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Monkeypox in children and women remains rare, CDC data show
Monkeypox cases in the United States continue to be rare in children younger than 15, women, and in individuals older than 60, according to new data released by the Centers for Disease Control and Prevention. Men aged 26-40 make up the highest proportion of cases.
The age distribution of cases is similar to those of sexually transmitted infections, said Monica Gandhi, MD, MPH, associate chief of the division of HIV, infectious diseases, and global medicine at the University of California, San Francisco. It is most common in younger to middle-aged age groups, and less common in children and older individuals. As of Aug. 21, only 17 children younger than 15 have been diagnosed with monkeypox in the United States, and women make up fewer than 1.5% of cases.
“This data should be very reassuring to parents and to children going to back to school,” Dr. Gandhi said in an interview. After 3 months of monitoring the virus, the data suggest that monkeypox is primarily spreading in networks of men who have sex with men (MSM) through sexual activity, “and that isn’t something we worry about with school-spread illness.”
In addition to the reassuring data about children and monkeypox, the CDC released laboratory testing data, a behavioral survey of MSM, patient data on the antiviral medication tecovirimat (TPOXX), and other case demographics and symptoms.
Though the number of positive monkeypox tests have continued to rise, the test-positivity rates have declined over the past month, data show. Since July 16, the positivity rate has dipped from 54% to 23%. This trend is likely because of an increase in testing availability, said Randolph Hubach, PhD, MPH, the director of the Sexual Health Research Lab at Purdue University, West Lafayette, Ind.
“We also saw this with COVID early on with testing: it was really limited to folks who were symptomatic,” he said in an interview . “As testing ramped up in accessibility, you had a lot more negative results, but because testing was more widely available, you were able to capture more positive results.”
The data also show that case numbers continue to grow in the United States, whereas in other countries that identified cases before the United States – Spain, the United Kingdom, and France, for example – cases have been leveling off, noted Dr. Gandhi.
The CDC also shared responses from a survey of gay, bisexual, and other MSM conducted from Aug. 5-15, about how they have changed their sexual behaviors in response to the monkeypox outbreak. Half of respondents reported reduced one-time sexual encounters, 49% reported reducing sex with partners met on dating apps or at sex venues, and 48% reported reducing their number of sex partners. These responses are “heartening to see,” Dr. Gandhi said, and shows that individuals are taking proactive steps to reduce their potential exposure risk to monkeypox.
More detailed demographic data showed that Black, Hispanic, or Latinx individuals make up an increasing proportion of cases in the United States. In May, 71% of people with reported monkeypox infection were White and 29% were Black. For the week of August 8-14, about a third (31%) of monkeypox cases were in White people, 32% were in Hispanic or Latinx people, and 33% were in Black people.
The most common symptoms of monkeypox were rash (98.6%), malaise (72.7%), fever (72.1%), and chills (68.9%). Rectal pain was reported in 43.9% of patients, and 25% had rectal bleeding.
The CDC also released information on 288 patients with monkeypox treated with TPOXX under compassionate use. The median age of patients was 37 and 98.9% were male. About 40% of recipients were White, 35% were Hispanic, and about 16% were Black. This information does not include every patient treated with TPOXX, the agency said, as providers can begin treatment before submitting paperwork. As of Aug. 18, the CDC had received 400 patient intake forms for TPOXX, according to its website.
The agency has yet to release data on vaccination rates, which Dr. Hubach is eager to see. Demographic information on who is receiving vaccinations, and where, can illuminate issues with access as vaccine eligibility continues to expand. “Vaccination is probably going to be the largest tool within our toolbox to try to inhibit disease acquisition and spread,” he said.
A version of this article first appeared on Medscape.com.
Monkeypox cases in the United States continue to be rare in children younger than 15, women, and in individuals older than 60, according to new data released by the Centers for Disease Control and Prevention. Men aged 26-40 make up the highest proportion of cases.
The age distribution of cases is similar to those of sexually transmitted infections, said Monica Gandhi, MD, MPH, associate chief of the division of HIV, infectious diseases, and global medicine at the University of California, San Francisco. It is most common in younger to middle-aged age groups, and less common in children and older individuals. As of Aug. 21, only 17 children younger than 15 have been diagnosed with monkeypox in the United States, and women make up fewer than 1.5% of cases.
“This data should be very reassuring to parents and to children going to back to school,” Dr. Gandhi said in an interview. After 3 months of monitoring the virus, the data suggest that monkeypox is primarily spreading in networks of men who have sex with men (MSM) through sexual activity, “and that isn’t something we worry about with school-spread illness.”
In addition to the reassuring data about children and monkeypox, the CDC released laboratory testing data, a behavioral survey of MSM, patient data on the antiviral medication tecovirimat (TPOXX), and other case demographics and symptoms.
Though the number of positive monkeypox tests have continued to rise, the test-positivity rates have declined over the past month, data show. Since July 16, the positivity rate has dipped from 54% to 23%. This trend is likely because of an increase in testing availability, said Randolph Hubach, PhD, MPH, the director of the Sexual Health Research Lab at Purdue University, West Lafayette, Ind.
“We also saw this with COVID early on with testing: it was really limited to folks who were symptomatic,” he said in an interview . “As testing ramped up in accessibility, you had a lot more negative results, but because testing was more widely available, you were able to capture more positive results.”
The data also show that case numbers continue to grow in the United States, whereas in other countries that identified cases before the United States – Spain, the United Kingdom, and France, for example – cases have been leveling off, noted Dr. Gandhi.
The CDC also shared responses from a survey of gay, bisexual, and other MSM conducted from Aug. 5-15, about how they have changed their sexual behaviors in response to the monkeypox outbreak. Half of respondents reported reduced one-time sexual encounters, 49% reported reducing sex with partners met on dating apps or at sex venues, and 48% reported reducing their number of sex partners. These responses are “heartening to see,” Dr. Gandhi said, and shows that individuals are taking proactive steps to reduce their potential exposure risk to monkeypox.
More detailed demographic data showed that Black, Hispanic, or Latinx individuals make up an increasing proportion of cases in the United States. In May, 71% of people with reported monkeypox infection were White and 29% were Black. For the week of August 8-14, about a third (31%) of monkeypox cases were in White people, 32% were in Hispanic or Latinx people, and 33% were in Black people.
The most common symptoms of monkeypox were rash (98.6%), malaise (72.7%), fever (72.1%), and chills (68.9%). Rectal pain was reported in 43.9% of patients, and 25% had rectal bleeding.
The CDC also released information on 288 patients with monkeypox treated with TPOXX under compassionate use. The median age of patients was 37 and 98.9% were male. About 40% of recipients were White, 35% were Hispanic, and about 16% were Black. This information does not include every patient treated with TPOXX, the agency said, as providers can begin treatment before submitting paperwork. As of Aug. 18, the CDC had received 400 patient intake forms for TPOXX, according to its website.
The agency has yet to release data on vaccination rates, which Dr. Hubach is eager to see. Demographic information on who is receiving vaccinations, and where, can illuminate issues with access as vaccine eligibility continues to expand. “Vaccination is probably going to be the largest tool within our toolbox to try to inhibit disease acquisition and spread,” he said.
A version of this article first appeared on Medscape.com.
Monkeypox cases in the United States continue to be rare in children younger than 15, women, and in individuals older than 60, according to new data released by the Centers for Disease Control and Prevention. Men aged 26-40 make up the highest proportion of cases.
The age distribution of cases is similar to those of sexually transmitted infections, said Monica Gandhi, MD, MPH, associate chief of the division of HIV, infectious diseases, and global medicine at the University of California, San Francisco. It is most common in younger to middle-aged age groups, and less common in children and older individuals. As of Aug. 21, only 17 children younger than 15 have been diagnosed with monkeypox in the United States, and women make up fewer than 1.5% of cases.
“This data should be very reassuring to parents and to children going to back to school,” Dr. Gandhi said in an interview. After 3 months of monitoring the virus, the data suggest that monkeypox is primarily spreading in networks of men who have sex with men (MSM) through sexual activity, “and that isn’t something we worry about with school-spread illness.”
In addition to the reassuring data about children and monkeypox, the CDC released laboratory testing data, a behavioral survey of MSM, patient data on the antiviral medication tecovirimat (TPOXX), and other case demographics and symptoms.
Though the number of positive monkeypox tests have continued to rise, the test-positivity rates have declined over the past month, data show. Since July 16, the positivity rate has dipped from 54% to 23%. This trend is likely because of an increase in testing availability, said Randolph Hubach, PhD, MPH, the director of the Sexual Health Research Lab at Purdue University, West Lafayette, Ind.
“We also saw this with COVID early on with testing: it was really limited to folks who were symptomatic,” he said in an interview . “As testing ramped up in accessibility, you had a lot more negative results, but because testing was more widely available, you were able to capture more positive results.”
The data also show that case numbers continue to grow in the United States, whereas in other countries that identified cases before the United States – Spain, the United Kingdom, and France, for example – cases have been leveling off, noted Dr. Gandhi.
The CDC also shared responses from a survey of gay, bisexual, and other MSM conducted from Aug. 5-15, about how they have changed their sexual behaviors in response to the monkeypox outbreak. Half of respondents reported reduced one-time sexual encounters, 49% reported reducing sex with partners met on dating apps or at sex venues, and 48% reported reducing their number of sex partners. These responses are “heartening to see,” Dr. Gandhi said, and shows that individuals are taking proactive steps to reduce their potential exposure risk to monkeypox.
More detailed demographic data showed that Black, Hispanic, or Latinx individuals make up an increasing proportion of cases in the United States. In May, 71% of people with reported monkeypox infection were White and 29% were Black. For the week of August 8-14, about a third (31%) of monkeypox cases were in White people, 32% were in Hispanic or Latinx people, and 33% were in Black people.
The most common symptoms of monkeypox were rash (98.6%), malaise (72.7%), fever (72.1%), and chills (68.9%). Rectal pain was reported in 43.9% of patients, and 25% had rectal bleeding.
The CDC also released information on 288 patients with monkeypox treated with TPOXX under compassionate use. The median age of patients was 37 and 98.9% were male. About 40% of recipients were White, 35% were Hispanic, and about 16% were Black. This information does not include every patient treated with TPOXX, the agency said, as providers can begin treatment before submitting paperwork. As of Aug. 18, the CDC had received 400 patient intake forms for TPOXX, according to its website.
The agency has yet to release data on vaccination rates, which Dr. Hubach is eager to see. Demographic information on who is receiving vaccinations, and where, can illuminate issues with access as vaccine eligibility continues to expand. “Vaccination is probably going to be the largest tool within our toolbox to try to inhibit disease acquisition and spread,” he said.
A version of this article first appeared on Medscape.com.
COVID to blame as U.S. life expectancy falls
All 50 states and the District of Columbia saw drops in life expectancy, according to the report from the Centers for Disease Control and Prevention’s National Center for Health Statistics.
The declines were mostly because of COVID-19 and “unintentional injuries,” such as drug overdoses.
The overall drop took national life expectancy from 78.8 years in 2019 to 77 years in 2020, the first year of the pandemic, ABC News reported.
States in the West and Northwest generally had higher life expectancy, with states in the South having the lowest.
Hawaii had the highest life expectancy at 80.7 years. It was followed by Washington, Minnesota, California, and Massachusetts. Mississippi had the lowest at 71.9 years, the figures show. The others in the bottom five were West Virginia, Louisiana, Alabama, and Kentucky.
In 2020, COVID-19 was the third-highest cause of death, leading to more than 350,000, the CDC reported earlier this year. At the same time, more people are dying annually from drug overdoses. A record 83,500 fatal overdoses were reported in 2020.
A version of this article first appeared on WebMD.com.
All 50 states and the District of Columbia saw drops in life expectancy, according to the report from the Centers for Disease Control and Prevention’s National Center for Health Statistics.
The declines were mostly because of COVID-19 and “unintentional injuries,” such as drug overdoses.
The overall drop took national life expectancy from 78.8 years in 2019 to 77 years in 2020, the first year of the pandemic, ABC News reported.
States in the West and Northwest generally had higher life expectancy, with states in the South having the lowest.
Hawaii had the highest life expectancy at 80.7 years. It was followed by Washington, Minnesota, California, and Massachusetts. Mississippi had the lowest at 71.9 years, the figures show. The others in the bottom five were West Virginia, Louisiana, Alabama, and Kentucky.
In 2020, COVID-19 was the third-highest cause of death, leading to more than 350,000, the CDC reported earlier this year. At the same time, more people are dying annually from drug overdoses. A record 83,500 fatal overdoses were reported in 2020.
A version of this article first appeared on WebMD.com.
All 50 states and the District of Columbia saw drops in life expectancy, according to the report from the Centers for Disease Control and Prevention’s National Center for Health Statistics.
The declines were mostly because of COVID-19 and “unintentional injuries,” such as drug overdoses.
The overall drop took national life expectancy from 78.8 years in 2019 to 77 years in 2020, the first year of the pandemic, ABC News reported.
States in the West and Northwest generally had higher life expectancy, with states in the South having the lowest.
Hawaii had the highest life expectancy at 80.7 years. It was followed by Washington, Minnesota, California, and Massachusetts. Mississippi had the lowest at 71.9 years, the figures show. The others in the bottom five were West Virginia, Louisiana, Alabama, and Kentucky.
In 2020, COVID-19 was the third-highest cause of death, leading to more than 350,000, the CDC reported earlier this year. At the same time, more people are dying annually from drug overdoses. A record 83,500 fatal overdoses were reported in 2020.
A version of this article first appeared on WebMD.com.
No fish can escape this net ... of COVID testing
Something about this COVID testing smells fishy
The Chinese have been challenging America’s political and economic hegemony (yes, we did have to look that one up – you’re rude to ask) for some time, but now they’ve gone too far. Are we going to just sit here and let China do something more ridiculous than us in response to COVID? No way!
Here’s the deal: The government of the Chinese coastal city of Xiamen has decided that it’s not just the workers on returning fishing boats who have the potential to introduce COVID to the rest of the population. The fish also present a problem. So when the authorities say that everyone needs to be tested before they can enter the city, they mean everyone.
An employee of the municipal ocean development bureau told local media that “all people in Xiamen City need nucleic acid testing, and the fish catches must be tested as well,” according to the Guardian, which also said that “TV news reports showed officials swabbing the mouths of fish and the underside of crabs.”
In the words of George Takei: “Oh my.”
Hold on there a second, George Takei, because we here in the good old US of A have still got Los Angeles, where COVID testing also has taken a nonhuman turn. The LA County public health department recently announced that pets are now eligible for a free SARS-CoV-2 test through veterinarians and other animal care facilities.
“Our goal is to test many different species of animals including wildlife (deer, bats, raccoons), pets (dogs, cats, hamsters, pocket pets), marine mammals (seals), and more,” Veterinary Public Health announced.
Hegemony restored.
Not even God could save them from worms
The Dark Ages may not have been as dark and violent as many people think, but there’s no denying that life in medieval Europe kind of sucked. The only real alternative to serfdom was a job with the Catholic Church. Medieval friars, for example, lived in stone buildings, had access to fresh fruits and vegetables, and even had latrines and running water. Luxuries compared with the life of the average peasant.
So why then, despite having access to more modern sanitation and amenities, did the friars have so many gut parasites? That’s the question raised by a group of researchers from the University of Cambridge, who conducted a study of 19 medieval friars buried at a local friary (Oh, doesn’t your town have one of those?) and 25 local people buried at a nonreligious cemetery during a similar time period. Of those 19 friars, 11 were infected with worms and parasites, compared with just 8 of 25 townspeople.
This doesn’t make a lot of sense. The friars had a good life by old-time standards: They had basic sanitation down and a solid diet. These things should lead to a healthier population. The problem, the researchers found, is two pronged and a vicious cycle. First off, the friars had plenty of fresh food, but they used human feces to fertilize their produce. There’s a reason modern practice for human waste fertilization is to let the waste compost for 6 months: The waiting period allows the parasites a chance to kindly die off, which prevents reinfection.
Secondly, the friars’ diet of fresh fruits and vegetables mixed together into a salad, while appealing to our modern-day sensibilities, was not a great choice. By comparison, laypeople tended to eat a boiled mishmash of whatever they could find, and while that’s kind of gross, the key here is that their food was cooked. And heat kills parasites. The uncooked salads did no such thing, so the monks ate infected food, expelled infected poop, and grew more infected food with their infected poop.
Once the worms arrived, they never left, making them the worst kind of house guest. Read the room, worms, take your dinner and move on. You don’t have to go home, but you can’t stay here.
What’s a shared genotype between friends?
Do you find it hard to tell the difference between Katy Perry and Zooey Deschanel? They look alike, but they’re not related. Or are they? According to new research, people who look and act very similar but are not related may share DNA.
“Our study provides a rare insight into human likeness by showing that people with extreme look-alike faces share common genotypes, whereas they are discordant at the epigenome and microbiome levels,” senior author Manel Esteller of the Josep Carreras Leukemia Research Institute in Barcelona said in a written statement. “Genomics clusters them together, and the rest sets them apart.”
The Internet has been a great source in being able to find look-alikes. The research team found photos of doppelgangers photographed by François Brunelle, a Canadian artist. Using facial recognition algorithms, the investigators were able to measure likeness between the each pair of look-alikes. The participants also completed a questionnaire about lifestyle and provided a saliva sample.
The results showed that the look-alikes had similar genotypes but different DNA methylation and microbiome landscapes. The look-alikes also seemed to have similarities in weight, height, and behaviors such as smoking, proving that doppelgangers not only look alike but also share common interests.
Next time someone tells you that you look like their best friend Steve, you won’t have to wonder much what Steve is like.
The secret to a good relationship? It’s a secret
Strong relationships are built on honesty and trust, right? Being open with your partner and/or friends is usually a good practice for keeping the relationship healthy, but the latest evidence suggests that maybe you shouldn’t share everything.
According to the first known study on the emotional, behavioral, and relational aspect of consumer behavior, not disclosing certain purchases to your partner can actually be a good thing for the relationship. How? Well, it all has to do with guilt.
In a series of studies, the researchers asked couples about their secret consumptions. The most commonly hidden thing by far was a product (65%).
“We found that 90% of people have recently kept everyday consumer behaviors a secret from a close other – like a friend or spouse – even though they also report that they don’t think their partner would care if they knew about it,” Kelley Gullo Wight, one of the study’s two lead authors, said in a written statement.
Keeping a hidden stash of chocolate produces guilt, which the researchers found to be the key factor, making the perpetrator want to do more in the relationship to ease that sense of betrayal or dishonesty. They called it a “greater relationship investment,” meaning the person is more likely to do a little extra for their partner, like shell out more money for the next anniversary gift or yield to watching their partner’s favorite program.
So don’t feel too bad about that secret Amazon purchase. As long as the other person doesn’t see the box, nobody has to know. Your relationship can only improve.
Something about this COVID testing smells fishy
The Chinese have been challenging America’s political and economic hegemony (yes, we did have to look that one up – you’re rude to ask) for some time, but now they’ve gone too far. Are we going to just sit here and let China do something more ridiculous than us in response to COVID? No way!
Here’s the deal: The government of the Chinese coastal city of Xiamen has decided that it’s not just the workers on returning fishing boats who have the potential to introduce COVID to the rest of the population. The fish also present a problem. So when the authorities say that everyone needs to be tested before they can enter the city, they mean everyone.
An employee of the municipal ocean development bureau told local media that “all people in Xiamen City need nucleic acid testing, and the fish catches must be tested as well,” according to the Guardian, which also said that “TV news reports showed officials swabbing the mouths of fish and the underside of crabs.”
In the words of George Takei: “Oh my.”
Hold on there a second, George Takei, because we here in the good old US of A have still got Los Angeles, where COVID testing also has taken a nonhuman turn. The LA County public health department recently announced that pets are now eligible for a free SARS-CoV-2 test through veterinarians and other animal care facilities.
“Our goal is to test many different species of animals including wildlife (deer, bats, raccoons), pets (dogs, cats, hamsters, pocket pets), marine mammals (seals), and more,” Veterinary Public Health announced.
Hegemony restored.
Not even God could save them from worms
The Dark Ages may not have been as dark and violent as many people think, but there’s no denying that life in medieval Europe kind of sucked. The only real alternative to serfdom was a job with the Catholic Church. Medieval friars, for example, lived in stone buildings, had access to fresh fruits and vegetables, and even had latrines and running water. Luxuries compared with the life of the average peasant.
So why then, despite having access to more modern sanitation and amenities, did the friars have so many gut parasites? That’s the question raised by a group of researchers from the University of Cambridge, who conducted a study of 19 medieval friars buried at a local friary (Oh, doesn’t your town have one of those?) and 25 local people buried at a nonreligious cemetery during a similar time period. Of those 19 friars, 11 were infected with worms and parasites, compared with just 8 of 25 townspeople.
This doesn’t make a lot of sense. The friars had a good life by old-time standards: They had basic sanitation down and a solid diet. These things should lead to a healthier population. The problem, the researchers found, is two pronged and a vicious cycle. First off, the friars had plenty of fresh food, but they used human feces to fertilize their produce. There’s a reason modern practice for human waste fertilization is to let the waste compost for 6 months: The waiting period allows the parasites a chance to kindly die off, which prevents reinfection.
Secondly, the friars’ diet of fresh fruits and vegetables mixed together into a salad, while appealing to our modern-day sensibilities, was not a great choice. By comparison, laypeople tended to eat a boiled mishmash of whatever they could find, and while that’s kind of gross, the key here is that their food was cooked. And heat kills parasites. The uncooked salads did no such thing, so the monks ate infected food, expelled infected poop, and grew more infected food with their infected poop.
Once the worms arrived, they never left, making them the worst kind of house guest. Read the room, worms, take your dinner and move on. You don’t have to go home, but you can’t stay here.
What’s a shared genotype between friends?
Do you find it hard to tell the difference between Katy Perry and Zooey Deschanel? They look alike, but they’re not related. Or are they? According to new research, people who look and act very similar but are not related may share DNA.
“Our study provides a rare insight into human likeness by showing that people with extreme look-alike faces share common genotypes, whereas they are discordant at the epigenome and microbiome levels,” senior author Manel Esteller of the Josep Carreras Leukemia Research Institute in Barcelona said in a written statement. “Genomics clusters them together, and the rest sets them apart.”
The Internet has been a great source in being able to find look-alikes. The research team found photos of doppelgangers photographed by François Brunelle, a Canadian artist. Using facial recognition algorithms, the investigators were able to measure likeness between the each pair of look-alikes. The participants also completed a questionnaire about lifestyle and provided a saliva sample.
The results showed that the look-alikes had similar genotypes but different DNA methylation and microbiome landscapes. The look-alikes also seemed to have similarities in weight, height, and behaviors such as smoking, proving that doppelgangers not only look alike but also share common interests.
Next time someone tells you that you look like their best friend Steve, you won’t have to wonder much what Steve is like.
The secret to a good relationship? It’s a secret
Strong relationships are built on honesty and trust, right? Being open with your partner and/or friends is usually a good practice for keeping the relationship healthy, but the latest evidence suggests that maybe you shouldn’t share everything.
According to the first known study on the emotional, behavioral, and relational aspect of consumer behavior, not disclosing certain purchases to your partner can actually be a good thing for the relationship. How? Well, it all has to do with guilt.
In a series of studies, the researchers asked couples about their secret consumptions. The most commonly hidden thing by far was a product (65%).
“We found that 90% of people have recently kept everyday consumer behaviors a secret from a close other – like a friend or spouse – even though they also report that they don’t think their partner would care if they knew about it,” Kelley Gullo Wight, one of the study’s two lead authors, said in a written statement.
Keeping a hidden stash of chocolate produces guilt, which the researchers found to be the key factor, making the perpetrator want to do more in the relationship to ease that sense of betrayal or dishonesty. They called it a “greater relationship investment,” meaning the person is more likely to do a little extra for their partner, like shell out more money for the next anniversary gift or yield to watching their partner’s favorite program.
So don’t feel too bad about that secret Amazon purchase. As long as the other person doesn’t see the box, nobody has to know. Your relationship can only improve.
Something about this COVID testing smells fishy
The Chinese have been challenging America’s political and economic hegemony (yes, we did have to look that one up – you’re rude to ask) for some time, but now they’ve gone too far. Are we going to just sit here and let China do something more ridiculous than us in response to COVID? No way!
Here’s the deal: The government of the Chinese coastal city of Xiamen has decided that it’s not just the workers on returning fishing boats who have the potential to introduce COVID to the rest of the population. The fish also present a problem. So when the authorities say that everyone needs to be tested before they can enter the city, they mean everyone.
An employee of the municipal ocean development bureau told local media that “all people in Xiamen City need nucleic acid testing, and the fish catches must be tested as well,” according to the Guardian, which also said that “TV news reports showed officials swabbing the mouths of fish and the underside of crabs.”
In the words of George Takei: “Oh my.”
Hold on there a second, George Takei, because we here in the good old US of A have still got Los Angeles, where COVID testing also has taken a nonhuman turn. The LA County public health department recently announced that pets are now eligible for a free SARS-CoV-2 test through veterinarians and other animal care facilities.
“Our goal is to test many different species of animals including wildlife (deer, bats, raccoons), pets (dogs, cats, hamsters, pocket pets), marine mammals (seals), and more,” Veterinary Public Health announced.
Hegemony restored.
Not even God could save them from worms
The Dark Ages may not have been as dark and violent as many people think, but there’s no denying that life in medieval Europe kind of sucked. The only real alternative to serfdom was a job with the Catholic Church. Medieval friars, for example, lived in stone buildings, had access to fresh fruits and vegetables, and even had latrines and running water. Luxuries compared with the life of the average peasant.
So why then, despite having access to more modern sanitation and amenities, did the friars have so many gut parasites? That’s the question raised by a group of researchers from the University of Cambridge, who conducted a study of 19 medieval friars buried at a local friary (Oh, doesn’t your town have one of those?) and 25 local people buried at a nonreligious cemetery during a similar time period. Of those 19 friars, 11 were infected with worms and parasites, compared with just 8 of 25 townspeople.
This doesn’t make a lot of sense. The friars had a good life by old-time standards: They had basic sanitation down and a solid diet. These things should lead to a healthier population. The problem, the researchers found, is two pronged and a vicious cycle. First off, the friars had plenty of fresh food, but they used human feces to fertilize their produce. There’s a reason modern practice for human waste fertilization is to let the waste compost for 6 months: The waiting period allows the parasites a chance to kindly die off, which prevents reinfection.
Secondly, the friars’ diet of fresh fruits and vegetables mixed together into a salad, while appealing to our modern-day sensibilities, was not a great choice. By comparison, laypeople tended to eat a boiled mishmash of whatever they could find, and while that’s kind of gross, the key here is that their food was cooked. And heat kills parasites. The uncooked salads did no such thing, so the monks ate infected food, expelled infected poop, and grew more infected food with their infected poop.
Once the worms arrived, they never left, making them the worst kind of house guest. Read the room, worms, take your dinner and move on. You don’t have to go home, but you can’t stay here.
What’s a shared genotype between friends?
Do you find it hard to tell the difference between Katy Perry and Zooey Deschanel? They look alike, but they’re not related. Or are they? According to new research, people who look and act very similar but are not related may share DNA.
“Our study provides a rare insight into human likeness by showing that people with extreme look-alike faces share common genotypes, whereas they are discordant at the epigenome and microbiome levels,” senior author Manel Esteller of the Josep Carreras Leukemia Research Institute in Barcelona said in a written statement. “Genomics clusters them together, and the rest sets them apart.”
The Internet has been a great source in being able to find look-alikes. The research team found photos of doppelgangers photographed by François Brunelle, a Canadian artist. Using facial recognition algorithms, the investigators were able to measure likeness between the each pair of look-alikes. The participants also completed a questionnaire about lifestyle and provided a saliva sample.
The results showed that the look-alikes had similar genotypes but different DNA methylation and microbiome landscapes. The look-alikes also seemed to have similarities in weight, height, and behaviors such as smoking, proving that doppelgangers not only look alike but also share common interests.
Next time someone tells you that you look like their best friend Steve, you won’t have to wonder much what Steve is like.
The secret to a good relationship? It’s a secret
Strong relationships are built on honesty and trust, right? Being open with your partner and/or friends is usually a good practice for keeping the relationship healthy, but the latest evidence suggests that maybe you shouldn’t share everything.
According to the first known study on the emotional, behavioral, and relational aspect of consumer behavior, not disclosing certain purchases to your partner can actually be a good thing for the relationship. How? Well, it all has to do with guilt.
In a series of studies, the researchers asked couples about their secret consumptions. The most commonly hidden thing by far was a product (65%).
“We found that 90% of people have recently kept everyday consumer behaviors a secret from a close other – like a friend or spouse – even though they also report that they don’t think their partner would care if they knew about it,” Kelley Gullo Wight, one of the study’s two lead authors, said in a written statement.
Keeping a hidden stash of chocolate produces guilt, which the researchers found to be the key factor, making the perpetrator want to do more in the relationship to ease that sense of betrayal or dishonesty. They called it a “greater relationship investment,” meaning the person is more likely to do a little extra for their partner, like shell out more money for the next anniversary gift or yield to watching their partner’s favorite program.
So don’t feel too bad about that secret Amazon purchase. As long as the other person doesn’t see the box, nobody has to know. Your relationship can only improve.
Asian patients with psoriasis have shortest visits, study shows
(NAMCS) from 2010 to 2016.
Yet the reasons for the difference are unclear and in need of further research, said the investigators and dermatologists who were asked to comment on the research.
The study covered over 4 million visits for psoriasis and found that the mean duration of visits for Asian patients was 9.2 minutes, compared with 15.7 minutes for Hispanic or Latino patients, 20.7 minutes for non-Hispanic Black patients, and 15.4 minutes for non-Hispanic White patients.
The mean duration of visits with Asian patients was 39.9% shorter, compared with visits with White patients (beta coefficient, –5,747; 95% confidence interval, –11.026 to –0.469; P = .03), and 40.6% shorter, compared with visits with non-Asian patients combined (beta coefficient, –5.908; 95% CI, –11.147 to –0.669, P = .03), April W. Armstrong, MD, MPH, professor of dermatology and director of the psoriasis program at the University of Southern California, Los Angeles, and Kevin K. Wu, MD, a dermatology resident at USC, said in a research letter published in JAMA Dermatology.
“The etiology of these differences is unclear,” they wrote. “It is possible that factors such as unconscious bias, cultural differences in communication, or residual confounding may be responsible for the observed findings.”
Their findings came from multivariable linear regression analyses that adjusted for age, sex, type of visit (new or follow-up), visit complexity based on the number of reasons for the visit, insurance status (such as private insurance or Medicaid), psoriasis severity on the basis of systemic psoriasis treatment or phototherapy, and complex topical regimens (three or more topical agents).
Commenting on the results, Deborah A. Scott, MD, codirector of the skin of color dermatology program at Brigham and Women’s Hospital and assistant professor at Harvard Medical School, both in Boston, said in an interview that visit length “is a reasonable parameter to look at among many others” when investigating potential disparities in care.
“They’re equating [shorter visit times] with lack of time spent counseling patients,” said Dr. Scott, who was not involved in the research. But there are “many variables” that can affect visit time, such as language differences, time spent with interpreters, and differences in patient educational levels.
Clarissa Yang, MD, dermatologist-in-chief at Tufts Medical Center, Boston, agreed. “We’re worried about there being a quality of care issue. However, there could also be differences culturally in how [the patients] interact with their physicians – their styles and the questions they ask,” she said in an interview. “The study is a good first step to noting that there may be a disparity,” and there is a need to break down the differences “into more granularity.”
Previous research, the authors wrote, has found that Asian patients were less likely to receive counseling from physicians, compared with White patients. And “paradoxically,” they noted, Asian individuals tend to present with more severe psoriasis than patients of other races and ethnicities.
Dr. Scott said the tendency to present with more severe psoriasis has been documented in patients with skin of color broadly – likely because of delays in recognition and treatment.
Race and ethnicity in the study were self-reported by patients, and missing data were imputed by NAMCS researchers using a sequential regression method. Patients who did not report race and ethnicity may have different characteristics affecting visit duration than those who did report the information, Dr. Armstrong and Dr. Wu said in describing their study’s limitations.
Other differences found
In addition to visit length, they found significant differences in mean age and in the use of complex topical regimens. The mean ages of Asian, Hispanic or Latino, and non-Hispanic Black patients were 37.2, 44.7, and 33.3 years, respectively. Complex topical regimens were prescribed to 11.8% of Asian patients, compared with 1.5% of Black and 1.1% of White patients.
For practicing dermatologists, knowing for now that Asian patients have shorter visits “may bring to light some consciousness to how we practice,” Dr. Yang noted. “We may counsel differently, we may spend differing amounts of time – for reasons still unknown. But being generally aware can help us to shift any unconscious bias that may be there.”
Dermatologists, Dr. Armstrong and Dr. Wu wrote, “need to allow sufficient time to develop strong physician-patient communication regardless of patient background.”
The NAMCS – administered by the Center for Disease Control and Prevention’s National Center for Health Statistics – collects data on a sample of visits provided by non–federally employed office-based physicians.
Dr. Armstrong disclosed receiving personal fees from AbbVie and Regeneron for research funding and serving as a scientific adviser and speaker for additional pharmaceutical and therapeutic companies. Dr. Wu, Dr. Scott, and Dr. Yang did not report any disclosures.
(NAMCS) from 2010 to 2016.
Yet the reasons for the difference are unclear and in need of further research, said the investigators and dermatologists who were asked to comment on the research.
The study covered over 4 million visits for psoriasis and found that the mean duration of visits for Asian patients was 9.2 minutes, compared with 15.7 minutes for Hispanic or Latino patients, 20.7 minutes for non-Hispanic Black patients, and 15.4 minutes for non-Hispanic White patients.
The mean duration of visits with Asian patients was 39.9% shorter, compared with visits with White patients (beta coefficient, –5,747; 95% confidence interval, –11.026 to –0.469; P = .03), and 40.6% shorter, compared with visits with non-Asian patients combined (beta coefficient, –5.908; 95% CI, –11.147 to –0.669, P = .03), April W. Armstrong, MD, MPH, professor of dermatology and director of the psoriasis program at the University of Southern California, Los Angeles, and Kevin K. Wu, MD, a dermatology resident at USC, said in a research letter published in JAMA Dermatology.
“The etiology of these differences is unclear,” they wrote. “It is possible that factors such as unconscious bias, cultural differences in communication, or residual confounding may be responsible for the observed findings.”
Their findings came from multivariable linear regression analyses that adjusted for age, sex, type of visit (new or follow-up), visit complexity based on the number of reasons for the visit, insurance status (such as private insurance or Medicaid), psoriasis severity on the basis of systemic psoriasis treatment or phototherapy, and complex topical regimens (three or more topical agents).
Commenting on the results, Deborah A. Scott, MD, codirector of the skin of color dermatology program at Brigham and Women’s Hospital and assistant professor at Harvard Medical School, both in Boston, said in an interview that visit length “is a reasonable parameter to look at among many others” when investigating potential disparities in care.
“They’re equating [shorter visit times] with lack of time spent counseling patients,” said Dr. Scott, who was not involved in the research. But there are “many variables” that can affect visit time, such as language differences, time spent with interpreters, and differences in patient educational levels.
Clarissa Yang, MD, dermatologist-in-chief at Tufts Medical Center, Boston, agreed. “We’re worried about there being a quality of care issue. However, there could also be differences culturally in how [the patients] interact with their physicians – their styles and the questions they ask,” she said in an interview. “The study is a good first step to noting that there may be a disparity,” and there is a need to break down the differences “into more granularity.”
Previous research, the authors wrote, has found that Asian patients were less likely to receive counseling from physicians, compared with White patients. And “paradoxically,” they noted, Asian individuals tend to present with more severe psoriasis than patients of other races and ethnicities.
Dr. Scott said the tendency to present with more severe psoriasis has been documented in patients with skin of color broadly – likely because of delays in recognition and treatment.
Race and ethnicity in the study were self-reported by patients, and missing data were imputed by NAMCS researchers using a sequential regression method. Patients who did not report race and ethnicity may have different characteristics affecting visit duration than those who did report the information, Dr. Armstrong and Dr. Wu said in describing their study’s limitations.
Other differences found
In addition to visit length, they found significant differences in mean age and in the use of complex topical regimens. The mean ages of Asian, Hispanic or Latino, and non-Hispanic Black patients were 37.2, 44.7, and 33.3 years, respectively. Complex topical regimens were prescribed to 11.8% of Asian patients, compared with 1.5% of Black and 1.1% of White patients.
For practicing dermatologists, knowing for now that Asian patients have shorter visits “may bring to light some consciousness to how we practice,” Dr. Yang noted. “We may counsel differently, we may spend differing amounts of time – for reasons still unknown. But being generally aware can help us to shift any unconscious bias that may be there.”
Dermatologists, Dr. Armstrong and Dr. Wu wrote, “need to allow sufficient time to develop strong physician-patient communication regardless of patient background.”
The NAMCS – administered by the Center for Disease Control and Prevention’s National Center for Health Statistics – collects data on a sample of visits provided by non–federally employed office-based physicians.
Dr. Armstrong disclosed receiving personal fees from AbbVie and Regeneron for research funding and serving as a scientific adviser and speaker for additional pharmaceutical and therapeutic companies. Dr. Wu, Dr. Scott, and Dr. Yang did not report any disclosures.
(NAMCS) from 2010 to 2016.
Yet the reasons for the difference are unclear and in need of further research, said the investigators and dermatologists who were asked to comment on the research.
The study covered over 4 million visits for psoriasis and found that the mean duration of visits for Asian patients was 9.2 minutes, compared with 15.7 minutes for Hispanic or Latino patients, 20.7 minutes for non-Hispanic Black patients, and 15.4 minutes for non-Hispanic White patients.
The mean duration of visits with Asian patients was 39.9% shorter, compared with visits with White patients (beta coefficient, –5,747; 95% confidence interval, –11.026 to –0.469; P = .03), and 40.6% shorter, compared with visits with non-Asian patients combined (beta coefficient, –5.908; 95% CI, –11.147 to –0.669, P = .03), April W. Armstrong, MD, MPH, professor of dermatology and director of the psoriasis program at the University of Southern California, Los Angeles, and Kevin K. Wu, MD, a dermatology resident at USC, said in a research letter published in JAMA Dermatology.
“The etiology of these differences is unclear,” they wrote. “It is possible that factors such as unconscious bias, cultural differences in communication, or residual confounding may be responsible for the observed findings.”
Their findings came from multivariable linear regression analyses that adjusted for age, sex, type of visit (new or follow-up), visit complexity based on the number of reasons for the visit, insurance status (such as private insurance or Medicaid), psoriasis severity on the basis of systemic psoriasis treatment or phototherapy, and complex topical regimens (three or more topical agents).
Commenting on the results, Deborah A. Scott, MD, codirector of the skin of color dermatology program at Brigham and Women’s Hospital and assistant professor at Harvard Medical School, both in Boston, said in an interview that visit length “is a reasonable parameter to look at among many others” when investigating potential disparities in care.
“They’re equating [shorter visit times] with lack of time spent counseling patients,” said Dr. Scott, who was not involved in the research. But there are “many variables” that can affect visit time, such as language differences, time spent with interpreters, and differences in patient educational levels.
Clarissa Yang, MD, dermatologist-in-chief at Tufts Medical Center, Boston, agreed. “We’re worried about there being a quality of care issue. However, there could also be differences culturally in how [the patients] interact with their physicians – their styles and the questions they ask,” she said in an interview. “The study is a good first step to noting that there may be a disparity,” and there is a need to break down the differences “into more granularity.”
Previous research, the authors wrote, has found that Asian patients were less likely to receive counseling from physicians, compared with White patients. And “paradoxically,” they noted, Asian individuals tend to present with more severe psoriasis than patients of other races and ethnicities.
Dr. Scott said the tendency to present with more severe psoriasis has been documented in patients with skin of color broadly – likely because of delays in recognition and treatment.
Race and ethnicity in the study were self-reported by patients, and missing data were imputed by NAMCS researchers using a sequential regression method. Patients who did not report race and ethnicity may have different characteristics affecting visit duration than those who did report the information, Dr. Armstrong and Dr. Wu said in describing their study’s limitations.
Other differences found
In addition to visit length, they found significant differences in mean age and in the use of complex topical regimens. The mean ages of Asian, Hispanic or Latino, and non-Hispanic Black patients were 37.2, 44.7, and 33.3 years, respectively. Complex topical regimens were prescribed to 11.8% of Asian patients, compared with 1.5% of Black and 1.1% of White patients.
For practicing dermatologists, knowing for now that Asian patients have shorter visits “may bring to light some consciousness to how we practice,” Dr. Yang noted. “We may counsel differently, we may spend differing amounts of time – for reasons still unknown. But being generally aware can help us to shift any unconscious bias that may be there.”
Dermatologists, Dr. Armstrong and Dr. Wu wrote, “need to allow sufficient time to develop strong physician-patient communication regardless of patient background.”
The NAMCS – administered by the Center for Disease Control and Prevention’s National Center for Health Statistics – collects data on a sample of visits provided by non–federally employed office-based physicians.
Dr. Armstrong disclosed receiving personal fees from AbbVie and Regeneron for research funding and serving as a scientific adviser and speaker for additional pharmaceutical and therapeutic companies. Dr. Wu, Dr. Scott, and Dr. Yang did not report any disclosures.
FROM JAMA DERMATOLOGY
Second opinions on melanocytic lesions swayed when first opinion is known
, diminishing the value and accuracy of an independent analysis.
In a novel effort to determine whether previous interpretations sway second opinions, 149 dermatopathologists were asked to read melanocytic skin biopsy specimens without access to the initial pathology report. A year or more later they read them again but now with access to the initial reading.
The study showed that the participants, independent of many variables, such as years of experience or frequency with which they offered second options, were more likely to upgrade or downgrade the severity of the specimens in accordance with the initial report even if their original reading was correct.
If the goal of a second dermatopathologist opinion is to obtain an independent diagnostic opinion, the message from this study is that they “should be blinded to first opinions,” according to the authors of this study, led by Joann G. Elmore, MD, professor of medicine, University of California, Los Angeles. The study was published online in JAMA Dermatology.
Two-phase study has 1-year washout
The study was conducted in two phases. In phase 1, a nationally representative sample of volunteer dermatopathologists performed 878 interpretations. In phase 2, conducted after a washout period of 12 months or more, the dermatopathologists read a random subset of the same cases evaluated in phase 1, but this time, unlike the first, they were first exposed to prior pathology reports.
Ultimately, “the dermatologists provided more than 5,000 interpretations of study cases, which was a big contribution of time,” Dr. Elmore said in an interview. Grateful for their critical contribution, she speculated that they were driven by the importance of the question being asked.
When categorized by the Melanocytic Pathology Assessment Tool (MPAT), which rates specimens from benign (class 1) to pT1b invasive melanoma (class 4), the influence of the prior report went in both directions, so that the likelihood of upgrading or downgrading went in accordance with the grading in the original dermatopathology report.
As a result, the risk of a less severe interpretation on the second relative to the first reading was 38% greater if the initial dermatopathology report had a lower grade (relative risk, 1.38; 95% confidence interval [CI], 1.19-1.59). The risk of upgrading the second report if the initial pathology report had a higher grade was increased by more than 50% (RR, 1.52; 95% CI, 1.34-1.73).
The greater likelihood of upgrading than downgrading is “understandable,” Dr. Elmore said. “I think this is consistent with the concern about missing something,” she explained.
According to Dr. Elmore, one of the greatest concerns regarding the bias imposed by the original pathology report is that the switch of opinions often went from one that was accurate to one that was inaccurate.
If the phase 1 diagnosis was accurate but upgraded in the phase 2 diagnosis, the risk of inaccuracy was almost doubled (RR, 1.96; 95% CI, 1.31-2.93). If the phase 1 report was inaccurate, the relative risk of changing the phase 2 diagnosis was still high but lower than if it was accurate (RR, 1.46; 95% CI, 1.27-1.68).
“That is, even when the phase 1 diagnoses agreed with the consensus reference diagnosis, they were swayed away from the correct diagnosis in phase 2 [when the initial pathology report characterized the specimen as higher grade],” Dr. Elmore reported.
Conversely, the risk of downgrading was about the same whether the phase 1 evaluation was accurate (RR, 1.37; 95% CI, 1.14-1.64) or inaccurate (RR 1.32; 95% CI, 1.07-1.64).
Downward and upward shifts in severity from an accurate diagnosis are concerning because of the likelihood they will lead to overtreatment or undertreatment. The problem, according to data from this study, is that dermatologists making a second opinion cannot judge their own susceptibility to being swayed by the original report.
Pathologists might be unaware of bias
At baseline, the participants were asked whether they thought they were influenced by the first interpretation when providing a second opinion. Although 69% acknowledged that they might be “somewhat influenced,” 31% maintained that they do not take initial reports into consideration. When the two groups were compared, the risk of downgrading was nearly identical. The risk of upgrading was lower in those claiming to disregard initial reports (RR, 1.29) relative to those who said they were “somewhat influenced” by a previous diagnosis (RR, 1.64), but the difference was not significant.
The actual risk of bias incurred by prior pathology reports might be greater than that captured in this study for several reasons, according to the investigators. They pointed out that all participants were experienced and board-certified and might therefore be expected to be more confident in their interpretations than an unselected group of dermatopathologists. In addition, participants might have been more careful in their interpretations knowing they were participating in a study.
“There are a lot of data to support the value of second opinions [in dermatopathology and other areas], but we need to consider the process of how they are being obtained,” Dr. Elmore said. “There needs to be a greater emphasis on providing an independent analysis.”
More than 60% of the dermatologists participating in this study reported that they agreed or strongly agreed with the premise that they prefer to have the original dermatopathology report when they offer a second opinion. Dr. Elmore said that the desire of those offering a second opinion to have as much information in front of them as possible is understandable, but the bias imposed by the original report weakens the value of the second opinion.
Blind reading of pathology reports needed
“These data suggest that seeing the original report sways opinions and that includes swaying opinions away from an accurate reading,” Dr. Elmore said. She thinks that for dermatopathologists to render a valuable and independent second opinion, the specimens should be examined “at least initially” without access to the first report.
The results of this study were not surprising to Vishal Anil Patel, MD, director of the Cutaneous Oncology Program, George Washington University Cancer Center, Washington. He made the point that physicians “are human first and foremost and not perfect machines.” As a result, he suggested bias and error are inevitable.
Although strategies to avoid bias are likely to offer some protection against inaccuracy, he said that diagnostic support tools such as artificial intelligence might be the right direction for improving inter- and intra-rater reliability.
Ruifeng Guo, MD, PhD, a consultant in the division of anatomic pathology at the Mayo Clinic, Rochester, Minn., agreed with the basic premise of the study, but he cautioned that restricting access to the initial pathology report might not always be the right approach.
It is true that “dermatopathologists providing a second opinion in diagnosing cutaneous melanoma are mostly unaware of the risk of bias if they read the initial pathology report,” said Dr. Guo, but restricting access comes with risks.
“There are also times critical information may be contained in the initial pathology report that needs to be considered when providing a second opinion consultation,” he noted. Ultimately, the decision to read or not read the initial report should be decided “on an individual basis.”
The study was funded by grants from the National Cancer Institute. Dr. Elmore, Dr. Patel, and Dr. Guo reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, diminishing the value and accuracy of an independent analysis.
In a novel effort to determine whether previous interpretations sway second opinions, 149 dermatopathologists were asked to read melanocytic skin biopsy specimens without access to the initial pathology report. A year or more later they read them again but now with access to the initial reading.
The study showed that the participants, independent of many variables, such as years of experience or frequency with which they offered second options, were more likely to upgrade or downgrade the severity of the specimens in accordance with the initial report even if their original reading was correct.
If the goal of a second dermatopathologist opinion is to obtain an independent diagnostic opinion, the message from this study is that they “should be blinded to first opinions,” according to the authors of this study, led by Joann G. Elmore, MD, professor of medicine, University of California, Los Angeles. The study was published online in JAMA Dermatology.
Two-phase study has 1-year washout
The study was conducted in two phases. In phase 1, a nationally representative sample of volunteer dermatopathologists performed 878 interpretations. In phase 2, conducted after a washout period of 12 months or more, the dermatopathologists read a random subset of the same cases evaluated in phase 1, but this time, unlike the first, they were first exposed to prior pathology reports.
Ultimately, “the dermatologists provided more than 5,000 interpretations of study cases, which was a big contribution of time,” Dr. Elmore said in an interview. Grateful for their critical contribution, she speculated that they were driven by the importance of the question being asked.
When categorized by the Melanocytic Pathology Assessment Tool (MPAT), which rates specimens from benign (class 1) to pT1b invasive melanoma (class 4), the influence of the prior report went in both directions, so that the likelihood of upgrading or downgrading went in accordance with the grading in the original dermatopathology report.
As a result, the risk of a less severe interpretation on the second relative to the first reading was 38% greater if the initial dermatopathology report had a lower grade (relative risk, 1.38; 95% confidence interval [CI], 1.19-1.59). The risk of upgrading the second report if the initial pathology report had a higher grade was increased by more than 50% (RR, 1.52; 95% CI, 1.34-1.73).
The greater likelihood of upgrading than downgrading is “understandable,” Dr. Elmore said. “I think this is consistent with the concern about missing something,” she explained.
According to Dr. Elmore, one of the greatest concerns regarding the bias imposed by the original pathology report is that the switch of opinions often went from one that was accurate to one that was inaccurate.
If the phase 1 diagnosis was accurate but upgraded in the phase 2 diagnosis, the risk of inaccuracy was almost doubled (RR, 1.96; 95% CI, 1.31-2.93). If the phase 1 report was inaccurate, the relative risk of changing the phase 2 diagnosis was still high but lower than if it was accurate (RR, 1.46; 95% CI, 1.27-1.68).
“That is, even when the phase 1 diagnoses agreed with the consensus reference diagnosis, they were swayed away from the correct diagnosis in phase 2 [when the initial pathology report characterized the specimen as higher grade],” Dr. Elmore reported.
Conversely, the risk of downgrading was about the same whether the phase 1 evaluation was accurate (RR, 1.37; 95% CI, 1.14-1.64) or inaccurate (RR 1.32; 95% CI, 1.07-1.64).
Downward and upward shifts in severity from an accurate diagnosis are concerning because of the likelihood they will lead to overtreatment or undertreatment. The problem, according to data from this study, is that dermatologists making a second opinion cannot judge their own susceptibility to being swayed by the original report.
Pathologists might be unaware of bias
At baseline, the participants were asked whether they thought they were influenced by the first interpretation when providing a second opinion. Although 69% acknowledged that they might be “somewhat influenced,” 31% maintained that they do not take initial reports into consideration. When the two groups were compared, the risk of downgrading was nearly identical. The risk of upgrading was lower in those claiming to disregard initial reports (RR, 1.29) relative to those who said they were “somewhat influenced” by a previous diagnosis (RR, 1.64), but the difference was not significant.
The actual risk of bias incurred by prior pathology reports might be greater than that captured in this study for several reasons, according to the investigators. They pointed out that all participants were experienced and board-certified and might therefore be expected to be more confident in their interpretations than an unselected group of dermatopathologists. In addition, participants might have been more careful in their interpretations knowing they were participating in a study.
“There are a lot of data to support the value of second opinions [in dermatopathology and other areas], but we need to consider the process of how they are being obtained,” Dr. Elmore said. “There needs to be a greater emphasis on providing an independent analysis.”
More than 60% of the dermatologists participating in this study reported that they agreed or strongly agreed with the premise that they prefer to have the original dermatopathology report when they offer a second opinion. Dr. Elmore said that the desire of those offering a second opinion to have as much information in front of them as possible is understandable, but the bias imposed by the original report weakens the value of the second opinion.
Blind reading of pathology reports needed
“These data suggest that seeing the original report sways opinions and that includes swaying opinions away from an accurate reading,” Dr. Elmore said. She thinks that for dermatopathologists to render a valuable and independent second opinion, the specimens should be examined “at least initially” without access to the first report.
The results of this study were not surprising to Vishal Anil Patel, MD, director of the Cutaneous Oncology Program, George Washington University Cancer Center, Washington. He made the point that physicians “are human first and foremost and not perfect machines.” As a result, he suggested bias and error are inevitable.
Although strategies to avoid bias are likely to offer some protection against inaccuracy, he said that diagnostic support tools such as artificial intelligence might be the right direction for improving inter- and intra-rater reliability.
Ruifeng Guo, MD, PhD, a consultant in the division of anatomic pathology at the Mayo Clinic, Rochester, Minn., agreed with the basic premise of the study, but he cautioned that restricting access to the initial pathology report might not always be the right approach.
It is true that “dermatopathologists providing a second opinion in diagnosing cutaneous melanoma are mostly unaware of the risk of bias if they read the initial pathology report,” said Dr. Guo, but restricting access comes with risks.
“There are also times critical information may be contained in the initial pathology report that needs to be considered when providing a second opinion consultation,” he noted. Ultimately, the decision to read or not read the initial report should be decided “on an individual basis.”
The study was funded by grants from the National Cancer Institute. Dr. Elmore, Dr. Patel, and Dr. Guo reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, diminishing the value and accuracy of an independent analysis.
In a novel effort to determine whether previous interpretations sway second opinions, 149 dermatopathologists were asked to read melanocytic skin biopsy specimens without access to the initial pathology report. A year or more later they read them again but now with access to the initial reading.
The study showed that the participants, independent of many variables, such as years of experience or frequency with which they offered second options, were more likely to upgrade or downgrade the severity of the specimens in accordance with the initial report even if their original reading was correct.
If the goal of a second dermatopathologist opinion is to obtain an independent diagnostic opinion, the message from this study is that they “should be blinded to first opinions,” according to the authors of this study, led by Joann G. Elmore, MD, professor of medicine, University of California, Los Angeles. The study was published online in JAMA Dermatology.
Two-phase study has 1-year washout
The study was conducted in two phases. In phase 1, a nationally representative sample of volunteer dermatopathologists performed 878 interpretations. In phase 2, conducted after a washout period of 12 months or more, the dermatopathologists read a random subset of the same cases evaluated in phase 1, but this time, unlike the first, they were first exposed to prior pathology reports.
Ultimately, “the dermatologists provided more than 5,000 interpretations of study cases, which was a big contribution of time,” Dr. Elmore said in an interview. Grateful for their critical contribution, she speculated that they were driven by the importance of the question being asked.
When categorized by the Melanocytic Pathology Assessment Tool (MPAT), which rates specimens from benign (class 1) to pT1b invasive melanoma (class 4), the influence of the prior report went in both directions, so that the likelihood of upgrading or downgrading went in accordance with the grading in the original dermatopathology report.
As a result, the risk of a less severe interpretation on the second relative to the first reading was 38% greater if the initial dermatopathology report had a lower grade (relative risk, 1.38; 95% confidence interval [CI], 1.19-1.59). The risk of upgrading the second report if the initial pathology report had a higher grade was increased by more than 50% (RR, 1.52; 95% CI, 1.34-1.73).
The greater likelihood of upgrading than downgrading is “understandable,” Dr. Elmore said. “I think this is consistent with the concern about missing something,” she explained.
According to Dr. Elmore, one of the greatest concerns regarding the bias imposed by the original pathology report is that the switch of opinions often went from one that was accurate to one that was inaccurate.
If the phase 1 diagnosis was accurate but upgraded in the phase 2 diagnosis, the risk of inaccuracy was almost doubled (RR, 1.96; 95% CI, 1.31-2.93). If the phase 1 report was inaccurate, the relative risk of changing the phase 2 diagnosis was still high but lower than if it was accurate (RR, 1.46; 95% CI, 1.27-1.68).
“That is, even when the phase 1 diagnoses agreed with the consensus reference diagnosis, they were swayed away from the correct diagnosis in phase 2 [when the initial pathology report characterized the specimen as higher grade],” Dr. Elmore reported.
Conversely, the risk of downgrading was about the same whether the phase 1 evaluation was accurate (RR, 1.37; 95% CI, 1.14-1.64) or inaccurate (RR 1.32; 95% CI, 1.07-1.64).
Downward and upward shifts in severity from an accurate diagnosis are concerning because of the likelihood they will lead to overtreatment or undertreatment. The problem, according to data from this study, is that dermatologists making a second opinion cannot judge their own susceptibility to being swayed by the original report.
Pathologists might be unaware of bias
At baseline, the participants were asked whether they thought they were influenced by the first interpretation when providing a second opinion. Although 69% acknowledged that they might be “somewhat influenced,” 31% maintained that they do not take initial reports into consideration. When the two groups were compared, the risk of downgrading was nearly identical. The risk of upgrading was lower in those claiming to disregard initial reports (RR, 1.29) relative to those who said they were “somewhat influenced” by a previous diagnosis (RR, 1.64), but the difference was not significant.
The actual risk of bias incurred by prior pathology reports might be greater than that captured in this study for several reasons, according to the investigators. They pointed out that all participants were experienced and board-certified and might therefore be expected to be more confident in their interpretations than an unselected group of dermatopathologists. In addition, participants might have been more careful in their interpretations knowing they were participating in a study.
“There are a lot of data to support the value of second opinions [in dermatopathology and other areas], but we need to consider the process of how they are being obtained,” Dr. Elmore said. “There needs to be a greater emphasis on providing an independent analysis.”
More than 60% of the dermatologists participating in this study reported that they agreed or strongly agreed with the premise that they prefer to have the original dermatopathology report when they offer a second opinion. Dr. Elmore said that the desire of those offering a second opinion to have as much information in front of them as possible is understandable, but the bias imposed by the original report weakens the value of the second opinion.
Blind reading of pathology reports needed
“These data suggest that seeing the original report sways opinions and that includes swaying opinions away from an accurate reading,” Dr. Elmore said. She thinks that for dermatopathologists to render a valuable and independent second opinion, the specimens should be examined “at least initially” without access to the first report.
The results of this study were not surprising to Vishal Anil Patel, MD, director of the Cutaneous Oncology Program, George Washington University Cancer Center, Washington. He made the point that physicians “are human first and foremost and not perfect machines.” As a result, he suggested bias and error are inevitable.
Although strategies to avoid bias are likely to offer some protection against inaccuracy, he said that diagnostic support tools such as artificial intelligence might be the right direction for improving inter- and intra-rater reliability.
Ruifeng Guo, MD, PhD, a consultant in the division of anatomic pathology at the Mayo Clinic, Rochester, Minn., agreed with the basic premise of the study, but he cautioned that restricting access to the initial pathology report might not always be the right approach.
It is true that “dermatopathologists providing a second opinion in diagnosing cutaneous melanoma are mostly unaware of the risk of bias if they read the initial pathology report,” said Dr. Guo, but restricting access comes with risks.
“There are also times critical information may be contained in the initial pathology report that needs to be considered when providing a second opinion consultation,” he noted. Ultimately, the decision to read or not read the initial report should be decided “on an individual basis.”
The study was funded by grants from the National Cancer Institute. Dr. Elmore, Dr. Patel, and Dr. Guo reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Are we up the creek without a paddle? What COVID, monkeypox, and nature are trying to tell us
Monkeypox. Polio. Covid. A quick glance at the news on any given day seems to indicate that outbreaks, epidemics, and perhaps even pandemics are increasing in frequency.
Granted, these types of events are hardly new; from the plagues of the 5th and 13th centuries to the Spanish flu in the 20th century and SARS-CoV-2 today, they’ve been with us from time immemorial.
What appears to be different, however, is not their frequency, but their intensity, with research reinforcing that we may be facing unique challenges and smaller windows to intervene as we move forward.
Findings from a modeling study, published in 2021 in Proceedings of the National Academy of Sciences, underscore that without effective intervention, the probability of extreme events like COVID-19 will likely increase threefold in the coming decades.
Amesh Adalja, MD, senior scholar, Johns Hopkins Center for Health Security, Baltimore, told this news organization.
“It’s all been based on some unusual cluster of cases that were causing severe disease and overwhelming local authorities. So often, like Indiana Jones, somebody got dispatched to deal with an outbreak,” Dr. Adalja said.
In a perfect post-COVID world, government bodies, scientists, clinicians, and others would cross silos to coordinate pandemic prevention, not just preparedness. The public would trust those who carry the title “public health” in their daily responsibilities, and in turn, public health experts would get back to their core responsibility – infectious disease preparedness – the role they were initially assigned following Europe’s Black Death during the 14th century. Instead, the world finds itself at a crossroads, with emerging and reemerging infectious disease outbreaks that on the surface appear to arise haphazardly but in reality are the result of decades of reaction and containment policies aimed at putting out fires, not addressing their cause.
Dr. Adalja noted that only when the threat of biological weapons became a reality in the mid-2000s was there a realization that economies of scale could be exploited by merging interests and efforts to develop health security medical countermeasures. For example, it encouraged governments to more closely integrate agencies like the Biomedical Advanced Research and Development Authority and infectious disease research organizations and individuals.
Still, while significant strides have been made in certain areas, the ongoing COVID-19 pandemic has revealed substantial weaknesses remaining in public and private health systems, as well as major gaps in infectious disease preparedness.
The role of spillover events
No matter whom you ask, scientists, public health and conservation experts, and infectious disease clinicians all point to one of the most important threats to human health. As Walt Kelly’s Pogo famously put it, “We have met the enemy, and he is us.”
“The reason why these outbreaks of novel infectious diseases are increasingly occurring is because of human-driven environmental change, particularly land use, unsafe practices when raising farmed animals, and commercial wildlife markets,” Neil M. Vora, MD, a physician specializing in pandemic prevention at Conservation International and a former Centers for Disease Control and Prevention epidemic intelligence officer, said in an interview.
In fact, more than 60% of emerging infections and diseases are due to these “spillover events” (zoonotic spillover) that occur when pathogens that commonly circulate in wildlife jump over to new, human hosts.
Several examples come to mind.
COVID-19 may have begun as an enzootic virus from two undetermined animals, using the Huanan Seafood Market as a possible intermediate reservoir, according to a July 26 preprint in the journal Science.
Likewise, while the Ebola virus was originally attributed to deforestation efforts to create palm oil (which allowed fruit bat carriers to transfer the virus to humans), recent research suggests that bats dwelling in the walls of human dwellings and hospitals are responsible for the 2018 outbreak in the Democratic Republic of Congo.
(Incidentally, just this week, a new Ebola case was confirmed in Eastern Congo, and it has been genetically linked to the previous outbreak, despite that outbreak having been declared over in early July.)
“When we clear forests, we create opportunities for humans to live alongside the forest edge and displace wildlife. There’s evidence that shows when [these] biodiverse areas are cleared, specialist species that evolved to live in the forests first start to disappear, whereas generalist species – rodents and bats – continue to survive and are able to carry pathogens that can be passed on to humans,” Dr. Vora explained.
So far, China’s outbreak of the novel Langya henipavirus is believed to have spread (either directly or indirectly) by rodents and shrews, according to reports from public health authorities like the European Centre for Disease Prevention and Control, which is currently monitoring the situation.
Yet, an overreliance on surveillance and containment only perpetuates what Dr. Vora says are cycles of panic and neglect.
“We saw it with Ebola in 2015, in 2016 to 2017 with Zika, you see it with tuberculosis, with sexually transmitted infections, and with COVID. You have policymakers working on solutions, and once they think that they’ve fixed the problem, they’re going to move on to the next crisis.”
It’s also a question of equity.
Reports detailing the reemergence of monkeypox in Nigeria in 2017 were largely ignored, despite the fact that the United States assisted in diagnosing an early case in an 11-year-old boy. At the time, it was clear that the virus was spreading by human-to-human transmission versus animal-to-human transmission, something that had not been seen previously.
“The current model [is] waiting for pathogens to spill over and then [continuing] to spread signals that rich countries are tolerant of these outbreaks so long as they don’t grow into epidemics or pandemics,” Dr. Vora said.
This model is clearly broken; roughly 5 years after Nigeria reported the resurgence of monkeypox, the United States has more than 14,000 confirmed cases, which represents more than a quarter of the total number of cases reported worldwide.
Public health on the brink
I’s difficult to imagine a future without outbreaks and more pandemics, and if experts are to be believed, we are ill-prepared.
“I think that we are in a situation where this is a major threat, and people have become complacent about it,” said Dr. Adalja, who noted that we should be asking ourselves if the “government is actually in a position to be able to respond in a way that we need them to or is [that response] tied up in bureaucracy and inefficiency?”
COVID-19 should have been seen as a wake-up call, and many of those deaths were preventable. “With monkeypox, they’re faltering; it should have been a layup, not a disaster,” he emphasized.
Ellen Eaton, MD, associate professor of infectious diseases at the University of Alabama at Birmingham, also pointed to the reality that by the time COVID-19 reached North America, the United States had already moved away from the model of the public health department as the epicenter of knowledge, education, awareness, and, ironically, public health.
“Thinking about my community, very few people knew the face and name of our local and state health officers,” she told this news organization.
“There was just this inherent mistrust of these people. If you add in a lot of talking heads, a lot of politicians and messaging from non-experts that countered what was coming out of our public health agencies early, you had this huge disconnect; in the South, it was the perfect storm for vaccine hesitancy.”
At last count, this perfect storm has led to 1.46 million COVID cases and just over 20,000 deaths – many of which were preventable – in Alabama alone.
“In certain parts of America, we were starting with a broken system with limited resources and few providers,” Dr. Eaton explained.
Dr. Eaton said that a lot of fields, not just medicine and public health, have finite resources that have been stretched to capacity by COVID, and now monkeypox, and wondered what was next as we’re headed into autumn and influenza season. But she also mentioned the tremendous implications of climate change on infectious diseases and community health and wellness.
“There’s a tremendous need to have the ability to survey not just humans but also how the disease burden in our environment that is fluctuating with climate change is going to impact communities in really important ways,” Dr. Eaton said.
Upstream prevention
Dr. Vora said he could not agree more and believes that upstream prevention holds the key.
“We have to make sure while there’s tension on this issue that the right solutions are implemented,” he said.
In coming years, postspillover containment strategies – vaccine research and development and strengthening health care surveillance, for example – are likely to become inadequate.
“We saw it with COVID and we are seeing it again with monkeypox,” Dr. Vora said. “We also have to invest further upstream to prevent spillovers in the first place, for example, by addressing deforestation, commercial wildlife markets and trade, [and] infection control when raising farm animals.”
“The thing is, when you invest in those upstream solutions, you are also mitigating climate change and loss of biodiversity. I’m not saying that we should not invest in postspillover containment efforts; we’re never going to contain every spillover. But we also have to invest in prevention,” he added.
In a piece published in Nature, Dr. Vora and his coauthors acknowledge that several international bodies such as the World Health Organization and G7 have invested in initiatives to facilitate coordinated, global responses to climate change, pandemic preparedness, and response. But they point out that these efforts fail to “explicitly address the negative feedback cycle between environmental degradation, wildlife exploitation, and the emergence of pathogens.”
“Environmental conservation is no longer a left-wing fringe issue, it’s moving into public consciousness, and ... it is public health,” Dr. Vora said. “When we destroy nature, we’re destroying our own ability to survive.”
Dr. Adalja, Dr. Vora, and Dr. Eaton report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Monkeypox. Polio. Covid. A quick glance at the news on any given day seems to indicate that outbreaks, epidemics, and perhaps even pandemics are increasing in frequency.
Granted, these types of events are hardly new; from the plagues of the 5th and 13th centuries to the Spanish flu in the 20th century and SARS-CoV-2 today, they’ve been with us from time immemorial.
What appears to be different, however, is not their frequency, but their intensity, with research reinforcing that we may be facing unique challenges and smaller windows to intervene as we move forward.
Findings from a modeling study, published in 2021 in Proceedings of the National Academy of Sciences, underscore that without effective intervention, the probability of extreme events like COVID-19 will likely increase threefold in the coming decades.
Amesh Adalja, MD, senior scholar, Johns Hopkins Center for Health Security, Baltimore, told this news organization.
“It’s all been based on some unusual cluster of cases that were causing severe disease and overwhelming local authorities. So often, like Indiana Jones, somebody got dispatched to deal with an outbreak,” Dr. Adalja said.
In a perfect post-COVID world, government bodies, scientists, clinicians, and others would cross silos to coordinate pandemic prevention, not just preparedness. The public would trust those who carry the title “public health” in their daily responsibilities, and in turn, public health experts would get back to their core responsibility – infectious disease preparedness – the role they were initially assigned following Europe’s Black Death during the 14th century. Instead, the world finds itself at a crossroads, with emerging and reemerging infectious disease outbreaks that on the surface appear to arise haphazardly but in reality are the result of decades of reaction and containment policies aimed at putting out fires, not addressing their cause.
Dr. Adalja noted that only when the threat of biological weapons became a reality in the mid-2000s was there a realization that economies of scale could be exploited by merging interests and efforts to develop health security medical countermeasures. For example, it encouraged governments to more closely integrate agencies like the Biomedical Advanced Research and Development Authority and infectious disease research organizations and individuals.
Still, while significant strides have been made in certain areas, the ongoing COVID-19 pandemic has revealed substantial weaknesses remaining in public and private health systems, as well as major gaps in infectious disease preparedness.
The role of spillover events
No matter whom you ask, scientists, public health and conservation experts, and infectious disease clinicians all point to one of the most important threats to human health. As Walt Kelly’s Pogo famously put it, “We have met the enemy, and he is us.”
“The reason why these outbreaks of novel infectious diseases are increasingly occurring is because of human-driven environmental change, particularly land use, unsafe practices when raising farmed animals, and commercial wildlife markets,” Neil M. Vora, MD, a physician specializing in pandemic prevention at Conservation International and a former Centers for Disease Control and Prevention epidemic intelligence officer, said in an interview.
In fact, more than 60% of emerging infections and diseases are due to these “spillover events” (zoonotic spillover) that occur when pathogens that commonly circulate in wildlife jump over to new, human hosts.
Several examples come to mind.
COVID-19 may have begun as an enzootic virus from two undetermined animals, using the Huanan Seafood Market as a possible intermediate reservoir, according to a July 26 preprint in the journal Science.
Likewise, while the Ebola virus was originally attributed to deforestation efforts to create palm oil (which allowed fruit bat carriers to transfer the virus to humans), recent research suggests that bats dwelling in the walls of human dwellings and hospitals are responsible for the 2018 outbreak in the Democratic Republic of Congo.
(Incidentally, just this week, a new Ebola case was confirmed in Eastern Congo, and it has been genetically linked to the previous outbreak, despite that outbreak having been declared over in early July.)
“When we clear forests, we create opportunities for humans to live alongside the forest edge and displace wildlife. There’s evidence that shows when [these] biodiverse areas are cleared, specialist species that evolved to live in the forests first start to disappear, whereas generalist species – rodents and bats – continue to survive and are able to carry pathogens that can be passed on to humans,” Dr. Vora explained.
So far, China’s outbreak of the novel Langya henipavirus is believed to have spread (either directly or indirectly) by rodents and shrews, according to reports from public health authorities like the European Centre for Disease Prevention and Control, which is currently monitoring the situation.
Yet, an overreliance on surveillance and containment only perpetuates what Dr. Vora says are cycles of panic and neglect.
“We saw it with Ebola in 2015, in 2016 to 2017 with Zika, you see it with tuberculosis, with sexually transmitted infections, and with COVID. You have policymakers working on solutions, and once they think that they’ve fixed the problem, they’re going to move on to the next crisis.”
It’s also a question of equity.
Reports detailing the reemergence of monkeypox in Nigeria in 2017 were largely ignored, despite the fact that the United States assisted in diagnosing an early case in an 11-year-old boy. At the time, it was clear that the virus was spreading by human-to-human transmission versus animal-to-human transmission, something that had not been seen previously.
“The current model [is] waiting for pathogens to spill over and then [continuing] to spread signals that rich countries are tolerant of these outbreaks so long as they don’t grow into epidemics or pandemics,” Dr. Vora said.
This model is clearly broken; roughly 5 years after Nigeria reported the resurgence of monkeypox, the United States has more than 14,000 confirmed cases, which represents more than a quarter of the total number of cases reported worldwide.
Public health on the brink
I’s difficult to imagine a future without outbreaks and more pandemics, and if experts are to be believed, we are ill-prepared.
“I think that we are in a situation where this is a major threat, and people have become complacent about it,” said Dr. Adalja, who noted that we should be asking ourselves if the “government is actually in a position to be able to respond in a way that we need them to or is [that response] tied up in bureaucracy and inefficiency?”
COVID-19 should have been seen as a wake-up call, and many of those deaths were preventable. “With monkeypox, they’re faltering; it should have been a layup, not a disaster,” he emphasized.
Ellen Eaton, MD, associate professor of infectious diseases at the University of Alabama at Birmingham, also pointed to the reality that by the time COVID-19 reached North America, the United States had already moved away from the model of the public health department as the epicenter of knowledge, education, awareness, and, ironically, public health.
“Thinking about my community, very few people knew the face and name of our local and state health officers,” she told this news organization.
“There was just this inherent mistrust of these people. If you add in a lot of talking heads, a lot of politicians and messaging from non-experts that countered what was coming out of our public health agencies early, you had this huge disconnect; in the South, it was the perfect storm for vaccine hesitancy.”
At last count, this perfect storm has led to 1.46 million COVID cases and just over 20,000 deaths – many of which were preventable – in Alabama alone.
“In certain parts of America, we were starting with a broken system with limited resources and few providers,” Dr. Eaton explained.
Dr. Eaton said that a lot of fields, not just medicine and public health, have finite resources that have been stretched to capacity by COVID, and now monkeypox, and wondered what was next as we’re headed into autumn and influenza season. But she also mentioned the tremendous implications of climate change on infectious diseases and community health and wellness.
“There’s a tremendous need to have the ability to survey not just humans but also how the disease burden in our environment that is fluctuating with climate change is going to impact communities in really important ways,” Dr. Eaton said.
Upstream prevention
Dr. Vora said he could not agree more and believes that upstream prevention holds the key.
“We have to make sure while there’s tension on this issue that the right solutions are implemented,” he said.
In coming years, postspillover containment strategies – vaccine research and development and strengthening health care surveillance, for example – are likely to become inadequate.
“We saw it with COVID and we are seeing it again with monkeypox,” Dr. Vora said. “We also have to invest further upstream to prevent spillovers in the first place, for example, by addressing deforestation, commercial wildlife markets and trade, [and] infection control when raising farm animals.”
“The thing is, when you invest in those upstream solutions, you are also mitigating climate change and loss of biodiversity. I’m not saying that we should not invest in postspillover containment efforts; we’re never going to contain every spillover. But we also have to invest in prevention,” he added.
In a piece published in Nature, Dr. Vora and his coauthors acknowledge that several international bodies such as the World Health Organization and G7 have invested in initiatives to facilitate coordinated, global responses to climate change, pandemic preparedness, and response. But they point out that these efforts fail to “explicitly address the negative feedback cycle between environmental degradation, wildlife exploitation, and the emergence of pathogens.”
“Environmental conservation is no longer a left-wing fringe issue, it’s moving into public consciousness, and ... it is public health,” Dr. Vora said. “When we destroy nature, we’re destroying our own ability to survive.”
Dr. Adalja, Dr. Vora, and Dr. Eaton report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Monkeypox. Polio. Covid. A quick glance at the news on any given day seems to indicate that outbreaks, epidemics, and perhaps even pandemics are increasing in frequency.
Granted, these types of events are hardly new; from the plagues of the 5th and 13th centuries to the Spanish flu in the 20th century and SARS-CoV-2 today, they’ve been with us from time immemorial.
What appears to be different, however, is not their frequency, but their intensity, with research reinforcing that we may be facing unique challenges and smaller windows to intervene as we move forward.
Findings from a modeling study, published in 2021 in Proceedings of the National Academy of Sciences, underscore that without effective intervention, the probability of extreme events like COVID-19 will likely increase threefold in the coming decades.
Amesh Adalja, MD, senior scholar, Johns Hopkins Center for Health Security, Baltimore, told this news organization.
“It’s all been based on some unusual cluster of cases that were causing severe disease and overwhelming local authorities. So often, like Indiana Jones, somebody got dispatched to deal with an outbreak,” Dr. Adalja said.
In a perfect post-COVID world, government bodies, scientists, clinicians, and others would cross silos to coordinate pandemic prevention, not just preparedness. The public would trust those who carry the title “public health” in their daily responsibilities, and in turn, public health experts would get back to their core responsibility – infectious disease preparedness – the role they were initially assigned following Europe’s Black Death during the 14th century. Instead, the world finds itself at a crossroads, with emerging and reemerging infectious disease outbreaks that on the surface appear to arise haphazardly but in reality are the result of decades of reaction and containment policies aimed at putting out fires, not addressing their cause.
Dr. Adalja noted that only when the threat of biological weapons became a reality in the mid-2000s was there a realization that economies of scale could be exploited by merging interests and efforts to develop health security medical countermeasures. For example, it encouraged governments to more closely integrate agencies like the Biomedical Advanced Research and Development Authority and infectious disease research organizations and individuals.
Still, while significant strides have been made in certain areas, the ongoing COVID-19 pandemic has revealed substantial weaknesses remaining in public and private health systems, as well as major gaps in infectious disease preparedness.
The role of spillover events
No matter whom you ask, scientists, public health and conservation experts, and infectious disease clinicians all point to one of the most important threats to human health. As Walt Kelly’s Pogo famously put it, “We have met the enemy, and he is us.”
“The reason why these outbreaks of novel infectious diseases are increasingly occurring is because of human-driven environmental change, particularly land use, unsafe practices when raising farmed animals, and commercial wildlife markets,” Neil M. Vora, MD, a physician specializing in pandemic prevention at Conservation International and a former Centers for Disease Control and Prevention epidemic intelligence officer, said in an interview.
In fact, more than 60% of emerging infections and diseases are due to these “spillover events” (zoonotic spillover) that occur when pathogens that commonly circulate in wildlife jump over to new, human hosts.
Several examples come to mind.
COVID-19 may have begun as an enzootic virus from two undetermined animals, using the Huanan Seafood Market as a possible intermediate reservoir, according to a July 26 preprint in the journal Science.
Likewise, while the Ebola virus was originally attributed to deforestation efforts to create palm oil (which allowed fruit bat carriers to transfer the virus to humans), recent research suggests that bats dwelling in the walls of human dwellings and hospitals are responsible for the 2018 outbreak in the Democratic Republic of Congo.
(Incidentally, just this week, a new Ebola case was confirmed in Eastern Congo, and it has been genetically linked to the previous outbreak, despite that outbreak having been declared over in early July.)
“When we clear forests, we create opportunities for humans to live alongside the forest edge and displace wildlife. There’s evidence that shows when [these] biodiverse areas are cleared, specialist species that evolved to live in the forests first start to disappear, whereas generalist species – rodents and bats – continue to survive and are able to carry pathogens that can be passed on to humans,” Dr. Vora explained.
So far, China’s outbreak of the novel Langya henipavirus is believed to have spread (either directly or indirectly) by rodents and shrews, according to reports from public health authorities like the European Centre for Disease Prevention and Control, which is currently monitoring the situation.
Yet, an overreliance on surveillance and containment only perpetuates what Dr. Vora says are cycles of panic and neglect.
“We saw it with Ebola in 2015, in 2016 to 2017 with Zika, you see it with tuberculosis, with sexually transmitted infections, and with COVID. You have policymakers working on solutions, and once they think that they’ve fixed the problem, they’re going to move on to the next crisis.”
It’s also a question of equity.
Reports detailing the reemergence of monkeypox in Nigeria in 2017 were largely ignored, despite the fact that the United States assisted in diagnosing an early case in an 11-year-old boy. At the time, it was clear that the virus was spreading by human-to-human transmission versus animal-to-human transmission, something that had not been seen previously.
“The current model [is] waiting for pathogens to spill over and then [continuing] to spread signals that rich countries are tolerant of these outbreaks so long as they don’t grow into epidemics or pandemics,” Dr. Vora said.
This model is clearly broken; roughly 5 years after Nigeria reported the resurgence of monkeypox, the United States has more than 14,000 confirmed cases, which represents more than a quarter of the total number of cases reported worldwide.
Public health on the brink
I’s difficult to imagine a future without outbreaks and more pandemics, and if experts are to be believed, we are ill-prepared.
“I think that we are in a situation where this is a major threat, and people have become complacent about it,” said Dr. Adalja, who noted that we should be asking ourselves if the “government is actually in a position to be able to respond in a way that we need them to or is [that response] tied up in bureaucracy and inefficiency?”
COVID-19 should have been seen as a wake-up call, and many of those deaths were preventable. “With monkeypox, they’re faltering; it should have been a layup, not a disaster,” he emphasized.
Ellen Eaton, MD, associate professor of infectious diseases at the University of Alabama at Birmingham, also pointed to the reality that by the time COVID-19 reached North America, the United States had already moved away from the model of the public health department as the epicenter of knowledge, education, awareness, and, ironically, public health.
“Thinking about my community, very few people knew the face and name of our local and state health officers,” she told this news organization.
“There was just this inherent mistrust of these people. If you add in a lot of talking heads, a lot of politicians and messaging from non-experts that countered what was coming out of our public health agencies early, you had this huge disconnect; in the South, it was the perfect storm for vaccine hesitancy.”
At last count, this perfect storm has led to 1.46 million COVID cases and just over 20,000 deaths – many of which were preventable – in Alabama alone.
“In certain parts of America, we were starting with a broken system with limited resources and few providers,” Dr. Eaton explained.
Dr. Eaton said that a lot of fields, not just medicine and public health, have finite resources that have been stretched to capacity by COVID, and now monkeypox, and wondered what was next as we’re headed into autumn and influenza season. But she also mentioned the tremendous implications of climate change on infectious diseases and community health and wellness.
“There’s a tremendous need to have the ability to survey not just humans but also how the disease burden in our environment that is fluctuating with climate change is going to impact communities in really important ways,” Dr. Eaton said.
Upstream prevention
Dr. Vora said he could not agree more and believes that upstream prevention holds the key.
“We have to make sure while there’s tension on this issue that the right solutions are implemented,” he said.
In coming years, postspillover containment strategies – vaccine research and development and strengthening health care surveillance, for example – are likely to become inadequate.
“We saw it with COVID and we are seeing it again with monkeypox,” Dr. Vora said. “We also have to invest further upstream to prevent spillovers in the first place, for example, by addressing deforestation, commercial wildlife markets and trade, [and] infection control when raising farm animals.”
“The thing is, when you invest in those upstream solutions, you are also mitigating climate change and loss of biodiversity. I’m not saying that we should not invest in postspillover containment efforts; we’re never going to contain every spillover. But we also have to invest in prevention,” he added.
In a piece published in Nature, Dr. Vora and his coauthors acknowledge that several international bodies such as the World Health Organization and G7 have invested in initiatives to facilitate coordinated, global responses to climate change, pandemic preparedness, and response. But they point out that these efforts fail to “explicitly address the negative feedback cycle between environmental degradation, wildlife exploitation, and the emergence of pathogens.”
“Environmental conservation is no longer a left-wing fringe issue, it’s moving into public consciousness, and ... it is public health,” Dr. Vora said. “When we destroy nature, we’re destroying our own ability to survive.”
Dr. Adalja, Dr. Vora, and Dr. Eaton report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Pink Nodule Behind the Ear
The Diagnosis: Acanthoma Fissuratum
Acanthoma fissuratum is a skin lesion that results from consistent pressure, typically from ill-fitting eyeglass frames.1 The chronic irritation leads to collagen deposition and inflammation that gradually creates the lesion. Many patients never seek care, making incidence figures undeterminable.2 It usually presents as a firm, tender, flesh-colored or pink nodule or plaque with a central indentation from where the frame rests. This indentation splits the lesion in half and classically gives the appearance of a coffee bean.1 The repeated minor trauma at this point of contact also may lead to centralized ulceration, which further blurs the diagnosis to include basal cell carcinoma (BCC).3,4 Although the postauricular groove is the most cited location, lesions also may occur at other contact points of the glasses, such as the lateral aspect of the bridge of the nose and the superior auricular sulcus.5 Acanthoma fissuratum is not limited to the external head. Other etiologies of local trauma and pressure have led to its diagnosis in the upper labioalveolar fold, posterior fourchette of the vulva, penis, and external auditory canal.6-9
The diagnosis of acanthoma fissuratum mainly is clinical; however, due to its similar appearance to BCC and other lesions, a biopsy can be taken to support the diagnosis; a biopsy was not performed in our patient. The main features seen on histopathology include acanthosis, hyperkeratosis, variable parakeratosis, and perivascular nonspecific inflammatory infiltration. The epidermis may reflect the macroscopic frame indentation with central attenuation of the epidermis, which potentially is filled with inflammatory cells or keratin.5
Treatment normally encompasses removing the illfitting frames or fixing the fit, which gradually leads to reduction of the lesion.4,5 This occurred in our patient, who changed eyeglasses and saw an 80% resolution of the lesion in 8 months. Such improvement after removal of a trauma-inducing stimulus would not be seen in malignancies (eg, BCC, squamous cell carcinoma [SCC]), keloids, or cylindromas. If the granulation tissue does not regress or recurs, other potential treatments include excision, intralesional corticosteroids, and electrosurgery.5
Basal cell carcinoma is a common nonmelanoma skin cancer that most often presents on the sun-exposed areas of the head and neck, especially the cheeks, nasolabial folds, and forehead. Although the nodular subtype may clinically appear similar to acanthoma fissuratum, it more typically presents as a pearly papule or nodule with a sharp border, small telangiectases, and potential ulceration.10 Squamous cell carcinoma is another common nonmelanoma skin cancer that often arises in sun-exposed areas, which can include the postauricular area. Although the lesion can be associated with chronic wounds and also can grow vertically, SCC typically has a scalier and more hyperkeratotic surface that can ulcerate.1 A cylindroma is a benign sweat gland tumor that most commonly presents on the head and neck (also known as the turban tumor), though it can develop on the ear. It appears as solitary or multiple nodules that often are flesh colored, red, or blue with a shiny surface.1 Cylindromas are not known to be associated with chronic local trauma or irritation,11 such as wearing ill-fitting eyeglasses. Unlike acanthoma fissuratum, the treatment of cylindromas, BCC, and SCC most often involves excision.1 A keloid presents as a flesh-colored, red, or purple exophytic plaque that is composed of dense dermal tissue and progressively forms after local trauma. Although keloids can spontaneously develop, they commonly form on the ears in susceptible individuals after skin excisions including prior keloid removal, piercings, repairment of auricular traumas, or infections.1 The patient’s coffee bean–like lesion that coincided with wearing new eyeglasses better fits the diagnosis of acanthoma fissuratum than a keloid. Additionally, keloids typically do not regress without treatment. Keloid treatment consists of intralesional steroid injections, occlusive silicone dressings, compression, cryotherapy, radiation, and excisional surgery.1
- Sand M, Sand D, Brors D, et al. Cutaneous lesions of the external ear. Head Face Med. 2008;4. doi:10.1186/1746-160X-4-2
- Orengo I, Robbins K, Marsch A. Pathology of the ear. Semin Plast Surg. 2011;25:279-287. doi:10.1055/s-0031-1288920
- Ramroop S. Successful treatment of acanthoma fissuratum with intralesional triamcinolone acetonide. Clin Case Rep. 2020;8:702-703. doi:10.1002/ccr3.2708
- Delaney TJ, Stewart TW. Granuloma fissuratum. Br J Dermatol. 1971;84:373-375. doi:10.1111/j.1365-2133.1971.tb14235.x
- Deshpande NS, Sen A, Vasudevan B, et al. Acanthoma fissuratum: lest we forget. Indian Dermatol Online J. 2017;8:141-143. doi:10.4103/2229- 5178.202267
- Surron RL Jr. A fissured granulomatous lesion of the upper labioalveolar fold. Arch Dermatol Syph. 1932;26:425. doi:10.1001 /archderm.1932.01450030423004
- Kennedy CM, Dewdney S, Galask RP. Vulvar granuloma fissuratum: a description of fissuring of the posterior fourchette and the repair. Obstet Gynecol. 2005;105:1018-1023. doi:10.1097/01. AOG.0000158863.70819.53
- Lee JL, Lee YB, Cho BK, et al. Acanthoma fissuratum on the penis. Int J Dermatol. 2013;52:382-384. doi:10.1111/j.1365-4632.2011.04903.x
- Gonzalez SA, Moore AGN. Acanthoma fissuratum of the outer auditory canal from a hearing aid. J Cutan Pathol. 1989;16:304.
- Fania L, Didona D, Morese R, et al. Basal cell carcinoma: from pathophysiology to novel therapeutic approaches. Biomedicines. 2020;8:449. doi:10.3390/biomedicines8110449
- Chauhan DS, Guruprasad Y. Dermal cylindroma of the scalp. Natl J Maxillofac Surg. 2012;3:59-61. doi:10.4103/0975-5950.102163
The Diagnosis: Acanthoma Fissuratum
Acanthoma fissuratum is a skin lesion that results from consistent pressure, typically from ill-fitting eyeglass frames.1 The chronic irritation leads to collagen deposition and inflammation that gradually creates the lesion. Many patients never seek care, making incidence figures undeterminable.2 It usually presents as a firm, tender, flesh-colored or pink nodule or plaque with a central indentation from where the frame rests. This indentation splits the lesion in half and classically gives the appearance of a coffee bean.1 The repeated minor trauma at this point of contact also may lead to centralized ulceration, which further blurs the diagnosis to include basal cell carcinoma (BCC).3,4 Although the postauricular groove is the most cited location, lesions also may occur at other contact points of the glasses, such as the lateral aspect of the bridge of the nose and the superior auricular sulcus.5 Acanthoma fissuratum is not limited to the external head. Other etiologies of local trauma and pressure have led to its diagnosis in the upper labioalveolar fold, posterior fourchette of the vulva, penis, and external auditory canal.6-9
The diagnosis of acanthoma fissuratum mainly is clinical; however, due to its similar appearance to BCC and other lesions, a biopsy can be taken to support the diagnosis; a biopsy was not performed in our patient. The main features seen on histopathology include acanthosis, hyperkeratosis, variable parakeratosis, and perivascular nonspecific inflammatory infiltration. The epidermis may reflect the macroscopic frame indentation with central attenuation of the epidermis, which potentially is filled with inflammatory cells or keratin.5
Treatment normally encompasses removing the illfitting frames or fixing the fit, which gradually leads to reduction of the lesion.4,5 This occurred in our patient, who changed eyeglasses and saw an 80% resolution of the lesion in 8 months. Such improvement after removal of a trauma-inducing stimulus would not be seen in malignancies (eg, BCC, squamous cell carcinoma [SCC]), keloids, or cylindromas. If the granulation tissue does not regress or recurs, other potential treatments include excision, intralesional corticosteroids, and electrosurgery.5
Basal cell carcinoma is a common nonmelanoma skin cancer that most often presents on the sun-exposed areas of the head and neck, especially the cheeks, nasolabial folds, and forehead. Although the nodular subtype may clinically appear similar to acanthoma fissuratum, it more typically presents as a pearly papule or nodule with a sharp border, small telangiectases, and potential ulceration.10 Squamous cell carcinoma is another common nonmelanoma skin cancer that often arises in sun-exposed areas, which can include the postauricular area. Although the lesion can be associated with chronic wounds and also can grow vertically, SCC typically has a scalier and more hyperkeratotic surface that can ulcerate.1 A cylindroma is a benign sweat gland tumor that most commonly presents on the head and neck (also known as the turban tumor), though it can develop on the ear. It appears as solitary or multiple nodules that often are flesh colored, red, or blue with a shiny surface.1 Cylindromas are not known to be associated with chronic local trauma or irritation,11 such as wearing ill-fitting eyeglasses. Unlike acanthoma fissuratum, the treatment of cylindromas, BCC, and SCC most often involves excision.1 A keloid presents as a flesh-colored, red, or purple exophytic plaque that is composed of dense dermal tissue and progressively forms after local trauma. Although keloids can spontaneously develop, they commonly form on the ears in susceptible individuals after skin excisions including prior keloid removal, piercings, repairment of auricular traumas, or infections.1 The patient’s coffee bean–like lesion that coincided with wearing new eyeglasses better fits the diagnosis of acanthoma fissuratum than a keloid. Additionally, keloids typically do not regress without treatment. Keloid treatment consists of intralesional steroid injections, occlusive silicone dressings, compression, cryotherapy, radiation, and excisional surgery.1
The Diagnosis: Acanthoma Fissuratum
Acanthoma fissuratum is a skin lesion that results from consistent pressure, typically from ill-fitting eyeglass frames.1 The chronic irritation leads to collagen deposition and inflammation that gradually creates the lesion. Many patients never seek care, making incidence figures undeterminable.2 It usually presents as a firm, tender, flesh-colored or pink nodule or plaque with a central indentation from where the frame rests. This indentation splits the lesion in half and classically gives the appearance of a coffee bean.1 The repeated minor trauma at this point of contact also may lead to centralized ulceration, which further blurs the diagnosis to include basal cell carcinoma (BCC).3,4 Although the postauricular groove is the most cited location, lesions also may occur at other contact points of the glasses, such as the lateral aspect of the bridge of the nose and the superior auricular sulcus.5 Acanthoma fissuratum is not limited to the external head. Other etiologies of local trauma and pressure have led to its diagnosis in the upper labioalveolar fold, posterior fourchette of the vulva, penis, and external auditory canal.6-9
The diagnosis of acanthoma fissuratum mainly is clinical; however, due to its similar appearance to BCC and other lesions, a biopsy can be taken to support the diagnosis; a biopsy was not performed in our patient. The main features seen on histopathology include acanthosis, hyperkeratosis, variable parakeratosis, and perivascular nonspecific inflammatory infiltration. The epidermis may reflect the macroscopic frame indentation with central attenuation of the epidermis, which potentially is filled with inflammatory cells or keratin.5
Treatment normally encompasses removing the illfitting frames or fixing the fit, which gradually leads to reduction of the lesion.4,5 This occurred in our patient, who changed eyeglasses and saw an 80% resolution of the lesion in 8 months. Such improvement after removal of a trauma-inducing stimulus would not be seen in malignancies (eg, BCC, squamous cell carcinoma [SCC]), keloids, or cylindromas. If the granulation tissue does not regress or recurs, other potential treatments include excision, intralesional corticosteroids, and electrosurgery.5
Basal cell carcinoma is a common nonmelanoma skin cancer that most often presents on the sun-exposed areas of the head and neck, especially the cheeks, nasolabial folds, and forehead. Although the nodular subtype may clinically appear similar to acanthoma fissuratum, it more typically presents as a pearly papule or nodule with a sharp border, small telangiectases, and potential ulceration.10 Squamous cell carcinoma is another common nonmelanoma skin cancer that often arises in sun-exposed areas, which can include the postauricular area. Although the lesion can be associated with chronic wounds and also can grow vertically, SCC typically has a scalier and more hyperkeratotic surface that can ulcerate.1 A cylindroma is a benign sweat gland tumor that most commonly presents on the head and neck (also known as the turban tumor), though it can develop on the ear. It appears as solitary or multiple nodules that often are flesh colored, red, or blue with a shiny surface.1 Cylindromas are not known to be associated with chronic local trauma or irritation,11 such as wearing ill-fitting eyeglasses. Unlike acanthoma fissuratum, the treatment of cylindromas, BCC, and SCC most often involves excision.1 A keloid presents as a flesh-colored, red, or purple exophytic plaque that is composed of dense dermal tissue and progressively forms after local trauma. Although keloids can spontaneously develop, they commonly form on the ears in susceptible individuals after skin excisions including prior keloid removal, piercings, repairment of auricular traumas, or infections.1 The patient’s coffee bean–like lesion that coincided with wearing new eyeglasses better fits the diagnosis of acanthoma fissuratum than a keloid. Additionally, keloids typically do not regress without treatment. Keloid treatment consists of intralesional steroid injections, occlusive silicone dressings, compression, cryotherapy, radiation, and excisional surgery.1
- Sand M, Sand D, Brors D, et al. Cutaneous lesions of the external ear. Head Face Med. 2008;4. doi:10.1186/1746-160X-4-2
- Orengo I, Robbins K, Marsch A. Pathology of the ear. Semin Plast Surg. 2011;25:279-287. doi:10.1055/s-0031-1288920
- Ramroop S. Successful treatment of acanthoma fissuratum with intralesional triamcinolone acetonide. Clin Case Rep. 2020;8:702-703. doi:10.1002/ccr3.2708
- Delaney TJ, Stewart TW. Granuloma fissuratum. Br J Dermatol. 1971;84:373-375. doi:10.1111/j.1365-2133.1971.tb14235.x
- Deshpande NS, Sen A, Vasudevan B, et al. Acanthoma fissuratum: lest we forget. Indian Dermatol Online J. 2017;8:141-143. doi:10.4103/2229- 5178.202267
- Surron RL Jr. A fissured granulomatous lesion of the upper labioalveolar fold. Arch Dermatol Syph. 1932;26:425. doi:10.1001 /archderm.1932.01450030423004
- Kennedy CM, Dewdney S, Galask RP. Vulvar granuloma fissuratum: a description of fissuring of the posterior fourchette and the repair. Obstet Gynecol. 2005;105:1018-1023. doi:10.1097/01. AOG.0000158863.70819.53
- Lee JL, Lee YB, Cho BK, et al. Acanthoma fissuratum on the penis. Int J Dermatol. 2013;52:382-384. doi:10.1111/j.1365-4632.2011.04903.x
- Gonzalez SA, Moore AGN. Acanthoma fissuratum of the outer auditory canal from a hearing aid. J Cutan Pathol. 1989;16:304.
- Fania L, Didona D, Morese R, et al. Basal cell carcinoma: from pathophysiology to novel therapeutic approaches. Biomedicines. 2020;8:449. doi:10.3390/biomedicines8110449
- Chauhan DS, Guruprasad Y. Dermal cylindroma of the scalp. Natl J Maxillofac Surg. 2012;3:59-61. doi:10.4103/0975-5950.102163
- Sand M, Sand D, Brors D, et al. Cutaneous lesions of the external ear. Head Face Med. 2008;4. doi:10.1186/1746-160X-4-2
- Orengo I, Robbins K, Marsch A. Pathology of the ear. Semin Plast Surg. 2011;25:279-287. doi:10.1055/s-0031-1288920
- Ramroop S. Successful treatment of acanthoma fissuratum with intralesional triamcinolone acetonide. Clin Case Rep. 2020;8:702-703. doi:10.1002/ccr3.2708
- Delaney TJ, Stewart TW. Granuloma fissuratum. Br J Dermatol. 1971;84:373-375. doi:10.1111/j.1365-2133.1971.tb14235.x
- Deshpande NS, Sen A, Vasudevan B, et al. Acanthoma fissuratum: lest we forget. Indian Dermatol Online J. 2017;8:141-143. doi:10.4103/2229- 5178.202267
- Surron RL Jr. A fissured granulomatous lesion of the upper labioalveolar fold. Arch Dermatol Syph. 1932;26:425. doi:10.1001 /archderm.1932.01450030423004
- Kennedy CM, Dewdney S, Galask RP. Vulvar granuloma fissuratum: a description of fissuring of the posterior fourchette and the repair. Obstet Gynecol. 2005;105:1018-1023. doi:10.1097/01. AOG.0000158863.70819.53
- Lee JL, Lee YB, Cho BK, et al. Acanthoma fissuratum on the penis. Int J Dermatol. 2013;52:382-384. doi:10.1111/j.1365-4632.2011.04903.x
- Gonzalez SA, Moore AGN. Acanthoma fissuratum of the outer auditory canal from a hearing aid. J Cutan Pathol. 1989;16:304.
- Fania L, Didona D, Morese R, et al. Basal cell carcinoma: from pathophysiology to novel therapeutic approaches. Biomedicines. 2020;8:449. doi:10.3390/biomedicines8110449
- Chauhan DS, Guruprasad Y. Dermal cylindroma of the scalp. Natl J Maxillofac Surg. 2012;3:59-61. doi:10.4103/0975-5950.102163
A 62-year-old man presented to the dermatology office with a 1.5-cm, pink, rubbery nodule behind the left ear that sometimes was tender. He stated that the lesion gradually grew in size over the last 2 years, and it developed after he was fitted for new glasses.
Parameters of Scratch Pleasurability in the Management of Pruritic Conditions
To the Editor:
The itch-scratch cycle refers to the sequence created when a pruritic skin condition leads to scratching and skin barrier disruption, ultimately facilitating secondary skin changes and neural activation that prolongs pruritus. In patients with pruritic conditions, the itch-scratch cycle often can run unrestrained, with patients unaware of their scratching habits. Understanding what drives a patient to scratch, such as the pleasure gained from scratching, may be beneficial for dermatologists combating a patient’s scratching habits. The earliest documented attempts to understand the mechanism of an itch were made in Greece around the fifth century, but the pathophysiology of this sensation still is not fully understood. The Latin term pruritus refers to itching, irritation, or sexual excitement, while the Greek term knêsmos and related words also denote itch in an irritating or pleasurable sense.1 This paradoxical duality of irritation and pleasure is a phenomenon all too well understood by those affected with pruritic symptoms.
Although there are many measured characteristics of an itch, the pleasure granted from scratching an itch rarely is addressed. Understanding the factors influencing the pleasurability of scratching could help improve management and outcomes of patients’ pruritic conditions.
Pruritus is associated with a wide array of etiologies including dermatologic, infectious, metabolic, and autoimmune, but unanimously it evokes a strong desire to scratch. Scratching an itch often yields temporary relief from the irritation by dispensing a complex sensory concoction between pleasure and pain.2 The neurobiology behind this pleasure phenomenon is inconclusive. Some hypotheses point to how scratching-induced pleasure may be derived from the deactivation or inhibition of the unpleasant sensation of an itch in the central nervous system, the stimulation of the reward signals in the C-fiber system in the peripheral nervous system, the release of pruritis-inhibiting prostaglandin D2, or a combination of these pathways. Levels of sensation and pleasure induced from itch attenuation by scratching even vary based on anatomic location. One study demonstrated that, when compared to the forearms, the ankles and back perceived baseline induced itch most intensely, but no significant difference in perceived itch intensity was found between the ankles and back. Additionally, scratching an itchy back or ankle notably induced more pleasure when compared to the forearms, but there was no significant difference in scratching pleasurability between the ankle and back.3
Although there are adequate questionnaires and scales (eg, ItchyQoL,4 Skindex-16, Skindex-29) to quantify the severity of pruritus and its effects on a patient’s quality of life, these measurements do not assess the pleasure yielded from scratching, the impact of scratch pleasure on the patient experience, or the effect of scratch pleasure on the disease state.4 It appears that there are inadequate assessment tools to define factors associated with the pleasurability of scratching. A PubMed search of articles indexed for MEDLINE using the terms scratching pleasure scale and pruritus pleasure questionnaire yielded scarce results measuring patient perspectives on scratching-associated pleasure. A pertinent study performed by O’Neill et al5 compared the differences in itch characteristics between patients with psoriasis and those with atopic dermatitis using a web-based questionnaire featuring a numerical pleasure scale (ranging from −5 [highly unpleasurable] to +5 [highly pleasurable]) on an 11-point Likert scale. The questionnaire sought to measure the effects of scratching during a typical episode of itch within the past 2 weeks. Scratching was found pleasurable in both groups of patients.5 Another web-based questionnaire that characterized pleasurability in scratching a typical episode of itch in individuals with atopic dermatitis using a −5 to +5 Likert scale (−5 [highly unpleasurable] to +5 [highly pleasurable]) found that most participants perceived scratching as pleasurable and that there was a positive correlation between itch intensity and scratch pleasurability.6 Both of these studies quantified that scratching an itch is pleasurable, a correlation that may not come as a surprise. This direct correlation suggests that a more detailed analysis of this scratch pleasure could be beneficial in the management of pruritic conditions.
Treating the underlying cause of an itch is key to inhibiting the sensation; in some cases, anti-itch medications must be used. Current medications have limited effects on itch relief, but an expanding understanding of itch pathophysiology through clinical and laboratory research in the fields of dermatology, immunology, and neurology is paving the way for promising new therapeutic medications.7-11 In a review of the literature, Sanders and Akiyama12 elucidated the influence of stress and anxiety in scratching an itch and the way in which both pharmacologic and nonpharmacologic (ie, psychological and educational interventions) may be used to help break the itch-scratch cycle. Possible techniques include habit-reversal training, relaxation therapy, and cognitive behavioral therapy.13 Understanding patient perspectives on the pleasure yielded from scratching an itch and the disease factors that influence this pleasure seeking are paramount to reducing patient scratching. In understanding the pleasurability of scratching in pruritic conditions, the itch-scratch cycle and its accompanying deleterious effects (eg, stress, anxiety, pain, infection, secondary skin changes) can be broken.
The pleasure yielded from scratching an itch is a component of patient scratching habits that should be analyzed and quantified to reduce itch in pruritic conditions, mitigate damaging consequences of scratching, and improve the quality of life of patients with pruritic conditions. Furthermore, this understanding may help guide clinicians in management, such as counseling patients on the itch-scratch cycle and deciding which forthcoming medications could ameliorate a patient’s pruritic symptoms.
- Weisshaar E, Grüll V, König A, et al. The symptom of itch in medical history: highlights through the centuries. Int J Dermatol. 2009;48:1385-1394.
- Lavery MJ, Kinney MO, Mochizuki H, et al. Pruritus: an overview. what drives people to scratch an itch? Ulster Med J. 2016;85:164-173.
- Bin Saif GA, Papoiu ADP, Banari L, et al. The pleasurability of scratching an itch: a psychophysical and topographical assessment. Br J Dermatol. 2012;166:981-985.
- Desai NS, Poindexter GB, Monthrope YM, et al. A pilot quality-of-life instrument for pruritus. J Am Acad Dermatol. 2008;59:234-244.
- O’Neill JL, Chan YH, Rapp SR, et al. Differences in itch characteristics between psoriasis and atopic dermatitis patients: results of a web-based questionnaire. Acta Derm Venereol. 2011;91:537-540.
- Dawn A, Papoiu ADP, Chan YH, et al. Itch characteristics in atopic dermatitis: results of a web-based questionnaire. Br J Dermatol. 2009;160:642-644.
- Yosipovitch G, Rosen JD, Hashimoto T. Itch: from mechanism to (novel) therapeutic approaches. J Allergy Clin Immunol. 2018;142:1375-1390.
- Yosipovitch G, Misery L, Proksch E, et al. Skin barrier damage and itch: review of mechanisms, topical management and future directions. Acta Derm Venereol. 2019;99:1201-1209.
- Dong X, Dong X. Peripheral and central mechanisms of itch. Neuron. 2018;98:482-494.
- Lerner EA. Pathophysiology of itch. Dermatol Clin. 2018;36:175-177.
- Cevikbas F, Lerner EA. Physiology and pathophysiology of itch. Physiol Rev. 2020;100:945-982.
- Sanders KM, Akiyama T. The vicious cycle of itch and anxiety. Neurosci Biobehav Rev. 2018;87:17-26.
- Sanders KM, Nattkemper LA, Yosipovitch G. Advances in understanding itching and scratching: a new era of targeted treatments [published online August 22, 2016]. F1000Res. doi:10.12688/f1000research.8659.
To the Editor:
The itch-scratch cycle refers to the sequence created when a pruritic skin condition leads to scratching and skin barrier disruption, ultimately facilitating secondary skin changes and neural activation that prolongs pruritus. In patients with pruritic conditions, the itch-scratch cycle often can run unrestrained, with patients unaware of their scratching habits. Understanding what drives a patient to scratch, such as the pleasure gained from scratching, may be beneficial for dermatologists combating a patient’s scratching habits. The earliest documented attempts to understand the mechanism of an itch were made in Greece around the fifth century, but the pathophysiology of this sensation still is not fully understood. The Latin term pruritus refers to itching, irritation, or sexual excitement, while the Greek term knêsmos and related words also denote itch in an irritating or pleasurable sense.1 This paradoxical duality of irritation and pleasure is a phenomenon all too well understood by those affected with pruritic symptoms.
Although there are many measured characteristics of an itch, the pleasure granted from scratching an itch rarely is addressed. Understanding the factors influencing the pleasurability of scratching could help improve management and outcomes of patients’ pruritic conditions.
Pruritus is associated with a wide array of etiologies including dermatologic, infectious, metabolic, and autoimmune, but unanimously it evokes a strong desire to scratch. Scratching an itch often yields temporary relief from the irritation by dispensing a complex sensory concoction between pleasure and pain.2 The neurobiology behind this pleasure phenomenon is inconclusive. Some hypotheses point to how scratching-induced pleasure may be derived from the deactivation or inhibition of the unpleasant sensation of an itch in the central nervous system, the stimulation of the reward signals in the C-fiber system in the peripheral nervous system, the release of pruritis-inhibiting prostaglandin D2, or a combination of these pathways. Levels of sensation and pleasure induced from itch attenuation by scratching even vary based on anatomic location. One study demonstrated that, when compared to the forearms, the ankles and back perceived baseline induced itch most intensely, but no significant difference in perceived itch intensity was found between the ankles and back. Additionally, scratching an itchy back or ankle notably induced more pleasure when compared to the forearms, but there was no significant difference in scratching pleasurability between the ankle and back.3
Although there are adequate questionnaires and scales (eg, ItchyQoL,4 Skindex-16, Skindex-29) to quantify the severity of pruritus and its effects on a patient’s quality of life, these measurements do not assess the pleasure yielded from scratching, the impact of scratch pleasure on the patient experience, or the effect of scratch pleasure on the disease state.4 It appears that there are inadequate assessment tools to define factors associated with the pleasurability of scratching. A PubMed search of articles indexed for MEDLINE using the terms scratching pleasure scale and pruritus pleasure questionnaire yielded scarce results measuring patient perspectives on scratching-associated pleasure. A pertinent study performed by O’Neill et al5 compared the differences in itch characteristics between patients with psoriasis and those with atopic dermatitis using a web-based questionnaire featuring a numerical pleasure scale (ranging from −5 [highly unpleasurable] to +5 [highly pleasurable]) on an 11-point Likert scale. The questionnaire sought to measure the effects of scratching during a typical episode of itch within the past 2 weeks. Scratching was found pleasurable in both groups of patients.5 Another web-based questionnaire that characterized pleasurability in scratching a typical episode of itch in individuals with atopic dermatitis using a −5 to +5 Likert scale (−5 [highly unpleasurable] to +5 [highly pleasurable]) found that most participants perceived scratching as pleasurable and that there was a positive correlation between itch intensity and scratch pleasurability.6 Both of these studies quantified that scratching an itch is pleasurable, a correlation that may not come as a surprise. This direct correlation suggests that a more detailed analysis of this scratch pleasure could be beneficial in the management of pruritic conditions.
Treating the underlying cause of an itch is key to inhibiting the sensation; in some cases, anti-itch medications must be used. Current medications have limited effects on itch relief, but an expanding understanding of itch pathophysiology through clinical and laboratory research in the fields of dermatology, immunology, and neurology is paving the way for promising new therapeutic medications.7-11 In a review of the literature, Sanders and Akiyama12 elucidated the influence of stress and anxiety in scratching an itch and the way in which both pharmacologic and nonpharmacologic (ie, psychological and educational interventions) may be used to help break the itch-scratch cycle. Possible techniques include habit-reversal training, relaxation therapy, and cognitive behavioral therapy.13 Understanding patient perspectives on the pleasure yielded from scratching an itch and the disease factors that influence this pleasure seeking are paramount to reducing patient scratching. In understanding the pleasurability of scratching in pruritic conditions, the itch-scratch cycle and its accompanying deleterious effects (eg, stress, anxiety, pain, infection, secondary skin changes) can be broken.
The pleasure yielded from scratching an itch is a component of patient scratching habits that should be analyzed and quantified to reduce itch in pruritic conditions, mitigate damaging consequences of scratching, and improve the quality of life of patients with pruritic conditions. Furthermore, this understanding may help guide clinicians in management, such as counseling patients on the itch-scratch cycle and deciding which forthcoming medications could ameliorate a patient’s pruritic symptoms.
To the Editor:
The itch-scratch cycle refers to the sequence created when a pruritic skin condition leads to scratching and skin barrier disruption, ultimately facilitating secondary skin changes and neural activation that prolongs pruritus. In patients with pruritic conditions, the itch-scratch cycle often can run unrestrained, with patients unaware of their scratching habits. Understanding what drives a patient to scratch, such as the pleasure gained from scratching, may be beneficial for dermatologists combating a patient’s scratching habits. The earliest documented attempts to understand the mechanism of an itch were made in Greece around the fifth century, but the pathophysiology of this sensation still is not fully understood. The Latin term pruritus refers to itching, irritation, or sexual excitement, while the Greek term knêsmos and related words also denote itch in an irritating or pleasurable sense.1 This paradoxical duality of irritation and pleasure is a phenomenon all too well understood by those affected with pruritic symptoms.
Although there are many measured characteristics of an itch, the pleasure granted from scratching an itch rarely is addressed. Understanding the factors influencing the pleasurability of scratching could help improve management and outcomes of patients’ pruritic conditions.
Pruritus is associated with a wide array of etiologies including dermatologic, infectious, metabolic, and autoimmune, but unanimously it evokes a strong desire to scratch. Scratching an itch often yields temporary relief from the irritation by dispensing a complex sensory concoction between pleasure and pain.2 The neurobiology behind this pleasure phenomenon is inconclusive. Some hypotheses point to how scratching-induced pleasure may be derived from the deactivation or inhibition of the unpleasant sensation of an itch in the central nervous system, the stimulation of the reward signals in the C-fiber system in the peripheral nervous system, the release of pruritis-inhibiting prostaglandin D2, or a combination of these pathways. Levels of sensation and pleasure induced from itch attenuation by scratching even vary based on anatomic location. One study demonstrated that, when compared to the forearms, the ankles and back perceived baseline induced itch most intensely, but no significant difference in perceived itch intensity was found between the ankles and back. Additionally, scratching an itchy back or ankle notably induced more pleasure when compared to the forearms, but there was no significant difference in scratching pleasurability between the ankle and back.3
Although there are adequate questionnaires and scales (eg, ItchyQoL,4 Skindex-16, Skindex-29) to quantify the severity of pruritus and its effects on a patient’s quality of life, these measurements do not assess the pleasure yielded from scratching, the impact of scratch pleasure on the patient experience, or the effect of scratch pleasure on the disease state.4 It appears that there are inadequate assessment tools to define factors associated with the pleasurability of scratching. A PubMed search of articles indexed for MEDLINE using the terms scratching pleasure scale and pruritus pleasure questionnaire yielded scarce results measuring patient perspectives on scratching-associated pleasure. A pertinent study performed by O’Neill et al5 compared the differences in itch characteristics between patients with psoriasis and those with atopic dermatitis using a web-based questionnaire featuring a numerical pleasure scale (ranging from −5 [highly unpleasurable] to +5 [highly pleasurable]) on an 11-point Likert scale. The questionnaire sought to measure the effects of scratching during a typical episode of itch within the past 2 weeks. Scratching was found pleasurable in both groups of patients.5 Another web-based questionnaire that characterized pleasurability in scratching a typical episode of itch in individuals with atopic dermatitis using a −5 to +5 Likert scale (−5 [highly unpleasurable] to +5 [highly pleasurable]) found that most participants perceived scratching as pleasurable and that there was a positive correlation between itch intensity and scratch pleasurability.6 Both of these studies quantified that scratching an itch is pleasurable, a correlation that may not come as a surprise. This direct correlation suggests that a more detailed analysis of this scratch pleasure could be beneficial in the management of pruritic conditions.
Treating the underlying cause of an itch is key to inhibiting the sensation; in some cases, anti-itch medications must be used. Current medications have limited effects on itch relief, but an expanding understanding of itch pathophysiology through clinical and laboratory research in the fields of dermatology, immunology, and neurology is paving the way for promising new therapeutic medications.7-11 In a review of the literature, Sanders and Akiyama12 elucidated the influence of stress and anxiety in scratching an itch and the way in which both pharmacologic and nonpharmacologic (ie, psychological and educational interventions) may be used to help break the itch-scratch cycle. Possible techniques include habit-reversal training, relaxation therapy, and cognitive behavioral therapy.13 Understanding patient perspectives on the pleasure yielded from scratching an itch and the disease factors that influence this pleasure seeking are paramount to reducing patient scratching. In understanding the pleasurability of scratching in pruritic conditions, the itch-scratch cycle and its accompanying deleterious effects (eg, stress, anxiety, pain, infection, secondary skin changes) can be broken.
The pleasure yielded from scratching an itch is a component of patient scratching habits that should be analyzed and quantified to reduce itch in pruritic conditions, mitigate damaging consequences of scratching, and improve the quality of life of patients with pruritic conditions. Furthermore, this understanding may help guide clinicians in management, such as counseling patients on the itch-scratch cycle and deciding which forthcoming medications could ameliorate a patient’s pruritic symptoms.
- Weisshaar E, Grüll V, König A, et al. The symptom of itch in medical history: highlights through the centuries. Int J Dermatol. 2009;48:1385-1394.
- Lavery MJ, Kinney MO, Mochizuki H, et al. Pruritus: an overview. what drives people to scratch an itch? Ulster Med J. 2016;85:164-173.
- Bin Saif GA, Papoiu ADP, Banari L, et al. The pleasurability of scratching an itch: a psychophysical and topographical assessment. Br J Dermatol. 2012;166:981-985.
- Desai NS, Poindexter GB, Monthrope YM, et al. A pilot quality-of-life instrument for pruritus. J Am Acad Dermatol. 2008;59:234-244.
- O’Neill JL, Chan YH, Rapp SR, et al. Differences in itch characteristics between psoriasis and atopic dermatitis patients: results of a web-based questionnaire. Acta Derm Venereol. 2011;91:537-540.
- Dawn A, Papoiu ADP, Chan YH, et al. Itch characteristics in atopic dermatitis: results of a web-based questionnaire. Br J Dermatol. 2009;160:642-644.
- Yosipovitch G, Rosen JD, Hashimoto T. Itch: from mechanism to (novel) therapeutic approaches. J Allergy Clin Immunol. 2018;142:1375-1390.
- Yosipovitch G, Misery L, Proksch E, et al. Skin barrier damage and itch: review of mechanisms, topical management and future directions. Acta Derm Venereol. 2019;99:1201-1209.
- Dong X, Dong X. Peripheral and central mechanisms of itch. Neuron. 2018;98:482-494.
- Lerner EA. Pathophysiology of itch. Dermatol Clin. 2018;36:175-177.
- Cevikbas F, Lerner EA. Physiology and pathophysiology of itch. Physiol Rev. 2020;100:945-982.
- Sanders KM, Akiyama T. The vicious cycle of itch and anxiety. Neurosci Biobehav Rev. 2018;87:17-26.
- Sanders KM, Nattkemper LA, Yosipovitch G. Advances in understanding itching and scratching: a new era of targeted treatments [published online August 22, 2016]. F1000Res. doi:10.12688/f1000research.8659.
- Weisshaar E, Grüll V, König A, et al. The symptom of itch in medical history: highlights through the centuries. Int J Dermatol. 2009;48:1385-1394.
- Lavery MJ, Kinney MO, Mochizuki H, et al. Pruritus: an overview. what drives people to scratch an itch? Ulster Med J. 2016;85:164-173.
- Bin Saif GA, Papoiu ADP, Banari L, et al. The pleasurability of scratching an itch: a psychophysical and topographical assessment. Br J Dermatol. 2012;166:981-985.
- Desai NS, Poindexter GB, Monthrope YM, et al. A pilot quality-of-life instrument for pruritus. J Am Acad Dermatol. 2008;59:234-244.
- O’Neill JL, Chan YH, Rapp SR, et al. Differences in itch characteristics between psoriasis and atopic dermatitis patients: results of a web-based questionnaire. Acta Derm Venereol. 2011;91:537-540.
- Dawn A, Papoiu ADP, Chan YH, et al. Itch characteristics in atopic dermatitis: results of a web-based questionnaire. Br J Dermatol. 2009;160:642-644.
- Yosipovitch G, Rosen JD, Hashimoto T. Itch: from mechanism to (novel) therapeutic approaches. J Allergy Clin Immunol. 2018;142:1375-1390.
- Yosipovitch G, Misery L, Proksch E, et al. Skin barrier damage and itch: review of mechanisms, topical management and future directions. Acta Derm Venereol. 2019;99:1201-1209.
- Dong X, Dong X. Peripheral and central mechanisms of itch. Neuron. 2018;98:482-494.
- Lerner EA. Pathophysiology of itch. Dermatol Clin. 2018;36:175-177.
- Cevikbas F, Lerner EA. Physiology and pathophysiology of itch. Physiol Rev. 2020;100:945-982.
- Sanders KM, Akiyama T. The vicious cycle of itch and anxiety. Neurosci Biobehav Rev. 2018;87:17-26.
- Sanders KM, Nattkemper LA, Yosipovitch G. Advances in understanding itching and scratching: a new era of targeted treatments [published online August 22, 2016]. F1000Res. doi:10.12688/f1000research.8659.
Practice Points
- In individuals with pruritic skin conditions, the itch-scratch cycle can have damaging consequences such as anxiety, infection, and secondary skin changes.
- Understanding the pleasurability of scratching in pruritic skin conditions allows providers to help patients break the itch-scratch cycle and improve quality of life.
Multiple Eruptive Dermatofibromas Associated With Down Syndrome
To the Editor:
Dermatofibromas (also known as fibrous histiocytomas) are benign fibrous nodules that most often arise as solitary lesions on the lower extremities. Multiple eruptive dermatofibromas (MEDFs) are uncommon and have been defined as more than 15 in number1 or 5 to 8 dermatofibromas appearing within 4 months.2 They have been reported in association with a number of conditions of immune dysregulation such as systemic lupus erythematosus, Sjögren syndrome, HIV infection, and leukemia.3 Multiple eruptive dermatofibromas also have been described in patients with Down syndrome (DS).4-7 We report a case of MEDFs in a patient with DS and review the literature on the association between MEDFs and DS.
A 38-year-old woman with DS, hidradenitis suppurativa, and hypothyroidism presented with multiple cutaneous lesions developing over the last year. The lesions continued to increase in number but were otherwise asymptomatic. Physical examination revealed approximately 20 rubbery, pink-tan papules measuring less than 1 cm in diameter that were scattered along the trunk (Figure, A), arms, and legs (Figure, B).
The patient had no known history of immunosuppression or rheumatologic disease and was otherwise healthy. Basic laboratory tests including a complete blood cell count and antinuclear antibody titer were within reference range. The lesions were clinically consistent with dermatofibromas, but due to their increasing number within a short period of time, a biopsy of a representative lesion was performed to confirm the diagnosis.
The exact incidence of MEDFs is unknown, but they are rare, with one review finding only 50 cases reported from 1960 to 2002.8 They are increasingly recognized as a sign of potential immune dysregulation. Approximately 56% to 70% of cases are seen in patients with an underlying disease state; 80% are immune mediated.8,9 Interestingly, DS has long been associated with notable immune dysfunction,10,11 with evidence suggesting that trisomy 21 may result in widespread changes in gene expression that can lead to interferon activation.12
A PubMed search of articles indexed for MEDLINE using the terms dermatofibroma and Down, dermatofibroma and Down syndrome, eruptive dermatofibroma and Down syndrome, and multiple dermatofibroma and Down syndrome revealed 6 cases of MEDFs in patients with DS that have been reported since 2005.4-7 An additional report by Honda et al13 described a patient with DS who developed 7 dermatofibromas, but no time frame of development was specified. We reviewed the characteristics of 8 patients with DS with MEDFs, which included our patient (Table). The average age at time of presentation was 39 years (median age, 40 years). Six patients (75%) were female and 2 (25%) were male. Dermatofibromas were reported to appear over the course of months to years. Comorbidities included psoriatic arthritis (treated with methotrexate),6 thyroid disorders (ie, Graves disease),6 hypercholesterolemia,6 hidradenitis suppurativa, long-standing mild lymphopenia (1.4×109/L [reference range, 1.5−4.0×109/L]),4 and acute megakaryoblastic leukemia13 treated 15 years before the appearance of dermatofibromas.
Many dermatologic conditions have been reported at increased rates in individuals with DS, including seborrheic dermatitis, alopecia areata, syringomas, elastosis perforans serpiginosa, cutis marmorata, xerosis, and palmoplantar hyperkeratosis.14,15 Although drawing conclusions about associations between MEDFs and DS is limited by our small sample size, we have reported this case and reviewed existing cases of MEDFs in DS to highlight a potential association that may be underrecognized or underreported. More evidence is needed to determine the strength of the association between MEDFs and DS, but dermatologists should be aware that MEDFs may be an additional skin finding associated with DS that is related to the syndrome’s immune dysregulation.
- Baraf CS, Shapiro L. Multiple histiocytomas: report of a case. Arch Dermatol. 1970;101:588-590.
- Ammirati CT, Mann C, Hornstra IK. Multiple eruptive dermatofibromas in three men with HIV infection. Dermatology. 1997;4:344-348.
- Zaccaria E, Rebora A, Rongioletti F. Multiple eruptive dermatofibromas and immunosuppression: report of two cases and review of the literature. Int J Dermatol. 2008;47:723-727.
- Lamb RC, Gangopadhyay M, MacDonald A. Multiple dermatofibromas in Down syndrome. Int J Dermatol. 2014;53:E274-E275.
- Monteagudo B, Álvarez-Fernández JC, Iglesias B, et al. Multiple eruptive dermatofibromas in a patient with Down’s syndrome [article in Spanish]. Actas Dermosifiliogr. 2005;96:199.
- Monteagudo B, Suárez-Amor O, Cabanillas M, et al. Down syndrome: another cause of immunosuppression associated with multiple eruptive dermatofibroma? [article in Spanish]. Dermatol Online J. 2009;15:15.
- Tanaka M, Hoashi T, Serizawa N, et al. Multiple unilaterally localized dermatofibromas in a patient with Down syndrome. J Dermatol. 2017;44:1074-1076.
- Niiyama S, Katsuoka K, Happle R, et al. Multiple eruptive dermatofibromas: a review of the literature. Acta Derm Venereol. 2002;82:241-244.
- Her Y, Ku SH, Kim KH. A case of multiple eruptive dermatofibromas in a healthy adult. Ann Dermatol. 2014;26:539-540.
- Bertotto A, Arcangeli C, Crupi S, et al. T cell response to anti-CD3 antibody in Down’s syndrome. Arch Dis Child. 1987;62:1148-1151.
- Kusters MA, Verstegen RH, Gemen EF, et al. Intrinsic defect of the immune system in children with Down syndrome: a review. Clin Exp Immunol. 2009;156:189-193.
- Sullivan KD, Evans D, Pandey A, et al. Trisomy 21 causes changes in the circulating proteome indicative of chronic inflammation. Sci Rep. 2017;7:14818.
- Honda M, Tomimura S, de Vega S, et al. Multiple dermatofibromas in a patient with Down syndrome. J Dermatol. 2016;43:346-348.
- Daneshpazhooh M, Nazemi TM, Bigdeloo L, et al. Mucocutaneous findings in 100 children with Down syndrome. Pediatr Dermatol. 2007;24:317-320.
- Madan V, Williams J, Lear JT. Dermatological manifestations of Down’s syndrome. Clin Exp Dermatol. 2006;31:623-629.
To the Editor:
Dermatofibromas (also known as fibrous histiocytomas) are benign fibrous nodules that most often arise as solitary lesions on the lower extremities. Multiple eruptive dermatofibromas (MEDFs) are uncommon and have been defined as more than 15 in number1 or 5 to 8 dermatofibromas appearing within 4 months.2 They have been reported in association with a number of conditions of immune dysregulation such as systemic lupus erythematosus, Sjögren syndrome, HIV infection, and leukemia.3 Multiple eruptive dermatofibromas also have been described in patients with Down syndrome (DS).4-7 We report a case of MEDFs in a patient with DS and review the literature on the association between MEDFs and DS.
A 38-year-old woman with DS, hidradenitis suppurativa, and hypothyroidism presented with multiple cutaneous lesions developing over the last year. The lesions continued to increase in number but were otherwise asymptomatic. Physical examination revealed approximately 20 rubbery, pink-tan papules measuring less than 1 cm in diameter that were scattered along the trunk (Figure, A), arms, and legs (Figure, B).
The patient had no known history of immunosuppression or rheumatologic disease and was otherwise healthy. Basic laboratory tests including a complete blood cell count and antinuclear antibody titer were within reference range. The lesions were clinically consistent with dermatofibromas, but due to their increasing number within a short period of time, a biopsy of a representative lesion was performed to confirm the diagnosis.
The exact incidence of MEDFs is unknown, but they are rare, with one review finding only 50 cases reported from 1960 to 2002.8 They are increasingly recognized as a sign of potential immune dysregulation. Approximately 56% to 70% of cases are seen in patients with an underlying disease state; 80% are immune mediated.8,9 Interestingly, DS has long been associated with notable immune dysfunction,10,11 with evidence suggesting that trisomy 21 may result in widespread changes in gene expression that can lead to interferon activation.12
A PubMed search of articles indexed for MEDLINE using the terms dermatofibroma and Down, dermatofibroma and Down syndrome, eruptive dermatofibroma and Down syndrome, and multiple dermatofibroma and Down syndrome revealed 6 cases of MEDFs in patients with DS that have been reported since 2005.4-7 An additional report by Honda et al13 described a patient with DS who developed 7 dermatofibromas, but no time frame of development was specified. We reviewed the characteristics of 8 patients with DS with MEDFs, which included our patient (Table). The average age at time of presentation was 39 years (median age, 40 years). Six patients (75%) were female and 2 (25%) were male. Dermatofibromas were reported to appear over the course of months to years. Comorbidities included psoriatic arthritis (treated with methotrexate),6 thyroid disorders (ie, Graves disease),6 hypercholesterolemia,6 hidradenitis suppurativa, long-standing mild lymphopenia (1.4×109/L [reference range, 1.5−4.0×109/L]),4 and acute megakaryoblastic leukemia13 treated 15 years before the appearance of dermatofibromas.
Many dermatologic conditions have been reported at increased rates in individuals with DS, including seborrheic dermatitis, alopecia areata, syringomas, elastosis perforans serpiginosa, cutis marmorata, xerosis, and palmoplantar hyperkeratosis.14,15 Although drawing conclusions about associations between MEDFs and DS is limited by our small sample size, we have reported this case and reviewed existing cases of MEDFs in DS to highlight a potential association that may be underrecognized or underreported. More evidence is needed to determine the strength of the association between MEDFs and DS, but dermatologists should be aware that MEDFs may be an additional skin finding associated with DS that is related to the syndrome’s immune dysregulation.
To the Editor:
Dermatofibromas (also known as fibrous histiocytomas) are benign fibrous nodules that most often arise as solitary lesions on the lower extremities. Multiple eruptive dermatofibromas (MEDFs) are uncommon and have been defined as more than 15 in number1 or 5 to 8 dermatofibromas appearing within 4 months.2 They have been reported in association with a number of conditions of immune dysregulation such as systemic lupus erythematosus, Sjögren syndrome, HIV infection, and leukemia.3 Multiple eruptive dermatofibromas also have been described in patients with Down syndrome (DS).4-7 We report a case of MEDFs in a patient with DS and review the literature on the association between MEDFs and DS.
A 38-year-old woman with DS, hidradenitis suppurativa, and hypothyroidism presented with multiple cutaneous lesions developing over the last year. The lesions continued to increase in number but were otherwise asymptomatic. Physical examination revealed approximately 20 rubbery, pink-tan papules measuring less than 1 cm in diameter that were scattered along the trunk (Figure, A), arms, and legs (Figure, B).
The patient had no known history of immunosuppression or rheumatologic disease and was otherwise healthy. Basic laboratory tests including a complete blood cell count and antinuclear antibody titer were within reference range. The lesions were clinically consistent with dermatofibromas, but due to their increasing number within a short period of time, a biopsy of a representative lesion was performed to confirm the diagnosis.
The exact incidence of MEDFs is unknown, but they are rare, with one review finding only 50 cases reported from 1960 to 2002.8 They are increasingly recognized as a sign of potential immune dysregulation. Approximately 56% to 70% of cases are seen in patients with an underlying disease state; 80% are immune mediated.8,9 Interestingly, DS has long been associated with notable immune dysfunction,10,11 with evidence suggesting that trisomy 21 may result in widespread changes in gene expression that can lead to interferon activation.12
A PubMed search of articles indexed for MEDLINE using the terms dermatofibroma and Down, dermatofibroma and Down syndrome, eruptive dermatofibroma and Down syndrome, and multiple dermatofibroma and Down syndrome revealed 6 cases of MEDFs in patients with DS that have been reported since 2005.4-7 An additional report by Honda et al13 described a patient with DS who developed 7 dermatofibromas, but no time frame of development was specified. We reviewed the characteristics of 8 patients with DS with MEDFs, which included our patient (Table). The average age at time of presentation was 39 years (median age, 40 years). Six patients (75%) were female and 2 (25%) were male. Dermatofibromas were reported to appear over the course of months to years. Comorbidities included psoriatic arthritis (treated with methotrexate),6 thyroid disorders (ie, Graves disease),6 hypercholesterolemia,6 hidradenitis suppurativa, long-standing mild lymphopenia (1.4×109/L [reference range, 1.5−4.0×109/L]),4 and acute megakaryoblastic leukemia13 treated 15 years before the appearance of dermatofibromas.
Many dermatologic conditions have been reported at increased rates in individuals with DS, including seborrheic dermatitis, alopecia areata, syringomas, elastosis perforans serpiginosa, cutis marmorata, xerosis, and palmoplantar hyperkeratosis.14,15 Although drawing conclusions about associations between MEDFs and DS is limited by our small sample size, we have reported this case and reviewed existing cases of MEDFs in DS to highlight a potential association that may be underrecognized or underreported. More evidence is needed to determine the strength of the association between MEDFs and DS, but dermatologists should be aware that MEDFs may be an additional skin finding associated with DS that is related to the syndrome’s immune dysregulation.
- Baraf CS, Shapiro L. Multiple histiocytomas: report of a case. Arch Dermatol. 1970;101:588-590.
- Ammirati CT, Mann C, Hornstra IK. Multiple eruptive dermatofibromas in three men with HIV infection. Dermatology. 1997;4:344-348.
- Zaccaria E, Rebora A, Rongioletti F. Multiple eruptive dermatofibromas and immunosuppression: report of two cases and review of the literature. Int J Dermatol. 2008;47:723-727.
- Lamb RC, Gangopadhyay M, MacDonald A. Multiple dermatofibromas in Down syndrome. Int J Dermatol. 2014;53:E274-E275.
- Monteagudo B, Álvarez-Fernández JC, Iglesias B, et al. Multiple eruptive dermatofibromas in a patient with Down’s syndrome [article in Spanish]. Actas Dermosifiliogr. 2005;96:199.
- Monteagudo B, Suárez-Amor O, Cabanillas M, et al. Down syndrome: another cause of immunosuppression associated with multiple eruptive dermatofibroma? [article in Spanish]. Dermatol Online J. 2009;15:15.
- Tanaka M, Hoashi T, Serizawa N, et al. Multiple unilaterally localized dermatofibromas in a patient with Down syndrome. J Dermatol. 2017;44:1074-1076.
- Niiyama S, Katsuoka K, Happle R, et al. Multiple eruptive dermatofibromas: a review of the literature. Acta Derm Venereol. 2002;82:241-244.
- Her Y, Ku SH, Kim KH. A case of multiple eruptive dermatofibromas in a healthy adult. Ann Dermatol. 2014;26:539-540.
- Bertotto A, Arcangeli C, Crupi S, et al. T cell response to anti-CD3 antibody in Down’s syndrome. Arch Dis Child. 1987;62:1148-1151.
- Kusters MA, Verstegen RH, Gemen EF, et al. Intrinsic defect of the immune system in children with Down syndrome: a review. Clin Exp Immunol. 2009;156:189-193.
- Sullivan KD, Evans D, Pandey A, et al. Trisomy 21 causes changes in the circulating proteome indicative of chronic inflammation. Sci Rep. 2017;7:14818.
- Honda M, Tomimura S, de Vega S, et al. Multiple dermatofibromas in a patient with Down syndrome. J Dermatol. 2016;43:346-348.
- Daneshpazhooh M, Nazemi TM, Bigdeloo L, et al. Mucocutaneous findings in 100 children with Down syndrome. Pediatr Dermatol. 2007;24:317-320.
- Madan V, Williams J, Lear JT. Dermatological manifestations of Down’s syndrome. Clin Exp Dermatol. 2006;31:623-629.
- Baraf CS, Shapiro L. Multiple histiocytomas: report of a case. Arch Dermatol. 1970;101:588-590.
- Ammirati CT, Mann C, Hornstra IK. Multiple eruptive dermatofibromas in three men with HIV infection. Dermatology. 1997;4:344-348.
- Zaccaria E, Rebora A, Rongioletti F. Multiple eruptive dermatofibromas and immunosuppression: report of two cases and review of the literature. Int J Dermatol. 2008;47:723-727.
- Lamb RC, Gangopadhyay M, MacDonald A. Multiple dermatofibromas in Down syndrome. Int J Dermatol. 2014;53:E274-E275.
- Monteagudo B, Álvarez-Fernández JC, Iglesias B, et al. Multiple eruptive dermatofibromas in a patient with Down’s syndrome [article in Spanish]. Actas Dermosifiliogr. 2005;96:199.
- Monteagudo B, Suárez-Amor O, Cabanillas M, et al. Down syndrome: another cause of immunosuppression associated with multiple eruptive dermatofibroma? [article in Spanish]. Dermatol Online J. 2009;15:15.
- Tanaka M, Hoashi T, Serizawa N, et al. Multiple unilaterally localized dermatofibromas in a patient with Down syndrome. J Dermatol. 2017;44:1074-1076.
- Niiyama S, Katsuoka K, Happle R, et al. Multiple eruptive dermatofibromas: a review of the literature. Acta Derm Venereol. 2002;82:241-244.
- Her Y, Ku SH, Kim KH. A case of multiple eruptive dermatofibromas in a healthy adult. Ann Dermatol. 2014;26:539-540.
- Bertotto A, Arcangeli C, Crupi S, et al. T cell response to anti-CD3 antibody in Down’s syndrome. Arch Dis Child. 1987;62:1148-1151.
- Kusters MA, Verstegen RH, Gemen EF, et al. Intrinsic defect of the immune system in children with Down syndrome: a review. Clin Exp Immunol. 2009;156:189-193.
- Sullivan KD, Evans D, Pandey A, et al. Trisomy 21 causes changes in the circulating proteome indicative of chronic inflammation. Sci Rep. 2017;7:14818.
- Honda M, Tomimura S, de Vega S, et al. Multiple dermatofibromas in a patient with Down syndrome. J Dermatol. 2016;43:346-348.
- Daneshpazhooh M, Nazemi TM, Bigdeloo L, et al. Mucocutaneous findings in 100 children with Down syndrome. Pediatr Dermatol. 2007;24:317-320.
- Madan V, Williams J, Lear JT. Dermatological manifestations of Down’s syndrome. Clin Exp Dermatol. 2006;31:623-629.
Practice Points
- Although dermatofibromas are common and benign skin lesions, multiple eruptive dermatofibromas have been associated with a number of underlying conditions, particularly those associated with immune dysregulation.
- The immune dysregulation reported in Down syndrome may explain the appearance of multiple dermatofibromas.
Abrocitinib evaluated in patients with and without prior dupilumab treatment
an industry-sponsored study reports.
“In this post hoc analysis, both the efficacy and the safety profiles of abrocitinib were consistent in patients with moderate-to-severe atopic dermatitis, regardless of prior biologic therapy use,” lead author Melinda Gooderham, MD, medical director of the SKiN Centre for Dermatology, Peterborough, Ont., said during an oral presentation at the Society for Investigative Dermatology (SID) 2022 Annual Meeting.
“These results ... support the use of abrocitinib in patients who might have received biologic therapy prior,” she added.
“Prior biologic use did not reveal any new safety signals ... keeping in mind the key limitation of this analysis is that it was done post hoc,” she noted.
Guidelines for moderate-to-severe atopic dermatitis refractory to topical or systemic therapy include systemic immunosuppressants and dupilumab, a monoclonal antibody that inhibits interleukin-4 and interleukin-13 cytokine-induced responses, Dr. Gooderham said.
The Food and Drug Administration recently approved abrocitinib, an oral once-a-day Janus kinase 1 (JAK1) inhibitor, to treat the disease. The approval came with a boxed warning about increased risk for serious infections, mortality, malignancy, and lymphoproliferative disorders, major adverse cardiovascular events, thrombosis, and laboratory abnormalities.
Comparing the bio-experienced with the bio-naive
Dr. Gooderham and colleagues investigated whether patients who’d been treated with a biologic would respond to abrocitinib differently than patients who had not received prior biologic treatment.
Researchers pooled data from two phase 3 placebo-controlled trials of abrocitinib that led to approval and an earlier phase 2b study. They identified 67 patients previously treated with dupilumab and 867 patients who were bio-naive. They repeated their analysis using data from another phase 3 study of abrocitinib on 86 patients previously treated with dupilumab and 1,147 who were bio-naive. On average, the bio-experienced patients were in their mid-30s to early 40s, and the bio-naive group was several years younger.
In the pooled phase 2b and phase 3 JADE MONO-1 and JADE MONO-2 monotherapy trials, patients received once-daily abrocitinib 100 or 200 mg or placebo for 12 weeks. In the phase 3 JADE REGIMEN, which they analyzed separately, eligible patients were enrolled in a 12-week open-label run-in period during which they received an induction treatment of abrocitinib 200 mg once a day.
Researchers compared results of two assessments: the IGA (Investigator Global Assessment) and EASI-75 (Eczema Area and Severity Index, 75% or greater improvement from baseline).
- At week 12, IGA 0/1 dose-dependent response rates were similar in the pooled groups, regardless of whether they had received prior biologic therapy. With abrocitinib 200 mg, 43.5% of those with prior dupilumab therapy responded versus 41.4% of bio-naive patients; with abrocitinib 100 mg, 24.1% versus 26.7% responded. In JADE REGIMEN, corresponding response rates with abrocitinib 200 mg were 53.5% versus 66.9%, respectively.
- At week 12, EASI-75 responses were also comparable. In the pooled groups by dose, with abrocitinib 200 mg, EASI-75 response rates were 65.2% in patients with prior dupilumab therapy versus 62.4% in those without; at abrocitinib 100 mg, 34.5% versus 42.7% responded. Corresponding rates in JADE REGIMEN were 64.0% versus 76.4%, respectively.
- Treatment-emergent adverse event rates among patients with versus without prior biologic therapy were, respectively, 71.7% versus 69.9% (abrocitinib 200 mg + 100 mg groups) in the pooled population. Rates in JADE REGIMEN with abrocitinib 200 mg were, respectively, 66.3% versus 66.5%.
- Abrocitinib efficacy and safety were consistent in patients with moderate-to-severe atopic dermatitis, regardless of prior biologic therapy. Adverse events in the pooled monotherapy trials and in JADE REGIMEN included acne, atopic dermatitis, diarrhea, headache, nasopharyngitis, nausea, upper abdominal pain, and upper respiratory tract infection.
The authors acknowledge that the post hoc study design is a limitation and recommend confirming these findings in a large, long-term prospective study.
JAK inhibitors expand treatment options
The results will help doctors treat their patients, Jami L. Miller, MD, associate professor of dermatology and dermatology clinic medical director at Vanderbilt University Medical Center, Nashville, Tenn., told this news organization.
“Because JAK inhibitors have potentially more side effects than inhibitors of interleukin-4 and interleukin-13, in clinical practice most dermatologists are more likely to treat patients first with dupilumab or similar meds and step up to a JAK inhibitor if they do not respond,” she added in an email.
“With more meds coming out to meet the needs of this population, this is an exciting time for patients with moderate-to-severe atopic dermatitis,” she commented.
Lindsay C. Strowd, MD, associate professor and vice chair of the department of dermatology at Wake Forest University, Winston-Salem, N.C., said JAK inhibitors are increasingly being studied and approved for use in various dermatologic diseases.
An oral JAK inhibitor (upadacitinib) is currently FDA approved for moderate-to-severe atopic dermatitis, and a topical JAK inhibitor (ruxolitinib) is also approved for use in atopic dermatitis, Dr. Strowd noted.
“The study results give providers important practical information,” added Dr. Strowd, who also was not involved with the study. “Those of us who care for patients with severe atopic dermatitis need to know how patients with prior biologic exposure will respond as newer agents come to market and the options for biologic use in atopic dermatitis continue to grow.”
The study was sponsored by Pfizer. All study authors have reported relevant financial relationships with, and several authors are employees of, Pfizer, the developer of abrocitinib. Dr. Strowd and Dr. Miller have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
an industry-sponsored study reports.
“In this post hoc analysis, both the efficacy and the safety profiles of abrocitinib were consistent in patients with moderate-to-severe atopic dermatitis, regardless of prior biologic therapy use,” lead author Melinda Gooderham, MD, medical director of the SKiN Centre for Dermatology, Peterborough, Ont., said during an oral presentation at the Society for Investigative Dermatology (SID) 2022 Annual Meeting.
“These results ... support the use of abrocitinib in patients who might have received biologic therapy prior,” she added.
“Prior biologic use did not reveal any new safety signals ... keeping in mind the key limitation of this analysis is that it was done post hoc,” she noted.
Guidelines for moderate-to-severe atopic dermatitis refractory to topical or systemic therapy include systemic immunosuppressants and dupilumab, a monoclonal antibody that inhibits interleukin-4 and interleukin-13 cytokine-induced responses, Dr. Gooderham said.
The Food and Drug Administration recently approved abrocitinib, an oral once-a-day Janus kinase 1 (JAK1) inhibitor, to treat the disease. The approval came with a boxed warning about increased risk for serious infections, mortality, malignancy, and lymphoproliferative disorders, major adverse cardiovascular events, thrombosis, and laboratory abnormalities.
Comparing the bio-experienced with the bio-naive
Dr. Gooderham and colleagues investigated whether patients who’d been treated with a biologic would respond to abrocitinib differently than patients who had not received prior biologic treatment.
Researchers pooled data from two phase 3 placebo-controlled trials of abrocitinib that led to approval and an earlier phase 2b study. They identified 67 patients previously treated with dupilumab and 867 patients who were bio-naive. They repeated their analysis using data from another phase 3 study of abrocitinib on 86 patients previously treated with dupilumab and 1,147 who were bio-naive. On average, the bio-experienced patients were in their mid-30s to early 40s, and the bio-naive group was several years younger.
In the pooled phase 2b and phase 3 JADE MONO-1 and JADE MONO-2 monotherapy trials, patients received once-daily abrocitinib 100 or 200 mg or placebo for 12 weeks. In the phase 3 JADE REGIMEN, which they analyzed separately, eligible patients were enrolled in a 12-week open-label run-in period during which they received an induction treatment of abrocitinib 200 mg once a day.
Researchers compared results of two assessments: the IGA (Investigator Global Assessment) and EASI-75 (Eczema Area and Severity Index, 75% or greater improvement from baseline).
- At week 12, IGA 0/1 dose-dependent response rates were similar in the pooled groups, regardless of whether they had received prior biologic therapy. With abrocitinib 200 mg, 43.5% of those with prior dupilumab therapy responded versus 41.4% of bio-naive patients; with abrocitinib 100 mg, 24.1% versus 26.7% responded. In JADE REGIMEN, corresponding response rates with abrocitinib 200 mg were 53.5% versus 66.9%, respectively.
- At week 12, EASI-75 responses were also comparable. In the pooled groups by dose, with abrocitinib 200 mg, EASI-75 response rates were 65.2% in patients with prior dupilumab therapy versus 62.4% in those without; at abrocitinib 100 mg, 34.5% versus 42.7% responded. Corresponding rates in JADE REGIMEN were 64.0% versus 76.4%, respectively.
- Treatment-emergent adverse event rates among patients with versus without prior biologic therapy were, respectively, 71.7% versus 69.9% (abrocitinib 200 mg + 100 mg groups) in the pooled population. Rates in JADE REGIMEN with abrocitinib 200 mg were, respectively, 66.3% versus 66.5%.
- Abrocitinib efficacy and safety were consistent in patients with moderate-to-severe atopic dermatitis, regardless of prior biologic therapy. Adverse events in the pooled monotherapy trials and in JADE REGIMEN included acne, atopic dermatitis, diarrhea, headache, nasopharyngitis, nausea, upper abdominal pain, and upper respiratory tract infection.
The authors acknowledge that the post hoc study design is a limitation and recommend confirming these findings in a large, long-term prospective study.
JAK inhibitors expand treatment options
The results will help doctors treat their patients, Jami L. Miller, MD, associate professor of dermatology and dermatology clinic medical director at Vanderbilt University Medical Center, Nashville, Tenn., told this news organization.
“Because JAK inhibitors have potentially more side effects than inhibitors of interleukin-4 and interleukin-13, in clinical practice most dermatologists are more likely to treat patients first with dupilumab or similar meds and step up to a JAK inhibitor if they do not respond,” she added in an email.
“With more meds coming out to meet the needs of this population, this is an exciting time for patients with moderate-to-severe atopic dermatitis,” she commented.
Lindsay C. Strowd, MD, associate professor and vice chair of the department of dermatology at Wake Forest University, Winston-Salem, N.C., said JAK inhibitors are increasingly being studied and approved for use in various dermatologic diseases.
An oral JAK inhibitor (upadacitinib) is currently FDA approved for moderate-to-severe atopic dermatitis, and a topical JAK inhibitor (ruxolitinib) is also approved for use in atopic dermatitis, Dr. Strowd noted.
“The study results give providers important practical information,” added Dr. Strowd, who also was not involved with the study. “Those of us who care for patients with severe atopic dermatitis need to know how patients with prior biologic exposure will respond as newer agents come to market and the options for biologic use in atopic dermatitis continue to grow.”
The study was sponsored by Pfizer. All study authors have reported relevant financial relationships with, and several authors are employees of, Pfizer, the developer of abrocitinib. Dr. Strowd and Dr. Miller have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
an industry-sponsored study reports.
“In this post hoc analysis, both the efficacy and the safety profiles of abrocitinib were consistent in patients with moderate-to-severe atopic dermatitis, regardless of prior biologic therapy use,” lead author Melinda Gooderham, MD, medical director of the SKiN Centre for Dermatology, Peterborough, Ont., said during an oral presentation at the Society for Investigative Dermatology (SID) 2022 Annual Meeting.
“These results ... support the use of abrocitinib in patients who might have received biologic therapy prior,” she added.
“Prior biologic use did not reveal any new safety signals ... keeping in mind the key limitation of this analysis is that it was done post hoc,” she noted.
Guidelines for moderate-to-severe atopic dermatitis refractory to topical or systemic therapy include systemic immunosuppressants and dupilumab, a monoclonal antibody that inhibits interleukin-4 and interleukin-13 cytokine-induced responses, Dr. Gooderham said.
The Food and Drug Administration recently approved abrocitinib, an oral once-a-day Janus kinase 1 (JAK1) inhibitor, to treat the disease. The approval came with a boxed warning about increased risk for serious infections, mortality, malignancy, and lymphoproliferative disorders, major adverse cardiovascular events, thrombosis, and laboratory abnormalities.
Comparing the bio-experienced with the bio-naive
Dr. Gooderham and colleagues investigated whether patients who’d been treated with a biologic would respond to abrocitinib differently than patients who had not received prior biologic treatment.
Researchers pooled data from two phase 3 placebo-controlled trials of abrocitinib that led to approval and an earlier phase 2b study. They identified 67 patients previously treated with dupilumab and 867 patients who were bio-naive. They repeated their analysis using data from another phase 3 study of abrocitinib on 86 patients previously treated with dupilumab and 1,147 who were bio-naive. On average, the bio-experienced patients were in their mid-30s to early 40s, and the bio-naive group was several years younger.
In the pooled phase 2b and phase 3 JADE MONO-1 and JADE MONO-2 monotherapy trials, patients received once-daily abrocitinib 100 or 200 mg or placebo for 12 weeks. In the phase 3 JADE REGIMEN, which they analyzed separately, eligible patients were enrolled in a 12-week open-label run-in period during which they received an induction treatment of abrocitinib 200 mg once a day.
Researchers compared results of two assessments: the IGA (Investigator Global Assessment) and EASI-75 (Eczema Area and Severity Index, 75% or greater improvement from baseline).
- At week 12, IGA 0/1 dose-dependent response rates were similar in the pooled groups, regardless of whether they had received prior biologic therapy. With abrocitinib 200 mg, 43.5% of those with prior dupilumab therapy responded versus 41.4% of bio-naive patients; with abrocitinib 100 mg, 24.1% versus 26.7% responded. In JADE REGIMEN, corresponding response rates with abrocitinib 200 mg were 53.5% versus 66.9%, respectively.
- At week 12, EASI-75 responses were also comparable. In the pooled groups by dose, with abrocitinib 200 mg, EASI-75 response rates were 65.2% in patients with prior dupilumab therapy versus 62.4% in those without; at abrocitinib 100 mg, 34.5% versus 42.7% responded. Corresponding rates in JADE REGIMEN were 64.0% versus 76.4%, respectively.
- Treatment-emergent adverse event rates among patients with versus without prior biologic therapy were, respectively, 71.7% versus 69.9% (abrocitinib 200 mg + 100 mg groups) in the pooled population. Rates in JADE REGIMEN with abrocitinib 200 mg were, respectively, 66.3% versus 66.5%.
- Abrocitinib efficacy and safety were consistent in patients with moderate-to-severe atopic dermatitis, regardless of prior biologic therapy. Adverse events in the pooled monotherapy trials and in JADE REGIMEN included acne, atopic dermatitis, diarrhea, headache, nasopharyngitis, nausea, upper abdominal pain, and upper respiratory tract infection.
The authors acknowledge that the post hoc study design is a limitation and recommend confirming these findings in a large, long-term prospective study.
JAK inhibitors expand treatment options
The results will help doctors treat their patients, Jami L. Miller, MD, associate professor of dermatology and dermatology clinic medical director at Vanderbilt University Medical Center, Nashville, Tenn., told this news organization.
“Because JAK inhibitors have potentially more side effects than inhibitors of interleukin-4 and interleukin-13, in clinical practice most dermatologists are more likely to treat patients first with dupilumab or similar meds and step up to a JAK inhibitor if they do not respond,” she added in an email.
“With more meds coming out to meet the needs of this population, this is an exciting time for patients with moderate-to-severe atopic dermatitis,” she commented.
Lindsay C. Strowd, MD, associate professor and vice chair of the department of dermatology at Wake Forest University, Winston-Salem, N.C., said JAK inhibitors are increasingly being studied and approved for use in various dermatologic diseases.
An oral JAK inhibitor (upadacitinib) is currently FDA approved for moderate-to-severe atopic dermatitis, and a topical JAK inhibitor (ruxolitinib) is also approved for use in atopic dermatitis, Dr. Strowd noted.
“The study results give providers important practical information,” added Dr. Strowd, who also was not involved with the study. “Those of us who care for patients with severe atopic dermatitis need to know how patients with prior biologic exposure will respond as newer agents come to market and the options for biologic use in atopic dermatitis continue to grow.”
The study was sponsored by Pfizer. All study authors have reported relevant financial relationships with, and several authors are employees of, Pfizer, the developer of abrocitinib. Dr. Strowd and Dr. Miller have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.