MDedge Dermatology

The White House has filled in more details of its newly announced plans to blunt the impact of COVID-19 in the United States.

The emergency rule ordering large employers to require COVID-19 vaccines or weekly tests for their workers could be ready “within weeks,” officials said in a news briefing Sept. 10.

Labor Secretary Martin Walsh will oversee the Occupational Safety and Health Administration as the agency drafts what’s known as an emergency temporary standard, similar to the one that was issued a few months ago to protect health care workers during the pandemic.

The rule should be ready within weeks, said Jeff Zients, coordinator of the White House COVID-19 response team.

He said the ultimate goal of the president’s plan is to increase vaccinations as quickly as possible to keep schools open, the economy recovering, and to decrease hospitalizations and deaths from COVID.

Mr. Zients declined to set hard numbers around those goals, but other experts did.

“What we need to get to is 85% to 90% population immunity, and that’s going to be immunity both from vaccines and infections, before that really begins to have a substantial dampening effect on viral spread,” Ashish Jha, MD, dean of the Brown University School of Public Health, Providence, R.I., said on a call with reporters Sept. 9.

He said immunity needs to be that high because the Delta variant is so contagious.

Mandates are seen as the most effective way to increase immunity and do it quickly.

David Michaels, PhD, an epidemiologist and professor at George Washington University, Washington, says OSHA will have to work through a number of steps to develop the rule.

“OSHA will have to write a preamble explaining the standard, its justifications, its costs, and how it will be enforced,” says Dr. Michaels, who led OSHA for the Obama administration. After that, the rule will be reviewed by the White House. Then employers will have some time – typically 30 days – to comply.

In addition to drafting the standard, OSHA will oversee its enforcement.

Companies that refuse to follow the standard could be fined $13,600 per violation, Mr. Zients said.

Dr. Michaels said he doesn’t expect enforcement to be a big issue, and he said we’re likely to see the rule well before it is final.

“Most employers are law-abiding. When OSHA issues a standard, they try to meet whatever those requirements are, and generally that starts to happen when the rule is announced, even before it goes into effect,” he said.

The rule may face legal challenges as well. Several governors and state attorneys general, as well as the Republican National Committee, have promised lawsuits to stop the vaccine mandates.

Critics of the new mandates say they impinge on personal freedom and impose burdens on businesses.

But the president hit back at that notion Sept. 10.

“Look, I am so disappointed that, particularly some of the Republican governors, have been so cavalier with the health of these kids, so cavalier of the health of their communities,” President Biden told reporters.

“I don’t know of any scientist out there in this field who doesn’t think it makes considerable sense to do the six things I’ve suggested.”

Yet, others feel the new requirements didn’t go far enough.

“These are good steps in the right direction, but they’re not enough to get the job done,” said Leana Wen, MD, in an op-ed for The Washington Post.

Dr. Wen, an expert in public health, wondered why President Biden didn’t mandate vaccinations for plane and train travel. She was disappointed that children 12 and older weren’t required to be vaccinated, too.

“There are mandates for childhood immunizations in every state. The coronavirus vaccine should be no different,” she wrote.

Vaccines remain the cornerstone of U.S. plans to control the pandemic.

On Sept. 10, there was new research from the CDC and state health departments showing that the COVID-19 vaccines continue to be highly effective at preventing severe illness and death.

But the study also found that the vaccines became less effective in the United States after Delta became the dominant cause of infections here.

The study, which included more than 600,000 COVID-19 cases, analyzed breakthrough infections – cases where people got sick despite being fully vaccinated – in 13 jurisdictions in the United States between April 4 and July 17, 2021.

Epidemiologists compared breakthrough infections between two distinct points in time: Before and after the period when the Delta variant began causing most infections.

From April 4 to June 19, fully vaccinated people made up just 5% of cases, 7% of hospitalizations, and 8% of deaths. From June 20 to July 17, 18% of cases, 14% of hospitalizations, and 16% of deaths occurred in fully vaccinated people.

“After the week of June 20, 2021, when the SARS-CoV-2 Delta variant became predominant, the percentage of fully vaccinated persons among cases increased more than expected,” the study authors wrote.

Even after Delta swept the United States, fully vaccinated people were 5 times less likely to get a COVID-19 infection and more than 10 times less likely to be hospitalized or die from one.

“As we have shown in study after study, vaccination works,” CDC Director Rochelle Walensky, MD, said during the White House news briefing.

“We have the scientific tools we need to turn the corner on this pandemic. Vaccination works and will protect us from the severe complications of COVID-19,” she said.

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

The White House has filled in more details of its newly announced plans to blunt the impact of COVID-19 in the United States.

The emergency rule ordering large employers to require COVID-19 vaccines or weekly tests for their workers could be ready “within weeks,” officials said in a news briefing Sept. 10.

Labor Secretary Martin Walsh will oversee the Occupational Safety and Health Administration as the agency drafts what’s known as an emergency temporary standard, similar to the one that was issued a few months ago to protect health care workers during the pandemic.

The rule should be ready within weeks, said Jeff Zients, coordinator of the White House COVID-19 response team.

He said the ultimate goal of the president’s plan is to increase vaccinations as quickly as possible to keep schools open, the economy recovering, and to decrease hospitalizations and deaths from COVID.

Mr. Zients declined to set hard numbers around those goals, but other experts did.

“What we need to get to is 85% to 90% population immunity, and that’s going to be immunity both from vaccines and infections, before that really begins to have a substantial dampening effect on viral spread,” Ashish Jha, MD, dean of the Brown University School of Public Health, Providence, R.I., said on a call with reporters Sept. 9.

He said immunity needs to be that high because the Delta variant is so contagious.

Mandates are seen as the most effective way to increase immunity and do it quickly.

David Michaels, PhD, an epidemiologist and professor at George Washington University, Washington, says OSHA will have to work through a number of steps to develop the rule.

“OSHA will have to write a preamble explaining the standard, its justifications, its costs, and how it will be enforced,” says Dr. Michaels, who led OSHA for the Obama administration. After that, the rule will be reviewed by the White House. Then employers will have some time – typically 30 days – to comply.

In addition to drafting the standard, OSHA will oversee its enforcement.

Companies that refuse to follow the standard could be fined $13,600 per violation, Mr. Zients said.

Dr. Michaels said he doesn’t expect enforcement to be a big issue, and he said we’re likely to see the rule well before it is final.

“Most employers are law-abiding. When OSHA issues a standard, they try to meet whatever those requirements are, and generally that starts to happen when the rule is announced, even before it goes into effect,” he said.

The rule may face legal challenges as well. Several governors and state attorneys general, as well as the Republican National Committee, have promised lawsuits to stop the vaccine mandates.

Critics of the new mandates say they impinge on personal freedom and impose burdens on businesses.

But the president hit back at that notion Sept. 10.

“Look, I am so disappointed that, particularly some of the Republican governors, have been so cavalier with the health of these kids, so cavalier of the health of their communities,” President Biden told reporters.

“I don’t know of any scientist out there in this field who doesn’t think it makes considerable sense to do the six things I’ve suggested.”

Yet, others feel the new requirements didn’t go far enough.

“These are good steps in the right direction, but they’re not enough to get the job done,” said Leana Wen, MD, in an op-ed for The Washington Post.

Dr. Wen, an expert in public health, wondered why President Biden didn’t mandate vaccinations for plane and train travel. She was disappointed that children 12 and older weren’t required to be vaccinated, too.

“There are mandates for childhood immunizations in every state. The coronavirus vaccine should be no different,” she wrote.

Vaccines remain the cornerstone of U.S. plans to control the pandemic.

On Sept. 10, there was new research from the CDC and state health departments showing that the COVID-19 vaccines continue to be highly effective at preventing severe illness and death.

But the study also found that the vaccines became less effective in the United States after Delta became the dominant cause of infections here.

The study, which included more than 600,000 COVID-19 cases, analyzed breakthrough infections – cases where people got sick despite being fully vaccinated – in 13 jurisdictions in the United States between April 4 and July 17, 2021.

Epidemiologists compared breakthrough infections between two distinct points in time: Before and after the period when the Delta variant began causing most infections.

From April 4 to June 19, fully vaccinated people made up just 5% of cases, 7% of hospitalizations, and 8% of deaths. From June 20 to July 17, 18% of cases, 14% of hospitalizations, and 16% of deaths occurred in fully vaccinated people.

“After the week of June 20, 2021, when the SARS-CoV-2 Delta variant became predominant, the percentage of fully vaccinated persons among cases increased more than expected,” the study authors wrote.

Even after Delta swept the United States, fully vaccinated people were 5 times less likely to get a COVID-19 infection and more than 10 times less likely to be hospitalized or die from one.

“As we have shown in study after study, vaccination works,” CDC Director Rochelle Walensky, MD, said during the White House news briefing.

“We have the scientific tools we need to turn the corner on this pandemic. Vaccination works and will protect us from the severe complications of COVID-19,” she said.

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

The White House has filled in more details of its newly announced plans to blunt the impact of COVID-19 in the United States.

The emergency rule ordering large employers to require COVID-19 vaccines or weekly tests for their workers could be ready “within weeks,” officials said in a news briefing Sept. 10.

Labor Secretary Martin Walsh will oversee the Occupational Safety and Health Administration as the agency drafts what’s known as an emergency temporary standard, similar to the one that was issued a few months ago to protect health care workers during the pandemic.

The rule should be ready within weeks, said Jeff Zients, coordinator of the White House COVID-19 response team.

He said the ultimate goal of the president’s plan is to increase vaccinations as quickly as possible to keep schools open, the economy recovering, and to decrease hospitalizations and deaths from COVID.

Mr. Zients declined to set hard numbers around those goals, but other experts did.

“What we need to get to is 85% to 90% population immunity, and that’s going to be immunity both from vaccines and infections, before that really begins to have a substantial dampening effect on viral spread,” Ashish Jha, MD, dean of the Brown University School of Public Health, Providence, R.I., said on a call with reporters Sept. 9.

He said immunity needs to be that high because the Delta variant is so contagious.

Mandates are seen as the most effective way to increase immunity and do it quickly.

David Michaels, PhD, an epidemiologist and professor at George Washington University, Washington, says OSHA will have to work through a number of steps to develop the rule.

“OSHA will have to write a preamble explaining the standard, its justifications, its costs, and how it will be enforced,” says Dr. Michaels, who led OSHA for the Obama administration. After that, the rule will be reviewed by the White House. Then employers will have some time – typically 30 days – to comply.

In addition to drafting the standard, OSHA will oversee its enforcement.

Companies that refuse to follow the standard could be fined $13,600 per violation, Mr. Zients said.

Dr. Michaels said he doesn’t expect enforcement to be a big issue, and he said we’re likely to see the rule well before it is final.

“Most employers are law-abiding. When OSHA issues a standard, they try to meet whatever those requirements are, and generally that starts to happen when the rule is announced, even before it goes into effect,” he said.

The rule may face legal challenges as well. Several governors and state attorneys general, as well as the Republican National Committee, have promised lawsuits to stop the vaccine mandates.

Critics of the new mandates say they impinge on personal freedom and impose burdens on businesses.

But the president hit back at that notion Sept. 10.

“Look, I am so disappointed that, particularly some of the Republican governors, have been so cavalier with the health of these kids, so cavalier of the health of their communities,” President Biden told reporters.

“I don’t know of any scientist out there in this field who doesn’t think it makes considerable sense to do the six things I’ve suggested.”

Yet, others feel the new requirements didn’t go far enough.

“These are good steps in the right direction, but they’re not enough to get the job done,” said Leana Wen, MD, in an op-ed for The Washington Post.

Dr. Wen, an expert in public health, wondered why President Biden didn’t mandate vaccinations for plane and train travel. She was disappointed that children 12 and older weren’t required to be vaccinated, too.

“There are mandates for childhood immunizations in every state. The coronavirus vaccine should be no different,” she wrote.

Vaccines remain the cornerstone of U.S. plans to control the pandemic.

On Sept. 10, there was new research from the CDC and state health departments showing that the COVID-19 vaccines continue to be highly effective at preventing severe illness and death.

But the study also found that the vaccines became less effective in the United States after Delta became the dominant cause of infections here.

The study, which included more than 600,000 COVID-19 cases, analyzed breakthrough infections – cases where people got sick despite being fully vaccinated – in 13 jurisdictions in the United States between April 4 and July 17, 2021.

Epidemiologists compared breakthrough infections between two distinct points in time: Before and after the period when the Delta variant began causing most infections.

From April 4 to June 19, fully vaccinated people made up just 5% of cases, 7% of hospitalizations, and 8% of deaths. From June 20 to July 17, 18% of cases, 14% of hospitalizations, and 16% of deaths occurred in fully vaccinated people.

“After the week of June 20, 2021, when the SARS-CoV-2 Delta variant became predominant, the percentage of fully vaccinated persons among cases increased more than expected,” the study authors wrote.

Even after Delta swept the United States, fully vaccinated people were 5 times less likely to get a COVID-19 infection and more than 10 times less likely to be hospitalized or die from one.

“As we have shown in study after study, vaccination works,” CDC Director Rochelle Walensky, MD, said during the White House news briefing.

“We have the scientific tools we need to turn the corner on this pandemic. Vaccination works and will protect us from the severe complications of COVID-19,” she said.

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

After Russell Jordan sent a stool sample through the mail to the microbiome company Viome, his idea of what he should eat shifted. The gym owner in Sacramento, had always consumed large quantities of leafy greens. But the results from the test – which sequenced and analyzed the microbes in a pea-sized stool sample – recommended he steer clear of spinach, kale, and broccoli.

“Things I’ve been eating for the better part of 30 years,” said Mr. Jordan, 31. “And it worked.” Soon, his mild indigestion subsided. He recommended the product to his girlfriend.

She took the test in late February, when the company – which sells its “Gut Intelligence” test for $129 and a more extensive “Health Intelligence” test, which requires a blood sample, for $199 – began experiencing hiccups. Viome had promised results within 4 weeks once the sample arrived at a testing facility, but Mr. Jordan said his girlfriend has been waiting more than 5 months and has submitted fresh blood and stool samples – twice.

Other Viome customers have flocked to social media to complain about similar problems: stool samples lost in the mail, months-long waits with no communication from the company, samples being rejected because of shipping or lab-processing snafus. (I, too, have a stool sample lost in transit, which I mailed after a first vial was rejected because it “leaked.”) The company’s CEO, Naveen Jain, took to Facebook to apologize in late July.

Viome’s troubles provide a cautionary tale for consumers in the wild west of microbiome startups, which have been alternately hailed for health breakthroughs and indicted for fraud.

The nascent industry offers individualized diet regimens based on analyzing gut bacteria – collectively known as the gut microbiome. Consumers pay hundreds of dollars for tests not covered by insurance, hoping to get answers to health problems ranging from irritable bowel syndrome to obesity.

Venture capitalists pumped $1 billion into these kinds of startups from 2015 to 2020, according to Crunchbase, buoyed by promising research and consumers’ embrace of at-home testing. PitchBook has identified more than a dozen direct-to-consumer gut health providers.

But not all the startups are equal. Some are supported by peer-reviewed studies. Others are peddling murky science – and not just because poop samples are getting lost in the mail.

“A lot of companies are interested in the space, but they don’t have the research to show that it’s actually working,” said Christopher Lynch, acting director of the National Institutes of Health Office of Nutrition Research. “And the research is really expensive.”

With nearly $160 million in government funding, the NIH Common Fund’s Nutrition for Precision Health research program, expected to launch by early 2022, seeks to enroll 1 million people to study the interactions among diet, the microbiome, genes, metabolism and other factors.

The gut microbiome is a complex community of trillions of bacteria. Research over the past 15 years has determined that these microbes, both good and bad, are an integral part of human biology, and that altering a person’s gut microbes can fundamentally change their metabolism, immune function – and, potentially, cure diseases, explained Justin Sonnenburg, PhD, a microbiology and immunology associate professor at Stanford (Calif.) University.

Metagenomic sequencing, which identifies the unique set of bugs in someone’s gut (similar to what 23andMe does with its saliva test), has also improved dramatically, making the process cheaper for companies to reproduce.

“It’s seen as one of the exciting areas of precision health,” said Dr. Sonnenburg, who recently coauthored a study that found a fermented food diet increases microbiome diversity – which is considered positive – and reduces markers of inflammation. That includes foods like yogurt, kefir, and kimchi.

“The difficulty for the consumer is to differentiate which of these companies is based on solid science versus overreaching the current limits of the field,” he added via email. “And for those companies based on solid science, what are the limits of what they should be recommending?”

San Francisco–based uBiome, founded in 2012, was one of the first to offer fecal sample testing.

But as uBiome began marketing its tests as “clinical” – and seeking reimbursement from insurers for up to nearly $3,000 – its business tactics came under scrutiny. The company was raided by the FBI and later filed for bankruptcy. Earlier this year, its cofounders were indicted for defrauding insurers into paying for tests that “were not validated and not medically necessary” in order to please investors, the Department of Justice alleges.

But for Tim Spector, a professor of genetic epidemiology at King’s College London and cofounder of the startup Zoe, being associated with uBiome is insulting.

Zoe has spent more than 2 years conducting trials, which have included dietary assessments, standardized meals, testing glycemic responses and gut microbiome profiling on thousands of participants. In January, the findings were published in Nature Medicine.

The company offers a $354 test that requires a stool sample, a completed questionnaire, and then a blood sample after eating muffins designed to test blood fat and sugar levels. Customers can also opt in to a 2-week, continuous glucose monitoring test.

The results are run through the company’s algorithm to create a customized library of foods and meals – and how customers are likely to respond to those foods.

DayTwo, a Walnut Creek, Calif., company that recently raised $37 million to expand its precision nutrition program, focuses on people with prediabetes or diabetes. It sells to large employers – and, soon, to health insurance plans – rather than directly to consumers, charging “a few thousand dollars” per person, said Jan Berger, MD, chief clinical strategist.

Based on a decade of research, DayTwo has worked with nearly 75,000 people. It sends participants a testing kit and survey, and arranges for them to chat with a dietitian while their stool sample is processing. Then, when the results come in, it makes recommendations, Dr. Berger said.

“I can still eat two scoops of ice cream, but I need to add walnuts in it to regulate my blood sugar,” she offered as an example.

Viome says it has tested more than 200,000 customers and has published its methodology for analyzing stool samples, which is different from other gut health companies. But the paper does not address Viome’s larger claims of connecting the microbiome to dietary advice, and researcher Elisabeth Bik called the claims “far fetched” in a 2019 review of the preprint version.

Viome makes additional money by selling supplements, probiotics and prebiotics based on consumers’ test results. It has also rebranded as Viome Life Sciences, expanding into precision diagnostics and therapeutics, such as saliva tests to detect throat cancer. Meanwhile, its gut health program has been mired in logistical missteps.

One customer who posted on Facebook tracked her sample through the U.S. Postal Service as it boomeranged between Los Alamos, N.M., and Bothell, Wash., where it was supposed to be picked up. Another fought for a refund after waiting 6 weeks to hear her sample was not viable and learning a second attempt had expired after spending too long in transit. The company’s expected lab processing time jumped from 4 weeks in February, when Mr. Jordan said his girlfriend took her first test, to 6 in summer. (Three weeks after I mailed my second sample in July, it still hadn’t made it to the lab, so I called it quits and asked for a refund.)

In Mr. Jain’s July apology posted to the private Facebook group for Viome users, he said the company recently moved its lab from New Mexico to Washington state, close to its headquarters, which prompted a mail-forwarding fiasco. It bought new robotics that “refused to cooperate,” he wrote. “Many things didn’t go as planned during the move.”

Spokesperson Kendall Donohue said Viome has been working on the problems but laid much of the blame on the Postal Service.

She also said Viome has been notifying customers – even though many (including myself) had not been contacted.

It is Viome’s “top priority right now to ensure complete customer satisfaction, but unfortunately USPS needs to sort the issue internally for further action to be taken,” she said.

She also offered me a free “Health Intelligence” test. I declined.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

After Russell Jordan sent a stool sample through the mail to the microbiome company Viome, his idea of what he should eat shifted. The gym owner in Sacramento, had always consumed large quantities of leafy greens. But the results from the test – which sequenced and analyzed the microbes in a pea-sized stool sample – recommended he steer clear of spinach, kale, and broccoli.

“Things I’ve been eating for the better part of 30 years,” said Mr. Jordan, 31. “And it worked.” Soon, his mild indigestion subsided. He recommended the product to his girlfriend.

She took the test in late February, when the company – which sells its “Gut Intelligence” test for $129 and a more extensive “Health Intelligence” test, which requires a blood sample, for $199 – began experiencing hiccups. Viome had promised results within 4 weeks once the sample arrived at a testing facility, but Mr. Jordan said his girlfriend has been waiting more than 5 months and has submitted fresh blood and stool samples – twice.

Other Viome customers have flocked to social media to complain about similar problems: stool samples lost in the mail, months-long waits with no communication from the company, samples being rejected because of shipping or lab-processing snafus. (I, too, have a stool sample lost in transit, which I mailed after a first vial was rejected because it “leaked.”) The company’s CEO, Naveen Jain, took to Facebook to apologize in late July.

Viome’s troubles provide a cautionary tale for consumers in the wild west of microbiome startups, which have been alternately hailed for health breakthroughs and indicted for fraud.

The nascent industry offers individualized diet regimens based on analyzing gut bacteria – collectively known as the gut microbiome. Consumers pay hundreds of dollars for tests not covered by insurance, hoping to get answers to health problems ranging from irritable bowel syndrome to obesity.

Venture capitalists pumped $1 billion into these kinds of startups from 2015 to 2020, according to Crunchbase, buoyed by promising research and consumers’ embrace of at-home testing. PitchBook has identified more than a dozen direct-to-consumer gut health providers.

But not all the startups are equal. Some are supported by peer-reviewed studies. Others are peddling murky science – and not just because poop samples are getting lost in the mail.

“A lot of companies are interested in the space, but they don’t have the research to show that it’s actually working,” said Christopher Lynch, acting director of the National Institutes of Health Office of Nutrition Research. “And the research is really expensive.”

With nearly $160 million in government funding, the NIH Common Fund’s Nutrition for Precision Health research program, expected to launch by early 2022, seeks to enroll 1 million people to study the interactions among diet, the microbiome, genes, metabolism and other factors.

The gut microbiome is a complex community of trillions of bacteria. Research over the past 15 years has determined that these microbes, both good and bad, are an integral part of human biology, and that altering a person’s gut microbes can fundamentally change their metabolism, immune function – and, potentially, cure diseases, explained Justin Sonnenburg, PhD, a microbiology and immunology associate professor at Stanford (Calif.) University.

Metagenomic sequencing, which identifies the unique set of bugs in someone’s gut (similar to what 23andMe does with its saliva test), has also improved dramatically, making the process cheaper for companies to reproduce.

“It’s seen as one of the exciting areas of precision health,” said Dr. Sonnenburg, who recently coauthored a study that found a fermented food diet increases microbiome diversity – which is considered positive – and reduces markers of inflammation. That includes foods like yogurt, kefir, and kimchi.

“The difficulty for the consumer is to differentiate which of these companies is based on solid science versus overreaching the current limits of the field,” he added via email. “And for those companies based on solid science, what are the limits of what they should be recommending?”

San Francisco–based uBiome, founded in 2012, was one of the first to offer fecal sample testing.

But as uBiome began marketing its tests as “clinical” – and seeking reimbursement from insurers for up to nearly $3,000 – its business tactics came under scrutiny. The company was raided by the FBI and later filed for bankruptcy. Earlier this year, its cofounders were indicted for defrauding insurers into paying for tests that “were not validated and not medically necessary” in order to please investors, the Department of Justice alleges.

But for Tim Spector, a professor of genetic epidemiology at King’s College London and cofounder of the startup Zoe, being associated with uBiome is insulting.

Zoe has spent more than 2 years conducting trials, which have included dietary assessments, standardized meals, testing glycemic responses and gut microbiome profiling on thousands of participants. In January, the findings were published in Nature Medicine.

The company offers a $354 test that requires a stool sample, a completed questionnaire, and then a blood sample after eating muffins designed to test blood fat and sugar levels. Customers can also opt in to a 2-week, continuous glucose monitoring test.

The results are run through the company’s algorithm to create a customized library of foods and meals – and how customers are likely to respond to those foods.

DayTwo, a Walnut Creek, Calif., company that recently raised $37 million to expand its precision nutrition program, focuses on people with prediabetes or diabetes. It sells to large employers – and, soon, to health insurance plans – rather than directly to consumers, charging “a few thousand dollars” per person, said Jan Berger, MD, chief clinical strategist.

Based on a decade of research, DayTwo has worked with nearly 75,000 people. It sends participants a testing kit and survey, and arranges for them to chat with a dietitian while their stool sample is processing. Then, when the results come in, it makes recommendations, Dr. Berger said.

“I can still eat two scoops of ice cream, but I need to add walnuts in it to regulate my blood sugar,” she offered as an example.

Viome says it has tested more than 200,000 customers and has published its methodology for analyzing stool samples, which is different from other gut health companies. But the paper does not address Viome’s larger claims of connecting the microbiome to dietary advice, and researcher Elisabeth Bik called the claims “far fetched” in a 2019 review of the preprint version.

Viome makes additional money by selling supplements, probiotics and prebiotics based on consumers’ test results. It has also rebranded as Viome Life Sciences, expanding into precision diagnostics and therapeutics, such as saliva tests to detect throat cancer. Meanwhile, its gut health program has been mired in logistical missteps.

One customer who posted on Facebook tracked her sample through the U.S. Postal Service as it boomeranged between Los Alamos, N.M., and Bothell, Wash., where it was supposed to be picked up. Another fought for a refund after waiting 6 weeks to hear her sample was not viable and learning a second attempt had expired after spending too long in transit. The company’s expected lab processing time jumped from 4 weeks in February, when Mr. Jordan said his girlfriend took her first test, to 6 in summer. (Three weeks after I mailed my second sample in July, it still hadn’t made it to the lab, so I called it quits and asked for a refund.)

In Mr. Jain’s July apology posted to the private Facebook group for Viome users, he said the company recently moved its lab from New Mexico to Washington state, close to its headquarters, which prompted a mail-forwarding fiasco. It bought new robotics that “refused to cooperate,” he wrote. “Many things didn’t go as planned during the move.”

Spokesperson Kendall Donohue said Viome has been working on the problems but laid much of the blame on the Postal Service.

She also said Viome has been notifying customers – even though many (including myself) had not been contacted.

It is Viome’s “top priority right now to ensure complete customer satisfaction, but unfortunately USPS needs to sort the issue internally for further action to be taken,” she said.

She also offered me a free “Health Intelligence” test. I declined.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

After Russell Jordan sent a stool sample through the mail to the microbiome company Viome, his idea of what he should eat shifted. The gym owner in Sacramento, had always consumed large quantities of leafy greens. But the results from the test – which sequenced and analyzed the microbes in a pea-sized stool sample – recommended he steer clear of spinach, kale, and broccoli.

“Things I’ve been eating for the better part of 30 years,” said Mr. Jordan, 31. “And it worked.” Soon, his mild indigestion subsided. He recommended the product to his girlfriend.

She took the test in late February, when the company – which sells its “Gut Intelligence” test for $129 and a more extensive “Health Intelligence” test, which requires a blood sample, for $199 – began experiencing hiccups. Viome had promised results within 4 weeks once the sample arrived at a testing facility, but Mr. Jordan said his girlfriend has been waiting more than 5 months and has submitted fresh blood and stool samples – twice.

Other Viome customers have flocked to social media to complain about similar problems: stool samples lost in the mail, months-long waits with no communication from the company, samples being rejected because of shipping or lab-processing snafus. (I, too, have a stool sample lost in transit, which I mailed after a first vial was rejected because it “leaked.”) The company’s CEO, Naveen Jain, took to Facebook to apologize in late July.

Viome’s troubles provide a cautionary tale for consumers in the wild west of microbiome startups, which have been alternately hailed for health breakthroughs and indicted for fraud.

The nascent industry offers individualized diet regimens based on analyzing gut bacteria – collectively known as the gut microbiome. Consumers pay hundreds of dollars for tests not covered by insurance, hoping to get answers to health problems ranging from irritable bowel syndrome to obesity.

Venture capitalists pumped $1 billion into these kinds of startups from 2015 to 2020, according to Crunchbase, buoyed by promising research and consumers’ embrace of at-home testing. PitchBook has identified more than a dozen direct-to-consumer gut health providers.

But not all the startups are equal. Some are supported by peer-reviewed studies. Others are peddling murky science – and not just because poop samples are getting lost in the mail.

“A lot of companies are interested in the space, but they don’t have the research to show that it’s actually working,” said Christopher Lynch, acting director of the National Institutes of Health Office of Nutrition Research. “And the research is really expensive.”

With nearly $160 million in government funding, the NIH Common Fund’s Nutrition for Precision Health research program, expected to launch by early 2022, seeks to enroll 1 million people to study the interactions among diet, the microbiome, genes, metabolism and other factors.

The gut microbiome is a complex community of trillions of bacteria. Research over the past 15 years has determined that these microbes, both good and bad, are an integral part of human biology, and that altering a person’s gut microbes can fundamentally change their metabolism, immune function – and, potentially, cure diseases, explained Justin Sonnenburg, PhD, a microbiology and immunology associate professor at Stanford (Calif.) University.

Metagenomic sequencing, which identifies the unique set of bugs in someone’s gut (similar to what 23andMe does with its saliva test), has also improved dramatically, making the process cheaper for companies to reproduce.

“It’s seen as one of the exciting areas of precision health,” said Dr. Sonnenburg, who recently coauthored a study that found a fermented food diet increases microbiome diversity – which is considered positive – and reduces markers of inflammation. That includes foods like yogurt, kefir, and kimchi.

“The difficulty for the consumer is to differentiate which of these companies is based on solid science versus overreaching the current limits of the field,” he added via email. “And for those companies based on solid science, what are the limits of what they should be recommending?”

San Francisco–based uBiome, founded in 2012, was one of the first to offer fecal sample testing.

But as uBiome began marketing its tests as “clinical” – and seeking reimbursement from insurers for up to nearly $3,000 – its business tactics came under scrutiny. The company was raided by the FBI and later filed for bankruptcy. Earlier this year, its cofounders were indicted for defrauding insurers into paying for tests that “were not validated and not medically necessary” in order to please investors, the Department of Justice alleges.

But for Tim Spector, a professor of genetic epidemiology at King’s College London and cofounder of the startup Zoe, being associated with uBiome is insulting.

Zoe has spent more than 2 years conducting trials, which have included dietary assessments, standardized meals, testing glycemic responses and gut microbiome profiling on thousands of participants. In January, the findings were published in Nature Medicine.

The company offers a $354 test that requires a stool sample, a completed questionnaire, and then a blood sample after eating muffins designed to test blood fat and sugar levels. Customers can also opt in to a 2-week, continuous glucose monitoring test.

The results are run through the company’s algorithm to create a customized library of foods and meals – and how customers are likely to respond to those foods.

DayTwo, a Walnut Creek, Calif., company that recently raised $37 million to expand its precision nutrition program, focuses on people with prediabetes or diabetes. It sells to large employers – and, soon, to health insurance plans – rather than directly to consumers, charging “a few thousand dollars” per person, said Jan Berger, MD, chief clinical strategist.

Based on a decade of research, DayTwo has worked with nearly 75,000 people. It sends participants a testing kit and survey, and arranges for them to chat with a dietitian while their stool sample is processing. Then, when the results come in, it makes recommendations, Dr. Berger said.

“I can still eat two scoops of ice cream, but I need to add walnuts in it to regulate my blood sugar,” she offered as an example.

Viome says it has tested more than 200,000 customers and has published its methodology for analyzing stool samples, which is different from other gut health companies. But the paper does not address Viome’s larger claims of connecting the microbiome to dietary advice, and researcher Elisabeth Bik called the claims “far fetched” in a 2019 review of the preprint version.

Viome makes additional money by selling supplements, probiotics and prebiotics based on consumers’ test results. It has also rebranded as Viome Life Sciences, expanding into precision diagnostics and therapeutics, such as saliva tests to detect throat cancer. Meanwhile, its gut health program has been mired in logistical missteps.

One customer who posted on Facebook tracked her sample through the U.S. Postal Service as it boomeranged between Los Alamos, N.M., and Bothell, Wash., where it was supposed to be picked up. Another fought for a refund after waiting 6 weeks to hear her sample was not viable and learning a second attempt had expired after spending too long in transit. The company’s expected lab processing time jumped from 4 weeks in February, when Mr. Jordan said his girlfriend took her first test, to 6 in summer. (Three weeks after I mailed my second sample in July, it still hadn’t made it to the lab, so I called it quits and asked for a refund.)

In Mr. Jain’s July apology posted to the private Facebook group for Viome users, he said the company recently moved its lab from New Mexico to Washington state, close to its headquarters, which prompted a mail-forwarding fiasco. It bought new robotics that “refused to cooperate,” he wrote. “Many things didn’t go as planned during the move.”

Spokesperson Kendall Donohue said Viome has been working on the problems but laid much of the blame on the Postal Service.

She also said Viome has been notifying customers – even though many (including myself) had not been contacted.

It is Viome’s “top priority right now to ensure complete customer satisfaction, but unfortunately USPS needs to sort the issue internally for further action to be taken,” she said.

She also offered me a free “Health Intelligence” test. I declined.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

An expert panel of 48 dermatologists from 13 countries has developed recommendations to guide efforts aimed at preventing cutaneous squamous cell carcinoma (CSCC) in solid organ transplant recipients.

The recommendations were published online on Sept. 1 in JAMA Dermatology.

Because of lifelong immunosuppression, solid organ transplant recipients (SOTRs) have a risk of CSCC that is 20-200 times higher than in the general population and despite a growing literature on prevention of CSCC in these patients, uncertainty remains regarding best practices for various patient scenarios.

Paul Massey, MD, MPH, of the department of dermatology, Brigham and Women’s Hospital, Boston, and colleagues used a Delphi process to identify consensus-based medical management recommendations for prevention of CSCC in SOTRs.

The survey design was guided by a novel actinic damage and skin cancer index (AD-SCI) made up of six ordinal stages corresponding to an increasing burden of actinic damage and CSCC.

The AD-SCI stage-based recommendations were established when consensus was reached (80% or higher concordance) or near consensus was reached (70%-80% concordance) among panel members.

For five of the six AD-SCI stages, the panel was able to make recommendations. Key recommendations include:
 

• Cryotherapy for scattered AK.
• Field therapy for AK when grouped in one site, unless AKs are thick, in which case field therapy and cryotherapy are recommended.
• Combination lesion-directed and field therapy with fluorouracil for field cancerized skin.
• Initiation of acitretin therapy and discussion of immunosuppression reduction or modification for patients who develop multiple CSCCs at a high rate (10 per year) or develop high-risk CSCC (defined by a tumor with roughly ≥20% risk of nodal metastasis). The panel did not make a recommendation as to the best immunosuppression modification strategy to pursue.

Lingering questions

The panel was unable to reach consensus on a recommendation for SOTRs with a first low-risk CSCC, reflecting “clinical equipoise” in this situation and the need for further study in this clinical scenario, they say.

The panel did not make a recommendation for use of nicotinamide or capecitabine in any of the six stages, which is “notable,” they acknowledge, given results of a double-blind randomized controlled trial in immunocompetent patients demonstrating benefit in preventing AKs and CSCCs, as reported previously.

Nearly three-quarters of the panel felt that a lack of efficacy data specifically for the SOTR population limited their use of nicotinamide. “Given the low cost, high safety, and demonstration of CSCC reduction in non-SOTRs, nicotinamide administration may be an area for further consideration and expanded study,” the panel wrote.

As for capecitabine, the panel notes that case series in SOTRs have found efficacy for chemoprevention, but randomized controlled studies are lacking. More than half of the panel noted that they did not have routine access to capecitabine in their practice.

The panel recommended routine skin surveillance and sunscreen use for all patients.

“These recommendations reflect consensus among expert transplant dermatologists and the incorporation of limited and sometimes contradictory evidence into real-world clinical experience across a range of CSCC disease severity,” the panel said.

“Areas of consensus may aid physicians in establishing best practices regarding prevention of CSCC in SOTRs in the setting of limited high level of evidence data in this population,” they added.

This research had no specific funding. Author disclosures included serving as a consultant to Regeneron, Sanofi, and receiving research funding from Castle Biosciences, Regeneron, Novartis, and Genentech. A complete list of disclosures for panel members is available with the original article.

An expert panel of 48 dermatologists from 13 countries has developed recommendations to guide efforts aimed at preventing cutaneous squamous cell carcinoma (CSCC) in solid organ transplant recipients.

The recommendations were published online on Sept. 1 in JAMA Dermatology.

Because of lifelong immunosuppression, solid organ transplant recipients (SOTRs) have a risk of CSCC that is 20-200 times higher than in the general population and despite a growing literature on prevention of CSCC in these patients, uncertainty remains regarding best practices for various patient scenarios.

Paul Massey, MD, MPH, of the department of dermatology, Brigham and Women’s Hospital, Boston, and colleagues used a Delphi process to identify consensus-based medical management recommendations for prevention of CSCC in SOTRs.

The survey design was guided by a novel actinic damage and skin cancer index (AD-SCI) made up of six ordinal stages corresponding to an increasing burden of actinic damage and CSCC.

The AD-SCI stage-based recommendations were established when consensus was reached (80% or higher concordance) or near consensus was reached (70%-80% concordance) among panel members.

For five of the six AD-SCI stages, the panel was able to make recommendations. Key recommendations include:
 

• Cryotherapy for scattered AK.
• Field therapy for AK when grouped in one site, unless AKs are thick, in which case field therapy and cryotherapy are recommended.
• Combination lesion-directed and field therapy with fluorouracil for field cancerized skin.
• Initiation of acitretin therapy and discussion of immunosuppression reduction or modification for patients who develop multiple CSCCs at a high rate (10 per year) or develop high-risk CSCC (defined by a tumor with roughly ≥20% risk of nodal metastasis). The panel did not make a recommendation as to the best immunosuppression modification strategy to pursue.

Lingering questions

The panel was unable to reach consensus on a recommendation for SOTRs with a first low-risk CSCC, reflecting “clinical equipoise” in this situation and the need for further study in this clinical scenario, they say.

The panel did not make a recommendation for use of nicotinamide or capecitabine in any of the six stages, which is “notable,” they acknowledge, given results of a double-blind randomized controlled trial in immunocompetent patients demonstrating benefit in preventing AKs and CSCCs, as reported previously.

Nearly three-quarters of the panel felt that a lack of efficacy data specifically for the SOTR population limited their use of nicotinamide. “Given the low cost, high safety, and demonstration of CSCC reduction in non-SOTRs, nicotinamide administration may be an area for further consideration and expanded study,” the panel wrote.

As for capecitabine, the panel notes that case series in SOTRs have found efficacy for chemoprevention, but randomized controlled studies are lacking. More than half of the panel noted that they did not have routine access to capecitabine in their practice.

The panel recommended routine skin surveillance and sunscreen use for all patients.

“These recommendations reflect consensus among expert transplant dermatologists and the incorporation of limited and sometimes contradictory evidence into real-world clinical experience across a range of CSCC disease severity,” the panel said.

“Areas of consensus may aid physicians in establishing best practices regarding prevention of CSCC in SOTRs in the setting of limited high level of evidence data in this population,” they added.

This research had no specific funding. Author disclosures included serving as a consultant to Regeneron, Sanofi, and receiving research funding from Castle Biosciences, Regeneron, Novartis, and Genentech. A complete list of disclosures for panel members is available with the original article.

An expert panel of 48 dermatologists from 13 countries has developed recommendations to guide efforts aimed at preventing cutaneous squamous cell carcinoma (CSCC) in solid organ transplant recipients.

The recommendations were published online on Sept. 1 in JAMA Dermatology.

Because of lifelong immunosuppression, solid organ transplant recipients (SOTRs) have a risk of CSCC that is 20-200 times higher than in the general population and despite a growing literature on prevention of CSCC in these patients, uncertainty remains regarding best practices for various patient scenarios.

Paul Massey, MD, MPH, of the department of dermatology, Brigham and Women’s Hospital, Boston, and colleagues used a Delphi process to identify consensus-based medical management recommendations for prevention of CSCC in SOTRs.

The survey design was guided by a novel actinic damage and skin cancer index (AD-SCI) made up of six ordinal stages corresponding to an increasing burden of actinic damage and CSCC.

The AD-SCI stage-based recommendations were established when consensus was reached (80% or higher concordance) or near consensus was reached (70%-80% concordance) among panel members.

For five of the six AD-SCI stages, the panel was able to make recommendations. Key recommendations include:
 

• Cryotherapy for scattered AK.
• Field therapy for AK when grouped in one site, unless AKs are thick, in which case field therapy and cryotherapy are recommended.
• Combination lesion-directed and field therapy with fluorouracil for field cancerized skin.
• Initiation of acitretin therapy and discussion of immunosuppression reduction or modification for patients who develop multiple CSCCs at a high rate (10 per year) or develop high-risk CSCC (defined by a tumor with roughly ≥20% risk of nodal metastasis). The panel did not make a recommendation as to the best immunosuppression modification strategy to pursue.

Lingering questions

The panel was unable to reach consensus on a recommendation for SOTRs with a first low-risk CSCC, reflecting “clinical equipoise” in this situation and the need for further study in this clinical scenario, they say.

The panel did not make a recommendation for use of nicotinamide or capecitabine in any of the six stages, which is “notable,” they acknowledge, given results of a double-blind randomized controlled trial in immunocompetent patients demonstrating benefit in preventing AKs and CSCCs, as reported previously.

Nearly three-quarters of the panel felt that a lack of efficacy data specifically for the SOTR population limited their use of nicotinamide. “Given the low cost, high safety, and demonstration of CSCC reduction in non-SOTRs, nicotinamide administration may be an area for further consideration and expanded study,” the panel wrote.

As for capecitabine, the panel notes that case series in SOTRs have found efficacy for chemoprevention, but randomized controlled studies are lacking. More than half of the panel noted that they did not have routine access to capecitabine in their practice.

The panel recommended routine skin surveillance and sunscreen use for all patients.

“These recommendations reflect consensus among expert transplant dermatologists and the incorporation of limited and sometimes contradictory evidence into real-world clinical experience across a range of CSCC disease severity,” the panel said.

“Areas of consensus may aid physicians in establishing best practices regarding prevention of CSCC in SOTRs in the setting of limited high level of evidence data in this population,” they added.

This research had no specific funding. Author disclosures included serving as a consultant to Regeneron, Sanofi, and receiving research funding from Castle Biosciences, Regeneron, Novartis, and Genentech. A complete list of disclosures for panel members is available with the original article.

Long-term symptoms, like those linked with COVID-19, were common in people who had even just a single positive test, new Centers for Disease Control and Prevention data show.

The data show that symptoms in this group – including fatigue, cough, and headache – tended to last for more than a month. 

Frequency of symptoms in people with a positive test was 1.5 times higher, compared with people whose tests had always been negative, according to the research published in the CDC’s latest Morbidity and Mortality Weekly Report.

Lead author Valentine Wanga, PhD, with the CDC’s COVID-19 response team, and colleagues conducted a non–probability-based internet panel survey of about 6,000 U.S. adults to assess long-term symptoms often associated with COVID-19 among those who had ever tested positive or always tested negative for COVID-19 between January 2020 and April 2021.

William Schaffner, MD, an infectious disease expert at Vanderbilt University, Nashville, Tenn., said in an interview that this research “establishes more securely than before that you don’t have to be hospitalized with COVID in order to develop long COVID symptoms.”

That’s better known among infectious disease experts, he said, but added that “this survey really gives a firm database for that.”
 

Study results

The study’s results showed that, compared with respondents who had a negative test result, those who received a positive result reported a significantly higher prevalence of any long-term symptom (65.9% vs. 42.9%), fatigue (22.5% vs. 12.0%), change in sense of smell or taste (17.3% vs. 1.7%), shortness of breath (15.5% vs. 5.2%), cough (14.5% vs. 4.9%), and headache (13.8% vs. 9.9%).

More people who had a positive test result (76.2%) reported persistence for more than a month of at least one initially occurring symptom, compared with those whose test results were always negative (69.6%).

The numbers are further proof, Dr. Schaffner said, that COVID not only will be an acute stressor on the health care system but patients with long COVID will need help with managing care for the long term.

“We still don’t know what the COVID virus does that results in these long COVID symptoms,” he said. Vanderbilt and many other institutions have developed “long COVID” centers as a testament to how important the problem is.

Long COVID symptoms are not well understood and most studies have looked at the effects from patients who had been hospitalized with COVID-19.

In this survey, respondents self-reported whether they had ever had a positive SARS-CoV-2 test result (698), always received a negative test result (2,437), or never were tested for SARS-CoV-2 (2,750).

Compared with those who always tested negative, a larger proportion of those who tested positive (28.7% vs. 15.7%) reported believing that receiving a COVID-19 vaccine made their long-term symptoms better. No difference was found in reported beliefs that a vaccine made long-term symptoms worse.

Dr. Schaffner said he found that survey result interesting, but said that is not backed up by current data and would need further study.

“I would treat that with great caution,” he said. “I’m not dismissing it, but you can’t take that at face value. All of us who get sick and those of us who care for people who are sick – if there’s an intervention, we all hope for the best. We’re being optimistic. It’s when you do a randomized, double-blind, placebo-controlled study that you can find out whether your instincts or hopes were correct.”

The authors said that findings can inform public health preparedness, help guide care for people with post-COVID conditions, and help make the case for vaccines.

The study authors and Dr. Schaffner disclosed no relevant financial relationships.

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

Long-term symptoms, like those linked with COVID-19, were common in people who had even just a single positive test, new Centers for Disease Control and Prevention data show.

The data show that symptoms in this group – including fatigue, cough, and headache – tended to last for more than a month. 

Frequency of symptoms in people with a positive test was 1.5 times higher, compared with people whose tests had always been negative, according to the research published in the CDC’s latest Morbidity and Mortality Weekly Report.

Lead author Valentine Wanga, PhD, with the CDC’s COVID-19 response team, and colleagues conducted a non–probability-based internet panel survey of about 6,000 U.S. adults to assess long-term symptoms often associated with COVID-19 among those who had ever tested positive or always tested negative for COVID-19 between January 2020 and April 2021.

William Schaffner, MD, an infectious disease expert at Vanderbilt University, Nashville, Tenn., said in an interview that this research “establishes more securely than before that you don’t have to be hospitalized with COVID in order to develop long COVID symptoms.”

That’s better known among infectious disease experts, he said, but added that “this survey really gives a firm database for that.”
 

Study results

The study’s results showed that, compared with respondents who had a negative test result, those who received a positive result reported a significantly higher prevalence of any long-term symptom (65.9% vs. 42.9%), fatigue (22.5% vs. 12.0%), change in sense of smell or taste (17.3% vs. 1.7%), shortness of breath (15.5% vs. 5.2%), cough (14.5% vs. 4.9%), and headache (13.8% vs. 9.9%).

More people who had a positive test result (76.2%) reported persistence for more than a month of at least one initially occurring symptom, compared with those whose test results were always negative (69.6%).

The numbers are further proof, Dr. Schaffner said, that COVID not only will be an acute stressor on the health care system but patients with long COVID will need help with managing care for the long term.

“We still don’t know what the COVID virus does that results in these long COVID symptoms,” he said. Vanderbilt and many other institutions have developed “long COVID” centers as a testament to how important the problem is.

Long COVID symptoms are not well understood and most studies have looked at the effects from patients who had been hospitalized with COVID-19.

In this survey, respondents self-reported whether they had ever had a positive SARS-CoV-2 test result (698), always received a negative test result (2,437), or never were tested for SARS-CoV-2 (2,750).

Compared with those who always tested negative, a larger proportion of those who tested positive (28.7% vs. 15.7%) reported believing that receiving a COVID-19 vaccine made their long-term symptoms better. No difference was found in reported beliefs that a vaccine made long-term symptoms worse.

Dr. Schaffner said he found that survey result interesting, but said that is not backed up by current data and would need further study.

“I would treat that with great caution,” he said. “I’m not dismissing it, but you can’t take that at face value. All of us who get sick and those of us who care for people who are sick – if there’s an intervention, we all hope for the best. We’re being optimistic. It’s when you do a randomized, double-blind, placebo-controlled study that you can find out whether your instincts or hopes were correct.”

The authors said that findings can inform public health preparedness, help guide care for people with post-COVID conditions, and help make the case for vaccines.

The study authors and Dr. Schaffner disclosed no relevant financial relationships.

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

Long-term symptoms, like those linked with COVID-19, were common in people who had even just a single positive test, new Centers for Disease Control and Prevention data show.

The data show that symptoms in this group – including fatigue, cough, and headache – tended to last for more than a month. 

Frequency of symptoms in people with a positive test was 1.5 times higher, compared with people whose tests had always been negative, according to the research published in the CDC’s latest Morbidity and Mortality Weekly Report.

Lead author Valentine Wanga, PhD, with the CDC’s COVID-19 response team, and colleagues conducted a non–probability-based internet panel survey of about 6,000 U.S. adults to assess long-term symptoms often associated with COVID-19 among those who had ever tested positive or always tested negative for COVID-19 between January 2020 and April 2021.

William Schaffner, MD, an infectious disease expert at Vanderbilt University, Nashville, Tenn., said in an interview that this research “establishes more securely than before that you don’t have to be hospitalized with COVID in order to develop long COVID symptoms.”

That’s better known among infectious disease experts, he said, but added that “this survey really gives a firm database for that.”
 

Study results

The study’s results showed that, compared with respondents who had a negative test result, those who received a positive result reported a significantly higher prevalence of any long-term symptom (65.9% vs. 42.9%), fatigue (22.5% vs. 12.0%), change in sense of smell or taste (17.3% vs. 1.7%), shortness of breath (15.5% vs. 5.2%), cough (14.5% vs. 4.9%), and headache (13.8% vs. 9.9%).

More people who had a positive test result (76.2%) reported persistence for more than a month of at least one initially occurring symptom, compared with those whose test results were always negative (69.6%).

The numbers are further proof, Dr. Schaffner said, that COVID not only will be an acute stressor on the health care system but patients with long COVID will need help with managing care for the long term.

“We still don’t know what the COVID virus does that results in these long COVID symptoms,” he said. Vanderbilt and many other institutions have developed “long COVID” centers as a testament to how important the problem is.

Long COVID symptoms are not well understood and most studies have looked at the effects from patients who had been hospitalized with COVID-19.

In this survey, respondents self-reported whether they had ever had a positive SARS-CoV-2 test result (698), always received a negative test result (2,437), or never were tested for SARS-CoV-2 (2,750).

Compared with those who always tested negative, a larger proportion of those who tested positive (28.7% vs. 15.7%) reported believing that receiving a COVID-19 vaccine made their long-term symptoms better. No difference was found in reported beliefs that a vaccine made long-term symptoms worse.

Dr. Schaffner said he found that survey result interesting, but said that is not backed up by current data and would need further study.

“I would treat that with great caution,” he said. “I’m not dismissing it, but you can’t take that at face value. All of us who get sick and those of us who care for people who are sick – if there’s an intervention, we all hope for the best. We’re being optimistic. It’s when you do a randomized, double-blind, placebo-controlled study that you can find out whether your instincts or hopes were correct.”

The authors said that findings can inform public health preparedness, help guide care for people with post-COVID conditions, and help make the case for vaccines.

The study authors and Dr. Schaffner disclosed no relevant financial relationships.

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

Three primary care boards have issued a joint statement backing the Federation of State Medical Boards’ recent statement saying that, if physicians spread misinformation about COVID-19, their medical license could be suspended or revoked.

Leaders of the American Board of Family Medicine, the American Board of Internal Medicine, and the American Board of Pediatrics said Sept. 9 that they support FSMB’s position.

“We also want all physicians certified by our boards to know that such unethical or unprofessional conduct may prompt their respective Board to take action that could put their certification at risk,” a statement read. 

“Expertise matters, and board-certified physicians have demonstrated that they have stayed current in their field. Spreading misinformation or falsehoods to the public during a time of a public health emergency goes against everything our boards and our community of board-certified physicians stand for,” the leaders wrote.

“The evidence that we have safe, effective, and widely available vaccines against COVID-19 is overwhelming. We are particularly concerned about physicians who use their authority to denigrate vaccination at a time when vaccines continue to demonstrate excellent effectiveness against severe illness, hospitalization, and death.”
 

Small number spread false information

However, a small number of doctors continue to spread misinformation against the vaccines and communicate other false information surrounding COVID-19.

Some of the misinformation spreaders have had ultra-viral reach.

Among them is Daniel Stock, MD, a family physician in Indiana who has come out against COVID-19 vaccines. At a recent meeting of the Mt. Vernon Community School board in Indiana, he gave a speech urging the board to ignore the prevailing recommendations around COVID-19, such as test-and-trace measures.

Forbes reported in August that versions of the video of Stock›s speech on Facebook “have collected a total of 90 million engagements – a metric encompassing things such as comments, likes and shares – according to data collected by Media Matters for America, a liberal tech-watchdog group.”

This news organization published a story in August asking whether physicians who spread such information should lose their license and the question drew rapid-fire comments.

Commenters who argued with potential disciplinary actions raised questions about where the line will be drawn between misinformation and deeply held beliefs in terms of care.

Several comments centered on ivermectin, which is not approved by the Food and Drug Administration to treat COVID-19 but is enthusiastically supported as a COVID-19 treatment by a group of physicians called the Front Line COVID-19 Critical Care Alliance, whose website includes requests for donations.

Some cited free speech protections.
 

‘Not consistent with standards’

As for ivermectin, David G. Nichols, MD, president and CEO of the American Board of Pediatrics, gave this news organization an example: “Spreading the notion that one would not need to get vaccinated because if you get sick you could take ivermectin is a very dangerous statement. That is not consistent with the standards of professionalism required for certification or licensure.”

Ivermectin, he noted, is not an approved treatment for COVID-19.

“To say that it is or has any benefit is a false statement. We’re not willing to allow individuals who make false statements to devalue the terrific work of tens of thousands of physicians across the United States doing work under very difficult circumstances,” Dr. Nichols said.

He continued: “To suggest treatments that are known not to be effective in exchange for treatment that is known to be effective is dangerous – and ivermectin falls under that category.”

Asked whether such suggestions could result in suspension or revocation of a physician’s license, Dr. Nichols said, “It’s the kind of thing that would certainly trigger a review.”

He said the standard for separating misinformation from personal beliefs is based on whether there is scientific evidence to support the belief.

The boards are not, with this statement, attempting to referee legitimate scientific debate, he said.

The misinformation the boards are referring to, Dr. Nichols said, is “where the evidence is 100% on one side and zero on another. And the zero is not only that the opinions or beliefs are unsupported or unsubstantiated, they are indeed harmful if followed. That’s the distinction we’re trying to make here.”

As for free-speech arguments, he said, “Free speech is a constitutional right. You can say whatever you want. The issue here is you do not have the right to expect continued professional sanction of a board certificate if you are lying to the public.”

The board statement also said: “We all look to board-certified physicians to provide outstanding care and guidance; providing misinformation about a lethal disease is unethical, unprofessional, and dangerous. In times of medical emergency, the community of expert physicians committed to science and evidence collectively shares a responsibility for giving the public the most accurate and timely health information available, so they can make decisions that work best for themselves and their families.”

In addition to Dr. Nichols, the statement was signed by Warren Newton, MD, MPH, president and CEO of the American Board of Family Medicine, and Richard J. Baron, MD, president and CEO of the American Board of Internal Medicine.

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

Three primary care boards have issued a joint statement backing the Federation of State Medical Boards’ recent statement saying that, if physicians spread misinformation about COVID-19, their medical license could be suspended or revoked.

Leaders of the American Board of Family Medicine, the American Board of Internal Medicine, and the American Board of Pediatrics said Sept. 9 that they support FSMB’s position.

“We also want all physicians certified by our boards to know that such unethical or unprofessional conduct may prompt their respective Board to take action that could put their certification at risk,” a statement read. 

“Expertise matters, and board-certified physicians have demonstrated that they have stayed current in their field. Spreading misinformation or falsehoods to the public during a time of a public health emergency goes against everything our boards and our community of board-certified physicians stand for,” the leaders wrote.

“The evidence that we have safe, effective, and widely available vaccines against COVID-19 is overwhelming. We are particularly concerned about physicians who use their authority to denigrate vaccination at a time when vaccines continue to demonstrate excellent effectiveness against severe illness, hospitalization, and death.”
 

Small number spread false information

However, a small number of doctors continue to spread misinformation against the vaccines and communicate other false information surrounding COVID-19.

Some of the misinformation spreaders have had ultra-viral reach.

Among them is Daniel Stock, MD, a family physician in Indiana who has come out against COVID-19 vaccines. At a recent meeting of the Mt. Vernon Community School board in Indiana, he gave a speech urging the board to ignore the prevailing recommendations around COVID-19, such as test-and-trace measures.

Forbes reported in August that versions of the video of Stock›s speech on Facebook “have collected a total of 90 million engagements – a metric encompassing things such as comments, likes and shares – according to data collected by Media Matters for America, a liberal tech-watchdog group.”

This news organization published a story in August asking whether physicians who spread such information should lose their license and the question drew rapid-fire comments.

Commenters who argued with potential disciplinary actions raised questions about where the line will be drawn between misinformation and deeply held beliefs in terms of care.

Several comments centered on ivermectin, which is not approved by the Food and Drug Administration to treat COVID-19 but is enthusiastically supported as a COVID-19 treatment by a group of physicians called the Front Line COVID-19 Critical Care Alliance, whose website includes requests for donations.

Some cited free speech protections.
 

‘Not consistent with standards’

As for ivermectin, David G. Nichols, MD, president and CEO of the American Board of Pediatrics, gave this news organization an example: “Spreading the notion that one would not need to get vaccinated because if you get sick you could take ivermectin is a very dangerous statement. That is not consistent with the standards of professionalism required for certification or licensure.”

Ivermectin, he noted, is not an approved treatment for COVID-19.

“To say that it is or has any benefit is a false statement. We’re not willing to allow individuals who make false statements to devalue the terrific work of tens of thousands of physicians across the United States doing work under very difficult circumstances,” Dr. Nichols said.

He continued: “To suggest treatments that are known not to be effective in exchange for treatment that is known to be effective is dangerous – and ivermectin falls under that category.”

Asked whether such suggestions could result in suspension or revocation of a physician’s license, Dr. Nichols said, “It’s the kind of thing that would certainly trigger a review.”

He said the standard for separating misinformation from personal beliefs is based on whether there is scientific evidence to support the belief.

The boards are not, with this statement, attempting to referee legitimate scientific debate, he said.

The misinformation the boards are referring to, Dr. Nichols said, is “where the evidence is 100% on one side and zero on another. And the zero is not only that the opinions or beliefs are unsupported or unsubstantiated, they are indeed harmful if followed. That’s the distinction we’re trying to make here.”

As for free-speech arguments, he said, “Free speech is a constitutional right. You can say whatever you want. The issue here is you do not have the right to expect continued professional sanction of a board certificate if you are lying to the public.”

The board statement also said: “We all look to board-certified physicians to provide outstanding care and guidance; providing misinformation about a lethal disease is unethical, unprofessional, and dangerous. In times of medical emergency, the community of expert physicians committed to science and evidence collectively shares a responsibility for giving the public the most accurate and timely health information available, so they can make decisions that work best for themselves and their families.”

In addition to Dr. Nichols, the statement was signed by Warren Newton, MD, MPH, president and CEO of the American Board of Family Medicine, and Richard J. Baron, MD, president and CEO of the American Board of Internal Medicine.

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

Three primary care boards have issued a joint statement backing the Federation of State Medical Boards’ recent statement saying that, if physicians spread misinformation about COVID-19, their medical license could be suspended or revoked.

Leaders of the American Board of Family Medicine, the American Board of Internal Medicine, and the American Board of Pediatrics said Sept. 9 that they support FSMB’s position.

“We also want all physicians certified by our boards to know that such unethical or unprofessional conduct may prompt their respective Board to take action that could put their certification at risk,” a statement read. 

“Expertise matters, and board-certified physicians have demonstrated that they have stayed current in their field. Spreading misinformation or falsehoods to the public during a time of a public health emergency goes against everything our boards and our community of board-certified physicians stand for,” the leaders wrote.

“The evidence that we have safe, effective, and widely available vaccines against COVID-19 is overwhelming. We are particularly concerned about physicians who use their authority to denigrate vaccination at a time when vaccines continue to demonstrate excellent effectiveness against severe illness, hospitalization, and death.”
 

Small number spread false information

However, a small number of doctors continue to spread misinformation against the vaccines and communicate other false information surrounding COVID-19.

Some of the misinformation spreaders have had ultra-viral reach.

Among them is Daniel Stock, MD, a family physician in Indiana who has come out against COVID-19 vaccines. At a recent meeting of the Mt. Vernon Community School board in Indiana, he gave a speech urging the board to ignore the prevailing recommendations around COVID-19, such as test-and-trace measures.

Forbes reported in August that versions of the video of Stock›s speech on Facebook “have collected a total of 90 million engagements – a metric encompassing things such as comments, likes and shares – according to data collected by Media Matters for America, a liberal tech-watchdog group.”

This news organization published a story in August asking whether physicians who spread such information should lose their license and the question drew rapid-fire comments.

Commenters who argued with potential disciplinary actions raised questions about where the line will be drawn between misinformation and deeply held beliefs in terms of care.

Several comments centered on ivermectin, which is not approved by the Food and Drug Administration to treat COVID-19 but is enthusiastically supported as a COVID-19 treatment by a group of physicians called the Front Line COVID-19 Critical Care Alliance, whose website includes requests for donations.

Some cited free speech protections.
 

‘Not consistent with standards’

As for ivermectin, David G. Nichols, MD, president and CEO of the American Board of Pediatrics, gave this news organization an example: “Spreading the notion that one would not need to get vaccinated because if you get sick you could take ivermectin is a very dangerous statement. That is not consistent with the standards of professionalism required for certification or licensure.”

Ivermectin, he noted, is not an approved treatment for COVID-19.

“To say that it is or has any benefit is a false statement. We’re not willing to allow individuals who make false statements to devalue the terrific work of tens of thousands of physicians across the United States doing work under very difficult circumstances,” Dr. Nichols said.

He continued: “To suggest treatments that are known not to be effective in exchange for treatment that is known to be effective is dangerous – and ivermectin falls under that category.”

Asked whether such suggestions could result in suspension or revocation of a physician’s license, Dr. Nichols said, “It’s the kind of thing that would certainly trigger a review.”

He said the standard for separating misinformation from personal beliefs is based on whether there is scientific evidence to support the belief.

The boards are not, with this statement, attempting to referee legitimate scientific debate, he said.

The misinformation the boards are referring to, Dr. Nichols said, is “where the evidence is 100% on one side and zero on another. And the zero is not only that the opinions or beliefs are unsupported or unsubstantiated, they are indeed harmful if followed. That’s the distinction we’re trying to make here.”

As for free-speech arguments, he said, “Free speech is a constitutional right. You can say whatever you want. The issue here is you do not have the right to expect continued professional sanction of a board certificate if you are lying to the public.”

The board statement also said: “We all look to board-certified physicians to provide outstanding care and guidance; providing misinformation about a lethal disease is unethical, unprofessional, and dangerous. In times of medical emergency, the community of expert physicians committed to science and evidence collectively shares a responsibility for giving the public the most accurate and timely health information available, so they can make decisions that work best for themselves and their families.”

In addition to Dr. Nichols, the statement was signed by Warren Newton, MD, MPH, president and CEO of the American Board of Family Medicine, and Richard J. Baron, MD, president and CEO of the American Board of Internal Medicine.

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

Those who are unhappy about losing their hair might be interested to hear about a new approach where scientists use mechanical stimulation to promote hair regrowth.

Currently, Food and Drug Administration–approved drugs for hair loss include minoxidil (Rogaine) and finasteride (Propecia). But there are side effects, and the treatments only work when continuously used for an extended time.

Some people may opt instead to have hair follicle transplants, but study coauthor Fangyuan Li, PhD, from the College of Pharmaceutical Sciences at Zhejiang University in Hangzhou, China, explains, the surgery is painful and not always successful because it depends a lot on the quality of donor hair follicles, which can vary.

Seeking to develop a new nonsurgical option, the scientists, led by Jianqing Gao, vice dean of the College of Pharmaceutical Sciences at Zhejiang University, designed a dissolvable microneedle patch to deliver treatment near hair roots beneath the skin.

Male- or female-pattern baldness can be permanent when there aren’t enough blood vessels surrounding hair follicles to deliver nutrients and other essential molecules. A buildup of reactive oxygen in the scalp can prompt the death of cells that would otherwise grow new hair.

In a previous investigation, the researchers found that nanoparticles containing cerium, a silvery-white metal, can mimic the enzymes inside the body that can help ease oxidative stress.

The scientists coated cerium nanoparticles with a biodegradable compound. Then they made the microneedle patch by pouring a mixture of hyaluronic acid with cerium-containing nanoparticles into a mold.

The small needles don’t hurt when applied, Dr. Li said, as they deliver treatment to a region under the skin with no pain receptors.

The researchers tested control patches and the cerium-containing ones on male mice with bald spots created by a hair-removal cream. Both applications stimulated new blood vessels to form around the mice hair follicles. But those treated with the nanoparticle patch showed faster signs of hair recuperation at the root.

The mice also had fewer oxidative stress compounds in their skin. Microneedle patch use resulted in faster hair regrowth, compared with a cream-based treatment, and could be applied less frequently.

And though the idea is not yet ready to be tried on people, it represents an inventive step forward in addressing a common problem.

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

Those who are unhappy about losing their hair might be interested to hear about a new approach where scientists use mechanical stimulation to promote hair regrowth.

Currently, Food and Drug Administration–approved drugs for hair loss include minoxidil (Rogaine) and finasteride (Propecia). But there are side effects, and the treatments only work when continuously used for an extended time.

Some people may opt instead to have hair follicle transplants, but study coauthor Fangyuan Li, PhD, from the College of Pharmaceutical Sciences at Zhejiang University in Hangzhou, China, explains, the surgery is painful and not always successful because it depends a lot on the quality of donor hair follicles, which can vary.

Seeking to develop a new nonsurgical option, the scientists, led by Jianqing Gao, vice dean of the College of Pharmaceutical Sciences at Zhejiang University, designed a dissolvable microneedle patch to deliver treatment near hair roots beneath the skin.

Male- or female-pattern baldness can be permanent when there aren’t enough blood vessels surrounding hair follicles to deliver nutrients and other essential molecules. A buildup of reactive oxygen in the scalp can prompt the death of cells that would otherwise grow new hair.

In a previous investigation, the researchers found that nanoparticles containing cerium, a silvery-white metal, can mimic the enzymes inside the body that can help ease oxidative stress.

The scientists coated cerium nanoparticles with a biodegradable compound. Then they made the microneedle patch by pouring a mixture of hyaluronic acid with cerium-containing nanoparticles into a mold.

The small needles don’t hurt when applied, Dr. Li said, as they deliver treatment to a region under the skin with no pain receptors.

The researchers tested control patches and the cerium-containing ones on male mice with bald spots created by a hair-removal cream. Both applications stimulated new blood vessels to form around the mice hair follicles. But those treated with the nanoparticle patch showed faster signs of hair recuperation at the root.

The mice also had fewer oxidative stress compounds in their skin. Microneedle patch use resulted in faster hair regrowth, compared with a cream-based treatment, and could be applied less frequently.

And though the idea is not yet ready to be tried on people, it represents an inventive step forward in addressing a common problem.

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

Those who are unhappy about losing their hair might be interested to hear about a new approach where scientists use mechanical stimulation to promote hair regrowth.

Currently, Food and Drug Administration–approved drugs for hair loss include minoxidil (Rogaine) and finasteride (Propecia). But there are side effects, and the treatments only work when continuously used for an extended time.

Some people may opt instead to have hair follicle transplants, but study coauthor Fangyuan Li, PhD, from the College of Pharmaceutical Sciences at Zhejiang University in Hangzhou, China, explains, the surgery is painful and not always successful because it depends a lot on the quality of donor hair follicles, which can vary.

Seeking to develop a new nonsurgical option, the scientists, led by Jianqing Gao, vice dean of the College of Pharmaceutical Sciences at Zhejiang University, designed a dissolvable microneedle patch to deliver treatment near hair roots beneath the skin.

Male- or female-pattern baldness can be permanent when there aren’t enough blood vessels surrounding hair follicles to deliver nutrients and other essential molecules. A buildup of reactive oxygen in the scalp can prompt the death of cells that would otherwise grow new hair.

In a previous investigation, the researchers found that nanoparticles containing cerium, a silvery-white metal, can mimic the enzymes inside the body that can help ease oxidative stress.

The scientists coated cerium nanoparticles with a biodegradable compound. Then they made the microneedle patch by pouring a mixture of hyaluronic acid with cerium-containing nanoparticles into a mold.

The small needles don’t hurt when applied, Dr. Li said, as they deliver treatment to a region under the skin with no pain receptors.

The researchers tested control patches and the cerium-containing ones on male mice with bald spots created by a hair-removal cream. Both applications stimulated new blood vessels to form around the mice hair follicles. But those treated with the nanoparticle patch showed faster signs of hair recuperation at the root.

The mice also had fewer oxidative stress compounds in their skin. Microneedle patch use resulted in faster hair regrowth, compared with a cream-based treatment, and could be applied less frequently.

And though the idea is not yet ready to be tried on people, it represents an inventive step forward in addressing a common problem.

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

The Diagnosis: Primary Cutaneous Carcinosarcoma

The immunohistochemical findings supported an epithelial component consistent with moderately differentiated squamous cell carcinoma (SCC) and a mesenchymal component with features consistent with a sarcoma. Consequently, the lesion was diagnosed as a primary cutaneous carcinosarcoma (PCCS).

Primary cutaneous carcinosarcoma is a rare biphasic neoplasm consisting of malignant epithelial (carcinoma) and mesenchymal (sarcoma) components.¹ Primary cutaneous carcinosarcomas are uncommon, poorly understood, primary cutaneous tumors.^2,3 Characteristic of this tumor, cytokeratins highlight the epithelial component while vimentin highlights the mesenchymal component.⁴ Histologically, the sarcomatous components of PCCS often are highly variable, with an absence of transitional areas within the epithelial component, which frequently resembles basal cell carcinoma and/ or SCC.^5-7 Primary cutaneous carcinosarcoma favors areas of chronic UV radiation exposure, particularly on the head and neck. Most tumors present with a slowly growing, polypoid, flesh-colored to erythematous nodule due to the infiltrative mesenchymal component.⁷ Primary cutaneous carcinosarcoma primarily is diagnosed in elderly patients, with the majority of cases diagnosed in the eighth or ninth decades of life (range, 32–98 years).^1,8 Men appear to be twice as likely to be diagnosed with a PCCS compared to women.¹ Primary cutaneous carcinosarcomas are recognized as aggressive tumors with a high propensity to metastasize and recur locally, necessitating early diagnosis and treatment.⁴ Accurate diagnosis of PCCSs can be challenging due to the biphasic nature of the neoplasm as well as poor differentiation or unequal proportions of the epithelial and mesenchymal components.⁵ Additionally, overlapping diagnostic criteria coupled with vague demarcation between soft-tissue sarcomas and distinct carcinomas also may contribute to a delay in diagnosis.⁹ Treatment is achieved surgically by complete wide resection, with no evidence to support the use of adjuvant or neoadjuvant external beam radiation therapy. Due to the small number of reported cases, no treatment recommendations currently exist.¹

Surgical management with wide local excision has been disappointing, with recurrence rates reported as high as 33%.⁶ Primary cutaneous carcinosarcoma has an estimated overall recurrence rate of 19% and a 5-year disease-free rate of 50%.¹⁰ Risk factors associated with poorer prognosis include tumors with adnexal subtype, age less than 65 years, rapid tumor growth, a tumor greater than 20 mm at presentation, and a long-standing tumor lasting up to 30 years.^2,4 Although wide local excision and Mohs micrographic surgery (MMS) both have been utilized successfully, MMS has been shown to result in a cure rate of greater than 98%.⁶

Atypical fibroxanthoma (AFX) is a cutaneous tumor of fibrohistiocytic mesenchymal origin that typically manifests on sun-damaged skin in elderly individuals. Clinically, it presents as a rapidly growing neoplasm that often ulcerates and bleeds. These heterogenous neoplasms have several distinct characteristics, including dense cellularity with disorganized, large, pleomorphic, and atypical-appearing spindle-shaped cells arising in the upper layers of the dermis, often disseminating into the reticular dermis and occasionally into the subcutaneous fat (Figure 1). The neoplastic cells often exhibit hyperchromic and irregular nuclei, multinucleated giant cells, and atypical mitotic figures. In most cases, negative immunohistochemical staining with SOX-10, S-100, cytokeratins, desmin, and caldesmon will allow pathologists to differentiate between AFX and other common tumors on the differential diagnosis, such as SCC, melanoma, and leiomyosarcoma. CD10 and procollagen type 1 are positive antigenic markers in AFX, but they are not specific. The standard treatment of AFX includes wide local excision or MMS for superior margin control.¹¹

Spindle cell SCC presents as a raised or exophytic nodule, often with spontaneous bleeding and central ulceration. It usually presents on sun-damaged skin or in individuals with a history of ionizing radiation. Histologically, it is characterized by atypical spindleshaped keratinocytes in the dermis existing as single cells or cohesive nests along with keratin pearls (Figure 2). The atypical spindle cells may comprise the entire tumor or only a small portion. The use of immunohistochemical markers often is required to establish a definitive diagnosis. Spindle cell SCC stains positively, albeit frequently focally, for p63, p40, and high-molecular-weight cytokeratins such as cytokeratin 5/6, while S-100 protein, SOX-10, MART-1/Melan-A, and muscle-specific actin stains typically are negative. Wide local excision or MMS is recommended for treatment of these lesions.¹²

Primary cutaneous myoepithelial carcinomas are uncommon neoplasms of myoepithelial differentiation. Clinically, they often arise as soft nodular lesions on the head, neck, and lower extremities with a bimodal age distribution (50 years). Histologically cutaneous myoepithelial tumors are well-differentiated, dermal-based nodules without connection to the overlying epidermis (Figure 3). The myoepithelial cells can exhibit spindled, epithelioid, plasmacytoid, or clear cell morphologic features and show variability in cell growth patterns. One of the most common growth patterns is oval to round cells forming cords and chains in a chondromyxoid stroma. Most cases display an immunophenotyped co-expression of an epithelial cytokeratin and S-100 protein. Myoepithelial markers also may be present, including keratins, smooth muscle actin, calponin, glial fibrillary acidic protein, p63, and desmin. Surgical removal with wide local excision or MMS is essential.¹³

Leiomyosarcoma (LMS) is a tumor that originates from smooth muscle and rarely develops in the dermis.¹⁴ Pleomorphic LMS is a morphologic variant of LMS that has a low propensity to metastasize but commonly exhibits local recurrence.¹⁵ Leiomyosarcoma can present in any age group but most commonly manifests in individuals aged 50 to 70 years. Clinically, LMS presents as a firm solitary nodule with a smooth pink surface or a more exophytic tumor with a reddish or brown color on the extensor surface of the lower limbs; it is less common on the scalp and face.¹⁴ Histologically, most cases of pleomorphic LMS show small foci of fascicles consisting of smooth muscle tumor cells in addition to cellular pleomorphism (Figure 4).¹⁵ Many of these cells demonstrate a clear perinuclear vacuole that generally is appreciated in neoplastic smooth muscle cells.¹⁴ Pleomorphic LMS typically stains positively for at least one smooth muscle marker including desmin, h-caldesmon, muscle-specific actin, α-smooth muscle actin, or smooth muscle myosin in the leiomyosarcomatous fascicular areas.¹⁶ Complete surgical excision is the treatment of choice, and the best results are obtained with MMS.¹⁴

The Diagnosis: Primary Cutaneous Carcinosarcoma

The immunohistochemical findings supported an epithelial component consistent with moderately differentiated squamous cell carcinoma (SCC) and a mesenchymal component with features consistent with a sarcoma. Consequently, the lesion was diagnosed as a primary cutaneous carcinosarcoma (PCCS).

Primary cutaneous carcinosarcoma is a rare biphasic neoplasm consisting of malignant epithelial (carcinoma) and mesenchymal (sarcoma) components.¹ Primary cutaneous carcinosarcomas are uncommon, poorly understood, primary cutaneous tumors.^2,3 Characteristic of this tumor, cytokeratins highlight the epithelial component while vimentin highlights the mesenchymal component.⁴ Histologically, the sarcomatous components of PCCS often are highly variable, with an absence of transitional areas within the epithelial component, which frequently resembles basal cell carcinoma and/ or SCC.^5-7 Primary cutaneous carcinosarcoma favors areas of chronic UV radiation exposure, particularly on the head and neck. Most tumors present with a slowly growing, polypoid, flesh-colored to erythematous nodule due to the infiltrative mesenchymal component.⁷ Primary cutaneous carcinosarcoma primarily is diagnosed in elderly patients, with the majority of cases diagnosed in the eighth or ninth decades of life (range, 32–98 years).^1,8 Men appear to be twice as likely to be diagnosed with a PCCS compared to women.¹ Primary cutaneous carcinosarcomas are recognized as aggressive tumors with a high propensity to metastasize and recur locally, necessitating early diagnosis and treatment.⁴ Accurate diagnosis of PCCSs can be challenging due to the biphasic nature of the neoplasm as well as poor differentiation or unequal proportions of the epithelial and mesenchymal components.⁵ Additionally, overlapping diagnostic criteria coupled with vague demarcation between soft-tissue sarcomas and distinct carcinomas also may contribute to a delay in diagnosis.⁹ Treatment is achieved surgically by complete wide resection, with no evidence to support the use of adjuvant or neoadjuvant external beam radiation therapy. Due to the small number of reported cases, no treatment recommendations currently exist.¹

Surgical management with wide local excision has been disappointing, with recurrence rates reported as high as 33%.⁶ Primary cutaneous carcinosarcoma has an estimated overall recurrence rate of 19% and a 5-year disease-free rate of 50%.¹⁰ Risk factors associated with poorer prognosis include tumors with adnexal subtype, age less than 65 years, rapid tumor growth, a tumor greater than 20 mm at presentation, and a long-standing tumor lasting up to 30 years.^2,4 Although wide local excision and Mohs micrographic surgery (MMS) both have been utilized successfully, MMS has been shown to result in a cure rate of greater than 98%.⁶

Atypical fibroxanthoma (AFX) is a cutaneous tumor of fibrohistiocytic mesenchymal origin that typically manifests on sun-damaged skin in elderly individuals. Clinically, it presents as a rapidly growing neoplasm that often ulcerates and bleeds. These heterogenous neoplasms have several distinct characteristics, including dense cellularity with disorganized, large, pleomorphic, and atypical-appearing spindle-shaped cells arising in the upper layers of the dermis, often disseminating into the reticular dermis and occasionally into the subcutaneous fat (Figure 1). The neoplastic cells often exhibit hyperchromic and irregular nuclei, multinucleated giant cells, and atypical mitotic figures. In most cases, negative immunohistochemical staining with SOX-10, S-100, cytokeratins, desmin, and caldesmon will allow pathologists to differentiate between AFX and other common tumors on the differential diagnosis, such as SCC, melanoma, and leiomyosarcoma. CD10 and procollagen type 1 are positive antigenic markers in AFX, but they are not specific. The standard treatment of AFX includes wide local excision or MMS for superior margin control.¹¹

Spindle cell SCC presents as a raised or exophytic nodule, often with spontaneous bleeding and central ulceration. It usually presents on sun-damaged skin or in individuals with a history of ionizing radiation. Histologically, it is characterized by atypical spindleshaped keratinocytes in the dermis existing as single cells or cohesive nests along with keratin pearls (Figure 2). The atypical spindle cells may comprise the entire tumor or only a small portion. The use of immunohistochemical markers often is required to establish a definitive diagnosis. Spindle cell SCC stains positively, albeit frequently focally, for p63, p40, and high-molecular-weight cytokeratins such as cytokeratin 5/6, while S-100 protein, SOX-10, MART-1/Melan-A, and muscle-specific actin stains typically are negative. Wide local excision or MMS is recommended for treatment of these lesions.¹²

Primary cutaneous myoepithelial carcinomas are uncommon neoplasms of myoepithelial differentiation. Clinically, they often arise as soft nodular lesions on the head, neck, and lower extremities with a bimodal age distribution (50 years). Histologically cutaneous myoepithelial tumors are well-differentiated, dermal-based nodules without connection to the overlying epidermis (Figure 3). The myoepithelial cells can exhibit spindled, epithelioid, plasmacytoid, or clear cell morphologic features and show variability in cell growth patterns. One of the most common growth patterns is oval to round cells forming cords and chains in a chondromyxoid stroma. Most cases display an immunophenotyped co-expression of an epithelial cytokeratin and S-100 protein. Myoepithelial markers also may be present, including keratins, smooth muscle actin, calponin, glial fibrillary acidic protein, p63, and desmin. Surgical removal with wide local excision or MMS is essential.¹³

Leiomyosarcoma (LMS) is a tumor that originates from smooth muscle and rarely develops in the dermis.¹⁴ Pleomorphic LMS is a morphologic variant of LMS that has a low propensity to metastasize but commonly exhibits local recurrence.¹⁵ Leiomyosarcoma can present in any age group but most commonly manifests in individuals aged 50 to 70 years. Clinically, LMS presents as a firm solitary nodule with a smooth pink surface or a more exophytic tumor with a reddish or brown color on the extensor surface of the lower limbs; it is less common on the scalp and face.¹⁴ Histologically, most cases of pleomorphic LMS show small foci of fascicles consisting of smooth muscle tumor cells in addition to cellular pleomorphism (Figure 4).¹⁵ Many of these cells demonstrate a clear perinuclear vacuole that generally is appreciated in neoplastic smooth muscle cells.¹⁴ Pleomorphic LMS typically stains positively for at least one smooth muscle marker including desmin, h-caldesmon, muscle-specific actin, α-smooth muscle actin, or smooth muscle myosin in the leiomyosarcomatous fascicular areas.¹⁶ Complete surgical excision is the treatment of choice, and the best results are obtained with MMS.¹⁴

The Diagnosis: Primary Cutaneous Carcinosarcoma

The immunohistochemical findings supported an epithelial component consistent with moderately differentiated squamous cell carcinoma (SCC) and a mesenchymal component with features consistent with a sarcoma. Consequently, the lesion was diagnosed as a primary cutaneous carcinosarcoma (PCCS).

Primary cutaneous carcinosarcoma is a rare biphasic neoplasm consisting of malignant epithelial (carcinoma) and mesenchymal (sarcoma) components.¹ Primary cutaneous carcinosarcomas are uncommon, poorly understood, primary cutaneous tumors.^2,3 Characteristic of this tumor, cytokeratins highlight the epithelial component while vimentin highlights the mesenchymal component.⁴ Histologically, the sarcomatous components of PCCS often are highly variable, with an absence of transitional areas within the epithelial component, which frequently resembles basal cell carcinoma and/ or SCC.^5-7 Primary cutaneous carcinosarcoma favors areas of chronic UV radiation exposure, particularly on the head and neck. Most tumors present with a slowly growing, polypoid, flesh-colored to erythematous nodule due to the infiltrative mesenchymal component.⁷ Primary cutaneous carcinosarcoma primarily is diagnosed in elderly patients, with the majority of cases diagnosed in the eighth or ninth decades of life (range, 32–98 years).^1,8 Men appear to be twice as likely to be diagnosed with a PCCS compared to women.¹ Primary cutaneous carcinosarcomas are recognized as aggressive tumors with a high propensity to metastasize and recur locally, necessitating early diagnosis and treatment.⁴ Accurate diagnosis of PCCSs can be challenging due to the biphasic nature of the neoplasm as well as poor differentiation or unequal proportions of the epithelial and mesenchymal components.⁵ Additionally, overlapping diagnostic criteria coupled with vague demarcation between soft-tissue sarcomas and distinct carcinomas also may contribute to a delay in diagnosis.⁹ Treatment is achieved surgically by complete wide resection, with no evidence to support the use of adjuvant or neoadjuvant external beam radiation therapy. Due to the small number of reported cases, no treatment recommendations currently exist.¹

Surgical management with wide local excision has been disappointing, with recurrence rates reported as high as 33%.⁶ Primary cutaneous carcinosarcoma has an estimated overall recurrence rate of 19% and a 5-year disease-free rate of 50%.¹⁰ Risk factors associated with poorer prognosis include tumors with adnexal subtype, age less than 65 years, rapid tumor growth, a tumor greater than 20 mm at presentation, and a long-standing tumor lasting up to 30 years.^2,4 Although wide local excision and Mohs micrographic surgery (MMS) both have been utilized successfully, MMS has been shown to result in a cure rate of greater than 98%.⁶

Atypical fibroxanthoma (AFX) is a cutaneous tumor of fibrohistiocytic mesenchymal origin that typically manifests on sun-damaged skin in elderly individuals. Clinically, it presents as a rapidly growing neoplasm that often ulcerates and bleeds. These heterogenous neoplasms have several distinct characteristics, including dense cellularity with disorganized, large, pleomorphic, and atypical-appearing spindle-shaped cells arising in the upper layers of the dermis, often disseminating into the reticular dermis and occasionally into the subcutaneous fat (Figure 1). The neoplastic cells often exhibit hyperchromic and irregular nuclei, multinucleated giant cells, and atypical mitotic figures. In most cases, negative immunohistochemical staining with SOX-10, S-100, cytokeratins, desmin, and caldesmon will allow pathologists to differentiate between AFX and other common tumors on the differential diagnosis, such as SCC, melanoma, and leiomyosarcoma. CD10 and procollagen type 1 are positive antigenic markers in AFX, but they are not specific. The standard treatment of AFX includes wide local excision or MMS for superior margin control.¹¹

Spindle cell SCC presents as a raised or exophytic nodule, often with spontaneous bleeding and central ulceration. It usually presents on sun-damaged skin or in individuals with a history of ionizing radiation. Histologically, it is characterized by atypical spindleshaped keratinocytes in the dermis existing as single cells or cohesive nests along with keratin pearls (Figure 2). The atypical spindle cells may comprise the entire tumor or only a small portion. The use of immunohistochemical markers often is required to establish a definitive diagnosis. Spindle cell SCC stains positively, albeit frequently focally, for p63, p40, and high-molecular-weight cytokeratins such as cytokeratin 5/6, while S-100 protein, SOX-10, MART-1/Melan-A, and muscle-specific actin stains typically are negative. Wide local excision or MMS is recommended for treatment of these lesions.¹²

Primary cutaneous myoepithelial carcinomas are uncommon neoplasms of myoepithelial differentiation. Clinically, they often arise as soft nodular lesions on the head, neck, and lower extremities with a bimodal age distribution (50 years). Histologically cutaneous myoepithelial tumors are well-differentiated, dermal-based nodules without connection to the overlying epidermis (Figure 3). The myoepithelial cells can exhibit spindled, epithelioid, plasmacytoid, or clear cell morphologic features and show variability in cell growth patterns. One of the most common growth patterns is oval to round cells forming cords and chains in a chondromyxoid stroma. Most cases display an immunophenotyped co-expression of an epithelial cytokeratin and S-100 protein. Myoepithelial markers also may be present, including keratins, smooth muscle actin, calponin, glial fibrillary acidic protein, p63, and desmin. Surgical removal with wide local excision or MMS is essential.¹³

Leiomyosarcoma (LMS) is a tumor that originates from smooth muscle and rarely develops in the dermis.¹⁴ Pleomorphic LMS is a morphologic variant of LMS that has a low propensity to metastasize but commonly exhibits local recurrence.¹⁵ Leiomyosarcoma can present in any age group but most commonly manifests in individuals aged 50 to 70 years. Clinically, LMS presents as a firm solitary nodule with a smooth pink surface or a more exophytic tumor with a reddish or brown color on the extensor surface of the lower limbs; it is less common on the scalp and face.¹⁴ Histologically, most cases of pleomorphic LMS show small foci of fascicles consisting of smooth muscle tumor cells in addition to cellular pleomorphism (Figure 4).¹⁵ Many of these cells demonstrate a clear perinuclear vacuole that generally is appreciated in neoplastic smooth muscle cells.¹⁴ Pleomorphic LMS typically stains positively for at least one smooth muscle marker including desmin, h-caldesmon, muscle-specific actin, α-smooth muscle actin, or smooth muscle myosin in the leiomyosarcomatous fascicular areas.¹⁶ Complete surgical excision is the treatment of choice, and the best results are obtained with MMS.¹⁴

For some patients with atopic dermatitis, disease activity may increase into mid-adulthood, and this subtype of AD may be linked with poorer physical and mental health, giving reason to observe patients beyond the pediatric stage, according to a cohort study of more than 30,000 patients.

Early-life environmental factors, such as tobacco smoke exposure, were not reliable predictors of increasing AD into mid-adulthood, suggesting that a patient’s contemporaneous environment may impact disease course throughout life, reported lead author Katrina Abuabara, MD, associate professor of dermatology at the University of California, San Francisco, and colleagues.

“There is a lack of studies that prospectively examine the course of atopic eczema beyond adolescence/early adulthood, and a more comprehensive understanding of disease activity across the life span is needed,” the investigators wrote in JAMA Dermatology. “Data on long-term disease course may offer insight into mechanisms for disease onset and persistence, are important when counseling patients, and would establish baseline trajectories for future studies of whether new treatments can modify disease course and development of comorbidities.”

The present study included 30,905 patients from two population-based birth cohorts: the 1958 National Childhood Development Study (NCDS) and the 1970 British Cohort Study (BCS70). Follow-up data were collected between 1958 and 2016 via nine waves of standardized questionnaires, and subtypes of atopic eczema patterns were identified “based on parent-reported or self-reported atopic eczema period prevalence.”

This measure “was previously shown to coincide with standardized clinical examinations among children in the NCDS, and a similar questionnaire demonstrated high sensitivity and specificity for physician-diagnosed atopic eczema in U.S. populations,” the investigators noted.

Latent class analysis identified four disease subtypes based on probability of reporting prevalent AD into midlife: low (88%-91%), decreasing (4%), increasing (2%-6%), and persistently high (2%-3%) probability.

Next, the investigators looked for associations between these subtypes and established early-life risk factors, such as history of breastfeeding and childhood smoke exposure. None of the childhood environmental factors differentiated between high versus decreasing disease in adulthood, or increasing versus decreasing disease in adulthood. In contrast, female sex predicted the high versus decreasing adult subtype (odds ratio, 1.99; 95% confidence interval, 1.66-2.38), and the increasing versus decreasing adult subtype (OR, 1.99; 95% CI, 1.69-2.35).

These findings suggest that “disease trajectory is modifiable and may be influenced by environmental factors throughout life,” the investigators wrote.

Further analysis uncovered associations between adult AD subtypes and other health outcomes. For example, compared with adults in the low probability group, those in the high probability group were significantly more likely to report rhinitis (OR, 2.70; 95% CI, 2.24-3.26) and asthma (OR, 3.45; 95% CI, 2.82-4.21). Adults with the increasing subtype also had elevated rates of asthma and rhinitis, along with worse self-reported mental health at age 42 (OR, 1.45; 95% CI, 1.23-1.72) and poor general health at age 46/50 (OR, 1.29; 95% CI, 1.09-1.53).

“When extending the window of observation beyond childhood, clear subtypes of atopic eczema based on patterns of disease activity emerged,” the investigators concluded. “In particular, a newly identified subtype with increasing probability of activity in adulthood warrants additional attention given associations with poor self-reported physical and mental health in midlife.”

Commenting on these results, Robert Sidbury, MD, professor of dermatology at the University of Washington, Seattle, said that this is an “important study” because it adds to our understanding of natural disease course over time.

This knowledge, as a pediatric dermatologist, will help Dr. Sidbury answer one of the most common questions he hears from parents: When is it going to stop?

“Trying to put a little bit more evidence-based heft behind the answer ... is really important,” he said in an interview.

Based on available data, up to 10% of children with AD may have disease activity into adulthood, according to Dr. Sidbury, who is also chief of dermatology at Seattle Children’s Hospital.

“I would hazard to guess that most of those adults who have atopic dermatitis – at least the ones who had it in childhood – were told that they would grow out of it,” he said. “And so I think awareness is important – that [resolution with age] does not always happen.”

The findings also support the possibility that AD is a systemic disease, and that underlying immune dysregulation may be linked with serious health consequences later in life, Dr. Sidbury said, noting that “the stakes get higher and higher when you start speculating in that way.”

According to Dr. Sidbury, the reported link between childhood AD and poor midlife health raises questions about how modifiable the disease course may be, particularly in response to earlier intervention with emerging AD medications, which “seem to be much more effective and potent.”

“Will the advent of these medications and their adoption and use in treatment perhaps have a significant impact, not just on the prevention of atopic dermatitis itself, but maybe other comorbidities?” he asked.

For the time being, this question remains unanswered.

The study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the Wellcome Trust. Dr. Abuabara received grants from the National Institutes of Health during the study, as well as personal fees from Target RWE and Pfizer outside of this study. One author reported receiving NIH grants during the study, another reported receiving grants from the Wellcome Trust and the Innovative Medicine Initiative Horizon 2020 (BIOMAP project) during the study; there were no other disclosures. Dr. Sidbury disclosed relationships with Galderma, Regeneron, and Pfizer.
 

For some patients with atopic dermatitis, disease activity may increase into mid-adulthood, and this subtype of AD may be linked with poorer physical and mental health, giving reason to observe patients beyond the pediatric stage, according to a cohort study of more than 30,000 patients.

Early-life environmental factors, such as tobacco smoke exposure, were not reliable predictors of increasing AD into mid-adulthood, suggesting that a patient’s contemporaneous environment may impact disease course throughout life, reported lead author Katrina Abuabara, MD, associate professor of dermatology at the University of California, San Francisco, and colleagues.

“There is a lack of studies that prospectively examine the course of atopic eczema beyond adolescence/early adulthood, and a more comprehensive understanding of disease activity across the life span is needed,” the investigators wrote in JAMA Dermatology. “Data on long-term disease course may offer insight into mechanisms for disease onset and persistence, are important when counseling patients, and would establish baseline trajectories for future studies of whether new treatments can modify disease course and development of comorbidities.”

The present study included 30,905 patients from two population-based birth cohorts: the 1958 National Childhood Development Study (NCDS) and the 1970 British Cohort Study (BCS70). Follow-up data were collected between 1958 and 2016 via nine waves of standardized questionnaires, and subtypes of atopic eczema patterns were identified “based on parent-reported or self-reported atopic eczema period prevalence.”

This measure “was previously shown to coincide with standardized clinical examinations among children in the NCDS, and a similar questionnaire demonstrated high sensitivity and specificity for physician-diagnosed atopic eczema in U.S. populations,” the investigators noted.

Latent class analysis identified four disease subtypes based on probability of reporting prevalent AD into midlife: low (88%-91%), decreasing (4%), increasing (2%-6%), and persistently high (2%-3%) probability.

Next, the investigators looked for associations between these subtypes and established early-life risk factors, such as history of breastfeeding and childhood smoke exposure. None of the childhood environmental factors differentiated between high versus decreasing disease in adulthood, or increasing versus decreasing disease in adulthood. In contrast, female sex predicted the high versus decreasing adult subtype (odds ratio, 1.99; 95% confidence interval, 1.66-2.38), and the increasing versus decreasing adult subtype (OR, 1.99; 95% CI, 1.69-2.35).

These findings suggest that “disease trajectory is modifiable and may be influenced by environmental factors throughout life,” the investigators wrote.

Further analysis uncovered associations between adult AD subtypes and other health outcomes. For example, compared with adults in the low probability group, those in the high probability group were significantly more likely to report rhinitis (OR, 2.70; 95% CI, 2.24-3.26) and asthma (OR, 3.45; 95% CI, 2.82-4.21). Adults with the increasing subtype also had elevated rates of asthma and rhinitis, along with worse self-reported mental health at age 42 (OR, 1.45; 95% CI, 1.23-1.72) and poor general health at age 46/50 (OR, 1.29; 95% CI, 1.09-1.53).

“When extending the window of observation beyond childhood, clear subtypes of atopic eczema based on patterns of disease activity emerged,” the investigators concluded. “In particular, a newly identified subtype with increasing probability of activity in adulthood warrants additional attention given associations with poor self-reported physical and mental health in midlife.”

Commenting on these results, Robert Sidbury, MD, professor of dermatology at the University of Washington, Seattle, said that this is an “important study” because it adds to our understanding of natural disease course over time.

This knowledge, as a pediatric dermatologist, will help Dr. Sidbury answer one of the most common questions he hears from parents: When is it going to stop?

“Trying to put a little bit more evidence-based heft behind the answer ... is really important,” he said in an interview.

Based on available data, up to 10% of children with AD may have disease activity into adulthood, according to Dr. Sidbury, who is also chief of dermatology at Seattle Children’s Hospital.

“I would hazard to guess that most of those adults who have atopic dermatitis – at least the ones who had it in childhood – were told that they would grow out of it,” he said. “And so I think awareness is important – that [resolution with age] does not always happen.”

The findings also support the possibility that AD is a systemic disease, and that underlying immune dysregulation may be linked with serious health consequences later in life, Dr. Sidbury said, noting that “the stakes get higher and higher when you start speculating in that way.”

According to Dr. Sidbury, the reported link between childhood AD and poor midlife health raises questions about how modifiable the disease course may be, particularly in response to earlier intervention with emerging AD medications, which “seem to be much more effective and potent.”

“Will the advent of these medications and their adoption and use in treatment perhaps have a significant impact, not just on the prevention of atopic dermatitis itself, but maybe other comorbidities?” he asked.

For the time being, this question remains unanswered.

The study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the Wellcome Trust. Dr. Abuabara received grants from the National Institutes of Health during the study, as well as personal fees from Target RWE and Pfizer outside of this study. One author reported receiving NIH grants during the study, another reported receiving grants from the Wellcome Trust and the Innovative Medicine Initiative Horizon 2020 (BIOMAP project) during the study; there were no other disclosures. Dr. Sidbury disclosed relationships with Galderma, Regeneron, and Pfizer.
 

For some patients with atopic dermatitis, disease activity may increase into mid-adulthood, and this subtype of AD may be linked with poorer physical and mental health, giving reason to observe patients beyond the pediatric stage, according to a cohort study of more than 30,000 patients.

Early-life environmental factors, such as tobacco smoke exposure, were not reliable predictors of increasing AD into mid-adulthood, suggesting that a patient’s contemporaneous environment may impact disease course throughout life, reported lead author Katrina Abuabara, MD, associate professor of dermatology at the University of California, San Francisco, and colleagues.

“There is a lack of studies that prospectively examine the course of atopic eczema beyond adolescence/early adulthood, and a more comprehensive understanding of disease activity across the life span is needed,” the investigators wrote in JAMA Dermatology. “Data on long-term disease course may offer insight into mechanisms for disease onset and persistence, are important when counseling patients, and would establish baseline trajectories for future studies of whether new treatments can modify disease course and development of comorbidities.”

The present study included 30,905 patients from two population-based birth cohorts: the 1958 National Childhood Development Study (NCDS) and the 1970 British Cohort Study (BCS70). Follow-up data were collected between 1958 and 2016 via nine waves of standardized questionnaires, and subtypes of atopic eczema patterns were identified “based on parent-reported or self-reported atopic eczema period prevalence.”

This measure “was previously shown to coincide with standardized clinical examinations among children in the NCDS, and a similar questionnaire demonstrated high sensitivity and specificity for physician-diagnosed atopic eczema in U.S. populations,” the investigators noted.

Latent class analysis identified four disease subtypes based on probability of reporting prevalent AD into midlife: low (88%-91%), decreasing (4%), increasing (2%-6%), and persistently high (2%-3%) probability.

Next, the investigators looked for associations between these subtypes and established early-life risk factors, such as history of breastfeeding and childhood smoke exposure. None of the childhood environmental factors differentiated between high versus decreasing disease in adulthood, or increasing versus decreasing disease in adulthood. In contrast, female sex predicted the high versus decreasing adult subtype (odds ratio, 1.99; 95% confidence interval, 1.66-2.38), and the increasing versus decreasing adult subtype (OR, 1.99; 95% CI, 1.69-2.35).

These findings suggest that “disease trajectory is modifiable and may be influenced by environmental factors throughout life,” the investigators wrote.

Further analysis uncovered associations between adult AD subtypes and other health outcomes. For example, compared with adults in the low probability group, those in the high probability group were significantly more likely to report rhinitis (OR, 2.70; 95% CI, 2.24-3.26) and asthma (OR, 3.45; 95% CI, 2.82-4.21). Adults with the increasing subtype also had elevated rates of asthma and rhinitis, along with worse self-reported mental health at age 42 (OR, 1.45; 95% CI, 1.23-1.72) and poor general health at age 46/50 (OR, 1.29; 95% CI, 1.09-1.53).

“When extending the window of observation beyond childhood, clear subtypes of atopic eczema based on patterns of disease activity emerged,” the investigators concluded. “In particular, a newly identified subtype with increasing probability of activity in adulthood warrants additional attention given associations with poor self-reported physical and mental health in midlife.”

Commenting on these results, Robert Sidbury, MD, professor of dermatology at the University of Washington, Seattle, said that this is an “important study” because it adds to our understanding of natural disease course over time.

This knowledge, as a pediatric dermatologist, will help Dr. Sidbury answer one of the most common questions he hears from parents: When is it going to stop?

“Trying to put a little bit more evidence-based heft behind the answer ... is really important,” he said in an interview.

Based on available data, up to 10% of children with AD may have disease activity into adulthood, according to Dr. Sidbury, who is also chief of dermatology at Seattle Children’s Hospital.

“I would hazard to guess that most of those adults who have atopic dermatitis – at least the ones who had it in childhood – were told that they would grow out of it,” he said. “And so I think awareness is important – that [resolution with age] does not always happen.”

The findings also support the possibility that AD is a systemic disease, and that underlying immune dysregulation may be linked with serious health consequences later in life, Dr. Sidbury said, noting that “the stakes get higher and higher when you start speculating in that way.”

According to Dr. Sidbury, the reported link between childhood AD and poor midlife health raises questions about how modifiable the disease course may be, particularly in response to earlier intervention with emerging AD medications, which “seem to be much more effective and potent.”

“Will the advent of these medications and their adoption and use in treatment perhaps have a significant impact, not just on the prevention of atopic dermatitis itself, but maybe other comorbidities?” he asked.

For the time being, this question remains unanswered.

The study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the Wellcome Trust. Dr. Abuabara received grants from the National Institutes of Health during the study, as well as personal fees from Target RWE and Pfizer outside of this study. One author reported receiving NIH grants during the study, another reported receiving grants from the Wellcome Trust and the Innovative Medicine Initiative Horizon 2020 (BIOMAP project) during the study; there were no other disclosures. Dr. Sidbury disclosed relationships with Galderma, Regeneron, and Pfizer.
 

President Joe Biden has announced a host of new plans to rein in COVID-19’s runaway transmission in the United States, including sweeping vaccine mandates that will affect 100 million American workers, nearly two-thirds of the country’s workforce.

itsmejust/Thinkstock

“As your president, I’m announcing tonight a new plan to get more Americans vaccinated to combat those blocking public health,” he said Sept. 9.

As part of a six-part plan unveiled in a speech from the State Dining Room of the White House, President Biden said he would require vaccinations for nearly 4 million federal workers and the employees of companies that contract with the federal government.

He has also directed the Occupational Safety and Health Administration to develop a rule that will require large employers -- those with at least 100 employees -- to ensure their workers are vaccinated or tested weekly.

Nearly 17 million health care workers will face new vaccine mandates as part of the conditions of participation in the Medicare and Medicaid programs.

President Biden said the federal government will require staff at federally funded Head Start programs and schools to be vaccinated. He’s also calling on all states to mandate vaccines for teachers.

“A distinct minority of Americans, supported by a distinct minority of elected officials, are keeping us from turning the corner,” PresidentBiden said. “These pandemic politics, as I refer to them, are making people sick, causing unvaccinated people to die.”

One public health official said he was glad to see the president’s bold action.

“What I saw today was the federal government trying to use its powers to create greater safety in the American population,” said Ashish K. Jha, MD, dean of the school of public health at Brown University, Providence, R.I., in a call with reporters after the speech.

National Nurses United, the largest union of registered nurses in the United States, issued a statement in support of President Biden’s new vaccination requirements, but pushed back on his language.

“…as advocates for public health, registered nurses want to be extremely clear: There is no such thing as a pandemic of only the unvaccinated. The science of epidemiology tells us there is just one deadly, global pandemic that has not yet ended, and we are all in it together. To get out of it, we must act together. All of us,” the statement says.

A host of other professional groups, including the American Medical Association and the Association of State and Territorial Health Officials, also issued statements of support for President Biden’s plan.

But the plan was not well received by all.

“I will pursue every legal option available to the state of Georgia to stop this blatantly unlawful overreach by the Biden Administration,” said Georgia Governor Brian Kemp, a Republican, in a Tweet.

The National Council for Occupational Safety and Health called the plan “a missed opportunity” because it failed to include workplace protections for essential workers such as grocery, postal, and transit workers.

“Social distancing, improved ventilation, shift rotation, and protective equipment to reduce exposure are important components of an overall plan to reduce risk and stop the virus. These tools are missing from the new steps President Biden announced today,” said Jessica Martinez, co-executive director of the group.

In addition to the new vaccination requirements, President Biden said extra doses would be on the way for people who have already been fully vaccinated in order to protect against waning immunity, starting on Sept. 20. But he noted that those plans would be contingent on the Food and Drug Administration’s approval for third doses and the Centers for Disease Control and Prevention’s recommendation of the shots.

President Biden pledged to use the Defense Production Act to ramp up production of at-home tests, which have been selling out across the nation as the Delta variant spreads.

He also announced plans to expand access to COVID-19 testing, including offering testing for free at thousands of pharmacies nationwide and getting major retailers to sell at-home COVID-19 tests at cost.

The BinaxNow test kit, which currently retails for $23.99, will now cost about $15 for two tests at Kroger, Amazon, and Walmart, according to the White House. Food banks and community health centers will get free tests, too.

He called on states to set up COVID-19 testing programs at all schools.

Jha said that in his view, the big, game-changing news out of the president’s speech was the expansion of testing.

“Our country has failed to deploy tests in a way that can really bring this pandemic under control,” Jha said. “There are plenty of reasons, data, experience to indicate that if these were widely available, it would make a dramatic difference in reducing infection numbers across our country.”.

Dr. Jha said the private market had not worked effectively to make testing more widely available, so it was “absolutely a requirement of the federal government to step in and make testing more widely available,” he said.

President Biden also announced new economic stimulus programs, saying he’s expanding loan programs to small businesses and streamlining the loan forgiveness process.

President Biden said he’s boosting help for overburdened hospitals, doubling the number of federal surge response teams sent to hard-hit areas to reduce the strain on local health care workers. He said he would increase the pace of antibody treatments to states by 50%.

“We made so much progress during the past 7 months of this pandemic. Even so, we remain at a critical moment, a critical time,” he said. “We have the tools. Now, we just have to finish the job with truth, with science, with confidence and together as one nation.”

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

President Joe Biden has announced a host of new plans to rein in COVID-19’s runaway transmission in the United States, including sweeping vaccine mandates that will affect 100 million American workers, nearly two-thirds of the country’s workforce.

itsmejust/Thinkstock

“As your president, I’m announcing tonight a new plan to get more Americans vaccinated to combat those blocking public health,” he said Sept. 9.

As part of a six-part plan unveiled in a speech from the State Dining Room of the White House, President Biden said he would require vaccinations for nearly 4 million federal workers and the employees of companies that contract with the federal government.

He has also directed the Occupational Safety and Health Administration to develop a rule that will require large employers -- those with at least 100 employees -- to ensure their workers are vaccinated or tested weekly.

Nearly 17 million health care workers will face new vaccine mandates as part of the conditions of participation in the Medicare and Medicaid programs.

President Biden said the federal government will require staff at federally funded Head Start programs and schools to be vaccinated. He’s also calling on all states to mandate vaccines for teachers.

“A distinct minority of Americans, supported by a distinct minority of elected officials, are keeping us from turning the corner,” PresidentBiden said. “These pandemic politics, as I refer to them, are making people sick, causing unvaccinated people to die.”

One public health official said he was glad to see the president’s bold action.

“What I saw today was the federal government trying to use its powers to create greater safety in the American population,” said Ashish K. Jha, MD, dean of the school of public health at Brown University, Providence, R.I., in a call with reporters after the speech.

National Nurses United, the largest union of registered nurses in the United States, issued a statement in support of President Biden’s new vaccination requirements, but pushed back on his language.

“…as advocates for public health, registered nurses want to be extremely clear: There is no such thing as a pandemic of only the unvaccinated. The science of epidemiology tells us there is just one deadly, global pandemic that has not yet ended, and we are all in it together. To get out of it, we must act together. All of us,” the statement says.

A host of other professional groups, including the American Medical Association and the Association of State and Territorial Health Officials, also issued statements of support for President Biden’s plan.

But the plan was not well received by all.

“I will pursue every legal option available to the state of Georgia to stop this blatantly unlawful overreach by the Biden Administration,” said Georgia Governor Brian Kemp, a Republican, in a Tweet.

The National Council for Occupational Safety and Health called the plan “a missed opportunity” because it failed to include workplace protections for essential workers such as grocery, postal, and transit workers.

“Social distancing, improved ventilation, shift rotation, and protective equipment to reduce exposure are important components of an overall plan to reduce risk and stop the virus. These tools are missing from the new steps President Biden announced today,” said Jessica Martinez, co-executive director of the group.

In addition to the new vaccination requirements, President Biden said extra doses would be on the way for people who have already been fully vaccinated in order to protect against waning immunity, starting on Sept. 20. But he noted that those plans would be contingent on the Food and Drug Administration’s approval for third doses and the Centers for Disease Control and Prevention’s recommendation of the shots.

President Biden pledged to use the Defense Production Act to ramp up production of at-home tests, which have been selling out across the nation as the Delta variant spreads.

He also announced plans to expand access to COVID-19 testing, including offering testing for free at thousands of pharmacies nationwide and getting major retailers to sell at-home COVID-19 tests at cost.

The BinaxNow test kit, which currently retails for $23.99, will now cost about $15 for two tests at Kroger, Amazon, and Walmart, according to the White House. Food banks and community health centers will get free tests, too.

He called on states to set up COVID-19 testing programs at all schools.

Jha said that in his view, the big, game-changing news out of the president’s speech was the expansion of testing.

“Our country has failed to deploy tests in a way that can really bring this pandemic under control,” Jha said. “There are plenty of reasons, data, experience to indicate that if these were widely available, it would make a dramatic difference in reducing infection numbers across our country.”.

Dr. Jha said the private market had not worked effectively to make testing more widely available, so it was “absolutely a requirement of the federal government to step in and make testing more widely available,” he said.

President Biden also announced new economic stimulus programs, saying he’s expanding loan programs to small businesses and streamlining the loan forgiveness process.

President Biden said he’s boosting help for overburdened hospitals, doubling the number of federal surge response teams sent to hard-hit areas to reduce the strain on local health care workers. He said he would increase the pace of antibody treatments to states by 50%.

“We made so much progress during the past 7 months of this pandemic. Even so, we remain at a critical moment, a critical time,” he said. “We have the tools. Now, we just have to finish the job with truth, with science, with confidence and together as one nation.”

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

President Joe Biden has announced a host of new plans to rein in COVID-19’s runaway transmission in the United States, including sweeping vaccine mandates that will affect 100 million American workers, nearly two-thirds of the country’s workforce.

itsmejust/Thinkstock

“As your president, I’m announcing tonight a new plan to get more Americans vaccinated to combat those blocking public health,” he said Sept. 9.

As part of a six-part plan unveiled in a speech from the State Dining Room of the White House, President Biden said he would require vaccinations for nearly 4 million federal workers and the employees of companies that contract with the federal government.

He has also directed the Occupational Safety and Health Administration to develop a rule that will require large employers -- those with at least 100 employees -- to ensure their workers are vaccinated or tested weekly.

Nearly 17 million health care workers will face new vaccine mandates as part of the conditions of participation in the Medicare and Medicaid programs.

President Biden said the federal government will require staff at federally funded Head Start programs and schools to be vaccinated. He’s also calling on all states to mandate vaccines for teachers.

“A distinct minority of Americans, supported by a distinct minority of elected officials, are keeping us from turning the corner,” PresidentBiden said. “These pandemic politics, as I refer to them, are making people sick, causing unvaccinated people to die.”

One public health official said he was glad to see the president’s bold action.

“What I saw today was the federal government trying to use its powers to create greater safety in the American population,” said Ashish K. Jha, MD, dean of the school of public health at Brown University, Providence, R.I., in a call with reporters after the speech.

National Nurses United, the largest union of registered nurses in the United States, issued a statement in support of President Biden’s new vaccination requirements, but pushed back on his language.

“…as advocates for public health, registered nurses want to be extremely clear: There is no such thing as a pandemic of only the unvaccinated. The science of epidemiology tells us there is just one deadly, global pandemic that has not yet ended, and we are all in it together. To get out of it, we must act together. All of us,” the statement says.

A host of other professional groups, including the American Medical Association and the Association of State and Territorial Health Officials, also issued statements of support for President Biden’s plan.

But the plan was not well received by all.

“I will pursue every legal option available to the state of Georgia to stop this blatantly unlawful overreach by the Biden Administration,” said Georgia Governor Brian Kemp, a Republican, in a Tweet.

The National Council for Occupational Safety and Health called the plan “a missed opportunity” because it failed to include workplace protections for essential workers such as grocery, postal, and transit workers.

“Social distancing, improved ventilation, shift rotation, and protective equipment to reduce exposure are important components of an overall plan to reduce risk and stop the virus. These tools are missing from the new steps President Biden announced today,” said Jessica Martinez, co-executive director of the group.

In addition to the new vaccination requirements, President Biden said extra doses would be on the way for people who have already been fully vaccinated in order to protect against waning immunity, starting on Sept. 20. But he noted that those plans would be contingent on the Food and Drug Administration’s approval for third doses and the Centers for Disease Control and Prevention’s recommendation of the shots.

President Biden pledged to use the Defense Production Act to ramp up production of at-home tests, which have been selling out across the nation as the Delta variant spreads.

He also announced plans to expand access to COVID-19 testing, including offering testing for free at thousands of pharmacies nationwide and getting major retailers to sell at-home COVID-19 tests at cost.

The BinaxNow test kit, which currently retails for $23.99, will now cost about $15 for two tests at Kroger, Amazon, and Walmart, according to the White House. Food banks and community health centers will get free tests, too.

He called on states to set up COVID-19 testing programs at all schools.

Jha said that in his view, the big, game-changing news out of the president’s speech was the expansion of testing.

“Our country has failed to deploy tests in a way that can really bring this pandemic under control,” Jha said. “There are plenty of reasons, data, experience to indicate that if these were widely available, it would make a dramatic difference in reducing infection numbers across our country.”.

Dr. Jha said the private market had not worked effectively to make testing more widely available, so it was “absolutely a requirement of the federal government to step in and make testing more widely available,” he said.

President Biden also announced new economic stimulus programs, saying he’s expanding loan programs to small businesses and streamlining the loan forgiveness process.

President Biden said he’s boosting help for overburdened hospitals, doubling the number of federal surge response teams sent to hard-hit areas to reduce the strain on local health care workers. He said he would increase the pace of antibody treatments to states by 50%.

“We made so much progress during the past 7 months of this pandemic. Even so, we remain at a critical moment, a critical time,” he said. “We have the tools. Now, we just have to finish the job with truth, with science, with confidence and together as one nation.”

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

The Diagnosis: Recurrent Cutaneous T-Cell Lymphoma

The skin biopsy revealed alternating orthokeratosis and parakeratosis with mild to moderate spongiosis and intraepidermal vesiculation as well as individual and nested atypical mononuclear cells with moderately enlarged hyperchromatic nuclei in the epidermis. There was a superficial interstitial lymphocytic infiltrate with occasional enlarged cells (Figure, A and B), and atypical cells in the epidermis and dermis stained with antibodies against CD3 and CD4 (Figure, C and D) but not against CD20 or CD8. These histopathologic findings were consistent with cutaneous T-cell lymphoma (CTCL), mycosis fungoides (MF) type. Additional application of bexarotene gel on days the patient received narrowband UVB was recommended with noted improvement of the skin.

Cutaneous T-cell lymphomas are a heterogenous group of diseases with monoclonal proliferation of T lymphocytes that largely are confined to the skin at the time of diagnosis.¹ The incidence of CTCL rose steadily for more than 25 years, with an annual age-adjusted incidence of 6.4 to 9.6 cases per million individuals in the United States from 1973 to 2002.² Mycosis fungoides is the most common classification of CTCL. It usually is characterized by patches or plaques of scaly erythema or poikiloderma; however, it also can present with annular, arcuate, concentrative, annular and linear morphologies. Mycosis fungoides tumor cells typically express a mature memory T helper cell phenotype of CD3+, CD4+, and CD8−, but there are different variants that have been discovered.³ Mycosis fungoides distributed in a spiral pattern is a distinctly unusual manifestation. Mechanisms of such dynamic morphologies are unknown but may represent an interplay between malignant cell proliferation and lost immune responses in temporospatial relationships.

The presence of keratotic gyrate lesions on acral surfaces should raise the possibility of pagetoid reticulosis. However, our patient had a history of MF involving areas of the body beyond the extremities, making this diagnosis less likely. Pagetoid reticulosis is categorized as an MF variant under the current World Health Organization– European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas.⁴ Pagetoid reticulosis clinically presents as a solitary psoriasiform or hyperkeratotic patch or plaque that affects the distal extremities. Variable immunophenotypes have been shown in pagetoid reticulosis, such as CD4−/CD8+ and CD4−/CD8−, while classic MF typically shows CD4+/CD8−, as in our case.⁵

Tinea pedis is a superficial fungal infection usually caused by anthropophilic dermatophytes, with Trichophyton rubrum being the most common organism. Four common clinical presentations of tinea pedis have been identified: interdigital, moccasin, vesicular, and acute ulcerative. Clinical presentation ranges from macerations, ulcerations, and erosions in the toe web spaces to dry hyperkeratotic scaling and fissures on the plantar foot.⁶ Tinea pedis primarily affects the plantar and interdigital spaces, sparing the dorsal foot and ankle. Treatment is recommended to alleviate symptoms and limit the spread of infection; topical antifungals for 4 weeks is the treatment of choice. However, recurrence is common, and maintenance therapy often is indicated. Oral antifungals or a combination of both topical and oral medications may be needed in certain cases.⁷

Erythema annulare centrifugum (EAC) is a rare dermatologic disease described as erythematous or urticarial papules that can enlarge centrifugally to form annular lesions that clear centrally. Thought to be a hypersensitivity reaction to an underlying condition, EAC has been associated with fungal infections, various cutaneous diseases, and even internal malignancies. Clinically, EAC can be divided into 2 forms: deep and superficial. Deep gyrate erythema is characterized by a firm indurated border with rare scaling and pruritus that histologically shows perivascular lymphocytic infiltration in the upper and deep dermis. Superficial gyrate erythema has minimally elevated lesions with an indistinct border and trailing scales and pruritus; histopathologic findings present a dense, perivascular, lymphocytic infiltration restricted to the upper dermis.⁸ Therapy for EAC is directed at relieving symptoms and treating the underlying condition if there is one associated.

Granuloma annulare (GA) is a common skin disorder classically characterized by ringed erythematous plaques, though many variants have been identified. Localized GA is the most common variant and presents with pink-red, nonscaly, annular patches or plaques, typically affecting the hands and feet. Generalized GA is characterized as diffuse annular patches or plaques classically affecting the trunk and extremities. Histology is notable for mucin with a palisading or interstitial pattern of granulomatous inflammation, which was not evident in our patient.⁹ Topical or intralesional corticosteroids are the first-line treatment of localized GA; however, localized GA generally is self-limited, and treatment often is not necessary. Treatment with cryosurgery, laser therapy, and topical dapsone and tacrolimus also has been described, but evidence of the efficacy of these agents is limited. For generalized GA, phototherapy currently is the most reliable therapy. Systemic therapies include antimalarials, fumaric acid esters, biologics, antimicrobials, and isotretinoin.¹⁰

Erythema gyratum repens (EGR) is a rare dermatologic disease described as erythematous concentric bands arranged in parallel rings that can be annular, figurate, or gyrate, with a fine scale trailing the leading edge. Histopathologic features of EGR are nonspecific but are characterized by a perivascular, superficial, mononuclear dermatitis. Diagnosis is based on its characteristic clinical presentation. Although EGR commonly is associated with internal malignancies such as bronchial carcinoma, it also may be associated with benign conditions.¹¹ Improvement often is seen with successful therapy of the underlying associated malignancy.¹²

Treatment of MF is based on tumor-node-metastasisblood classification, prognostic factors, and clinical stage at the time of diagnosis. Early-stage MF (IA–IIA) commonly is treated with skin-directed therapies such as topical corticosteroids, topical mechlorethamine, topical retinoids, UV phototherapy, and localized radiotherapy. In late stages (IIB–IV), systemic therapy is indicated and includes systemic retinoids, interferon alfa, chemotherapy, monoclonal antibodies, and psoralen plus UVA.¹³ In many cases, patients may require combination therapy to achieve remission or better control of their condition, as in our patient.

The Diagnosis: Recurrent Cutaneous T-Cell Lymphoma

The skin biopsy revealed alternating orthokeratosis and parakeratosis with mild to moderate spongiosis and intraepidermal vesiculation as well as individual and nested atypical mononuclear cells with moderately enlarged hyperchromatic nuclei in the epidermis. There was a superficial interstitial lymphocytic infiltrate with occasional enlarged cells (Figure, A and B), and atypical cells in the epidermis and dermis stained with antibodies against CD3 and CD4 (Figure, C and D) but not against CD20 or CD8. These histopathologic findings were consistent with cutaneous T-cell lymphoma (CTCL), mycosis fungoides (MF) type. Additional application of bexarotene gel on days the patient received narrowband UVB was recommended with noted improvement of the skin.

Cutaneous T-cell lymphomas are a heterogenous group of diseases with monoclonal proliferation of T lymphocytes that largely are confined to the skin at the time of diagnosis.¹ The incidence of CTCL rose steadily for more than 25 years, with an annual age-adjusted incidence of 6.4 to 9.6 cases per million individuals in the United States from 1973 to 2002.² Mycosis fungoides is the most common classification of CTCL. It usually is characterized by patches or plaques of scaly erythema or poikiloderma; however, it also can present with annular, arcuate, concentrative, annular and linear morphologies. Mycosis fungoides tumor cells typically express a mature memory T helper cell phenotype of CD3+, CD4+, and CD8−, but there are different variants that have been discovered.³ Mycosis fungoides distributed in a spiral pattern is a distinctly unusual manifestation. Mechanisms of such dynamic morphologies are unknown but may represent an interplay between malignant cell proliferation and lost immune responses in temporospatial relationships.

The presence of keratotic gyrate lesions on acral surfaces should raise the possibility of pagetoid reticulosis. However, our patient had a history of MF involving areas of the body beyond the extremities, making this diagnosis less likely. Pagetoid reticulosis is categorized as an MF variant under the current World Health Organization– European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas.⁴ Pagetoid reticulosis clinically presents as a solitary psoriasiform or hyperkeratotic patch or plaque that affects the distal extremities. Variable immunophenotypes have been shown in pagetoid reticulosis, such as CD4−/CD8+ and CD4−/CD8−, while classic MF typically shows CD4+/CD8−, as in our case.⁵

Tinea pedis is a superficial fungal infection usually caused by anthropophilic dermatophytes, with Trichophyton rubrum being the most common organism. Four common clinical presentations of tinea pedis have been identified: interdigital, moccasin, vesicular, and acute ulcerative. Clinical presentation ranges from macerations, ulcerations, and erosions in the toe web spaces to dry hyperkeratotic scaling and fissures on the plantar foot.⁶ Tinea pedis primarily affects the plantar and interdigital spaces, sparing the dorsal foot and ankle. Treatment is recommended to alleviate symptoms and limit the spread of infection; topical antifungals for 4 weeks is the treatment of choice. However, recurrence is common, and maintenance therapy often is indicated. Oral antifungals or a combination of both topical and oral medications may be needed in certain cases.⁷

Erythema annulare centrifugum (EAC) is a rare dermatologic disease described as erythematous or urticarial papules that can enlarge centrifugally to form annular lesions that clear centrally. Thought to be a hypersensitivity reaction to an underlying condition, EAC has been associated with fungal infections, various cutaneous diseases, and even internal malignancies. Clinically, EAC can be divided into 2 forms: deep and superficial. Deep gyrate erythema is characterized by a firm indurated border with rare scaling and pruritus that histologically shows perivascular lymphocytic infiltration in the upper and deep dermis. Superficial gyrate erythema has minimally elevated lesions with an indistinct border and trailing scales and pruritus; histopathologic findings present a dense, perivascular, lymphocytic infiltration restricted to the upper dermis.⁸ Therapy for EAC is directed at relieving symptoms and treating the underlying condition if there is one associated.

Granuloma annulare (GA) is a common skin disorder classically characterized by ringed erythematous plaques, though many variants have been identified. Localized GA is the most common variant and presents with pink-red, nonscaly, annular patches or plaques, typically affecting the hands and feet. Generalized GA is characterized as diffuse annular patches or plaques classically affecting the trunk and extremities. Histology is notable for mucin with a palisading or interstitial pattern of granulomatous inflammation, which was not evident in our patient.⁹ Topical or intralesional corticosteroids are the first-line treatment of localized GA; however, localized GA generally is self-limited, and treatment often is not necessary. Treatment with cryosurgery, laser therapy, and topical dapsone and tacrolimus also has been described, but evidence of the efficacy of these agents is limited. For generalized GA, phototherapy currently is the most reliable therapy. Systemic therapies include antimalarials, fumaric acid esters, biologics, antimicrobials, and isotretinoin.¹⁰

Erythema gyratum repens (EGR) is a rare dermatologic disease described as erythematous concentric bands arranged in parallel rings that can be annular, figurate, or gyrate, with a fine scale trailing the leading edge. Histopathologic features of EGR are nonspecific but are characterized by a perivascular, superficial, mononuclear dermatitis. Diagnosis is based on its characteristic clinical presentation. Although EGR commonly is associated with internal malignancies such as bronchial carcinoma, it also may be associated with benign conditions.¹¹ Improvement often is seen with successful therapy of the underlying associated malignancy.¹²

Treatment of MF is based on tumor-node-metastasisblood classification, prognostic factors, and clinical stage at the time of diagnosis. Early-stage MF (IA–IIA) commonly is treated with skin-directed therapies such as topical corticosteroids, topical mechlorethamine, topical retinoids, UV phototherapy, and localized radiotherapy. In late stages (IIB–IV), systemic therapy is indicated and includes systemic retinoids, interferon alfa, chemotherapy, monoclonal antibodies, and psoralen plus UVA.¹³ In many cases, patients may require combination therapy to achieve remission or better control of their condition, as in our patient.

The Diagnosis: Recurrent Cutaneous T-Cell Lymphoma

The skin biopsy revealed alternating orthokeratosis and parakeratosis with mild to moderate spongiosis and intraepidermal vesiculation as well as individual and nested atypical mononuclear cells with moderately enlarged hyperchromatic nuclei in the epidermis. There was a superficial interstitial lymphocytic infiltrate with occasional enlarged cells (Figure, A and B), and atypical cells in the epidermis and dermis stained with antibodies against CD3 and CD4 (Figure, C and D) but not against CD20 or CD8. These histopathologic findings were consistent with cutaneous T-cell lymphoma (CTCL), mycosis fungoides (MF) type. Additional application of bexarotene gel on days the patient received narrowband UVB was recommended with noted improvement of the skin.

Cutaneous T-cell lymphomas are a heterogenous group of diseases with monoclonal proliferation of T lymphocytes that largely are confined to the skin at the time of diagnosis.¹ The incidence of CTCL rose steadily for more than 25 years, with an annual age-adjusted incidence of 6.4 to 9.6 cases per million individuals in the United States from 1973 to 2002.² Mycosis fungoides is the most common classification of CTCL. It usually is characterized by patches or plaques of scaly erythema or poikiloderma; however, it also can present with annular, arcuate, concentrative, annular and linear morphologies. Mycosis fungoides tumor cells typically express a mature memory T helper cell phenotype of CD3+, CD4+, and CD8−, but there are different variants that have been discovered.³ Mycosis fungoides distributed in a spiral pattern is a distinctly unusual manifestation. Mechanisms of such dynamic morphologies are unknown but may represent an interplay between malignant cell proliferation and lost immune responses in temporospatial relationships.

The presence of keratotic gyrate lesions on acral surfaces should raise the possibility of pagetoid reticulosis. However, our patient had a history of MF involving areas of the body beyond the extremities, making this diagnosis less likely. Pagetoid reticulosis is categorized as an MF variant under the current World Health Organization– European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas.⁴ Pagetoid reticulosis clinically presents as a solitary psoriasiform or hyperkeratotic patch or plaque that affects the distal extremities. Variable immunophenotypes have been shown in pagetoid reticulosis, such as CD4−/CD8+ and CD4−/CD8−, while classic MF typically shows CD4+/CD8−, as in our case.⁵

Tinea pedis is a superficial fungal infection usually caused by anthropophilic dermatophytes, with Trichophyton rubrum being the most common organism. Four common clinical presentations of tinea pedis have been identified: interdigital, moccasin, vesicular, and acute ulcerative. Clinical presentation ranges from macerations, ulcerations, and erosions in the toe web spaces to dry hyperkeratotic scaling and fissures on the plantar foot.⁶ Tinea pedis primarily affects the plantar and interdigital spaces, sparing the dorsal foot and ankle. Treatment is recommended to alleviate symptoms and limit the spread of infection; topical antifungals for 4 weeks is the treatment of choice. However, recurrence is common, and maintenance therapy often is indicated. Oral antifungals or a combination of both topical and oral medications may be needed in certain cases.⁷

Erythema annulare centrifugum (EAC) is a rare dermatologic disease described as erythematous or urticarial papules that can enlarge centrifugally to form annular lesions that clear centrally. Thought to be a hypersensitivity reaction to an underlying condition, EAC has been associated with fungal infections, various cutaneous diseases, and even internal malignancies. Clinically, EAC can be divided into 2 forms: deep and superficial. Deep gyrate erythema is characterized by a firm indurated border with rare scaling and pruritus that histologically shows perivascular lymphocytic infiltration in the upper and deep dermis. Superficial gyrate erythema has minimally elevated lesions with an indistinct border and trailing scales and pruritus; histopathologic findings present a dense, perivascular, lymphocytic infiltration restricted to the upper dermis.⁸ Therapy for EAC is directed at relieving symptoms and treating the underlying condition if there is one associated.

Granuloma annulare (GA) is a common skin disorder classically characterized by ringed erythematous plaques, though many variants have been identified. Localized GA is the most common variant and presents with pink-red, nonscaly, annular patches or plaques, typically affecting the hands and feet. Generalized GA is characterized as diffuse annular patches or plaques classically affecting the trunk and extremities. Histology is notable for mucin with a palisading or interstitial pattern of granulomatous inflammation, which was not evident in our patient.⁹ Topical or intralesional corticosteroids are the first-line treatment of localized GA; however, localized GA generally is self-limited, and treatment often is not necessary. Treatment with cryosurgery, laser therapy, and topical dapsone and tacrolimus also has been described, but evidence of the efficacy of these agents is limited. For generalized GA, phototherapy currently is the most reliable therapy. Systemic therapies include antimalarials, fumaric acid esters, biologics, antimicrobials, and isotretinoin.¹⁰

Erythema gyratum repens (EGR) is a rare dermatologic disease described as erythematous concentric bands arranged in parallel rings that can be annular, figurate, or gyrate, with a fine scale trailing the leading edge. Histopathologic features of EGR are nonspecific but are characterized by a perivascular, superficial, mononuclear dermatitis. Diagnosis is based on its characteristic clinical presentation. Although EGR commonly is associated with internal malignancies such as bronchial carcinoma, it also may be associated with benign conditions.¹¹ Improvement often is seen with successful therapy of the underlying associated malignancy.¹²

Treatment of MF is based on tumor-node-metastasisblood classification, prognostic factors, and clinical stage at the time of diagnosis. Early-stage MF (IA–IIA) commonly is treated with skin-directed therapies such as topical corticosteroids, topical mechlorethamine, topical retinoids, UV phototherapy, and localized radiotherapy. In late stages (IIB–IV), systemic therapy is indicated and includes systemic retinoids, interferon alfa, chemotherapy, monoclonal antibodies, and psoralen plus UVA.¹³ In many cases, patients may require combination therapy to achieve remission or better control of their condition, as in our patient.