substances found included some that break down into other chemicals that are known to be highly toxic and environmentally harmful.

“It’s concerning that some of the products we tested appear to be intentionally using PFAS, but not listing those ingredients on the label,” Dr. Bruton said. “I do think that it is helpful for consumers to read labels, but beyond that, there’s not a lot of ways that consumers themselves can solve this problem. ... We think that the industry needs to be more proactive about moving away from this group of chemicals.”

Dr. Sunderland said a resource people can use when trying to avoid PFAS is the Environmental Working Group, a nonprofit organization that maintains an extensive database of cosmetics and personal care products.

“At this point, there is very little regulatory activity related to PFAS in cosmetics,” Dr. Sunderland said. “The best thing to happen now would be for consumers to indicate that they prefer products without PFAS and to demand better transparency in product ingredient lists.”

A similar study done in 2018 by the Danish Environmental Protection Agency found high levels of PFAS in nearly one-third of the cosmetics products it tested.

People can also be exposed to PFAS by eating or drinking contaminated food or water and through food packaging. Dr. Sunderland said some wild foods like seafood are known to accumulate these compounds in the environment.

“There are examples of contaminated biosolids leading to accumulation of PFAS in vegetables and milk,” Dr. Sunderland explained. “Food packaging is another concern because it can also result in PFAS accumulation in the foods we eat.”

Although it’s difficult to avoid PFAS altogether, the CDC suggests lowering exposure rates by avoiding contaminated water and food. If you’re not sure if your water is contaminated, you should ask your local or state health and environmental quality departments for fish or water advisories in your area.

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

People may be absorbing and ingesting potentially toxic chemicals from their cosmetic products, a new study suggests.

Researchers found high fluorine levels in most of the waterproof mascara, liquid lipsticks, and foundations they tested, indicating the probable presence of what’s known as PFAS – per- and polyfluoroalkyl substances. Many of these chemicals were not included on the product labels, making it difficult for consumers to consciously avoid them.

Environmental Science & Technology

“This study is very helpful for elucidating the PFAS content of different types of cosmetics in the U.S. and Canadian markets,” said Elsie Sunderland, PhD, an environmental scientist who was not involved with the study.

“Previously, all the data had been collected in Europe, and this study shows we are dealing with similar problems in the North American marketplace,” said Dr. Sunderland, a professor of environmental chemistry at the Harvard School of Public Health, Boston.

PFAS are a class of chemicals used in a variety of consumer products, such as nonstick cookware, stain-resistant carpeting, and water-repellent clothing, according to the Centers for Disease Control and Prevention. They are added to cosmetics to make the products more durable and spreadable, researchers said in the study.

“[PFAS] are added to change the properties of surfaces, to make them nonstick or resistant to stay in water or oils,” said study coauthor Tom Bruton, PhD, senior scientist at the Green Science Policy Institute in Berkeley, Calif. “The concerning thing about cosmetics is that these are products that you’re applying to your skin and face every day, so there’s the skin absorption route that’s of concern, but also incidental ingestion of cosmetics is also a concern as well.”

The CDC says some of the potential health effects of PFAS exposure includes increased cholesterol levels, increased risk of kidney and testicular cancer, changes in liver enzymes, decreased vaccine response in children, and a higher risk of high blood pressure or preeclampsia in pregnant women.

JackF/iStock/Getty Images

“PFAS are a large class of chemicals. In humans, exposure to some of these chemicals has been associated with impaired immune function, certain cancers, increased risks of diabetes, obesity and endocrine disruption,” Dr. Sunderland said. “They appear to be harmful to every major organ system in the human body.”

For the current study, published online in Environmental Science & Technology Letters, Dr. Bruton and colleagues purchased 231 cosmetic products in the United States and Canada from retailers such as Ulta Beauty, Sephora, Target, and Bed Bath & Beyond. They then screened them for fluorine.Three-quarters of waterproof mascara samples contained high fluorine concentrations, as did nearly two-thirds of foundations and liquid lipsticks, and more than half of the eye and lip products tested.

The authors found that different categories of makeup tended to have higher or lower fluorine concentrations. “High fluorine levels were found in products commonly advertised as ‘wear-resistant’ to water and oils or ‘long-lasting,’ including foundations, liquid lipsticks, and waterproof mascaras,” Dr. Bruton and colleagues wrote.

When they further analyzed a subset of 29 products to determine what types of chemicals were present, they found that each cosmetic product contained at least 4 PFAS, with one product containing 13.The PFAS substances found included some that break down into other chemicals that are known to be highly toxic and environmentally harmful.

“It’s concerning that some of the products we tested appear to be intentionally using PFAS, but not listing those ingredients on the label,” Dr. Bruton said. “I do think that it is helpful for consumers to read labels, but beyond that, there’s not a lot of ways that consumers themselves can solve this problem. ... We think that the industry needs to be more proactive about moving away from this group of chemicals.”

Dr. Sunderland said a resource people can use when trying to avoid PFAS is the Environmental Working Group, a nonprofit organization that maintains an extensive database of cosmetics and personal care products.

“At this point, there is very little regulatory activity related to PFAS in cosmetics,” Dr. Sunderland said. “The best thing to happen now would be for consumers to indicate that they prefer products without PFAS and to demand better transparency in product ingredient lists.”

A similar study done in 2018 by the Danish Environmental Protection Agency found high levels of PFAS in nearly one-third of the cosmetics products it tested.

People can also be exposed to PFAS by eating or drinking contaminated food or water and through food packaging. Dr. Sunderland said some wild foods like seafood are known to accumulate these compounds in the environment.

“There are examples of contaminated biosolids leading to accumulation of PFAS in vegetables and milk,” Dr. Sunderland explained. “Food packaging is another concern because it can also result in PFAS accumulation in the foods we eat.”

Although it’s difficult to avoid PFAS altogether, the CDC suggests lowering exposure rates by avoiding contaminated water and food. If you’re not sure if your water is contaminated, you should ask your local or state health and environmental quality departments for fish or water advisories in your area.

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

Gradually, we are emerging from the chaos, isolation, and anxiety of COVID-19. As the Centers for Disease Control and Prevention adjusts its recommendations and vaccinations become more widely available, our communities are beginning to return to normalcy. We are encouraged to put aside our masks if vaccinated and rejoin society, to venture out with less hesitancy and anxiety. As family and friends reunite, memories of confusion, frustration, and fear are beginning to fade to black. Despite the prevailing belief that we should move on, look forward, and remember the past to safeguard our future, remnants of the pandemic remain.

shironosov/Getty Images

Unvaccinated individuals, notably children under the age of 12, are quite significant in number. The use of telehealth is now standard practice.

For several years, we were warned about the looming “mental health crisis.” The past year has demonstrated that a crisis no longer looms – it has arrived. Our patients can reveal the vulnerability COVID-19 has wrought – from the devastation of lives lost, supply shortages, loss of employment and financial stability – to a lack of access to computers and thereby, the risk of educational decline. Those factors, coupled with isolation and uncertainty about the future, have led to an influx of individuals with anxiety, depression, and other mood disorders seeking mental health treatment.
 

Doctors, others suffering

As result of a medical culture guided by the sacred oath to which care, compassion, and dedication held as true in ancient Greece as it does today, the focus centers on those around us – while signs of our own weariness are waved away as “a bad day.” Even though several support groups are readily available to offer a listening ear and mental health physicians who focus on the treatment of health care professionals are becoming more ubiquitous, the vestiges of past doctrine remain.

In this modern age of medical training, there is often as much sacrifice as there is attainment of knowledge. This philosophy is so ingrained that throughout training and practice one may come across colleagues experiencing an abundance of guilt when leave is needed for personal reasons. We are quick to recommend such steps for our patients, family, and friends, but hesitant to consider such for ourselves. Yet, of all the lessons this past year has wrought, the importance of mental health and self-care cannot be overstated. This raises the question: How do we incorporate wellness into our routines while navigating the complexity of medicine?

It is vital to accept our humanity as something not to repair, treat, or overcome but to understand. There is strength and power in vulnerability. If we do not perceive and validate this process within ourselves, how can we do so for others? In other words, the oxygen mask must be placed on us first before we can place it on anyone else – patients or otherwise.

Chiefly and above all else, the importance of identifying individual signs of stress is essential. Where do you hold tension? Are you prone to GI distress or headaches when taxed? Do you tend toward irritability, apathy, or exhaustion?

Once this is determined, it is important to assess your stress on a numerical scale, such as those used for pain. Are you a 5 or an 8? Finally, are there identifiable triggers or reliable alleviators? Is there a time of day or day of the week that is most difficult to manage? Can you anticipate potential stressors? Understanding your triggers, listening to your body, and practicing the language of self is the first step toward wellness.

Following introspection and observation, the next step is inventory. Take stock of your reserves. What replenishes? What depletes? What brings joy? What brings dread? Are there certain activities that mitigate stress? If so, how much time do they entail? Identify your number on a scale and associate that number with specific strategies or techniques. Remember that decompression for a 6 might be excessive for a 4. Furthermore, what is the duration of these feelings? Chronic stressors may incur gradual change verses sudden impact if acute. Through identifying personal signs, devising and using a scale, as well as escalating or de-escalating factors, individuals become more in tune with their bodies and therefore, more likely to intervene before burnout takes hold.

With this process well integrated, one can now consider stylized approaches for stress management. For example, those inclined toward mindfulness practices may find yoga, meditation, and relaxation exercises beneficial. Others may thrive on positive affirmations, gratitude, and thankfulness. While some might find relief in physical activity, be it strenuous or casual, the creative arts might appeal to those who find joy in painting, writing, or doing crafts. In addition, baking, reading, dancing, and/or listening to music might help lift stress.

Along with those discoveries, or in some cases, rediscoveries, basic needs such as dietary habits and nutrition, hydration, and sleep are vital toward emotional regulation, physiological homeostasis, and stress modulation. Remember HALT: Hungry, Angry, Lonely, Tired, Too hot, Too cold, Sad or Stressed. Those strategies are meant to guide self-care and highlight the importance of allowing time for self-awareness. Imagine yourself as if you are meeting a new patient. Establish rapport, identify symptoms, and explore options for treatment. When we give time to ourselves, we can give time more freely to others. With this in mind, try following the 5-minute wellness check that I formulated:

1. How am I feeling? What am I feeling?

2. Assess HALTS.

3. Identify the number on your scale.

4. Methods of quick de-escalation:

• Designate and schedule personal time.
• Write down daily goals.
• Repeat positive affirmations or write down words of gratitude.
• Use deep breathing exercises.
• Stretch or take a brief walk.
• Engage in mindfulness practices, such as meditation.

Once we develop a habit of monitoring, assessing, and practicing self-care, the process becomes more efficient and effective. Think of the way a seasoned attending can manage workflow with ease, compared with an intern. Recognizing signs and using these strategies routinely can become a quick daily measure of well-being.
 

Dr. Thomas is a board-certified adult psychiatrist with interests in chronic illness, women’s behavioral health, and minority mental health. She currently practices in North Kingstown and East Providence, R.I. Dr. Thomas has no conflicts of interest.

Gradually, we are emerging from the chaos, isolation, and anxiety of COVID-19. As the Centers for Disease Control and Prevention adjusts its recommendations and vaccinations become more widely available, our communities are beginning to return to normalcy. We are encouraged to put aside our masks if vaccinated and rejoin society, to venture out with less hesitancy and anxiety. As family and friends reunite, memories of confusion, frustration, and fear are beginning to fade to black. Despite the prevailing belief that we should move on, look forward, and remember the past to safeguard our future, remnants of the pandemic remain.

shironosov/Getty Images

Unvaccinated individuals, notably children under the age of 12, are quite significant in number. The use of telehealth is now standard practice.

For several years, we were warned about the looming “mental health crisis.” The past year has demonstrated that a crisis no longer looms – it has arrived. Our patients can reveal the vulnerability COVID-19 has wrought – from the devastation of lives lost, supply shortages, loss of employment and financial stability – to a lack of access to computers and thereby, the risk of educational decline. Those factors, coupled with isolation and uncertainty about the future, have led to an influx of individuals with anxiety, depression, and other mood disorders seeking mental health treatment.
 

Doctors, others suffering

As result of a medical culture guided by the sacred oath to which care, compassion, and dedication held as true in ancient Greece as it does today, the focus centers on those around us – while signs of our own weariness are waved away as “a bad day.” Even though several support groups are readily available to offer a listening ear and mental health physicians who focus on the treatment of health care professionals are becoming more ubiquitous, the vestiges of past doctrine remain.

In this modern age of medical training, there is often as much sacrifice as there is attainment of knowledge. This philosophy is so ingrained that throughout training and practice one may come across colleagues experiencing an abundance of guilt when leave is needed for personal reasons. We are quick to recommend such steps for our patients, family, and friends, but hesitant to consider such for ourselves. Yet, of all the lessons this past year has wrought, the importance of mental health and self-care cannot be overstated. This raises the question: How do we incorporate wellness into our routines while navigating the complexity of medicine?

It is vital to accept our humanity as something not to repair, treat, or overcome but to understand. There is strength and power in vulnerability. If we do not perceive and validate this process within ourselves, how can we do so for others? In other words, the oxygen mask must be placed on us first before we can place it on anyone else – patients or otherwise.

Chiefly and above all else, the importance of identifying individual signs of stress is essential. Where do you hold tension? Are you prone to GI distress or headaches when taxed? Do you tend toward irritability, apathy, or exhaustion?

Once this is determined, it is important to assess your stress on a numerical scale, such as those used for pain. Are you a 5 or an 8? Finally, are there identifiable triggers or reliable alleviators? Is there a time of day or day of the week that is most difficult to manage? Can you anticipate potential stressors? Understanding your triggers, listening to your body, and practicing the language of self is the first step toward wellness.

Following introspection and observation, the next step is inventory. Take stock of your reserves. What replenishes? What depletes? What brings joy? What brings dread? Are there certain activities that mitigate stress? If so, how much time do they entail? Identify your number on a scale and associate that number with specific strategies or techniques. Remember that decompression for a 6 might be excessive for a 4. Furthermore, what is the duration of these feelings? Chronic stressors may incur gradual change verses sudden impact if acute. Through identifying personal signs, devising and using a scale, as well as escalating or de-escalating factors, individuals become more in tune with their bodies and therefore, more likely to intervene before burnout takes hold.

With this process well integrated, one can now consider stylized approaches for stress management. For example, those inclined toward mindfulness practices may find yoga, meditation, and relaxation exercises beneficial. Others may thrive on positive affirmations, gratitude, and thankfulness. While some might find relief in physical activity, be it strenuous or casual, the creative arts might appeal to those who find joy in painting, writing, or doing crafts. In addition, baking, reading, dancing, and/or listening to music might help lift stress.

Along with those discoveries, or in some cases, rediscoveries, basic needs such as dietary habits and nutrition, hydration, and sleep are vital toward emotional regulation, physiological homeostasis, and stress modulation. Remember HALT: Hungry, Angry, Lonely, Tired, Too hot, Too cold, Sad or Stressed. Those strategies are meant to guide self-care and highlight the importance of allowing time for self-awareness. Imagine yourself as if you are meeting a new patient. Establish rapport, identify symptoms, and explore options for treatment. When we give time to ourselves, we can give time more freely to others. With this in mind, try following the 5-minute wellness check that I formulated:

1. How am I feeling? What am I feeling?

2. Assess HALTS.

3. Identify the number on your scale.

4. Methods of quick de-escalation:

• Designate and schedule personal time.
• Write down daily goals.
• Repeat positive affirmations or write down words of gratitude.
• Use deep breathing exercises.
• Stretch or take a brief walk.
• Engage in mindfulness practices, such as meditation.

Once we develop a habit of monitoring, assessing, and practicing self-care, the process becomes more efficient and effective. Think of the way a seasoned attending can manage workflow with ease, compared with an intern. Recognizing signs and using these strategies routinely can become a quick daily measure of well-being.
 

Dr. Thomas is a board-certified adult psychiatrist with interests in chronic illness, women’s behavioral health, and minority mental health. She currently practices in North Kingstown and East Providence, R.I. Dr. Thomas has no conflicts of interest.

Gradually, we are emerging from the chaos, isolation, and anxiety of COVID-19. As the Centers for Disease Control and Prevention adjusts its recommendations and vaccinations become more widely available, our communities are beginning to return to normalcy. We are encouraged to put aside our masks if vaccinated and rejoin society, to venture out with less hesitancy and anxiety. As family and friends reunite, memories of confusion, frustration, and fear are beginning to fade to black. Despite the prevailing belief that we should move on, look forward, and remember the past to safeguard our future, remnants of the pandemic remain.

shironosov/Getty Images

Unvaccinated individuals, notably children under the age of 12, are quite significant in number. The use of telehealth is now standard practice.

For several years, we were warned about the looming “mental health crisis.” The past year has demonstrated that a crisis no longer looms – it has arrived. Our patients can reveal the vulnerability COVID-19 has wrought – from the devastation of lives lost, supply shortages, loss of employment and financial stability – to a lack of access to computers and thereby, the risk of educational decline. Those factors, coupled with isolation and uncertainty about the future, have led to an influx of individuals with anxiety, depression, and other mood disorders seeking mental health treatment.
 

Doctors, others suffering

As result of a medical culture guided by the sacred oath to which care, compassion, and dedication held as true in ancient Greece as it does today, the focus centers on those around us – while signs of our own weariness are waved away as “a bad day.” Even though several support groups are readily available to offer a listening ear and mental health physicians who focus on the treatment of health care professionals are becoming more ubiquitous, the vestiges of past doctrine remain.

In this modern age of medical training, there is often as much sacrifice as there is attainment of knowledge. This philosophy is so ingrained that throughout training and practice one may come across colleagues experiencing an abundance of guilt when leave is needed for personal reasons. We are quick to recommend such steps for our patients, family, and friends, but hesitant to consider such for ourselves. Yet, of all the lessons this past year has wrought, the importance of mental health and self-care cannot be overstated. This raises the question: How do we incorporate wellness into our routines while navigating the complexity of medicine?

It is vital to accept our humanity as something not to repair, treat, or overcome but to understand. There is strength and power in vulnerability. If we do not perceive and validate this process within ourselves, how can we do so for others? In other words, the oxygen mask must be placed on us first before we can place it on anyone else – patients or otherwise.

Chiefly and above all else, the importance of identifying individual signs of stress is essential. Where do you hold tension? Are you prone to GI distress or headaches when taxed? Do you tend toward irritability, apathy, or exhaustion?

Once this is determined, it is important to assess your stress on a numerical scale, such as those used for pain. Are you a 5 or an 8? Finally, are there identifiable triggers or reliable alleviators? Is there a time of day or day of the week that is most difficult to manage? Can you anticipate potential stressors? Understanding your triggers, listening to your body, and practicing the language of self is the first step toward wellness.

Following introspection and observation, the next step is inventory. Take stock of your reserves. What replenishes? What depletes? What brings joy? What brings dread? Are there certain activities that mitigate stress? If so, how much time do they entail? Identify your number on a scale and associate that number with specific strategies or techniques. Remember that decompression for a 6 might be excessive for a 4. Furthermore, what is the duration of these feelings? Chronic stressors may incur gradual change verses sudden impact if acute. Through identifying personal signs, devising and using a scale, as well as escalating or de-escalating factors, individuals become more in tune with their bodies and therefore, more likely to intervene before burnout takes hold.

With this process well integrated, one can now consider stylized approaches for stress management. For example, those inclined toward mindfulness practices may find yoga, meditation, and relaxation exercises beneficial. Others may thrive on positive affirmations, gratitude, and thankfulness. While some might find relief in physical activity, be it strenuous or casual, the creative arts might appeal to those who find joy in painting, writing, or doing crafts. In addition, baking, reading, dancing, and/or listening to music might help lift stress.

Along with those discoveries, or in some cases, rediscoveries, basic needs such as dietary habits and nutrition, hydration, and sleep are vital toward emotional regulation, physiological homeostasis, and stress modulation. Remember HALT: Hungry, Angry, Lonely, Tired, Too hot, Too cold, Sad or Stressed. Those strategies are meant to guide self-care and highlight the importance of allowing time for self-awareness. Imagine yourself as if you are meeting a new patient. Establish rapport, identify symptoms, and explore options for treatment. When we give time to ourselves, we can give time more freely to others. With this in mind, try following the 5-minute wellness check that I formulated:

1. How am I feeling? What am I feeling?

2. Assess HALTS.

3. Identify the number on your scale.

4. Methods of quick de-escalation:

• Designate and schedule personal time.
• Write down daily goals.
• Repeat positive affirmations or write down words of gratitude.
• Use deep breathing exercises.
• Stretch or take a brief walk.
• Engage in mindfulness practices, such as meditation.

Once we develop a habit of monitoring, assessing, and practicing self-care, the process becomes more efficient and effective. Think of the way a seasoned attending can manage workflow with ease, compared with an intern. Recognizing signs and using these strategies routinely can become a quick daily measure of well-being.
 

Dr. Thomas is a board-certified adult psychiatrist with interests in chronic illness, women’s behavioral health, and minority mental health. She currently practices in North Kingstown and East Providence, R.I. Dr. Thomas has no conflicts of interest.

A report by the American Medical Association’s medical education advisory body points to systemic racism or other systems of oppression as causing a lack of representation, exclusion, and marginalization in medical education and medicine.

The report received overwhelming support at the House of Delegates, the AMA’s legislative policy making body, during an online meeting held June 13.

The Council on Medical Education’s report recommends that the AMA acknowledge the harm caused by the Flexner Report, which was issued in 1910 and has since shaped medical education. The Flexner Report caused harm not only to historically Black medical schools, but also to physician workforce diversity and to the clinical outcomes of minority and marginalized patients, according to the medical education advisory body.

The council also recommended conducting a study on medical education with a focus on health equity and racial justice, improving diversity among healthcare workers, and fixing inequitable outcomes from minorities and marginalized patient populations.

The report comes on the heels of the resignation of JAMA editor-in-chief Howard Bauchner, MD, and another high-ranking editor following a February podcast on systemic racism in medicine. The AMA has since released a strategic plan addressing racism and health inequity that has divided membership.
 

Flexner Report’s effect on physician diversity

The Council on Medical Education’s report observed that as a result of the Flexner Report’s recommendations, 89 medical schools, including 5 of the 7 existing medical schools training Black physicians, were closed because they didn’t meet the report’s standards. In addition, the report created a limited role for Black physicians while “hint[ing] that Black physicians possessed less potential and ability than their White counterparts,” read the Council’s report.

In addition to consigning the role of the Black physician to “educating the [Black] race to know and to practice fundamental hygienic principles,” the Flexner Report also observed that “a well-taught negro sanitarian will be immensely useful,” per the Council’s report.

The impact of the closure of medical schools training Black physicians was dramatic. According to the Council’s report, in 1964, 93% of medical students in the United States were men and 97% of those students were non-Hispanic White.

Today, 56% of physicians identify as White, 17% as Asian, 6% as Hispanic, and 5% as Black or African American, per the Association of American Medical Colleges; nearly 14% of active physicians didn’t report their race in the survey. By means of contrast, the U.S. population in 2019 was 60% White, 19% Latino/Hispanic, 13% Black or African American, and 6% Asian American, according to the Brookings Institute.

Abraham Flexner, who wrote the Flexner Report, is often referred to as the “father of modern medical education,” according to the AAMC. In November, the AAMC observed that the Flexner Report contained racist and sexist ideas and that his work contributed to the closure of historically Black medical schools. Both statements were included in AAMC’s announcement about the removal of Flexner’s name from its most prestigious award. As of January, the award is now called the AAMC Award for Excellence in Medical Education.
 

Pathway programs can increase diversity

Pathway programs, which leverage targeted milestones along the journey to becoming a physician in order to increase diversity, were an area of focus in the council’s report. These programs “can exert a meaningful, positive effect on student outcomes and increase diversity across various levels of educational settings,” according to its report.

Centers of Excellence, which provides grants for mentorship and training programs, is one of many pathway programs. During the 2018-2019 academic year, Centers of Excellence supported more than 1,300 trainees – 99% of them were underrepresented minorities and 64% came from financially or educationally disadvantaged backgrounds. In 2006, federal funding was cut to these programs and the number of Centers of Excellence fell.

Still, the report cites the passage of federal funding in 2020 of $50 million for public institutions of higher education that train physicians; educational institutions in states with a projected primary care shortage in 2025 are given priority in the grant-funding process.
 

AMA council’s report garners support from delegates

Delegates voiced overwhelming support of the council’s report during the June 13 meeting. Lou Edje, MD, a Perrysburgh, Ohio–based family physician, voiced strong support for the council’s report, in particular its recommendations that recognize the harm caused by the Flexner Report. Dr. Edje observed that the Flexner Report, with its elimination of five of seven Black medical schools, “[set] back admissions of Black students into medicine by 50 years.”

“Empathy is what we are called to have as physicians. I implore you to simply substitute your ethnicity into these quotes to help understand the historic need for health equity in medicine today. This CME report is part of the antidote to Flexner. We support [it] fully,” concluded Dr. Edje, who spoke for the Great Lakes States Coalition of the AMA.

Rohan Khazanchi, a medical student at the University of Nebraska, Omaha, and a member of the council, said, “Our broad attempt with this report was twofold: to fill gaps in AMA policy with evidence-based recommendations which could improve diversity in our health workforce and, second, to enhance our organization’s vision for truth, reconciliation, and healing to redress the historic marginalization of minoritized physicians in medicine.”

According to an AMA spokesperson, the House of Delegates will vote on this and other policies this week, after which the policies are considered final.

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

A report by the American Medical Association’s medical education advisory body points to systemic racism or other systems of oppression as causing a lack of representation, exclusion, and marginalization in medical education and medicine.

The report received overwhelming support at the House of Delegates, the AMA’s legislative policy making body, during an online meeting held June 13.

The Council on Medical Education’s report recommends that the AMA acknowledge the harm caused by the Flexner Report, which was issued in 1910 and has since shaped medical education. The Flexner Report caused harm not only to historically Black medical schools, but also to physician workforce diversity and to the clinical outcomes of minority and marginalized patients, according to the medical education advisory body.

The council also recommended conducting a study on medical education with a focus on health equity and racial justice, improving diversity among healthcare workers, and fixing inequitable outcomes from minorities and marginalized patient populations.

The report comes on the heels of the resignation of JAMA editor-in-chief Howard Bauchner, MD, and another high-ranking editor following a February podcast on systemic racism in medicine. The AMA has since released a strategic plan addressing racism and health inequity that has divided membership.
 

Flexner Report’s effect on physician diversity

The Council on Medical Education’s report observed that as a result of the Flexner Report’s recommendations, 89 medical schools, including 5 of the 7 existing medical schools training Black physicians, were closed because they didn’t meet the report’s standards. In addition, the report created a limited role for Black physicians while “hint[ing] that Black physicians possessed less potential and ability than their White counterparts,” read the Council’s report.

In addition to consigning the role of the Black physician to “educating the [Black] race to know and to practice fundamental hygienic principles,” the Flexner Report also observed that “a well-taught negro sanitarian will be immensely useful,” per the Council’s report.

The impact of the closure of medical schools training Black physicians was dramatic. According to the Council’s report, in 1964, 93% of medical students in the United States were men and 97% of those students were non-Hispanic White.

Today, 56% of physicians identify as White, 17% as Asian, 6% as Hispanic, and 5% as Black or African American, per the Association of American Medical Colleges; nearly 14% of active physicians didn’t report their race in the survey. By means of contrast, the U.S. population in 2019 was 60% White, 19% Latino/Hispanic, 13% Black or African American, and 6% Asian American, according to the Brookings Institute.

Abraham Flexner, who wrote the Flexner Report, is often referred to as the “father of modern medical education,” according to the AAMC. In November, the AAMC observed that the Flexner Report contained racist and sexist ideas and that his work contributed to the closure of historically Black medical schools. Both statements were included in AAMC’s announcement about the removal of Flexner’s name from its most prestigious award. As of January, the award is now called the AAMC Award for Excellence in Medical Education.
 

Pathway programs can increase diversity

Pathway programs, which leverage targeted milestones along the journey to becoming a physician in order to increase diversity, were an area of focus in the council’s report. These programs “can exert a meaningful, positive effect on student outcomes and increase diversity across various levels of educational settings,” according to its report.

Centers of Excellence, which provides grants for mentorship and training programs, is one of many pathway programs. During the 2018-2019 academic year, Centers of Excellence supported more than 1,300 trainees – 99% of them were underrepresented minorities and 64% came from financially or educationally disadvantaged backgrounds. In 2006, federal funding was cut to these programs and the number of Centers of Excellence fell.

Still, the report cites the passage of federal funding in 2020 of $50 million for public institutions of higher education that train physicians; educational institutions in states with a projected primary care shortage in 2025 are given priority in the grant-funding process.
 

AMA council’s report garners support from delegates

Delegates voiced overwhelming support of the council’s report during the June 13 meeting. Lou Edje, MD, a Perrysburgh, Ohio–based family physician, voiced strong support for the council’s report, in particular its recommendations that recognize the harm caused by the Flexner Report. Dr. Edje observed that the Flexner Report, with its elimination of five of seven Black medical schools, “[set] back admissions of Black students into medicine by 50 years.”

“Empathy is what we are called to have as physicians. I implore you to simply substitute your ethnicity into these quotes to help understand the historic need for health equity in medicine today. This CME report is part of the antidote to Flexner. We support [it] fully,” concluded Dr. Edje, who spoke for the Great Lakes States Coalition of the AMA.

Rohan Khazanchi, a medical student at the University of Nebraska, Omaha, and a member of the council, said, “Our broad attempt with this report was twofold: to fill gaps in AMA policy with evidence-based recommendations which could improve diversity in our health workforce and, second, to enhance our organization’s vision for truth, reconciliation, and healing to redress the historic marginalization of minoritized physicians in medicine.”

According to an AMA spokesperson, the House of Delegates will vote on this and other policies this week, after which the policies are considered final.

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

A report by the American Medical Association’s medical education advisory body points to systemic racism or other systems of oppression as causing a lack of representation, exclusion, and marginalization in medical education and medicine.

The report received overwhelming support at the House of Delegates, the AMA’s legislative policy making body, during an online meeting held June 13.

The Council on Medical Education’s report recommends that the AMA acknowledge the harm caused by the Flexner Report, which was issued in 1910 and has since shaped medical education. The Flexner Report caused harm not only to historically Black medical schools, but also to physician workforce diversity and to the clinical outcomes of minority and marginalized patients, according to the medical education advisory body.

The council also recommended conducting a study on medical education with a focus on health equity and racial justice, improving diversity among healthcare workers, and fixing inequitable outcomes from minorities and marginalized patient populations.

The report comes on the heels of the resignation of JAMA editor-in-chief Howard Bauchner, MD, and another high-ranking editor following a February podcast on systemic racism in medicine. The AMA has since released a strategic plan addressing racism and health inequity that has divided membership.
 

Flexner Report’s effect on physician diversity

The Council on Medical Education’s report observed that as a result of the Flexner Report’s recommendations, 89 medical schools, including 5 of the 7 existing medical schools training Black physicians, were closed because they didn’t meet the report’s standards. In addition, the report created a limited role for Black physicians while “hint[ing] that Black physicians possessed less potential and ability than their White counterparts,” read the Council’s report.

In addition to consigning the role of the Black physician to “educating the [Black] race to know and to practice fundamental hygienic principles,” the Flexner Report also observed that “a well-taught negro sanitarian will be immensely useful,” per the Council’s report.

The impact of the closure of medical schools training Black physicians was dramatic. According to the Council’s report, in 1964, 93% of medical students in the United States were men and 97% of those students were non-Hispanic White.

Today, 56% of physicians identify as White, 17% as Asian, 6% as Hispanic, and 5% as Black or African American, per the Association of American Medical Colleges; nearly 14% of active physicians didn’t report their race in the survey. By means of contrast, the U.S. population in 2019 was 60% White, 19% Latino/Hispanic, 13% Black or African American, and 6% Asian American, according to the Brookings Institute.

Abraham Flexner, who wrote the Flexner Report, is often referred to as the “father of modern medical education,” according to the AAMC. In November, the AAMC observed that the Flexner Report contained racist and sexist ideas and that his work contributed to the closure of historically Black medical schools. Both statements were included in AAMC’s announcement about the removal of Flexner’s name from its most prestigious award. As of January, the award is now called the AAMC Award for Excellence in Medical Education.
 

Pathway programs can increase diversity

Pathway programs, which leverage targeted milestones along the journey to becoming a physician in order to increase diversity, were an area of focus in the council’s report. These programs “can exert a meaningful, positive effect on student outcomes and increase diversity across various levels of educational settings,” according to its report.

Centers of Excellence, which provides grants for mentorship and training programs, is one of many pathway programs. During the 2018-2019 academic year, Centers of Excellence supported more than 1,300 trainees – 99% of them were underrepresented minorities and 64% came from financially or educationally disadvantaged backgrounds. In 2006, federal funding was cut to these programs and the number of Centers of Excellence fell.

Still, the report cites the passage of federal funding in 2020 of $50 million for public institutions of higher education that train physicians; educational institutions in states with a projected primary care shortage in 2025 are given priority in the grant-funding process.
 

AMA council’s report garners support from delegates

Delegates voiced overwhelming support of the council’s report during the June 13 meeting. Lou Edje, MD, a Perrysburgh, Ohio–based family physician, voiced strong support for the council’s report, in particular its recommendations that recognize the harm caused by the Flexner Report. Dr. Edje observed that the Flexner Report, with its elimination of five of seven Black medical schools, “[set] back admissions of Black students into medicine by 50 years.”

“Empathy is what we are called to have as physicians. I implore you to simply substitute your ethnicity into these quotes to help understand the historic need for health equity in medicine today. This CME report is part of the antidote to Flexner. We support [it] fully,” concluded Dr. Edje, who spoke for the Great Lakes States Coalition of the AMA.

Rohan Khazanchi, a medical student at the University of Nebraska, Omaha, and a member of the council, said, “Our broad attempt with this report was twofold: to fill gaps in AMA policy with evidence-based recommendations which could improve diversity in our health workforce and, second, to enhance our organization’s vision for truth, reconciliation, and healing to redress the historic marginalization of minoritized physicians in medicine.”

According to an AMA spokesperson, the House of Delegates will vote on this and other policies this week, after which the policies are considered final.

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

Advances in photobiomodulation have propelled the use of therapeutic applications in a variety of medical specialties, according to Juanita J. Anders, PhD.

During the annual conference of the American Society for Laser Medicine and Surgery, Dr. Anders, professor of anatomy, physiology, and genetics at the Uniformed Services University of the Health Sciences, Bethesda, Md., defined photobiomodulation (PBM) as the mechanism by which nonionizing optical radiation in the visible and near-infrared spectral range is absorbed by endogenous chromophores to elicit photophysical and photochemical events at various biological scales. Photobiomodulation therapy (PBMT) involves the use of light sources including lasers, LEDs, and broadband light, that emit visible and/or near-infrared light to cause physiological changes in cells and tissues and result in therapeutic benefits.

In dermatology, LED light therapy devices are commonly used for PBMT in wavelengths that range from blue (415 nm) and red (633 nm) to near infrared (830 nm). “Often, when PBMT is referred to by dermatologists it’s called LED therapy or LED light therapy,” Dr. Anders noted. “Some people are under the impression that this is different from PBMT. But remember: It’s not the device that’s producing the photons that is clinically relevant, but it’s the photons themselves. In both cases, the same radiances and fluence ranges are being used and the mechanisms are the same, so it’s all PBMT.”

The therapy is used to treat a wide variety of medical and aesthetic disorders including acne vulgaris, psoriasis, burns, and wound healing. It has also been used in conjunction with surgical aesthetic and resurfacing procedures and has been reported to reduce erythema, edema, bruising, and days to healing. It’s been shown that PBMT stimulates fibroblast proliferation, collagen synthesis, and extracellular matrix resulting in lifting and tightening lax skin.

According to Dr. Anders, French dermatologists Linda Fouque, MD, and Michele Pelletier, MD, performed a series of in vivo and in vitro studies in which they tested the effects of yellow and red light for skin rejuvenation when used individually or in combination. “They found that fibroblasts and keratinocytes in vitro had great improvement in their morphology both with the yellow and red light, but the best improvement was seen with combination therapy,” Dr. Anders said. “This held true in their work looking at epidermal and dermal markers in the skin, where they found the best up-regulation in protein synthesis of such markers as collagens and fibronectin were produced when a combination wavelength light was used.”

Oral mucositis and pain

PBMT is also being used to treat oral mucositis (OM), a common adverse response to chemotherapy and/or radiation therapy, which causes pain, difficulty in swallowing and eating, and oral ulceration, and often interrupts the course of treatments. Authors of a recently published review on the risks and benefits of PBMT concluded that there is consistent evidence from a small number of high-quality studies that PBMT can help prevent the development of cancer therapy–induced OM, reduce pain intensity, as well as promote healing, and enhance patient quality of life.

“They also cautioned that, due to the limited long-term follow-up of patients, there is still concern for the potential long-term risks of PBMT in cancer cell mutation and amplification,” Dr. Anders said. “They advised that PBMT should be used carefully when the irradiation beam is in the direction of the tumor zone.”

Using PBMT for modulation of pain is another area of active research. Based on work from the laboratory of Dr. Anders and others, there are two methods to modulate pain. The first is to target tissue at irradiances below 100 mW/cm².

“In my laboratory, based on in vivo preclinical animal models of neuropathic pain, we used a 980-nm wavelength laser at 43.25 mW/cm² transcutaneously delivered to the level of the nerve for 20 seconds,” said Dr. Anders, who is a past president of the ASLMS. “Essentially, we found that the pain was modulated by reducing sensitivity to mechanical stimulation and also by causing an anti-inflammatory shift in microglial and macrophage phenotype in the dorsal root ganglion and spinal cord of affected segments.”

The second way to modulate pain, she continued, is to target tissue at irradiances above 250 mW/cm². She and her colleagues have conducted in vitro and in vivo studies, which indicate that treatment with an irradiance/fluence rate at 270 mW/cm² or higher at the nerve can rapidly block pain transmission.

“In vitro, we found that if we used an 810-nm wavelength light at 300 mW/cm², we got a disruption of microtubules in the DRG neurons in culture, specifically the small neurons, the nociceptive fibers, but we did not affect the proprioceptive fibers unless we increased the length of the treatment,” she said. “We essentially found the same thing in vivo in a rodent model of neuropathic pain.”

In a pilot study, Dr. Anders and coauthors examined the efficacy of laser irradiation of the dorsal root ganglion of the second lumbar spinal nerve for patients with chronic back pain.

They found that PBMT effectively reduced back pain equal to the effects of lidocaine.

Based on these two irradiation approaches of targeting tissue, Dr. Anders recommends that a combination therapy be used to modulate neuropathic pain going forward. “This approach would involve the initial use of a high-irradiance treatment [at least 250 mW/cm²] at the nerve to block the pain transmission,” she said. “That treatment would be followed by a series of low-irradiance treatments [10-100 mW/cm²] along the course of the involved nerve to alter chronic pathology and inflammation.”
 

Potential applications in neurology

Dr. Anders also discussed research efforts under way involving transcranial PBMT: the delivery of near-infrared light through the tissues of the scalp and skull to targeted brain regions to treat neurologic injuries and disorders. “There have been some exciting results in preclinical animal work and in small clinical pilot work that show that there could be possible beneficial effects in Parkinson’s disease, Alzheimer’s disease, depression, and improvement in cognition and memory after a brain injury, such as a TBI,” she said.

“Initially, though, there were a lot of questions about whether you could really deliver light to the brain through the scalp. In my laboratory, we used slices of nonfixed brain and found that the sulci within the human brain act as light-wave guides. We used an 808-nm near-infrared wavelength of light, so that the light could penetrate more deeply.” Using nonfixed cadaver heads, where the light was applied at the scalp surface, Dr. Anders and colleagues were able to measure photons down to the depth of 4 cm. “It’s generally agreed now, though, that it’s to a maximum depth of 2.5-3 cm that enough photons are delivered that would cause a beneficial therapeutic effect,” she said.

Dr. Anders disclosed that she has received equipment from LiteCure, grant funding from the Department of Defense, and that she holds advisory board roles with LiteCure and Neurothera. She has also served in leadership roles for the Optical Society and holds intellectual property rights for the Henry M. Jackson Foundation for the Advancement of Military Medicine.

[email protected]

Advances in photobiomodulation have propelled the use of therapeutic applications in a variety of medical specialties, according to Juanita J. Anders, PhD.

During the annual conference of the American Society for Laser Medicine and Surgery, Dr. Anders, professor of anatomy, physiology, and genetics at the Uniformed Services University of the Health Sciences, Bethesda, Md., defined photobiomodulation (PBM) as the mechanism by which nonionizing optical radiation in the visible and near-infrared spectral range is absorbed by endogenous chromophores to elicit photophysical and photochemical events at various biological scales. Photobiomodulation therapy (PBMT) involves the use of light sources including lasers, LEDs, and broadband light, that emit visible and/or near-infrared light to cause physiological changes in cells and tissues and result in therapeutic benefits.

In dermatology, LED light therapy devices are commonly used for PBMT in wavelengths that range from blue (415 nm) and red (633 nm) to near infrared (830 nm). “Often, when PBMT is referred to by dermatologists it’s called LED therapy or LED light therapy,” Dr. Anders noted. “Some people are under the impression that this is different from PBMT. But remember: It’s not the device that’s producing the photons that is clinically relevant, but it’s the photons themselves. In both cases, the same radiances and fluence ranges are being used and the mechanisms are the same, so it’s all PBMT.”

The therapy is used to treat a wide variety of medical and aesthetic disorders including acne vulgaris, psoriasis, burns, and wound healing. It has also been used in conjunction with surgical aesthetic and resurfacing procedures and has been reported to reduce erythema, edema, bruising, and days to healing. It’s been shown that PBMT stimulates fibroblast proliferation, collagen synthesis, and extracellular matrix resulting in lifting and tightening lax skin.

According to Dr. Anders, French dermatologists Linda Fouque, MD, and Michele Pelletier, MD, performed a series of in vivo and in vitro studies in which they tested the effects of yellow and red light for skin rejuvenation when used individually or in combination. “They found that fibroblasts and keratinocytes in vitro had great improvement in their morphology both with the yellow and red light, but the best improvement was seen with combination therapy,” Dr. Anders said. “This held true in their work looking at epidermal and dermal markers in the skin, where they found the best up-regulation in protein synthesis of such markers as collagens and fibronectin were produced when a combination wavelength light was used.”

Oral mucositis and pain

PBMT is also being used to treat oral mucositis (OM), a common adverse response to chemotherapy and/or radiation therapy, which causes pain, difficulty in swallowing and eating, and oral ulceration, and often interrupts the course of treatments. Authors of a recently published review on the risks and benefits of PBMT concluded that there is consistent evidence from a small number of high-quality studies that PBMT can help prevent the development of cancer therapy–induced OM, reduce pain intensity, as well as promote healing, and enhance patient quality of life.

“They also cautioned that, due to the limited long-term follow-up of patients, there is still concern for the potential long-term risks of PBMT in cancer cell mutation and amplification,” Dr. Anders said. “They advised that PBMT should be used carefully when the irradiation beam is in the direction of the tumor zone.”

Using PBMT for modulation of pain is another area of active research. Based on work from the laboratory of Dr. Anders and others, there are two methods to modulate pain. The first is to target tissue at irradiances below 100 mW/cm².

“In my laboratory, based on in vivo preclinical animal models of neuropathic pain, we used a 980-nm wavelength laser at 43.25 mW/cm² transcutaneously delivered to the level of the nerve for 20 seconds,” said Dr. Anders, who is a past president of the ASLMS. “Essentially, we found that the pain was modulated by reducing sensitivity to mechanical stimulation and also by causing an anti-inflammatory shift in microglial and macrophage phenotype in the dorsal root ganglion and spinal cord of affected segments.”

The second way to modulate pain, she continued, is to target tissue at irradiances above 250 mW/cm². She and her colleagues have conducted in vitro and in vivo studies, which indicate that treatment with an irradiance/fluence rate at 270 mW/cm² or higher at the nerve can rapidly block pain transmission.

“In vitro, we found that if we used an 810-nm wavelength light at 300 mW/cm², we got a disruption of microtubules in the DRG neurons in culture, specifically the small neurons, the nociceptive fibers, but we did not affect the proprioceptive fibers unless we increased the length of the treatment,” she said. “We essentially found the same thing in vivo in a rodent model of neuropathic pain.”

In a pilot study, Dr. Anders and coauthors examined the efficacy of laser irradiation of the dorsal root ganglion of the second lumbar spinal nerve for patients with chronic back pain.

They found that PBMT effectively reduced back pain equal to the effects of lidocaine.

Based on these two irradiation approaches of targeting tissue, Dr. Anders recommends that a combination therapy be used to modulate neuropathic pain going forward. “This approach would involve the initial use of a high-irradiance treatment [at least 250 mW/cm²] at the nerve to block the pain transmission,” she said. “That treatment would be followed by a series of low-irradiance treatments [10-100 mW/cm²] along the course of the involved nerve to alter chronic pathology and inflammation.”
 

Potential applications in neurology

Dr. Anders also discussed research efforts under way involving transcranial PBMT: the delivery of near-infrared light through the tissues of the scalp and skull to targeted brain regions to treat neurologic injuries and disorders. “There have been some exciting results in preclinical animal work and in small clinical pilot work that show that there could be possible beneficial effects in Parkinson’s disease, Alzheimer’s disease, depression, and improvement in cognition and memory after a brain injury, such as a TBI,” she said.

“Initially, though, there were a lot of questions about whether you could really deliver light to the brain through the scalp. In my laboratory, we used slices of nonfixed brain and found that the sulci within the human brain act as light-wave guides. We used an 808-nm near-infrared wavelength of light, so that the light could penetrate more deeply.” Using nonfixed cadaver heads, where the light was applied at the scalp surface, Dr. Anders and colleagues were able to measure photons down to the depth of 4 cm. “It’s generally agreed now, though, that it’s to a maximum depth of 2.5-3 cm that enough photons are delivered that would cause a beneficial therapeutic effect,” she said.

Dr. Anders disclosed that she has received equipment from LiteCure, grant funding from the Department of Defense, and that she holds advisory board roles with LiteCure and Neurothera. She has also served in leadership roles for the Optical Society and holds intellectual property rights for the Henry M. Jackson Foundation for the Advancement of Military Medicine.

[email protected]

Advances in photobiomodulation have propelled the use of therapeutic applications in a variety of medical specialties, according to Juanita J. Anders, PhD.

During the annual conference of the American Society for Laser Medicine and Surgery, Dr. Anders, professor of anatomy, physiology, and genetics at the Uniformed Services University of the Health Sciences, Bethesda, Md., defined photobiomodulation (PBM) as the mechanism by which nonionizing optical radiation in the visible and near-infrared spectral range is absorbed by endogenous chromophores to elicit photophysical and photochemical events at various biological scales. Photobiomodulation therapy (PBMT) involves the use of light sources including lasers, LEDs, and broadband light, that emit visible and/or near-infrared light to cause physiological changes in cells and tissues and result in therapeutic benefits.

In dermatology, LED light therapy devices are commonly used for PBMT in wavelengths that range from blue (415 nm) and red (633 nm) to near infrared (830 nm). “Often, when PBMT is referred to by dermatologists it’s called LED therapy or LED light therapy,” Dr. Anders noted. “Some people are under the impression that this is different from PBMT. But remember: It’s not the device that’s producing the photons that is clinically relevant, but it’s the photons themselves. In both cases, the same radiances and fluence ranges are being used and the mechanisms are the same, so it’s all PBMT.”

The therapy is used to treat a wide variety of medical and aesthetic disorders including acne vulgaris, psoriasis, burns, and wound healing. It has also been used in conjunction with surgical aesthetic and resurfacing procedures and has been reported to reduce erythema, edema, bruising, and days to healing. It’s been shown that PBMT stimulates fibroblast proliferation, collagen synthesis, and extracellular matrix resulting in lifting and tightening lax skin.

According to Dr. Anders, French dermatologists Linda Fouque, MD, and Michele Pelletier, MD, performed a series of in vivo and in vitro studies in which they tested the effects of yellow and red light for skin rejuvenation when used individually or in combination. “They found that fibroblasts and keratinocytes in vitro had great improvement in their morphology both with the yellow and red light, but the best improvement was seen with combination therapy,” Dr. Anders said. “This held true in their work looking at epidermal and dermal markers in the skin, where they found the best up-regulation in protein synthesis of such markers as collagens and fibronectin were produced when a combination wavelength light was used.”

Oral mucositis and pain

PBMT is also being used to treat oral mucositis (OM), a common adverse response to chemotherapy and/or radiation therapy, which causes pain, difficulty in swallowing and eating, and oral ulceration, and often interrupts the course of treatments. Authors of a recently published review on the risks and benefits of PBMT concluded that there is consistent evidence from a small number of high-quality studies that PBMT can help prevent the development of cancer therapy–induced OM, reduce pain intensity, as well as promote healing, and enhance patient quality of life.

“They also cautioned that, due to the limited long-term follow-up of patients, there is still concern for the potential long-term risks of PBMT in cancer cell mutation and amplification,” Dr. Anders said. “They advised that PBMT should be used carefully when the irradiation beam is in the direction of the tumor zone.”

Using PBMT for modulation of pain is another area of active research. Based on work from the laboratory of Dr. Anders and others, there are two methods to modulate pain. The first is to target tissue at irradiances below 100 mW/cm².

“In my laboratory, based on in vivo preclinical animal models of neuropathic pain, we used a 980-nm wavelength laser at 43.25 mW/cm² transcutaneously delivered to the level of the nerve for 20 seconds,” said Dr. Anders, who is a past president of the ASLMS. “Essentially, we found that the pain was modulated by reducing sensitivity to mechanical stimulation and also by causing an anti-inflammatory shift in microglial and macrophage phenotype in the dorsal root ganglion and spinal cord of affected segments.”

The second way to modulate pain, she continued, is to target tissue at irradiances above 250 mW/cm². She and her colleagues have conducted in vitro and in vivo studies, which indicate that treatment with an irradiance/fluence rate at 270 mW/cm² or higher at the nerve can rapidly block pain transmission.

“In vitro, we found that if we used an 810-nm wavelength light at 300 mW/cm², we got a disruption of microtubules in the DRG neurons in culture, specifically the small neurons, the nociceptive fibers, but we did not affect the proprioceptive fibers unless we increased the length of the treatment,” she said. “We essentially found the same thing in vivo in a rodent model of neuropathic pain.”

In a pilot study, Dr. Anders and coauthors examined the efficacy of laser irradiation of the dorsal root ganglion of the second lumbar spinal nerve for patients with chronic back pain.

They found that PBMT effectively reduced back pain equal to the effects of lidocaine.

Based on these two irradiation approaches of targeting tissue, Dr. Anders recommends that a combination therapy be used to modulate neuropathic pain going forward. “This approach would involve the initial use of a high-irradiance treatment [at least 250 mW/cm²] at the nerve to block the pain transmission,” she said. “That treatment would be followed by a series of low-irradiance treatments [10-100 mW/cm²] along the course of the involved nerve to alter chronic pathology and inflammation.”
 

Potential applications in neurology

Dr. Anders also discussed research efforts under way involving transcranial PBMT: the delivery of near-infrared light through the tissues of the scalp and skull to targeted brain regions to treat neurologic injuries and disorders. “There have been some exciting results in preclinical animal work and in small clinical pilot work that show that there could be possible beneficial effects in Parkinson’s disease, Alzheimer’s disease, depression, and improvement in cognition and memory after a brain injury, such as a TBI,” she said.

“Initially, though, there were a lot of questions about whether you could really deliver light to the brain through the scalp. In my laboratory, we used slices of nonfixed brain and found that the sulci within the human brain act as light-wave guides. We used an 808-nm near-infrared wavelength of light, so that the light could penetrate more deeply.” Using nonfixed cadaver heads, where the light was applied at the scalp surface, Dr. Anders and colleagues were able to measure photons down to the depth of 4 cm. “It’s generally agreed now, though, that it’s to a maximum depth of 2.5-3 cm that enough photons are delivered that would cause a beneficial therapeutic effect,” she said.

Dr. Anders disclosed that she has received equipment from LiteCure, grant funding from the Department of Defense, and that she holds advisory board roles with LiteCure and Neurothera. She has also served in leadership roles for the Optical Society and holds intellectual property rights for the Henry M. Jackson Foundation for the Advancement of Military Medicine.

[email protected]

Chilblain-like lesions seen in adolescents during the COVID-19 pandemic are nonischemic and not related to systemic or localized SARS-CoV-2 infection, suggests a case series from Italy.

These lesions are “most likely are benign” and resolve on their own after 2-6 weeks, Valentina Discepolo, MD, PhD, University of Naples Federico II, told this news organization.

“They do not seem to be the manifestation of systemic inflammatory or autoimmune phenomena. According to our experience, they should not require a SARS-CoV-2–specific molecular or serological test since in all cases in our series they were negative,” said Dr. Discepolo.

The study was published online June 10, 2021, in JAMA Network Open.
 

‘COVID toes’ a fallacy?

The temporal association between the COVID-19 pandemic and the increasing number of chilblain-like lesions has led some in the media to call it “COVID toes,” the investigators wrote. However, data on the association with SARS-CoV-2 are controversial.

For this report, Dr. Discepolo and colleagues evaluated 17 adolescents who presented with chilblain-like lesions of the toes during the first wave of the pandemic in southern Italy.

None had evidence of current, past, or local SARS-CoV-2 infection.

“In our experience, chilblain-like lesions are not a manifestation of COVID-19, as shown by negative serological and molecular specific for SARS-CoV2,” Dr. Discepolo said in an interview.

The lesions were bilaterally distributed in 16 adolescents (94.1%) and heel skin was involved in 7 (41.2%). Ulceration complicated one patient during the active phase of the disease, and desquamation developed over time in three patients (17.6%). Only two patients (11.8%) had concurrent involvement of the fingers.

Self-administered therapies included topical antibiotics and/or corticosteroids, disinfectants, and antifungal agents; systemic antibiotics or corticosteroids were used rarely.

None of the therapies substantially changed the course of the lesions. Duration was “extremely variable,” ranging from 49 to 145 days; however, at follow-up, all patients had full resolution.

Almost invariably, the lesions were characterized by a triad of red dots, white rosettes, and white streaks on an erythematous background, the investigators reported.

In more than half the patients (56%), red dots often appeared as dotted and comma-shaped congested vessels that surrounded the rosettes in the early stage of the lesions. In later stages, red dots were still present, but the rosettes had disappeared.

Although found inconsistently in inflammatory cutaneous conditions, these three signs do not characterize the dermoscopic picture of perniosis, suggesting a distinct disease process, the investigators said.

 

Don’t blame it on ischemia, clots

Histologic analysis revealed “remodeling of the dermal blood vessels with a lobular arrangement, wall thickening, and a mild perivascular lymphocytic infiltrate,” they noted.

Punch biopsy of the involved skin mostly showed endothelial hyperplasia, mild lymphocytic infiltrate, and vessels’ architecture disruption with no papillary dermal edema or eosinophilic or neutrophilic infiltrate.

Pathology did not reveal any ischemic changes, which argues against systemic vasculopathy, Farzam Gorouhi, MD, from Kaiser Permanente, South Sacramento Medical Center, noted in a linked editorial. “Thus, this study provides further evidence against the thromboembolic nature of the presented pattern in adolescents during the COVID-19 pandemic.”

Results of capillaroscopy, used to investigate structural changes in peripheral microcirculation, were either completely normal or showed rare ectasias, supporting a lack of systemic inflammatory process.

“The lack of capillaroscopic features of a major vasculopathic event in the study by Discepolo et al. argues against the ischemic nature of this disease and, thus, indicates that this presentation is not associated with systemic ischemia or an embolic event,” Dr. Gorouhi noted.

Chilblain-like lesions have been one of the most commonly described cutaneous manifestations during the COVID-19 pandemic, but their etiopathogenesis, including the role of SARS-CoV-2, has remained elusive, the investigators wrote.

The findings in this case series do not support the association of the lesions with SARS-CoV-2 infection, they concluded.

The fact that only three new cases of chilblain-like lesions were reported during the highest peaks of the pandemic further supports a lack of association with SARS-CoV-2 infection, they noted.

In addition, none of these patients tested positive for SARS-CoV-2 and all three cases during the second wave occurred in the winter months, suggesting that exposure to the cold might, at least in some cases, trigger the skin lesions, the investigators said.

In line with this hypothesis, seven of the adolescents in this case series (41.2%) relapsed during the winter months while again testing negative for SARS-CoV-2.

“We believe that lifestyle modifications [reduced physical activity, microtraumatisms caused by walking barefoot at home] during the first strict lockdown played a role, likely promoting a local inflammatory process promoted by vascular stasis that led in genetically susceptible individuals to the onset of these lesions,” Dr. Discepolo said in an interview.

This research had no specific funding. The investigators and Dr. Gorouhi declared no relevant conflicts of interest.
 

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

Chilblain-like lesions seen in adolescents during the COVID-19 pandemic are nonischemic and not related to systemic or localized SARS-CoV-2 infection, suggests a case series from Italy.

These lesions are “most likely are benign” and resolve on their own after 2-6 weeks, Valentina Discepolo, MD, PhD, University of Naples Federico II, told this news organization.

“They do not seem to be the manifestation of systemic inflammatory or autoimmune phenomena. According to our experience, they should not require a SARS-CoV-2–specific molecular or serological test since in all cases in our series they were negative,” said Dr. Discepolo.

The study was published online June 10, 2021, in JAMA Network Open.
 

‘COVID toes’ a fallacy?

The temporal association between the COVID-19 pandemic and the increasing number of chilblain-like lesions has led some in the media to call it “COVID toes,” the investigators wrote. However, data on the association with SARS-CoV-2 are controversial.

For this report, Dr. Discepolo and colleagues evaluated 17 adolescents who presented with chilblain-like lesions of the toes during the first wave of the pandemic in southern Italy.

None had evidence of current, past, or local SARS-CoV-2 infection.

“In our experience, chilblain-like lesions are not a manifestation of COVID-19, as shown by negative serological and molecular specific for SARS-CoV2,” Dr. Discepolo said in an interview.

The lesions were bilaterally distributed in 16 adolescents (94.1%) and heel skin was involved in 7 (41.2%). Ulceration complicated one patient during the active phase of the disease, and desquamation developed over time in three patients (17.6%). Only two patients (11.8%) had concurrent involvement of the fingers.

Self-administered therapies included topical antibiotics and/or corticosteroids, disinfectants, and antifungal agents; systemic antibiotics or corticosteroids were used rarely.

None of the therapies substantially changed the course of the lesions. Duration was “extremely variable,” ranging from 49 to 145 days; however, at follow-up, all patients had full resolution.

Almost invariably, the lesions were characterized by a triad of red dots, white rosettes, and white streaks on an erythematous background, the investigators reported.

In more than half the patients (56%), red dots often appeared as dotted and comma-shaped congested vessels that surrounded the rosettes in the early stage of the lesions. In later stages, red dots were still present, but the rosettes had disappeared.

Although found inconsistently in inflammatory cutaneous conditions, these three signs do not characterize the dermoscopic picture of perniosis, suggesting a distinct disease process, the investigators said.

 

Don’t blame it on ischemia, clots

Histologic analysis revealed “remodeling of the dermal blood vessels with a lobular arrangement, wall thickening, and a mild perivascular lymphocytic infiltrate,” they noted.

Punch biopsy of the involved skin mostly showed endothelial hyperplasia, mild lymphocytic infiltrate, and vessels’ architecture disruption with no papillary dermal edema or eosinophilic or neutrophilic infiltrate.

Pathology did not reveal any ischemic changes, which argues against systemic vasculopathy, Farzam Gorouhi, MD, from Kaiser Permanente, South Sacramento Medical Center, noted in a linked editorial. “Thus, this study provides further evidence against the thromboembolic nature of the presented pattern in adolescents during the COVID-19 pandemic.”

Results of capillaroscopy, used to investigate structural changes in peripheral microcirculation, were either completely normal or showed rare ectasias, supporting a lack of systemic inflammatory process.

“The lack of capillaroscopic features of a major vasculopathic event in the study by Discepolo et al. argues against the ischemic nature of this disease and, thus, indicates that this presentation is not associated with systemic ischemia or an embolic event,” Dr. Gorouhi noted.

Chilblain-like lesions have been one of the most commonly described cutaneous manifestations during the COVID-19 pandemic, but their etiopathogenesis, including the role of SARS-CoV-2, has remained elusive, the investigators wrote.

The findings in this case series do not support the association of the lesions with SARS-CoV-2 infection, they concluded.

The fact that only three new cases of chilblain-like lesions were reported during the highest peaks of the pandemic further supports a lack of association with SARS-CoV-2 infection, they noted.

In addition, none of these patients tested positive for SARS-CoV-2 and all three cases during the second wave occurred in the winter months, suggesting that exposure to the cold might, at least in some cases, trigger the skin lesions, the investigators said.

In line with this hypothesis, seven of the adolescents in this case series (41.2%) relapsed during the winter months while again testing negative for SARS-CoV-2.

“We believe that lifestyle modifications [reduced physical activity, microtraumatisms caused by walking barefoot at home] during the first strict lockdown played a role, likely promoting a local inflammatory process promoted by vascular stasis that led in genetically susceptible individuals to the onset of these lesions,” Dr. Discepolo said in an interview.

This research had no specific funding. The investigators and Dr. Gorouhi declared no relevant conflicts of interest.
 

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

Chilblain-like lesions seen in adolescents during the COVID-19 pandemic are nonischemic and not related to systemic or localized SARS-CoV-2 infection, suggests a case series from Italy.

These lesions are “most likely are benign” and resolve on their own after 2-6 weeks, Valentina Discepolo, MD, PhD, University of Naples Federico II, told this news organization.

“They do not seem to be the manifestation of systemic inflammatory or autoimmune phenomena. According to our experience, they should not require a SARS-CoV-2–specific molecular or serological test since in all cases in our series they were negative,” said Dr. Discepolo.

The study was published online June 10, 2021, in JAMA Network Open.
 

‘COVID toes’ a fallacy?

The temporal association between the COVID-19 pandemic and the increasing number of chilblain-like lesions has led some in the media to call it “COVID toes,” the investigators wrote. However, data on the association with SARS-CoV-2 are controversial.

For this report, Dr. Discepolo and colleagues evaluated 17 adolescents who presented with chilblain-like lesions of the toes during the first wave of the pandemic in southern Italy.

None had evidence of current, past, or local SARS-CoV-2 infection.

“In our experience, chilblain-like lesions are not a manifestation of COVID-19, as shown by negative serological and molecular specific for SARS-CoV2,” Dr. Discepolo said in an interview.

The lesions were bilaterally distributed in 16 adolescents (94.1%) and heel skin was involved in 7 (41.2%). Ulceration complicated one patient during the active phase of the disease, and desquamation developed over time in three patients (17.6%). Only two patients (11.8%) had concurrent involvement of the fingers.

Self-administered therapies included topical antibiotics and/or corticosteroids, disinfectants, and antifungal agents; systemic antibiotics or corticosteroids were used rarely.

None of the therapies substantially changed the course of the lesions. Duration was “extremely variable,” ranging from 49 to 145 days; however, at follow-up, all patients had full resolution.

Almost invariably, the lesions were characterized by a triad of red dots, white rosettes, and white streaks on an erythematous background, the investigators reported.

In more than half the patients (56%), red dots often appeared as dotted and comma-shaped congested vessels that surrounded the rosettes in the early stage of the lesions. In later stages, red dots were still present, but the rosettes had disappeared.

Although found inconsistently in inflammatory cutaneous conditions, these three signs do not characterize the dermoscopic picture of perniosis, suggesting a distinct disease process, the investigators said.

 

Don’t blame it on ischemia, clots

Histologic analysis revealed “remodeling of the dermal blood vessels with a lobular arrangement, wall thickening, and a mild perivascular lymphocytic infiltrate,” they noted.

Punch biopsy of the involved skin mostly showed endothelial hyperplasia, mild lymphocytic infiltrate, and vessels’ architecture disruption with no papillary dermal edema or eosinophilic or neutrophilic infiltrate.

Pathology did not reveal any ischemic changes, which argues against systemic vasculopathy, Farzam Gorouhi, MD, from Kaiser Permanente, South Sacramento Medical Center, noted in a linked editorial. “Thus, this study provides further evidence against the thromboembolic nature of the presented pattern in adolescents during the COVID-19 pandemic.”

Results of capillaroscopy, used to investigate structural changes in peripheral microcirculation, were either completely normal or showed rare ectasias, supporting a lack of systemic inflammatory process.

“The lack of capillaroscopic features of a major vasculopathic event in the study by Discepolo et al. argues against the ischemic nature of this disease and, thus, indicates that this presentation is not associated with systemic ischemia or an embolic event,” Dr. Gorouhi noted.

Chilblain-like lesions have been one of the most commonly described cutaneous manifestations during the COVID-19 pandemic, but their etiopathogenesis, including the role of SARS-CoV-2, has remained elusive, the investigators wrote.

The findings in this case series do not support the association of the lesions with SARS-CoV-2 infection, they concluded.

The fact that only three new cases of chilblain-like lesions were reported during the highest peaks of the pandemic further supports a lack of association with SARS-CoV-2 infection, they noted.

In addition, none of these patients tested positive for SARS-CoV-2 and all three cases during the second wave occurred in the winter months, suggesting that exposure to the cold might, at least in some cases, trigger the skin lesions, the investigators said.

In line with this hypothesis, seven of the adolescents in this case series (41.2%) relapsed during the winter months while again testing negative for SARS-CoV-2.

“We believe that lifestyle modifications [reduced physical activity, microtraumatisms caused by walking barefoot at home] during the first strict lockdown played a role, likely promoting a local inflammatory process promoted by vascular stasis that led in genetically susceptible individuals to the onset of these lesions,” Dr. Discepolo said in an interview.

This research had no specific funding. The investigators and Dr. Gorouhi declared no relevant conflicts of interest.
 

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

Quantitative assessment of the extent of interstitial lung disease in patients with systemic sclerosis and levels of certain proteins in bronchoalveolar lavage samples have potential for predicting mortality and disease progression, according to two analyses of data from the Scleroderma Lung Study I and II.

The analyses, presented at the annual European Congress of Rheumatology, aim to improve current prognostic abilities in patients with systemic sclerosis–interstitial lung disease (SSc-ILD). Although forced vital capacity is commonly used as a biomarker for survival in many SSc-ILD trials, other factors can affect FVC, such as respiratory muscle weakness and skin fibrosis. Further, FVC correlates poorly with patient-reported outcomes, explained first author Elizabeth Volkmann, MD, director of the scleroderma program at the University of California, Los Angeles, and the founder and codirector of the UCLA connective tissue disease–related interstitial lung disease program.

Dr. Volkmann presented two studies that investigated the potential of radiographic and protein biomarkers for predicting mortality and identifying patients at risk for ILD progression. The biomarkers may also help to identify patients who would benefit most from immunosuppressive therapy.

The first study found that tracking the quantitative extent of ILD (QILD) over time with high-resolution CT (HRCT) predicted poorer outcomes and could therefore act as a surrogate endpoint for mortality among patients with SSc-ILD. The other study identified associations between specific proteins from bronchoalveolar lavage (BAL) and the likelihood of ILD progression, although some associations were treatment dependent.

Jacob M. van Laar, MD, PhD, professor of rheumatology at the University Medical Center Utrecht (the Netherlands), who was not involved in the study, found the results intriguing and noted the importance of further validation in research before these biomarkers are considered for clinical use.

“It would be wonderful if we can tailor therapy based on BAL biomarkers in the future, as clinicians often struggle to decide on selection, timing, and duration of immunosuppressive treatment,” Dr. van Laar told this news organization. “This has become even more relevant with the introduction of new drugs such as nintedanib.”
 

Extent of ILD progression as a surrogate for mortality

Scleroderma Lung Study I involved 158 patients with SSc-ILD who were randomly assigned to receive either cyclophosphamide or placebo for 12 months. Scleroderma Lung Study II included 142 patients with SSc-ILD who were randomly assigned to receive either mycophenolate for 24 months or cyclophosphamide for 12 months followed by placebo for 12 months.

The researchers calculated QILD in the whole lung at baseline, at 12 months in the first trial, and at 24 months in the second trial. However, only 82 participants from the first trial and 90 participants from the second trial underwent HRCT. Demographic and disease characteristics were similar between the two groups on follow-up scans.

Follow-up continued for 12 years for patients in the first trial and 8 years in the second. The researchers compared survival rates between the 41% of participants from the first study and 31% of participants from the second study who had poorer QILD scores (at least a 2% increase) with the participants who had stable or improved scores (less than 2% increase).

Participants from both trials had significantly poorer long-term survival if their QILD scores had increased by at least 2% at follow-up (P = .01 for I; P = .019 for II). The association was no longer significant after adjustment for baseline FVC, age, and modified Rodnan skin score in the first trial (hazard ratio, 1.98; P = .089), but it remained significant for participants of the second trial (HR, 3.86; P = .014).

“Data from two independent trial cohorts demonstrated that radiographic progression of SSc-ILD at 1 and 2 years is associated with worse long-term survival,” Dr. Volkmann told attendees.

However, FVC did not significantly predict risk of mortality in either trial.

“To me, the most striking finding from the first study was that change in QILD performed better as a predictor of survival than change in FVC,” Dr. van Laar said in an interview. “This indicates QILD is fit for purpose and worth including in future clinical trials.”

Limitations of the study included lack of HRCT for all participants in the trials and the difference in timing (1 year and 2 years) of HRCT assessment between the two trials. The greater hazard ratio for worsened QILD in the second trial may suggest that assessment at 2 years provides more reliable data as a biomarker, Dr. Volkmann said.

“QILD may represent a better proxy for how a patient feels, functions, and survives than FVC,” she said.
 

Treatment-dependent biomarkers for worsening lung fibrosis

In the second study, the researchers looked for any associations between changes in the radiographic extent of SSc-ILD and 68 proteins from BAL.

“Being able to risk-stratify patients with interstitial lung disease at the time of diagnosis and predict which patients are likely to have a stable versus progressive disease course is critical for making important treatment decisions for these patients,” Dr. Volkmann told attendees.

The second study she presented involved Scleroderma Lung Study I. Of the 158 participants, 144 underwent a bronchoscopy, yielding BAL protein samples from 103 participants. The researchers determined the extent of radiographic fibrosis in the whole lung with quantitative imaging analysis of HRCT of the chest at baseline and 12 months.

Although the researchers identified several statistically significant associations between certain proteins and changes in radiographic fibrosis, “baseline protein levels were differentially associated with the course of ILD based on treatment status,” she told attendees.

For example, increased levels of the following proteins were linked to poor radiographic fibrosis scores for patients who received placebo:

• Granulocyte-macrophage colony-stimulating factor
• Interleukin-1
• Monocyte chemoattractant protein–3
• Chemokine ligand–5
• Transforming growth factor–beta
• Hepatocyte growth factor
• Stem cell factor
• IL-4
• TGF-alpha

Yet increases in these proteins predicted improvement in radiographic fibrosis in patients who had taken cyclophosphamide.

Independently of treatment, the researchers also identified an association between higher levels of fractalkine and poorer radiographic fibrosis scores and between higher IL-7 levels and improved radiographic fibrosis scores.

After adjusting for treatment arm and baseline severity of ILD, significant associations remained between change in radiographic fibrosis score and IL-1, MCP-3, surfactant protein C, IL-7 and CCL-5 levels.

“Biomarker discovery is really central to our ability to risk stratify patients with SSc-ILD,” Dr. Volkmann told attendees. “Understanding how biomarkers predict outcomes in treated and untreated patients may improve personalized medicine to patients with SSc-ILD and could also reveal novel treatment targets.”

Dr. van Laar said in an interview that this study’s biggest strength lay in its large sample size and in the comprehensiveness of the biomarkers studied.

“The findings are interesting from a research perspective and potentially relevant for clinical practice, but the utility of measuring biomarkers in BAL should be further studied for predictive value on clinical endpoints,” Dr. van Laar said. “BAL is an invasive procedure [that] is not routinely done.”

The research was funded by the National Institutes of Health. Dr. Volkmann has consulted for Boehringer Ingelheim and received grant funding from Corbus, Forbius, and Kadmon. Dr. van Laar has received grant funding or personal fees from Arthrogen, Arxx Therapeutics, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Gesynta, Leadiant, Merck Sharp & Dohme, Roche, Sanofi, and Thermofisher.

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

Quantitative assessment of the extent of interstitial lung disease in patients with systemic sclerosis and levels of certain proteins in bronchoalveolar lavage samples have potential for predicting mortality and disease progression, according to two analyses of data from the Scleroderma Lung Study I and II.

The analyses, presented at the annual European Congress of Rheumatology, aim to improve current prognostic abilities in patients with systemic sclerosis–interstitial lung disease (SSc-ILD). Although forced vital capacity is commonly used as a biomarker for survival in many SSc-ILD trials, other factors can affect FVC, such as respiratory muscle weakness and skin fibrosis. Further, FVC correlates poorly with patient-reported outcomes, explained first author Elizabeth Volkmann, MD, director of the scleroderma program at the University of California, Los Angeles, and the founder and codirector of the UCLA connective tissue disease–related interstitial lung disease program.

Dr. Volkmann presented two studies that investigated the potential of radiographic and protein biomarkers for predicting mortality and identifying patients at risk for ILD progression. The biomarkers may also help to identify patients who would benefit most from immunosuppressive therapy.

The first study found that tracking the quantitative extent of ILD (QILD) over time with high-resolution CT (HRCT) predicted poorer outcomes and could therefore act as a surrogate endpoint for mortality among patients with SSc-ILD. The other study identified associations between specific proteins from bronchoalveolar lavage (BAL) and the likelihood of ILD progression, although some associations were treatment dependent.

Jacob M. van Laar, MD, PhD, professor of rheumatology at the University Medical Center Utrecht (the Netherlands), who was not involved in the study, found the results intriguing and noted the importance of further validation in research before these biomarkers are considered for clinical use.

“It would be wonderful if we can tailor therapy based on BAL biomarkers in the future, as clinicians often struggle to decide on selection, timing, and duration of immunosuppressive treatment,” Dr. van Laar told this news organization. “This has become even more relevant with the introduction of new drugs such as nintedanib.”
 

Extent of ILD progression as a surrogate for mortality

Scleroderma Lung Study I involved 158 patients with SSc-ILD who were randomly assigned to receive either cyclophosphamide or placebo for 12 months. Scleroderma Lung Study II included 142 patients with SSc-ILD who were randomly assigned to receive either mycophenolate for 24 months or cyclophosphamide for 12 months followed by placebo for 12 months.

The researchers calculated QILD in the whole lung at baseline, at 12 months in the first trial, and at 24 months in the second trial. However, only 82 participants from the first trial and 90 participants from the second trial underwent HRCT. Demographic and disease characteristics were similar between the two groups on follow-up scans.

Follow-up continued for 12 years for patients in the first trial and 8 years in the second. The researchers compared survival rates between the 41% of participants from the first study and 31% of participants from the second study who had poorer QILD scores (at least a 2% increase) with the participants who had stable or improved scores (less than 2% increase).

Participants from both trials had significantly poorer long-term survival if their QILD scores had increased by at least 2% at follow-up (P = .01 for I; P = .019 for II). The association was no longer significant after adjustment for baseline FVC, age, and modified Rodnan skin score in the first trial (hazard ratio, 1.98; P = .089), but it remained significant for participants of the second trial (HR, 3.86; P = .014).

“Data from two independent trial cohorts demonstrated that radiographic progression of SSc-ILD at 1 and 2 years is associated with worse long-term survival,” Dr. Volkmann told attendees.

However, FVC did not significantly predict risk of mortality in either trial.

“To me, the most striking finding from the first study was that change in QILD performed better as a predictor of survival than change in FVC,” Dr. van Laar said in an interview. “This indicates QILD is fit for purpose and worth including in future clinical trials.”

Limitations of the study included lack of HRCT for all participants in the trials and the difference in timing (1 year and 2 years) of HRCT assessment between the two trials. The greater hazard ratio for worsened QILD in the second trial may suggest that assessment at 2 years provides more reliable data as a biomarker, Dr. Volkmann said.

“QILD may represent a better proxy for how a patient feels, functions, and survives than FVC,” she said.
 

Treatment-dependent biomarkers for worsening lung fibrosis

In the second study, the researchers looked for any associations between changes in the radiographic extent of SSc-ILD and 68 proteins from BAL.

“Being able to risk-stratify patients with interstitial lung disease at the time of diagnosis and predict which patients are likely to have a stable versus progressive disease course is critical for making important treatment decisions for these patients,” Dr. Volkmann told attendees.

The second study she presented involved Scleroderma Lung Study I. Of the 158 participants, 144 underwent a bronchoscopy, yielding BAL protein samples from 103 participants. The researchers determined the extent of radiographic fibrosis in the whole lung with quantitative imaging analysis of HRCT of the chest at baseline and 12 months.

Although the researchers identified several statistically significant associations between certain proteins and changes in radiographic fibrosis, “baseline protein levels were differentially associated with the course of ILD based on treatment status,” she told attendees.

For example, increased levels of the following proteins were linked to poor radiographic fibrosis scores for patients who received placebo:

• Granulocyte-macrophage colony-stimulating factor
• Interleukin-1
• Monocyte chemoattractant protein–3
• Chemokine ligand–5
• Transforming growth factor–beta
• Hepatocyte growth factor
• Stem cell factor
• IL-4
• TGF-alpha

Yet increases in these proteins predicted improvement in radiographic fibrosis in patients who had taken cyclophosphamide.

Independently of treatment, the researchers also identified an association between higher levels of fractalkine and poorer radiographic fibrosis scores and between higher IL-7 levels and improved radiographic fibrosis scores.

After adjusting for treatment arm and baseline severity of ILD, significant associations remained between change in radiographic fibrosis score and IL-1, MCP-3, surfactant protein C, IL-7 and CCL-5 levels.

“Biomarker discovery is really central to our ability to risk stratify patients with SSc-ILD,” Dr. Volkmann told attendees. “Understanding how biomarkers predict outcomes in treated and untreated patients may improve personalized medicine to patients with SSc-ILD and could also reveal novel treatment targets.”

Dr. van Laar said in an interview that this study’s biggest strength lay in its large sample size and in the comprehensiveness of the biomarkers studied.

“The findings are interesting from a research perspective and potentially relevant for clinical practice, but the utility of measuring biomarkers in BAL should be further studied for predictive value on clinical endpoints,” Dr. van Laar said. “BAL is an invasive procedure [that] is not routinely done.”

The research was funded by the National Institutes of Health. Dr. Volkmann has consulted for Boehringer Ingelheim and received grant funding from Corbus, Forbius, and Kadmon. Dr. van Laar has received grant funding or personal fees from Arthrogen, Arxx Therapeutics, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Gesynta, Leadiant, Merck Sharp & Dohme, Roche, Sanofi, and Thermofisher.

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

Quantitative assessment of the extent of interstitial lung disease in patients with systemic sclerosis and levels of certain proteins in bronchoalveolar lavage samples have potential for predicting mortality and disease progression, according to two analyses of data from the Scleroderma Lung Study I and II.

The analyses, presented at the annual European Congress of Rheumatology, aim to improve current prognostic abilities in patients with systemic sclerosis–interstitial lung disease (SSc-ILD). Although forced vital capacity is commonly used as a biomarker for survival in many SSc-ILD trials, other factors can affect FVC, such as respiratory muscle weakness and skin fibrosis. Further, FVC correlates poorly with patient-reported outcomes, explained first author Elizabeth Volkmann, MD, director of the scleroderma program at the University of California, Los Angeles, and the founder and codirector of the UCLA connective tissue disease–related interstitial lung disease program.

Dr. Volkmann presented two studies that investigated the potential of radiographic and protein biomarkers for predicting mortality and identifying patients at risk for ILD progression. The biomarkers may also help to identify patients who would benefit most from immunosuppressive therapy.

The first study found that tracking the quantitative extent of ILD (QILD) over time with high-resolution CT (HRCT) predicted poorer outcomes and could therefore act as a surrogate endpoint for mortality among patients with SSc-ILD. The other study identified associations between specific proteins from bronchoalveolar lavage (BAL) and the likelihood of ILD progression, although some associations were treatment dependent.

Jacob M. van Laar, MD, PhD, professor of rheumatology at the University Medical Center Utrecht (the Netherlands), who was not involved in the study, found the results intriguing and noted the importance of further validation in research before these biomarkers are considered for clinical use.

“It would be wonderful if we can tailor therapy based on BAL biomarkers in the future, as clinicians often struggle to decide on selection, timing, and duration of immunosuppressive treatment,” Dr. van Laar told this news organization. “This has become even more relevant with the introduction of new drugs such as nintedanib.”
 

Extent of ILD progression as a surrogate for mortality

Scleroderma Lung Study I involved 158 patients with SSc-ILD who were randomly assigned to receive either cyclophosphamide or placebo for 12 months. Scleroderma Lung Study II included 142 patients with SSc-ILD who were randomly assigned to receive either mycophenolate for 24 months or cyclophosphamide for 12 months followed by placebo for 12 months.

The researchers calculated QILD in the whole lung at baseline, at 12 months in the first trial, and at 24 months in the second trial. However, only 82 participants from the first trial and 90 participants from the second trial underwent HRCT. Demographic and disease characteristics were similar between the two groups on follow-up scans.

Follow-up continued for 12 years for patients in the first trial and 8 years in the second. The researchers compared survival rates between the 41% of participants from the first study and 31% of participants from the second study who had poorer QILD scores (at least a 2% increase) with the participants who had stable or improved scores (less than 2% increase).

Participants from both trials had significantly poorer long-term survival if their QILD scores had increased by at least 2% at follow-up (P = .01 for I; P = .019 for II). The association was no longer significant after adjustment for baseline FVC, age, and modified Rodnan skin score in the first trial (hazard ratio, 1.98; P = .089), but it remained significant for participants of the second trial (HR, 3.86; P = .014).

“Data from two independent trial cohorts demonstrated that radiographic progression of SSc-ILD at 1 and 2 years is associated with worse long-term survival,” Dr. Volkmann told attendees.

However, FVC did not significantly predict risk of mortality in either trial.

“To me, the most striking finding from the first study was that change in QILD performed better as a predictor of survival than change in FVC,” Dr. van Laar said in an interview. “This indicates QILD is fit for purpose and worth including in future clinical trials.”

Limitations of the study included lack of HRCT for all participants in the trials and the difference in timing (1 year and 2 years) of HRCT assessment between the two trials. The greater hazard ratio for worsened QILD in the second trial may suggest that assessment at 2 years provides more reliable data as a biomarker, Dr. Volkmann said.

“QILD may represent a better proxy for how a patient feels, functions, and survives than FVC,” she said.
 

Treatment-dependent biomarkers for worsening lung fibrosis

In the second study, the researchers looked for any associations between changes in the radiographic extent of SSc-ILD and 68 proteins from BAL.

“Being able to risk-stratify patients with interstitial lung disease at the time of diagnosis and predict which patients are likely to have a stable versus progressive disease course is critical for making important treatment decisions for these patients,” Dr. Volkmann told attendees.

The second study she presented involved Scleroderma Lung Study I. Of the 158 participants, 144 underwent a bronchoscopy, yielding BAL protein samples from 103 participants. The researchers determined the extent of radiographic fibrosis in the whole lung with quantitative imaging analysis of HRCT of the chest at baseline and 12 months.

Although the researchers identified several statistically significant associations between certain proteins and changes in radiographic fibrosis, “baseline protein levels were differentially associated with the course of ILD based on treatment status,” she told attendees.

For example, increased levels of the following proteins were linked to poor radiographic fibrosis scores for patients who received placebo:

• Granulocyte-macrophage colony-stimulating factor
• Interleukin-1
• Monocyte chemoattractant protein–3
• Chemokine ligand–5
• Transforming growth factor–beta
• Hepatocyte growth factor
• Stem cell factor
• IL-4
• TGF-alpha

Yet increases in these proteins predicted improvement in radiographic fibrosis in patients who had taken cyclophosphamide.

Independently of treatment, the researchers also identified an association between higher levels of fractalkine and poorer radiographic fibrosis scores and between higher IL-7 levels and improved radiographic fibrosis scores.

After adjusting for treatment arm and baseline severity of ILD, significant associations remained between change in radiographic fibrosis score and IL-1, MCP-3, surfactant protein C, IL-7 and CCL-5 levels.

“Biomarker discovery is really central to our ability to risk stratify patients with SSc-ILD,” Dr. Volkmann told attendees. “Understanding how biomarkers predict outcomes in treated and untreated patients may improve personalized medicine to patients with SSc-ILD and could also reveal novel treatment targets.”

Dr. van Laar said in an interview that this study’s biggest strength lay in its large sample size and in the comprehensiveness of the biomarkers studied.

“The findings are interesting from a research perspective and potentially relevant for clinical practice, but the utility of measuring biomarkers in BAL should be further studied for predictive value on clinical endpoints,” Dr. van Laar said. “BAL is an invasive procedure [that] is not routinely done.”

The research was funded by the National Institutes of Health. Dr. Volkmann has consulted for Boehringer Ingelheim and received grant funding from Corbus, Forbius, and Kadmon. Dr. van Laar has received grant funding or personal fees from Arthrogen, Arxx Therapeutics, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Gesynta, Leadiant, Merck Sharp & Dohme, Roche, Sanofi, and Thermofisher.

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

To the Editor:

Argyria is a rare disease caused by chronic exposure to products with high silver content (eg, oral ingestion, inhalation, percutaneous absorption). With time, the blood levels of silver surpass the body’s renal and hepatic excretory capacities that lead to silver granules being deposited in the skin and internal organs, including the liver, spleen, adrenal glands, and bone marrow.¹ The cutaneous deposition results in a blue or blue-gray pigmentation of the skin, mucous membranes, and nails. Intervals of exposure that span from 8 months to 5 years prior to symptom onset have been described in the literature.² The discoloration that results often is permanent, with no established way of effectively removing silver deposits from the tissue.³

A 22-year-old autistic man, who was completely dependent on his mother’s care, presented to the emergency department with a primary concern of abdominal pain. The mother reported that he was indicating abdominal pain by motioning to his stomach for the last 5 days. The mother also reported he did not have a bowel movement during this time, and she noticed his hands were shaking. Prior to presentation, the mother had given him 2 enemas and had him on a 3-day strict liquid fast consisting of water, lemon juice, cayenne pepper, honey, and orange juice. Notably, the mother had a strong history of using naturopathic remedies for treatment of her son’s ailments.

On admission, the patient was stable. There was a 2-point decrease in the patient’s body mass index over the last month. Initial serum electrolytes were highly abnormal with a serum sodium level of 124 mEq/L (reference range, 135–145 mEq/L), blood urea nitrogen of 3 mg/dL (reference range, 7–20 mg/dL), creatinine of 0.77 mg/dL (reference range, 0.74–1.35 mg/dL), and lactic acid of 2.1 mEq/L (reference range, 0.5–1 mEq/L). Serum osmolality was 272 mOsm/kg (reference range, 275–295 mOsm/kg). Urine osmolality was 114 mOsm/kg (reference range, 500–850 mOsm/kg) with a low-normal urine sodium level of 41 mmol/24 hr (reference range, 40–220 mmol/24 hr). Abnormalities were felt to be secondary to malnutrition from the strict liquid diet (blood urea nitrogen and creatinine ratio of 3:1 suggestive of notable protein calorie malnutrition). The patient was given 1 L of normal saline in the emergency department, with further fluids held so as not to increase serum sodium level too rapidly. A regular diet was started.

Physical examination revealed dry mucosal membranes but otherwise was unremarkable. Active bowel sounds were noted, as well as a soft, nontender, and nondistended abdomen; however, when examining the patient’s hands for reported shaking, a distinct abnormality of the nails was noticed. The patient had slate blue discoloration of the lunula, along with hyperpigmented violaceous discoloration of the proximal nail bed on all 10 fingernails (Figure 1). No abnormalities were seen on the toenails. The mother had a distinct bluish gray discoloration of the face as well as similar nail findings (Figure 2), strongly suggestive of colloidal silver use. An urgent serum silver level was ordered on the patient as well as a heavy metal panel. The mother was found applying numerous “natural remedies” to the patient’s skin while in the hospital, including a liquid spray and lotion, both in unmarked bottles. At that time, the mother was informed that no external supplements should be applied to her son. The serum silver level was elevated substantially at 94.3 ng/mL (reference range, <1.0 ng/mL). When the mother was confronted, she initially denied use of silver but later admitted to notable silver content in the cream she was applying to her son’s skin. The mother reported that she read online that colloidal silver had been historically used to cure numerous ailments and she was ordering products from an online company. She was counseled on the dangers of both topical application and ingestion of silver, and all supplements were removed from the home.

Initial differential diagnoses for altered nail pigmentation include drug-induced causes, systemic diseases, cyanosis, and exposure to metals.⁷ The most commonly indicated medications resulting in blue nail pigment changes include antimalarials, minocycline, zidovudine, and phenothiazine. Systemic diseases that may cause blue nail color change include Wilson disease, hemochromatosis, Addison disease, methemoglobinemia, and alkaptonuria.⁷ Metals include gold, mercury, arsenic, bismuth, lead, and silver.⁴ After a thorough review of the patient’s medications and lack of support for any underlying disease process, contact with metals, particularly silver, was ranked highly on our differential list. In support of this theory, the mother’s bluish gray facial skin led to high clinical suspicion that she was ingesting colloidal silver and also was exposing her son to silver.

Treatment of argyria is challenging but first and foremost involves discontinuation of the source of chronic silver exposure. Unfortunately, the discoloration of generalized argyria often is permanent. Sunscreen can be used to help prevent any further darkening of pigment. The pigment in localized argyria has been reported to slowly fade with time, and there also have been reports of successful treatment using a low-fluence Q-switched 1064-nm Nd:YAG laser.⁸

To the Editor:

Argyria is a rare disease caused by chronic exposure to products with high silver content (eg, oral ingestion, inhalation, percutaneous absorption). With time, the blood levels of silver surpass the body’s renal and hepatic excretory capacities that lead to silver granules being deposited in the skin and internal organs, including the liver, spleen, adrenal glands, and bone marrow.¹ The cutaneous deposition results in a blue or blue-gray pigmentation of the skin, mucous membranes, and nails. Intervals of exposure that span from 8 months to 5 years prior to symptom onset have been described in the literature.² The discoloration that results often is permanent, with no established way of effectively removing silver deposits from the tissue.³

A 22-year-old autistic man, who was completely dependent on his mother’s care, presented to the emergency department with a primary concern of abdominal pain. The mother reported that he was indicating abdominal pain by motioning to his stomach for the last 5 days. The mother also reported he did not have a bowel movement during this time, and she noticed his hands were shaking. Prior to presentation, the mother had given him 2 enemas and had him on a 3-day strict liquid fast consisting of water, lemon juice, cayenne pepper, honey, and orange juice. Notably, the mother had a strong history of using naturopathic remedies for treatment of her son’s ailments.

On admission, the patient was stable. There was a 2-point decrease in the patient’s body mass index over the last month. Initial serum electrolytes were highly abnormal with a serum sodium level of 124 mEq/L (reference range, 135–145 mEq/L), blood urea nitrogen of 3 mg/dL (reference range, 7–20 mg/dL), creatinine of 0.77 mg/dL (reference range, 0.74–1.35 mg/dL), and lactic acid of 2.1 mEq/L (reference range, 0.5–1 mEq/L). Serum osmolality was 272 mOsm/kg (reference range, 275–295 mOsm/kg). Urine osmolality was 114 mOsm/kg (reference range, 500–850 mOsm/kg) with a low-normal urine sodium level of 41 mmol/24 hr (reference range, 40–220 mmol/24 hr). Abnormalities were felt to be secondary to malnutrition from the strict liquid diet (blood urea nitrogen and creatinine ratio of 3:1 suggestive of notable protein calorie malnutrition). The patient was given 1 L of normal saline in the emergency department, with further fluids held so as not to increase serum sodium level too rapidly. A regular diet was started.

Physical examination revealed dry mucosal membranes but otherwise was unremarkable. Active bowel sounds were noted, as well as a soft, nontender, and nondistended abdomen; however, when examining the patient’s hands for reported shaking, a distinct abnormality of the nails was noticed. The patient had slate blue discoloration of the lunula, along with hyperpigmented violaceous discoloration of the proximal nail bed on all 10 fingernails (Figure 1). No abnormalities were seen on the toenails. The mother had a distinct bluish gray discoloration of the face as well as similar nail findings (Figure 2), strongly suggestive of colloidal silver use. An urgent serum silver level was ordered on the patient as well as a heavy metal panel. The mother was found applying numerous “natural remedies” to the patient’s skin while in the hospital, including a liquid spray and lotion, both in unmarked bottles. At that time, the mother was informed that no external supplements should be applied to her son. The serum silver level was elevated substantially at 94.3 ng/mL (reference range, <1.0 ng/mL). When the mother was confronted, she initially denied use of silver but later admitted to notable silver content in the cream she was applying to her son’s skin. The mother reported that she read online that colloidal silver had been historically used to cure numerous ailments and she was ordering products from an online company. She was counseled on the dangers of both topical application and ingestion of silver, and all supplements were removed from the home.

Initial differential diagnoses for altered nail pigmentation include drug-induced causes, systemic diseases, cyanosis, and exposure to metals.⁷ The most commonly indicated medications resulting in blue nail pigment changes include antimalarials, minocycline, zidovudine, and phenothiazine. Systemic diseases that may cause blue nail color change include Wilson disease, hemochromatosis, Addison disease, methemoglobinemia, and alkaptonuria.⁷ Metals include gold, mercury, arsenic, bismuth, lead, and silver.⁴ After a thorough review of the patient’s medications and lack of support for any underlying disease process, contact with metals, particularly silver, was ranked highly on our differential list. In support of this theory, the mother’s bluish gray facial skin led to high clinical suspicion that she was ingesting colloidal silver and also was exposing her son to silver.

Treatment of argyria is challenging but first and foremost involves discontinuation of the source of chronic silver exposure. Unfortunately, the discoloration of generalized argyria often is permanent. Sunscreen can be used to help prevent any further darkening of pigment. The pigment in localized argyria has been reported to slowly fade with time, and there also have been reports of successful treatment using a low-fluence Q-switched 1064-nm Nd:YAG laser.⁸

To the Editor:

Argyria is a rare disease caused by chronic exposure to products with high silver content (eg, oral ingestion, inhalation, percutaneous absorption). With time, the blood levels of silver surpass the body’s renal and hepatic excretory capacities that lead to silver granules being deposited in the skin and internal organs, including the liver, spleen, adrenal glands, and bone marrow.¹ The cutaneous deposition results in a blue or blue-gray pigmentation of the skin, mucous membranes, and nails. Intervals of exposure that span from 8 months to 5 years prior to symptom onset have been described in the literature.² The discoloration that results often is permanent, with no established way of effectively removing silver deposits from the tissue.³

A 22-year-old autistic man, who was completely dependent on his mother’s care, presented to the emergency department with a primary concern of abdominal pain. The mother reported that he was indicating abdominal pain by motioning to his stomach for the last 5 days. The mother also reported he did not have a bowel movement during this time, and she noticed his hands were shaking. Prior to presentation, the mother had given him 2 enemas and had him on a 3-day strict liquid fast consisting of water, lemon juice, cayenne pepper, honey, and orange juice. Notably, the mother had a strong history of using naturopathic remedies for treatment of her son’s ailments.

On admission, the patient was stable. There was a 2-point decrease in the patient’s body mass index over the last month. Initial serum electrolytes were highly abnormal with a serum sodium level of 124 mEq/L (reference range, 135–145 mEq/L), blood urea nitrogen of 3 mg/dL (reference range, 7–20 mg/dL), creatinine of 0.77 mg/dL (reference range, 0.74–1.35 mg/dL), and lactic acid of 2.1 mEq/L (reference range, 0.5–1 mEq/L). Serum osmolality was 272 mOsm/kg (reference range, 275–295 mOsm/kg). Urine osmolality was 114 mOsm/kg (reference range, 500–850 mOsm/kg) with a low-normal urine sodium level of 41 mmol/24 hr (reference range, 40–220 mmol/24 hr). Abnormalities were felt to be secondary to malnutrition from the strict liquid diet (blood urea nitrogen and creatinine ratio of 3:1 suggestive of notable protein calorie malnutrition). The patient was given 1 L of normal saline in the emergency department, with further fluids held so as not to increase serum sodium level too rapidly. A regular diet was started.

Physical examination revealed dry mucosal membranes but otherwise was unremarkable. Active bowel sounds were noted, as well as a soft, nontender, and nondistended abdomen; however, when examining the patient’s hands for reported shaking, a distinct abnormality of the nails was noticed. The patient had slate blue discoloration of the lunula, along with hyperpigmented violaceous discoloration of the proximal nail bed on all 10 fingernails (Figure 1). No abnormalities were seen on the toenails. The mother had a distinct bluish gray discoloration of the face as well as similar nail findings (Figure 2), strongly suggestive of colloidal silver use. An urgent serum silver level was ordered on the patient as well as a heavy metal panel. The mother was found applying numerous “natural remedies” to the patient’s skin while in the hospital, including a liquid spray and lotion, both in unmarked bottles. At that time, the mother was informed that no external supplements should be applied to her son. The serum silver level was elevated substantially at 94.3 ng/mL (reference range, <1.0 ng/mL). When the mother was confronted, she initially denied use of silver but later admitted to notable silver content in the cream she was applying to her son’s skin. The mother reported that she read online that colloidal silver had been historically used to cure numerous ailments and she was ordering products from an online company. She was counseled on the dangers of both topical application and ingestion of silver, and all supplements were removed from the home.

Initial differential diagnoses for altered nail pigmentation include drug-induced causes, systemic diseases, cyanosis, and exposure to metals.⁷ The most commonly indicated medications resulting in blue nail pigment changes include antimalarials, minocycline, zidovudine, and phenothiazine. Systemic diseases that may cause blue nail color change include Wilson disease, hemochromatosis, Addison disease, methemoglobinemia, and alkaptonuria.⁷ Metals include gold, mercury, arsenic, bismuth, lead, and silver.⁴ After a thorough review of the patient’s medications and lack of support for any underlying disease process, contact with metals, particularly silver, was ranked highly on our differential list. In support of this theory, the mother’s bluish gray facial skin led to high clinical suspicion that she was ingesting colloidal silver and also was exposing her son to silver.

Treatment of argyria is challenging but first and foremost involves discontinuation of the source of chronic silver exposure. Unfortunately, the discoloration of generalized argyria often is permanent. Sunscreen can be used to help prevent any further darkening of pigment. The pigment in localized argyria has been reported to slowly fade with time, and there also have been reports of successful treatment using a low-fluence Q-switched 1064-nm Nd:YAG laser.⁸

Squamoid eccrine ductal carcinoma (SEDC) is an aggressive underrecognized cutaneous malignancy of unknown etiology.¹ It is most likely to occur in sun-exposed areas of the body, most commonly the head and neck. Risk factors include male sex, increased age, and chronic immunosuppression.^1-4 Current reports suggest that SEDC is likely a high-grade subtype of squamous cell carcinoma (SCC) with a high risk for local recurrence (25%) and metastasis (13%).^1,3,5,6 There are as few as 56 cases of SEDC reported in the literature; however, the number of cases may be closer to 100 due to SEDC being classified as either adenosquamous carcinoma of the skin or ductal eccrine carcinoma with squamous differentiation.¹

Clinically, SEDC mimics keratinocyte carcinomas. Histologically, SEDC is biphasic, with a superficial portion resembling well-differentiated SCC and a deeply invasive portion having infiltrative irregular cords with ductal differentiation. Perineural invasion (PNI) frequently is present. Multiple connections to the overlying epidermis also can be seen, serving as a subtle clue to the diagnosis on broad superficial specimens.^1-3 Due to superficial sampling, approximately 50% of reported cases are misdiagnosed as SCC during the initial biopsy.⁴ The diagnosis of SEDC often is made during complete excision when deeper tissue is sampled. Establishing an accurate diagnosis is important given the more aggressive nature of SEDC compared with SCC and its proclivity for PNI.^1,3,6 The purpose of this review is to increase awareness of this underrecognized entity and describe the histologic findings that help distinguish SEDC from SCC.

Patient Chart Review

We reviewed chart notes as well as frozen and formalin-fixed paraffin-embedded tissue sections from all 5 patients diagnosed with SEDC at a single institution between November 2018 and May 2020. The mean age of patients was 81 years, and 4 were male. Four of the patients presented for MMS with a preoperative diagnosis of SCC per the original biopsy results. Only 1 patient had a preoperative diagnosis of SEDC. The details of each case are recorded in the Table. All tumors were greater than 2 cm in diameter on initial presentation, were located on the head, and clinically resembled keratinocyte carcinoma with either a nodular or plaquelike appearance (Figure 1).

Intraoperative histologic examination of the excised tissue revealed a biphasic pattern consisting of superficial SCC features overlying deeper dermal and subcutaneous infiltrative malignant ductal elements with gland formation in all 5 patients (Figures 2–4). Immunohistochemical staining with cytokeratin AE1/AE3 revealed thin strands of carcinoma in the mid to deeper dermis with squamous differentiation and eccrine ductal differentiation (Figure 5), thus confirming the diagnosis in all 5 patients.

Literature Review

A PubMed review of the literature using the search term squamoid eccrine ductal carcinoma resulted in 28 articles, 19 of which were included in the review based on inclusion criteria (original articles available in English, in full text, and pertained to SEDC). Our review yielded 56 cases of SEDC.^1-19 The mean age of patients with SEDC was 72 years. The number of male and female cases was 52% (29/56) and 48% (27/56), respectively. The most common location of SEDC was on the head or neck (71% [40/56]), followed by the extremities (19% [11/56]). Immunosuppression was noted in 9% (5/56) of cases. Wide local excision was the most commonly employed treatment modality (91% [51/56]), with MMS being used in 4 patients (7%). Adjuvant radiation was reported in 5% (3/56) of cases. Perineural invasion was reported in 34% (19/56) of cases. Recurrence was seen in 23% (13/56) of cases, with a mean time to recurrence of 10.4 months. Metastasis to regional lymph nodes was observed in 13% (7/56) of cases, with 7% (4/56) of those cases having distant metastases.

Comment

Squamoid eccrine ductal carcinoma was successfully treated with MMS in all 5 of the patients we reviewed. Recognition of a distinct biphasic pattern consisting of squamous differentiation superficially with epidermal connection overlying deeper dermal and subcutaneous infiltrative malignant ductal elements with gland formation should lead to consideration of this diagnosis. A thorough inspection for PNI also should be performed, as this finding was present in all of 5 cases and in 34% of reported cases in our literature review.

The differential diagnosis for SEDC includes SCC, metastatic adenocarcinoma with squamoid features, and eccrine tumors, including eccrine poroma, microcystic adnexal carcinoma (MAC), and porocarcinoma with squamous differentiation. The combination of histologic features with the immunoexpression profile of carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), cytokeratin (CK) 5/6, and p63 can effectively exclude the other entities in the differential and confirm the diagnosis of SEDC.^1,3,4 While the diagnosis of SEDC relies on the specific histologic features of multiple surface attachments and superficial squamoid changes with deep ductular elements, immunohistochemistry can nonetheless be adjunctive in difficult cases. Positive immunohistochemical staining for CEA and EMA can help to highlight and delineate true glandular elements, whereas CK5/6 highlights the overall contour of the tumor, displaying more clearly the multiple epidermal attachments and the subtle infiltrative nature of the deeper components of invasive cords and ducts. In addition, the combination of CK5/6 and p63 positivity supports the primary cutaneous nature of the lesion rather than metastatic adenocarcinoma.^13,20 Other markers of eccrine secretory coils, such as CK7, CAM5.2, and S100, also are sometimes used for confirmation, some of which can aid in distinction from noneccrine sweat gland differentiation, as CK7 and CAM5.2 are negative in both luminal and basal cells of the dermal duct while being positive within the secretory coil, and S100 protein is expressed within eccrine secretory coil but negative within the apocrine sweat glands.^2,4,21

The clinical findings from our chart review corroborated those reported in the literature. The mean age of SEDC in the 5 patients we reviewed was 81 years, and all cases presented on the head, consistent with the findings observed in the literature. Although 4 of our cases were male, there may not be a difference in risk based on sex as previously thought.¹ Our literature review revealed an almost equivalent percentage of male and female cases, with 52% being male.

Immunosuppression has been associated with an increased risk for SEDC. Our literature review revealed that approximately 9% (5/56) of cases occurred in immunosuppressed individuals. Two of these reported cases were in the setting of underlying chronic lymphocytic leukemia, 2 in individuals with a history of organ transplant, and 1 treated with azathioprine for myasthenia gravis.^2,4,10,12,13 Our chart review supported this correlation, as all 5 patients had a medical history potentially consistent with being in an immunocompromised state (Table). Notably, patient 5 represents a unique case of SEDC occurring in the setting of HIV. The patient had HIV for 33 years, with his most recent CD4⁺ count of 794 mm³ and HIV-1 RNA load of 35 copies/mL. Given that HIV-positive individuals may have more than a 2-fold increased risk of SCC, a greater degree of suspicion for SEDC should be maintained for these patients.^22,23

The etiology of SEDC is controversial but is thought to be either an SCC arising from eccrine glands or a variant of eccrine carcinoma with extensive squamoid differentiation.^{4,6,13,14,17,24} While SEDC certainly appears to share the proclivity for PNI with the malignant eccrine tumor MAC, it is simultaneously quite distinct, demonstrating nuclear pleomorphism and mitotic activity, both of which are lacking in the bland nature of MACs.^12,25

The exact prevalence of SEDC is difficult to ascertain because of its frequent misdiagnosis and variable nomenclature used within the literature. Most reported cases of SEDC are mistakenly diagnosed as SCC on the initial shave or punch biopsy because of superficial sampling. This also was the case in 4 of the patients we reviewed. In addition, there are reported cases of SEDC that were referred to by the investigators as cutaneous adenosquamous carcinoma (cASC), among other descriptors, such as ductal eccrine carcinoma with squamous differentiation, adnexal carcinoma with squamous and ductal differentiation, and syringoid eccrine carcinoma.^26-32 While the World Health Organization classifies SEDC as a distinct variant of cASC, which is a rare variant of SCC in itself, the 2 can be differentiated. Despite the similar clinical and histologic features shared between cASC and SEDC, the neoplastic aggregates in SEDC exhibit ductal differentiation containing lumina positive for CEA and EMA.⁴ Overall, we favor the term squamoid eccrine ductal carcinoma, as there has recently been more uniformity for the designation of this disease entity as such.

It is unclear whether the high incidence of local recurrence (23% [13/56]) of SEDC reported in the literature is related to the treatment modality employed (ie, wide local excision) or due to the innate aggressiveness of SEDC.^1,3,5 The literature has shown that MMS has lower recurrence rates than other treatments at 5-year follow-up for SCC (3.1%–5%) and eccrine carcinomas (0%–5%).^33,34 Although studies assessing tumor behavior or comparing treatment modalities are limited because of the rarity and underrecognition of SEDC, MMS has been used several times for SEDC with only 1 recurrence reported.^4,13,17,24 Given that all 5 of the patients we reviewed required more than 1 Mohs stage for complete tumor clearance and none demonstrated evidence of recurrence or metastasis (Table), we recommend MMS as the treatment of choice for SEDC.

Conclusion

Squamoid eccrine ductal carcinoma is a rare but likely underdiagnosed cutaneous tumor of uncertain etiology. Because of its propensity for recurrence and metastasis, excision of SEDC with complete circumferential peripheral and deep margin assessment with close follow-up is recommended.

Squamoid eccrine ductal carcinoma (SEDC) is an aggressive underrecognized cutaneous malignancy of unknown etiology.¹ It is most likely to occur in sun-exposed areas of the body, most commonly the head and neck. Risk factors include male sex, increased age, and chronic immunosuppression.^1-4 Current reports suggest that SEDC is likely a high-grade subtype of squamous cell carcinoma (SCC) with a high risk for local recurrence (25%) and metastasis (13%).^1,3,5,6 There are as few as 56 cases of SEDC reported in the literature; however, the number of cases may be closer to 100 due to SEDC being classified as either adenosquamous carcinoma of the skin or ductal eccrine carcinoma with squamous differentiation.¹

Clinically, SEDC mimics keratinocyte carcinomas. Histologically, SEDC is biphasic, with a superficial portion resembling well-differentiated SCC and a deeply invasive portion having infiltrative irregular cords with ductal differentiation. Perineural invasion (PNI) frequently is present. Multiple connections to the overlying epidermis also can be seen, serving as a subtle clue to the diagnosis on broad superficial specimens.^1-3 Due to superficial sampling, approximately 50% of reported cases are misdiagnosed as SCC during the initial biopsy.⁴ The diagnosis of SEDC often is made during complete excision when deeper tissue is sampled. Establishing an accurate diagnosis is important given the more aggressive nature of SEDC compared with SCC and its proclivity for PNI.^1,3,6 The purpose of this review is to increase awareness of this underrecognized entity and describe the histologic findings that help distinguish SEDC from SCC.

Patient Chart Review

We reviewed chart notes as well as frozen and formalin-fixed paraffin-embedded tissue sections from all 5 patients diagnosed with SEDC at a single institution between November 2018 and May 2020. The mean age of patients was 81 years, and 4 were male. Four of the patients presented for MMS with a preoperative diagnosis of SCC per the original biopsy results. Only 1 patient had a preoperative diagnosis of SEDC. The details of each case are recorded in the Table. All tumors were greater than 2 cm in diameter on initial presentation, were located on the head, and clinically resembled keratinocyte carcinoma with either a nodular or plaquelike appearance (Figure 1).

Intraoperative histologic examination of the excised tissue revealed a biphasic pattern consisting of superficial SCC features overlying deeper dermal and subcutaneous infiltrative malignant ductal elements with gland formation in all 5 patients (Figures 2–4). Immunohistochemical staining with cytokeratin AE1/AE3 revealed thin strands of carcinoma in the mid to deeper dermis with squamous differentiation and eccrine ductal differentiation (Figure 5), thus confirming the diagnosis in all 5 patients.

Literature Review

A PubMed review of the literature using the search term squamoid eccrine ductal carcinoma resulted in 28 articles, 19 of which were included in the review based on inclusion criteria (original articles available in English, in full text, and pertained to SEDC). Our review yielded 56 cases of SEDC.^1-19 The mean age of patients with SEDC was 72 years. The number of male and female cases was 52% (29/56) and 48% (27/56), respectively. The most common location of SEDC was on the head or neck (71% [40/56]), followed by the extremities (19% [11/56]). Immunosuppression was noted in 9% (5/56) of cases. Wide local excision was the most commonly employed treatment modality (91% [51/56]), with MMS being used in 4 patients (7%). Adjuvant radiation was reported in 5% (3/56) of cases. Perineural invasion was reported in 34% (19/56) of cases. Recurrence was seen in 23% (13/56) of cases, with a mean time to recurrence of 10.4 months. Metastasis to regional lymph nodes was observed in 13% (7/56) of cases, with 7% (4/56) of those cases having distant metastases.

Comment

Squamoid eccrine ductal carcinoma was successfully treated with MMS in all 5 of the patients we reviewed. Recognition of a distinct biphasic pattern consisting of squamous differentiation superficially with epidermal connection overlying deeper dermal and subcutaneous infiltrative malignant ductal elements with gland formation should lead to consideration of this diagnosis. A thorough inspection for PNI also should be performed, as this finding was present in all of 5 cases and in 34% of reported cases in our literature review.

The differential diagnosis for SEDC includes SCC, metastatic adenocarcinoma with squamoid features, and eccrine tumors, including eccrine poroma, microcystic adnexal carcinoma (MAC), and porocarcinoma with squamous differentiation. The combination of histologic features with the immunoexpression profile of carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), cytokeratin (CK) 5/6, and p63 can effectively exclude the other entities in the differential and confirm the diagnosis of SEDC.^1,3,4 While the diagnosis of SEDC relies on the specific histologic features of multiple surface attachments and superficial squamoid changes with deep ductular elements, immunohistochemistry can nonetheless be adjunctive in difficult cases. Positive immunohistochemical staining for CEA and EMA can help to highlight and delineate true glandular elements, whereas CK5/6 highlights the overall contour of the tumor, displaying more clearly the multiple epidermal attachments and the subtle infiltrative nature of the deeper components of invasive cords and ducts. In addition, the combination of CK5/6 and p63 positivity supports the primary cutaneous nature of the lesion rather than metastatic adenocarcinoma.^13,20 Other markers of eccrine secretory coils, such as CK7, CAM5.2, and S100, also are sometimes used for confirmation, some of which can aid in distinction from noneccrine sweat gland differentiation, as CK7 and CAM5.2 are negative in both luminal and basal cells of the dermal duct while being positive within the secretory coil, and S100 protein is expressed within eccrine secretory coil but negative within the apocrine sweat glands.^2,4,21

The clinical findings from our chart review corroborated those reported in the literature. The mean age of SEDC in the 5 patients we reviewed was 81 years, and all cases presented on the head, consistent with the findings observed in the literature. Although 4 of our cases were male, there may not be a difference in risk based on sex as previously thought.¹ Our literature review revealed an almost equivalent percentage of male and female cases, with 52% being male.

Immunosuppression has been associated with an increased risk for SEDC. Our literature review revealed that approximately 9% (5/56) of cases occurred in immunosuppressed individuals. Two of these reported cases were in the setting of underlying chronic lymphocytic leukemia, 2 in individuals with a history of organ transplant, and 1 treated with azathioprine for myasthenia gravis.^2,4,10,12,13 Our chart review supported this correlation, as all 5 patients had a medical history potentially consistent with being in an immunocompromised state (Table). Notably, patient 5 represents a unique case of SEDC occurring in the setting of HIV. The patient had HIV for 33 years, with his most recent CD4⁺ count of 794 mm³ and HIV-1 RNA load of 35 copies/mL. Given that HIV-positive individuals may have more than a 2-fold increased risk of SCC, a greater degree of suspicion for SEDC should be maintained for these patients.^22,23

The etiology of SEDC is controversial but is thought to be either an SCC arising from eccrine glands or a variant of eccrine carcinoma with extensive squamoid differentiation.^{4,6,13,14,17,24} While SEDC certainly appears to share the proclivity for PNI with the malignant eccrine tumor MAC, it is simultaneously quite distinct, demonstrating nuclear pleomorphism and mitotic activity, both of which are lacking in the bland nature of MACs.^12,25

The exact prevalence of SEDC is difficult to ascertain because of its frequent misdiagnosis and variable nomenclature used within the literature. Most reported cases of SEDC are mistakenly diagnosed as SCC on the initial shave or punch biopsy because of superficial sampling. This also was the case in 4 of the patients we reviewed. In addition, there are reported cases of SEDC that were referred to by the investigators as cutaneous adenosquamous carcinoma (cASC), among other descriptors, such as ductal eccrine carcinoma with squamous differentiation, adnexal carcinoma with squamous and ductal differentiation, and syringoid eccrine carcinoma.^26-32 While the World Health Organization classifies SEDC as a distinct variant of cASC, which is a rare variant of SCC in itself, the 2 can be differentiated. Despite the similar clinical and histologic features shared between cASC and SEDC, the neoplastic aggregates in SEDC exhibit ductal differentiation containing lumina positive for CEA and EMA.⁴ Overall, we favor the term squamoid eccrine ductal carcinoma, as there has recently been more uniformity for the designation of this disease entity as such.

It is unclear whether the high incidence of local recurrence (23% [13/56]) of SEDC reported in the literature is related to the treatment modality employed (ie, wide local excision) or due to the innate aggressiveness of SEDC.^1,3,5 The literature has shown that MMS has lower recurrence rates than other treatments at 5-year follow-up for SCC (3.1%–5%) and eccrine carcinomas (0%–5%).^33,34 Although studies assessing tumor behavior or comparing treatment modalities are limited because of the rarity and underrecognition of SEDC, MMS has been used several times for SEDC with only 1 recurrence reported.^4,13,17,24 Given that all 5 of the patients we reviewed required more than 1 Mohs stage for complete tumor clearance and none demonstrated evidence of recurrence or metastasis (Table), we recommend MMS as the treatment of choice for SEDC.

Conclusion

Squamoid eccrine ductal carcinoma is a rare but likely underdiagnosed cutaneous tumor of uncertain etiology. Because of its propensity for recurrence and metastasis, excision of SEDC with complete circumferential peripheral and deep margin assessment with close follow-up is recommended.

Squamoid eccrine ductal carcinoma (SEDC) is an aggressive underrecognized cutaneous malignancy of unknown etiology.¹ It is most likely to occur in sun-exposed areas of the body, most commonly the head and neck. Risk factors include male sex, increased age, and chronic immunosuppression.^1-4 Current reports suggest that SEDC is likely a high-grade subtype of squamous cell carcinoma (SCC) with a high risk for local recurrence (25%) and metastasis (13%).^1,3,5,6 There are as few as 56 cases of SEDC reported in the literature; however, the number of cases may be closer to 100 due to SEDC being classified as either adenosquamous carcinoma of the skin or ductal eccrine carcinoma with squamous differentiation.¹

Clinically, SEDC mimics keratinocyte carcinomas. Histologically, SEDC is biphasic, with a superficial portion resembling well-differentiated SCC and a deeply invasive portion having infiltrative irregular cords with ductal differentiation. Perineural invasion (PNI) frequently is present. Multiple connections to the overlying epidermis also can be seen, serving as a subtle clue to the diagnosis on broad superficial specimens.^1-3 Due to superficial sampling, approximately 50% of reported cases are misdiagnosed as SCC during the initial biopsy.⁴ The diagnosis of SEDC often is made during complete excision when deeper tissue is sampled. Establishing an accurate diagnosis is important given the more aggressive nature of SEDC compared with SCC and its proclivity for PNI.^1,3,6 The purpose of this review is to increase awareness of this underrecognized entity and describe the histologic findings that help distinguish SEDC from SCC.

Patient Chart Review

We reviewed chart notes as well as frozen and formalin-fixed paraffin-embedded tissue sections from all 5 patients diagnosed with SEDC at a single institution between November 2018 and May 2020. The mean age of patients was 81 years, and 4 were male. Four of the patients presented for MMS with a preoperative diagnosis of SCC per the original biopsy results. Only 1 patient had a preoperative diagnosis of SEDC. The details of each case are recorded in the Table. All tumors were greater than 2 cm in diameter on initial presentation, were located on the head, and clinically resembled keratinocyte carcinoma with either a nodular or plaquelike appearance (Figure 1).

Intraoperative histologic examination of the excised tissue revealed a biphasic pattern consisting of superficial SCC features overlying deeper dermal and subcutaneous infiltrative malignant ductal elements with gland formation in all 5 patients (Figures 2–4). Immunohistochemical staining with cytokeratin AE1/AE3 revealed thin strands of carcinoma in the mid to deeper dermis with squamous differentiation and eccrine ductal differentiation (Figure 5), thus confirming the diagnosis in all 5 patients.

Literature Review

A PubMed review of the literature using the search term squamoid eccrine ductal carcinoma resulted in 28 articles, 19 of which were included in the review based on inclusion criteria (original articles available in English, in full text, and pertained to SEDC). Our review yielded 56 cases of SEDC.^1-19 The mean age of patients with SEDC was 72 years. The number of male and female cases was 52% (29/56) and 48% (27/56), respectively. The most common location of SEDC was on the head or neck (71% [40/56]), followed by the extremities (19% [11/56]). Immunosuppression was noted in 9% (5/56) of cases. Wide local excision was the most commonly employed treatment modality (91% [51/56]), with MMS being used in 4 patients (7%). Adjuvant radiation was reported in 5% (3/56) of cases. Perineural invasion was reported in 34% (19/56) of cases. Recurrence was seen in 23% (13/56) of cases, with a mean time to recurrence of 10.4 months. Metastasis to regional lymph nodes was observed in 13% (7/56) of cases, with 7% (4/56) of those cases having distant metastases.

Comment

Squamoid eccrine ductal carcinoma was successfully treated with MMS in all 5 of the patients we reviewed. Recognition of a distinct biphasic pattern consisting of squamous differentiation superficially with epidermal connection overlying deeper dermal and subcutaneous infiltrative malignant ductal elements with gland formation should lead to consideration of this diagnosis. A thorough inspection for PNI also should be performed, as this finding was present in all of 5 cases and in 34% of reported cases in our literature review.

The differential diagnosis for SEDC includes SCC, metastatic adenocarcinoma with squamoid features, and eccrine tumors, including eccrine poroma, microcystic adnexal carcinoma (MAC), and porocarcinoma with squamous differentiation. The combination of histologic features with the immunoexpression profile of carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), cytokeratin (CK) 5/6, and p63 can effectively exclude the other entities in the differential and confirm the diagnosis of SEDC.^1,3,4 While the diagnosis of SEDC relies on the specific histologic features of multiple surface attachments and superficial squamoid changes with deep ductular elements, immunohistochemistry can nonetheless be adjunctive in difficult cases. Positive immunohistochemical staining for CEA and EMA can help to highlight and delineate true glandular elements, whereas CK5/6 highlights the overall contour of the tumor, displaying more clearly the multiple epidermal attachments and the subtle infiltrative nature of the deeper components of invasive cords and ducts. In addition, the combination of CK5/6 and p63 positivity supports the primary cutaneous nature of the lesion rather than metastatic adenocarcinoma.^13,20 Other markers of eccrine secretory coils, such as CK7, CAM5.2, and S100, also are sometimes used for confirmation, some of which can aid in distinction from noneccrine sweat gland differentiation, as CK7 and CAM5.2 are negative in both luminal and basal cells of the dermal duct while being positive within the secretory coil, and S100 protein is expressed within eccrine secretory coil but negative within the apocrine sweat glands.^2,4,21

The clinical findings from our chart review corroborated those reported in the literature. The mean age of SEDC in the 5 patients we reviewed was 81 years, and all cases presented on the head, consistent with the findings observed in the literature. Although 4 of our cases were male, there may not be a difference in risk based on sex as previously thought.¹ Our literature review revealed an almost equivalent percentage of male and female cases, with 52% being male.

Immunosuppression has been associated with an increased risk for SEDC. Our literature review revealed that approximately 9% (5/56) of cases occurred in immunosuppressed individuals. Two of these reported cases were in the setting of underlying chronic lymphocytic leukemia, 2 in individuals with a history of organ transplant, and 1 treated with azathioprine for myasthenia gravis.^2,4,10,12,13 Our chart review supported this correlation, as all 5 patients had a medical history potentially consistent with being in an immunocompromised state (Table). Notably, patient 5 represents a unique case of SEDC occurring in the setting of HIV. The patient had HIV for 33 years, with his most recent CD4⁺ count of 794 mm³ and HIV-1 RNA load of 35 copies/mL. Given that HIV-positive individuals may have more than a 2-fold increased risk of SCC, a greater degree of suspicion for SEDC should be maintained for these patients.^22,23

The etiology of SEDC is controversial but is thought to be either an SCC arising from eccrine glands or a variant of eccrine carcinoma with extensive squamoid differentiation.^{4,6,13,14,17,24} While SEDC certainly appears to share the proclivity for PNI with the malignant eccrine tumor MAC, it is simultaneously quite distinct, demonstrating nuclear pleomorphism and mitotic activity, both of which are lacking in the bland nature of MACs.^12,25

The exact prevalence of SEDC is difficult to ascertain because of its frequent misdiagnosis and variable nomenclature used within the literature. Most reported cases of SEDC are mistakenly diagnosed as SCC on the initial shave or punch biopsy because of superficial sampling. This also was the case in 4 of the patients we reviewed. In addition, there are reported cases of SEDC that were referred to by the investigators as cutaneous adenosquamous carcinoma (cASC), among other descriptors, such as ductal eccrine carcinoma with squamous differentiation, adnexal carcinoma with squamous and ductal differentiation, and syringoid eccrine carcinoma.^26-32 While the World Health Organization classifies SEDC as a distinct variant of cASC, which is a rare variant of SCC in itself, the 2 can be differentiated. Despite the similar clinical and histologic features shared between cASC and SEDC, the neoplastic aggregates in SEDC exhibit ductal differentiation containing lumina positive for CEA and EMA.⁴ Overall, we favor the term squamoid eccrine ductal carcinoma, as there has recently been more uniformity for the designation of this disease entity as such.

It is unclear whether the high incidence of local recurrence (23% [13/56]) of SEDC reported in the literature is related to the treatment modality employed (ie, wide local excision) or due to the innate aggressiveness of SEDC.^1,3,5 The literature has shown that MMS has lower recurrence rates than other treatments at 5-year follow-up for SCC (3.1%–5%) and eccrine carcinomas (0%–5%).^33,34 Although studies assessing tumor behavior or comparing treatment modalities are limited because of the rarity and underrecognition of SEDC, MMS has been used several times for SEDC with only 1 recurrence reported.^4,13,17,24 Given that all 5 of the patients we reviewed required more than 1 Mohs stage for complete tumor clearance and none demonstrated evidence of recurrence or metastasis (Table), we recommend MMS as the treatment of choice for SEDC.

Conclusion

Squamoid eccrine ductal carcinoma is a rare but likely underdiagnosed cutaneous tumor of uncertain etiology. Because of its propensity for recurrence and metastasis, excision of SEDC with complete circumferential peripheral and deep margin assessment with close follow-up is recommended.