Bringing you the latest news, research and reviews, exclusive interviews, podcasts, quizzes, and more.

Top Sections
Aesthetic Dermatology Update
Commentary
Dermpath Diagnosis
For Residents
Law & Medicine
Make the Diagnosis
Photo Challenge
Product Review
mdderm
Main menu
MD Dermatology Main Menu
Explore menu
MD Dermatology Explore Menu
Proclivity ID
18851001
Unpublish
Specialty Focus
Acne
Actinic Keratosis
Atopic Dermatitis
Psoriasis
Negative Keywords Excluded Elements
header[@id='header']
div[contains(@class, 'header__large-screen')]
div[contains(@class, 'read-next-article')]
div[contains(@class, 'nav-primary')]
nav[contains(@class, 'nav-primary')]
section[contains(@class, 'footer-nav-section-wrapper')]
footer[@id='footer']
div[contains(@class, 'main-prefix')]
section[contains(@class, 'nav-hidden')]
div[contains(@class, 'ce-card-content')]
nav[contains(@class, 'nav-ce-stack')]
Altmetric
Click for Credit Button Label
Click For Credit
DSM Affiliated
Display in offset block
Disqus Exclude
Best Practices
CE/CME
Education Center
Medical Education Library
Enable Disqus
Display Author and Disclosure Link
Publication Type
Clinical
Slot System
Featured Buckets
Disable Sticky Ads
Disable Ad Block Mitigation
Featured Buckets Admin
Publication LayerRX Default ID
960
Non-Overridden Topics
Show Ads on this Publication's Homepage
Consolidated Pub
Show Article Page Numbers on TOC
Expire Announcement Bar
Mon, 11/25/2024 - 23:12
Use larger logo size
On
publication_blueconic_enabled
Off
Show More Destinations Menu
Disable Adhesion on Publication
Off
Restore Menu Label on Mobile Navigation
Disable Facebook Pixel from Publication
Exclude this publication from publication selection on articles and quiz
Gating Strategy
First Peek Free
Challenge Center
Disable Inline Native ads
survey writer start date
Mon, 11/25/2024 - 23:12

FDA advisors vote to recommend Moderna boosters

Article Type
Changed
Fri, 10/15/2021 - 10:54

A panel of experts that advises the Food and Drug Administration on vaccine decisions voted unanimously Oct. 14 to approve booster doses of Moderna’s COVID-19 vaccine.

The 19 members of the FDA’s Vaccines and Related Biological Products Advisory Committee voted to authorize a 50-milligram dose -- half the dose used in the primary series of shots -- to boost immunity against COVID-19 at least 6 months after the second dose. Those who might need a booster are the same groups who’ve gotten a green light for third Pfizer doses. They include people:

  • Over age 65
  • Ages 18 to 64 who are at higher risk for severe COVID
  • Who are at higher risk of catching COVID because they live in group settings like nursing homes or prisons, or because they are frequently exposed at work, as health care workers are

The agency is not bound by the committee’s vote but usually follows its recommendations.

Some members of the committee said they weren’t satisfied with the data Moderna submitted to support its application but, for practical reasons, said it wouldn’t be fair to take booster doses off the table for Moderna recipients when Pfizer’s boosters were already available.

“The data are not perfect, but these are extraordinary times and we have to work with data that are not perfect,” said Eric Rubin, MD, editor-in-chief of TheNew England Journal of Medicine and a temporary voting member on the committee.

Patrick Moore, MD, a professor at the University of Pittsburgh Cancer Institute who is also a temporary voting member, said he voted to approve the Moderna boosters based “more on a gut feeling than on truly serious data.”

“I’ve got some real issues with this vote,” he said.

“We need to see good solid data, and it needs to be explained well,” Dr. Moore said, challenging companies making future applications to do better.

Next, the FDA will have to formally sign off on the emergency use authorization, which it is expected to do. Then, the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices will meet to make formal recommendations on use of the Moderna boosters. That group is scheduled to meet Oct. 21 to take up questions of exactly how these boosters should be used.

Peter Marks, MD, head of the FDA’s Center for Biologics Evaluation and Research, cautioned that the CDC is more constrained in making recommendations under an emergency use authorization than it would be if the boosters had gotten full approval. So it will likely align its vote with the conditions of the emergency use authorization from the FDA.

After the advisory committee votes, the director of the CDC has to approve its recommendation.

Overall, data show that two doses of the Moderna vaccine remains highly effective at preventing hospitalization and death. But over time, levels of the body’s first line of defense against a virus -- its neutralizing antibodies -- fall somewhat. This drop seems to correspond with an increased risk for breakthrough cases of COVID-19.

Data presented by Moderna Oct. 14 showed the risk of breakthrough infections increased by 36% in study participants who received the vaccine in their clinical trials, compared to people in the same study who received a placebo first, and got the vaccine later, when the trial was unblended. Their protection was more recent, and they had fewer breakthrough infections.

In considering booster doses, the FDA has asked drugmakers to do studies that look at the immune responses of small groups of study participants and compare them to the immune responses seen in study participants after their first two vaccine doses.

To be considered effective, boosters have to clear two bars. The first looks at the concentration of antibodies generated in the blood of boosted study volunteers. The second looks at how many boosted study participants saw a four-fold increase in their blood antibody levels a month after the booster minus the number of people who saw the same increase after their original two doses.

Moderna presented data that its boosters met the first criteria, but failed to meet the second, perhaps because so many people in the study had good responses after their first two doses of the vaccines.

The FDA’s advisory committee will reconvene Oct. 15 to hear evidence supporting the emergency use authorization of a booster dose of the Johnson & Johnson vaccine.

This article was updated Oct. 15 and first appeared on WebMD.com.

Publications
Topics
Sections

A panel of experts that advises the Food and Drug Administration on vaccine decisions voted unanimously Oct. 14 to approve booster doses of Moderna’s COVID-19 vaccine.

The 19 members of the FDA’s Vaccines and Related Biological Products Advisory Committee voted to authorize a 50-milligram dose -- half the dose used in the primary series of shots -- to boost immunity against COVID-19 at least 6 months after the second dose. Those who might need a booster are the same groups who’ve gotten a green light for third Pfizer doses. They include people:

  • Over age 65
  • Ages 18 to 64 who are at higher risk for severe COVID
  • Who are at higher risk of catching COVID because they live in group settings like nursing homes or prisons, or because they are frequently exposed at work, as health care workers are

The agency is not bound by the committee’s vote but usually follows its recommendations.

Some members of the committee said they weren’t satisfied with the data Moderna submitted to support its application but, for practical reasons, said it wouldn’t be fair to take booster doses off the table for Moderna recipients when Pfizer’s boosters were already available.

“The data are not perfect, but these are extraordinary times and we have to work with data that are not perfect,” said Eric Rubin, MD, editor-in-chief of TheNew England Journal of Medicine and a temporary voting member on the committee.

Patrick Moore, MD, a professor at the University of Pittsburgh Cancer Institute who is also a temporary voting member, said he voted to approve the Moderna boosters based “more on a gut feeling than on truly serious data.”

“I’ve got some real issues with this vote,” he said.

“We need to see good solid data, and it needs to be explained well,” Dr. Moore said, challenging companies making future applications to do better.

Next, the FDA will have to formally sign off on the emergency use authorization, which it is expected to do. Then, the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices will meet to make formal recommendations on use of the Moderna boosters. That group is scheduled to meet Oct. 21 to take up questions of exactly how these boosters should be used.

Peter Marks, MD, head of the FDA’s Center for Biologics Evaluation and Research, cautioned that the CDC is more constrained in making recommendations under an emergency use authorization than it would be if the boosters had gotten full approval. So it will likely align its vote with the conditions of the emergency use authorization from the FDA.

After the advisory committee votes, the director of the CDC has to approve its recommendation.

Overall, data show that two doses of the Moderna vaccine remains highly effective at preventing hospitalization and death. But over time, levels of the body’s first line of defense against a virus -- its neutralizing antibodies -- fall somewhat. This drop seems to correspond with an increased risk for breakthrough cases of COVID-19.

Data presented by Moderna Oct. 14 showed the risk of breakthrough infections increased by 36% in study participants who received the vaccine in their clinical trials, compared to people in the same study who received a placebo first, and got the vaccine later, when the trial was unblended. Their protection was more recent, and they had fewer breakthrough infections.

In considering booster doses, the FDA has asked drugmakers to do studies that look at the immune responses of small groups of study participants and compare them to the immune responses seen in study participants after their first two vaccine doses.

To be considered effective, boosters have to clear two bars. The first looks at the concentration of antibodies generated in the blood of boosted study volunteers. The second looks at how many boosted study participants saw a four-fold increase in their blood antibody levels a month after the booster minus the number of people who saw the same increase after their original two doses.

Moderna presented data that its boosters met the first criteria, but failed to meet the second, perhaps because so many people in the study had good responses after their first two doses of the vaccines.

The FDA’s advisory committee will reconvene Oct. 15 to hear evidence supporting the emergency use authorization of a booster dose of the Johnson & Johnson vaccine.

This article was updated Oct. 15 and first appeared on WebMD.com.

A panel of experts that advises the Food and Drug Administration on vaccine decisions voted unanimously Oct. 14 to approve booster doses of Moderna’s COVID-19 vaccine.

The 19 members of the FDA’s Vaccines and Related Biological Products Advisory Committee voted to authorize a 50-milligram dose -- half the dose used in the primary series of shots -- to boost immunity against COVID-19 at least 6 months after the second dose. Those who might need a booster are the same groups who’ve gotten a green light for third Pfizer doses. They include people:

  • Over age 65
  • Ages 18 to 64 who are at higher risk for severe COVID
  • Who are at higher risk of catching COVID because they live in group settings like nursing homes or prisons, or because they are frequently exposed at work, as health care workers are

The agency is not bound by the committee’s vote but usually follows its recommendations.

Some members of the committee said they weren’t satisfied with the data Moderna submitted to support its application but, for practical reasons, said it wouldn’t be fair to take booster doses off the table for Moderna recipients when Pfizer’s boosters were already available.

“The data are not perfect, but these are extraordinary times and we have to work with data that are not perfect,” said Eric Rubin, MD, editor-in-chief of TheNew England Journal of Medicine and a temporary voting member on the committee.

Patrick Moore, MD, a professor at the University of Pittsburgh Cancer Institute who is also a temporary voting member, said he voted to approve the Moderna boosters based “more on a gut feeling than on truly serious data.”

“I’ve got some real issues with this vote,” he said.

“We need to see good solid data, and it needs to be explained well,” Dr. Moore said, challenging companies making future applications to do better.

Next, the FDA will have to formally sign off on the emergency use authorization, which it is expected to do. Then, the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices will meet to make formal recommendations on use of the Moderna boosters. That group is scheduled to meet Oct. 21 to take up questions of exactly how these boosters should be used.

Peter Marks, MD, head of the FDA’s Center for Biologics Evaluation and Research, cautioned that the CDC is more constrained in making recommendations under an emergency use authorization than it would be if the boosters had gotten full approval. So it will likely align its vote with the conditions of the emergency use authorization from the FDA.

After the advisory committee votes, the director of the CDC has to approve its recommendation.

Overall, data show that two doses of the Moderna vaccine remains highly effective at preventing hospitalization and death. But over time, levels of the body’s first line of defense against a virus -- its neutralizing antibodies -- fall somewhat. This drop seems to correspond with an increased risk for breakthrough cases of COVID-19.

Data presented by Moderna Oct. 14 showed the risk of breakthrough infections increased by 36% in study participants who received the vaccine in their clinical trials, compared to people in the same study who received a placebo first, and got the vaccine later, when the trial was unblended. Their protection was more recent, and they had fewer breakthrough infections.

In considering booster doses, the FDA has asked drugmakers to do studies that look at the immune responses of small groups of study participants and compare them to the immune responses seen in study participants after their first two vaccine doses.

To be considered effective, boosters have to clear two bars. The first looks at the concentration of antibodies generated in the blood of boosted study volunteers. The second looks at how many boosted study participants saw a four-fold increase in their blood antibody levels a month after the booster minus the number of people who saw the same increase after their original two doses.

Moderna presented data that its boosters met the first criteria, but failed to meet the second, perhaps because so many people in the study had good responses after their first two doses of the vaccines.

The FDA’s advisory committee will reconvene Oct. 15 to hear evidence supporting the emergency use authorization of a booster dose of the Johnson & Johnson vaccine.

This article was updated Oct. 15 and first appeared on WebMD.com.

Publications
Publications
Topics
Article Type
Sections
Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME
Disqus Comments
Default
Use ProPublica
Hide sidebar & use full width
render the right sidebar.
Conference Recap Checkbox
Not Conference Recap
Clinical Edge
Display the Slideshow in this Article
Medscape Article
Display survey writer
Reuters content
Disable Inline Native ads
WebMD Article

New safety data regarding COVID vaccines

Article Type
Changed
Thu, 10/14/2021 - 12:20

 

Parsonage-Turner syndrome has been highlighted as a potential adverse effect of mRNA COVID vaccines in a recent pharmacovigilance monitoring report from the French National Agency for the Safety of Medicines and Health Products (ANSM).

The rare condition — more common in men than in women — is characterized by the sudden onset of severe pain in the shoulder, followed by arm paralysis. Its etiopathogenesis is not well understood, but vaccines, in particular the flu vaccine, have been implicated in some cases, the report states.

Six serious cases of the syndrome related to the Comirnaty (Pfizer) vaccine were reported by healthcare professionals and vaccinated individuals or their family and friends since the start of the monitoring program. Four of these cases occurred from September 3 to 16.

All six cases involved patients 19 to 69 years of age — two women and four men — who developed symptoms in the 50 days after vaccination. Half were reported after the first dose and half after the second dose. Four of the patients are currently recovering; the outcomes of the other two are unknown.

In the case of the Spikevax vaccine (Moderna), two cases of Parsonage-Turner syndrome were reported after vaccination (plus one that occurred after 50 days, which is currently being managed). The onset of symptoms in these two men — one in his early 30s and one in his early 60s — occurred less than 18 days after vaccination. One occurred after the first dose and one after the second dose. This timing indicates a possible link between the syndrome and the vaccine. Both men are currently in recovery.

This signal of mRNA vaccines is now “officially recognized,” according to the Pfizer and Moderna reports.

It is also considered a “potential signal” in the Vaxzevria (AstraZeneca) pharmacovigilance report, released October 8, which describes eight cases of Parsonage-Turner syndrome after vaccination.
 

Safety profile of mRNA COVID vaccines in youth

Between June 15, when children 12 years and older became eligible for vaccination, and August 26, there were 591 reports of potential adverse events — out of 6 million Pfizer doses administered — in 12- to 18-year-old children.

Of the 591 cases, 35.2% were deemed serious. The majority of these were cases of reactogenicity, malaise, or postvaccine discomfort (25%), followed by instances of myocarditis and pericarditis (15.9% and 7.2%, respectively). In eight of 10 cases, one of the first symptom reported was chest pain.

Myocarditis occurred in 39.4% of people after the first injection (mean time to onset, 13 days) and 54.5% after the second (mean time to onset, 4 days). Recorded progress was favorable in nearly nine of 10 cases.

Pericarditis occurred in 53.3% of people after the first injection (mean time to onset, 13 days), and 40.0% after the second (mean time to onset, 4 days).

Three cases of multisystem inflammatory syndrome in children (MISC) were reported after monitoring ended.

For this age group, “all reported events will continue to be monitored, especially serious events and multisystem inflammatory syndrome in children,” report authors conclude.

Data for adverse events after the Moderna vaccine remain limited, but the report stipulates that “the adverse events reported in 12- to 18-year-olds who received an injection do not display any particular pattern, compared with those reported in older subjects, with the exception of a roughly 100-fold lower incidence of reported adverse effects in the 12- to 17-year age group.”
 

No safety warnings for pregnant women

The pharmacovigilance report — which covered the period from December 27, 2020 to September 9, 2021 — “raises no safety warnings for pregnant or nursing women with any of the COVID-19 vaccines.” In addition, two recent studies — one published in JAMA and one in the New England Journal of Medicine — have shown no link between spontaneous miscarriage and mRNA vaccines.

“Moreover, it should be stressed that current data from the international literature consistently show that maternal SARS COV-2 infection increases the risk for fetal, maternal, and neonatal complications, and that this risk may increase with the arrival of the Alpha and Delta variants,” they write. “It is therefore important to reiterate the current recommendations to vaccinate all pregnant women, regardless of the stage of pregnancy.”

Some adverse effects, such as thromboembolic effects, in utero death, HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome, and uterine contractions, will continue to be monitored.
 

Questions regarding menstrual disorders

As for gynecological disorders reported after vaccination, questions still remain. “In most of the reported cases, it is difficult to accurately determine whether the vaccine played a role in the occurrence of menstrual/genital bleeding,” the authors of the pharmacovigilance monitoring report state.

“Nonetheless, these cases warrant attention,” they add, and further discussions with the French National Association of Obstetricians and Gynecologists and the French Society of Endocrinology are needed in regard to these potential safety signals.

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

Publications
Topics
Sections

 

Parsonage-Turner syndrome has been highlighted as a potential adverse effect of mRNA COVID vaccines in a recent pharmacovigilance monitoring report from the French National Agency for the Safety of Medicines and Health Products (ANSM).

The rare condition — more common in men than in women — is characterized by the sudden onset of severe pain in the shoulder, followed by arm paralysis. Its etiopathogenesis is not well understood, but vaccines, in particular the flu vaccine, have been implicated in some cases, the report states.

Six serious cases of the syndrome related to the Comirnaty (Pfizer) vaccine were reported by healthcare professionals and vaccinated individuals or their family and friends since the start of the monitoring program. Four of these cases occurred from September 3 to 16.

All six cases involved patients 19 to 69 years of age — two women and four men — who developed symptoms in the 50 days after vaccination. Half were reported after the first dose and half after the second dose. Four of the patients are currently recovering; the outcomes of the other two are unknown.

In the case of the Spikevax vaccine (Moderna), two cases of Parsonage-Turner syndrome were reported after vaccination (plus one that occurred after 50 days, which is currently being managed). The onset of symptoms in these two men — one in his early 30s and one in his early 60s — occurred less than 18 days after vaccination. One occurred after the first dose and one after the second dose. This timing indicates a possible link between the syndrome and the vaccine. Both men are currently in recovery.

This signal of mRNA vaccines is now “officially recognized,” according to the Pfizer and Moderna reports.

It is also considered a “potential signal” in the Vaxzevria (AstraZeneca) pharmacovigilance report, released October 8, which describes eight cases of Parsonage-Turner syndrome after vaccination.
 

Safety profile of mRNA COVID vaccines in youth

Between June 15, when children 12 years and older became eligible for vaccination, and August 26, there were 591 reports of potential adverse events — out of 6 million Pfizer doses administered — in 12- to 18-year-old children.

Of the 591 cases, 35.2% were deemed serious. The majority of these were cases of reactogenicity, malaise, or postvaccine discomfort (25%), followed by instances of myocarditis and pericarditis (15.9% and 7.2%, respectively). In eight of 10 cases, one of the first symptom reported was chest pain.

Myocarditis occurred in 39.4% of people after the first injection (mean time to onset, 13 days) and 54.5% after the second (mean time to onset, 4 days). Recorded progress was favorable in nearly nine of 10 cases.

Pericarditis occurred in 53.3% of people after the first injection (mean time to onset, 13 days), and 40.0% after the second (mean time to onset, 4 days).

Three cases of multisystem inflammatory syndrome in children (MISC) were reported after monitoring ended.

For this age group, “all reported events will continue to be monitored, especially serious events and multisystem inflammatory syndrome in children,” report authors conclude.

Data for adverse events after the Moderna vaccine remain limited, but the report stipulates that “the adverse events reported in 12- to 18-year-olds who received an injection do not display any particular pattern, compared with those reported in older subjects, with the exception of a roughly 100-fold lower incidence of reported adverse effects in the 12- to 17-year age group.”
 

No safety warnings for pregnant women

The pharmacovigilance report — which covered the period from December 27, 2020 to September 9, 2021 — “raises no safety warnings for pregnant or nursing women with any of the COVID-19 vaccines.” In addition, two recent studies — one published in JAMA and one in the New England Journal of Medicine — have shown no link between spontaneous miscarriage and mRNA vaccines.

“Moreover, it should be stressed that current data from the international literature consistently show that maternal SARS COV-2 infection increases the risk for fetal, maternal, and neonatal complications, and that this risk may increase with the arrival of the Alpha and Delta variants,” they write. “It is therefore important to reiterate the current recommendations to vaccinate all pregnant women, regardless of the stage of pregnancy.”

Some adverse effects, such as thromboembolic effects, in utero death, HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome, and uterine contractions, will continue to be monitored.
 

Questions regarding menstrual disorders

As for gynecological disorders reported after vaccination, questions still remain. “In most of the reported cases, it is difficult to accurately determine whether the vaccine played a role in the occurrence of menstrual/genital bleeding,” the authors of the pharmacovigilance monitoring report state.

“Nonetheless, these cases warrant attention,” they add, and further discussions with the French National Association of Obstetricians and Gynecologists and the French Society of Endocrinology are needed in regard to these potential safety signals.

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

 

Parsonage-Turner syndrome has been highlighted as a potential adverse effect of mRNA COVID vaccines in a recent pharmacovigilance monitoring report from the French National Agency for the Safety of Medicines and Health Products (ANSM).

The rare condition — more common in men than in women — is characterized by the sudden onset of severe pain in the shoulder, followed by arm paralysis. Its etiopathogenesis is not well understood, but vaccines, in particular the flu vaccine, have been implicated in some cases, the report states.

Six serious cases of the syndrome related to the Comirnaty (Pfizer) vaccine were reported by healthcare professionals and vaccinated individuals or their family and friends since the start of the monitoring program. Four of these cases occurred from September 3 to 16.

All six cases involved patients 19 to 69 years of age — two women and four men — who developed symptoms in the 50 days after vaccination. Half were reported after the first dose and half after the second dose. Four of the patients are currently recovering; the outcomes of the other two are unknown.

In the case of the Spikevax vaccine (Moderna), two cases of Parsonage-Turner syndrome were reported after vaccination (plus one that occurred after 50 days, which is currently being managed). The onset of symptoms in these two men — one in his early 30s and one in his early 60s — occurred less than 18 days after vaccination. One occurred after the first dose and one after the second dose. This timing indicates a possible link between the syndrome and the vaccine. Both men are currently in recovery.

This signal of mRNA vaccines is now “officially recognized,” according to the Pfizer and Moderna reports.

It is also considered a “potential signal” in the Vaxzevria (AstraZeneca) pharmacovigilance report, released October 8, which describes eight cases of Parsonage-Turner syndrome after vaccination.
 

Safety profile of mRNA COVID vaccines in youth

Between June 15, when children 12 years and older became eligible for vaccination, and August 26, there were 591 reports of potential adverse events — out of 6 million Pfizer doses administered — in 12- to 18-year-old children.

Of the 591 cases, 35.2% were deemed serious. The majority of these were cases of reactogenicity, malaise, or postvaccine discomfort (25%), followed by instances of myocarditis and pericarditis (15.9% and 7.2%, respectively). In eight of 10 cases, one of the first symptom reported was chest pain.

Myocarditis occurred in 39.4% of people after the first injection (mean time to onset, 13 days) and 54.5% after the second (mean time to onset, 4 days). Recorded progress was favorable in nearly nine of 10 cases.

Pericarditis occurred in 53.3% of people after the first injection (mean time to onset, 13 days), and 40.0% after the second (mean time to onset, 4 days).

Three cases of multisystem inflammatory syndrome in children (MISC) were reported after monitoring ended.

For this age group, “all reported events will continue to be monitored, especially serious events and multisystem inflammatory syndrome in children,” report authors conclude.

Data for adverse events after the Moderna vaccine remain limited, but the report stipulates that “the adverse events reported in 12- to 18-year-olds who received an injection do not display any particular pattern, compared with those reported in older subjects, with the exception of a roughly 100-fold lower incidence of reported adverse effects in the 12- to 17-year age group.”
 

No safety warnings for pregnant women

The pharmacovigilance report — which covered the period from December 27, 2020 to September 9, 2021 — “raises no safety warnings for pregnant or nursing women with any of the COVID-19 vaccines.” In addition, two recent studies — one published in JAMA and one in the New England Journal of Medicine — have shown no link between spontaneous miscarriage and mRNA vaccines.

“Moreover, it should be stressed that current data from the international literature consistently show that maternal SARS COV-2 infection increases the risk for fetal, maternal, and neonatal complications, and that this risk may increase with the arrival of the Alpha and Delta variants,” they write. “It is therefore important to reiterate the current recommendations to vaccinate all pregnant women, regardless of the stage of pregnancy.”

Some adverse effects, such as thromboembolic effects, in utero death, HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome, and uterine contractions, will continue to be monitored.
 

Questions regarding menstrual disorders

As for gynecological disorders reported after vaccination, questions still remain. “In most of the reported cases, it is difficult to accurately determine whether the vaccine played a role in the occurrence of menstrual/genital bleeding,” the authors of the pharmacovigilance monitoring report state.

“Nonetheless, these cases warrant attention,” they add, and further discussions with the French National Association of Obstetricians and Gynecologists and the French Society of Endocrinology are needed in regard to these potential safety signals.

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

Publications
Publications
Topics
Article Type
Sections
Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME
Disqus Comments
Default
Use ProPublica
Hide sidebar & use full width
render the right sidebar.
Conference Recap Checkbox
Not Conference Recap
Clinical Edge
Display the Slideshow in this Article
Medscape Article
Display survey writer
Reuters content
Disable Inline Native ads
WebMD Article

Stay tuned for CSI: Olive oil

Article Type
Changed
Thu, 10/14/2021 - 09:42

 

Cracking down on food fraud

How do you know the olive oil in your pantry is from Greece? Or that the avocados on your toast are from Mexico? The label, right? Well, maybe not. False claims of origin are a huge problem in the food industry, costing over $30 billion in economic damage annually.

©Volosina/thinkstockphotos.com

Fear not, citizens, because botanists are on the job, and they’ve found a cheaper and more efficient way to expose that non-Greek olive oil.

How? Florian Cueni, PhD, of the University of Basel, Switzerland, and associates developed a new model to simulate oxygen isotope ratios in plants from a specific region, based on the temperature, precipitation, growing season information, and humidity data. Previously, botanists had to collect reference data from the claimed origin country and from other regions to validate where the product actually came from.

“With minor adjustments to the parameters, our model can be used to determine all plant products,” said senior investigator Ansgar Kahmen. This can open up the door for even more plant forensics, including drug confiscations and illegal timber logging, with information that will hold up in court.

Why pay Greek-olive prices for olives from California?
 

Fear leads to anger, anger leads to unhelpful online reviews

And reading angry online reviews leads to hate and suffering. We may have co-opted Master Yoda’s wise words ever so slightly, but anyone who’s done any shopping online (so everyone) knows that the review section of any product can be downright villainous. Do these reviews affect what we buy?

clintspencer/E+

The angry online product review was the subject of a recent study published in MIS Quarterly. In a series of experiments, participants were shown a series of realistic online reviews with varying amounts of anger but with similar amounts of information. After reading the reviews, participants rated helpfulness, their personal opinion of the product/retailer, and whether or not they would buy the product.

Participants overwhelmingly rated calmly written reviews as more helpful than angrily written ones. One would expect, then, that those unhelpful angry reviews would have little effect on the participant’s view or willingness to buy a product, but the study investigators found the opposite. Reading angry reviews made the participants more likely to reject the product, even though they didn’t think the angry review was useful. And when you think about it, it does make sense. Anger means drama, and we can’t resist a juicy bit of drama.

So while we should all aspire to be Yoda and rise above anger and hatred, in reality we seem to be channeling Emperor Palpatine. We let the hate flow through us, and in our anger, we ignore perfectly good products. On the plus side, now we can shoot lightning out of our hands, so that’s pretty cool.
 

Health care is heading to the hall of fame

We couldn’t be happier here at LOTME because it’s that time of year again.

NIHF

No, we’re not talking about Healthcare Security and Safety Week or National Metric Week, although those are both kind of important. Hmm, maybe we should talk about health care security or the metric system. After all, in this country, medicine is one of the metric system’s biggest customers. And who doesn’t love picograms? They’re the unit-of-measurement equivalent of a koala.

So we’re doing the metric system, then? Nah.

We’re excited because the 2022 inductees to the National Inventors Hall of Fame were just announced, and, as usual, the world of health care is well represented.

First up is the surprisingly relevant (thanks to the party guest that won’t leave, SARS-CoV-2) pair of Katalin Karikó, PhD, and Drew Weissman, MD, who worked together in the early 2000s to modify mRNA “so it could avoid immediate immune detection, remain active longer and efficiently instruct cells to create antigens to protect against severe disease.” Their discoveries eventually led to the use of modified mRNA in the COVID-19 vaccines.

The second, albeit posthumous, physician-inductee is Patricia Bath, MD, who was the first Black female physician to receive a U.S. patent for a medical invention. The laserphaco device and technique to remove cataracts “performed all steps of cataract removal: making the incision, destroying the lens, and vacuuming out the fractured pieces.”

Two other inductees have somewhat tenuous connections to medical care. Lonnie Johnson invented the Super Soaker, a powerful squirt gun that has been criticized by psychologists for encouraging violence, and Carl Benz invented the automobile, which sort of means he invented the ambulance, so there you go.

The induction ceremony takes place on May 5, 2022, in Washington, DC. If you’re attending the black-tie dinner at The Anthem, let us know and we’ll split an Uber. It’s our only night to be fancy.

Publications
Topics
Sections

 

Cracking down on food fraud

How do you know the olive oil in your pantry is from Greece? Or that the avocados on your toast are from Mexico? The label, right? Well, maybe not. False claims of origin are a huge problem in the food industry, costing over $30 billion in economic damage annually.

©Volosina/thinkstockphotos.com

Fear not, citizens, because botanists are on the job, and they’ve found a cheaper and more efficient way to expose that non-Greek olive oil.

How? Florian Cueni, PhD, of the University of Basel, Switzerland, and associates developed a new model to simulate oxygen isotope ratios in plants from a specific region, based on the temperature, precipitation, growing season information, and humidity data. Previously, botanists had to collect reference data from the claimed origin country and from other regions to validate where the product actually came from.

“With minor adjustments to the parameters, our model can be used to determine all plant products,” said senior investigator Ansgar Kahmen. This can open up the door for even more plant forensics, including drug confiscations and illegal timber logging, with information that will hold up in court.

Why pay Greek-olive prices for olives from California?
 

Fear leads to anger, anger leads to unhelpful online reviews

And reading angry online reviews leads to hate and suffering. We may have co-opted Master Yoda’s wise words ever so slightly, but anyone who’s done any shopping online (so everyone) knows that the review section of any product can be downright villainous. Do these reviews affect what we buy?

clintspencer/E+

The angry online product review was the subject of a recent study published in MIS Quarterly. In a series of experiments, participants were shown a series of realistic online reviews with varying amounts of anger but with similar amounts of information. After reading the reviews, participants rated helpfulness, their personal opinion of the product/retailer, and whether or not they would buy the product.

Participants overwhelmingly rated calmly written reviews as more helpful than angrily written ones. One would expect, then, that those unhelpful angry reviews would have little effect on the participant’s view or willingness to buy a product, but the study investigators found the opposite. Reading angry reviews made the participants more likely to reject the product, even though they didn’t think the angry review was useful. And when you think about it, it does make sense. Anger means drama, and we can’t resist a juicy bit of drama.

So while we should all aspire to be Yoda and rise above anger and hatred, in reality we seem to be channeling Emperor Palpatine. We let the hate flow through us, and in our anger, we ignore perfectly good products. On the plus side, now we can shoot lightning out of our hands, so that’s pretty cool.
 

Health care is heading to the hall of fame

We couldn’t be happier here at LOTME because it’s that time of year again.

NIHF

No, we’re not talking about Healthcare Security and Safety Week or National Metric Week, although those are both kind of important. Hmm, maybe we should talk about health care security or the metric system. After all, in this country, medicine is one of the metric system’s biggest customers. And who doesn’t love picograms? They’re the unit-of-measurement equivalent of a koala.

So we’re doing the metric system, then? Nah.

We’re excited because the 2022 inductees to the National Inventors Hall of Fame were just announced, and, as usual, the world of health care is well represented.

First up is the surprisingly relevant (thanks to the party guest that won’t leave, SARS-CoV-2) pair of Katalin Karikó, PhD, and Drew Weissman, MD, who worked together in the early 2000s to modify mRNA “so it could avoid immediate immune detection, remain active longer and efficiently instruct cells to create antigens to protect against severe disease.” Their discoveries eventually led to the use of modified mRNA in the COVID-19 vaccines.

The second, albeit posthumous, physician-inductee is Patricia Bath, MD, who was the first Black female physician to receive a U.S. patent for a medical invention. The laserphaco device and technique to remove cataracts “performed all steps of cataract removal: making the incision, destroying the lens, and vacuuming out the fractured pieces.”

Two other inductees have somewhat tenuous connections to medical care. Lonnie Johnson invented the Super Soaker, a powerful squirt gun that has been criticized by psychologists for encouraging violence, and Carl Benz invented the automobile, which sort of means he invented the ambulance, so there you go.

The induction ceremony takes place on May 5, 2022, in Washington, DC. If you’re attending the black-tie dinner at The Anthem, let us know and we’ll split an Uber. It’s our only night to be fancy.

 

Cracking down on food fraud

How do you know the olive oil in your pantry is from Greece? Or that the avocados on your toast are from Mexico? The label, right? Well, maybe not. False claims of origin are a huge problem in the food industry, costing over $30 billion in economic damage annually.

©Volosina/thinkstockphotos.com

Fear not, citizens, because botanists are on the job, and they’ve found a cheaper and more efficient way to expose that non-Greek olive oil.

How? Florian Cueni, PhD, of the University of Basel, Switzerland, and associates developed a new model to simulate oxygen isotope ratios in plants from a specific region, based on the temperature, precipitation, growing season information, and humidity data. Previously, botanists had to collect reference data from the claimed origin country and from other regions to validate where the product actually came from.

“With minor adjustments to the parameters, our model can be used to determine all plant products,” said senior investigator Ansgar Kahmen. This can open up the door for even more plant forensics, including drug confiscations and illegal timber logging, with information that will hold up in court.

Why pay Greek-olive prices for olives from California?
 

Fear leads to anger, anger leads to unhelpful online reviews

And reading angry online reviews leads to hate and suffering. We may have co-opted Master Yoda’s wise words ever so slightly, but anyone who’s done any shopping online (so everyone) knows that the review section of any product can be downright villainous. Do these reviews affect what we buy?

clintspencer/E+

The angry online product review was the subject of a recent study published in MIS Quarterly. In a series of experiments, participants were shown a series of realistic online reviews with varying amounts of anger but with similar amounts of information. After reading the reviews, participants rated helpfulness, their personal opinion of the product/retailer, and whether or not they would buy the product.

Participants overwhelmingly rated calmly written reviews as more helpful than angrily written ones. One would expect, then, that those unhelpful angry reviews would have little effect on the participant’s view or willingness to buy a product, but the study investigators found the opposite. Reading angry reviews made the participants more likely to reject the product, even though they didn’t think the angry review was useful. And when you think about it, it does make sense. Anger means drama, and we can’t resist a juicy bit of drama.

So while we should all aspire to be Yoda and rise above anger and hatred, in reality we seem to be channeling Emperor Palpatine. We let the hate flow through us, and in our anger, we ignore perfectly good products. On the plus side, now we can shoot lightning out of our hands, so that’s pretty cool.
 

Health care is heading to the hall of fame

We couldn’t be happier here at LOTME because it’s that time of year again.

NIHF

No, we’re not talking about Healthcare Security and Safety Week or National Metric Week, although those are both kind of important. Hmm, maybe we should talk about health care security or the metric system. After all, in this country, medicine is one of the metric system’s biggest customers. And who doesn’t love picograms? They’re the unit-of-measurement equivalent of a koala.

So we’re doing the metric system, then? Nah.

We’re excited because the 2022 inductees to the National Inventors Hall of Fame were just announced, and, as usual, the world of health care is well represented.

First up is the surprisingly relevant (thanks to the party guest that won’t leave, SARS-CoV-2) pair of Katalin Karikó, PhD, and Drew Weissman, MD, who worked together in the early 2000s to modify mRNA “so it could avoid immediate immune detection, remain active longer and efficiently instruct cells to create antigens to protect against severe disease.” Their discoveries eventually led to the use of modified mRNA in the COVID-19 vaccines.

The second, albeit posthumous, physician-inductee is Patricia Bath, MD, who was the first Black female physician to receive a U.S. patent for a medical invention. The laserphaco device and technique to remove cataracts “performed all steps of cataract removal: making the incision, destroying the lens, and vacuuming out the fractured pieces.”

Two other inductees have somewhat tenuous connections to medical care. Lonnie Johnson invented the Super Soaker, a powerful squirt gun that has been criticized by psychologists for encouraging violence, and Carl Benz invented the automobile, which sort of means he invented the ambulance, so there you go.

The induction ceremony takes place on May 5, 2022, in Washington, DC. If you’re attending the black-tie dinner at The Anthem, let us know and we’ll split an Uber. It’s our only night to be fancy.

Publications
Publications
Topics
Article Type
Sections
Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME
Disqus Comments
Default
Use ProPublica
Hide sidebar & use full width
render the right sidebar.
Conference Recap Checkbox
Not Conference Recap
Clinical Edge
Display the Slideshow in this Article
Medscape Article
Display survey writer
Reuters content
Disable Inline Native ads
WebMD Article

Fecal microbiota transplants may improve resistance to melanoma immunotherapy

Article Type
Changed
Thu, 10/14/2021 - 15:39

In the fall of 2020, Hassane M. Zarour, MD, and colleagues began to pore over raw data from their phase 1 clinical trial designed to determine if fecal microbiota transplantation (FMT) could reprogram the gut microbiome in advanced melanoma patients who failed to respond to anti–programmed death 1immunotherapy.

Dr. Hassane M. Zarour

Preclinical mouse studies have demonstrated that the gut microbiota could influence the response of tumors to anti–PD-1 immunotherapy, but FMT had not been previously evaluated in human patients with malignant melanoma whose disease persisted or progressed after medical therapy. Only 30%-40% of melanoma patients respond to anti–PD-1 immunotherapy, so the researchers’ sense of anticipation was palpable. “It’s a high-risk, high-reward study, so you never know,” Dr. Zarour, a dermatologist and immunologist who is coleader of the melanoma program at the University of Pittsburgh Medical Center’s Hillman Cancer Center, said in an interview.

For the study, which was funded by the National Institutes of Health and published in Science, Dr. Zarour and a team of colleagues, including Diwakar Davar, MD, a medical oncologist/hematologist at UPMC and Giorgio Trinchieri, MD, head of the cancer immunology section at the National Cancer Institute, enrolled 16 patients with advanced melanoma whose disease had persisted or progressed with anti-PD-1 drugs; donors were 7 patients with advanced melanoma who had responded to pembrolizumab, 4 with a complete response and 3 with a partial response, with a median progression-free survival of 56 months.

After donors and patients underwent serial stool sampling and studies to stamp out the potential for transmitting infectious agents, the researchers administered the donor-derived FMT to patients via colonoscopy every 14 days for 3 weeks, followed by pembrolizumab. To their delight, 6 of the 15 evaluable recipients responded to treatment, with a reduction in tumor or long-term disease stabilization. Moreover, responders also showed increased abundance of taxa that were previously associated with response to immunotherapy, increased activation of CD8+ T cells, and decreased frequency of interleukin-8–expressing myeloid cells.

“This opens new doors for the future,” Dr. Zarour said. “It’s very encouraging, but I don’t want to overstate the data. It’s a small, nonrandomized trial, but one has to keep in mind that people were skeptical about this work; they didn’t think FMT would work. Now we see many people coming into the field to investigate the role of the microbiome as a therapeutic tool, which is great.”

Dr. Teri Greiling

Teri Greiling, MD, characterized the finding as a key development in understanding the microbiome’s potential to influence the course of melanoma and other diseases. “What’s emerging over the last decade of research is that our immune system has a close, back-and-forth relationship with our microbiota,” said Dr. Greiling, associate professor of dermatology at Oregon Health & Science University, Portland. “From day 1 of birth, we’re colonized by microbes that train our immune system how to function. In response, your immune system keeps those microbes in check and shapes which ones are allowed to colonize, and which ones are a target for attack. Thus, inflammatory responses are generated. Similarly, the goal of immunotherapy is to activate the immune system to fight cancer. This study shows that the immune system continues to need the colonizing microbes in our body to function optimally.”

Immunotherapy with checkpoint inhibitors was not an option for malignant melanoma patients until 2011, she noted, so the potential for FMT to further improve outcomes is welcome news for patients and their families. “We went from a less than 5% chance of survival with metastatic melanoma to now, with the right combination of checkpoint inhibitors, we’re up over 50%, which is amazing in a decade,” Dr. Greiling said. “Still, we’re losing half of our patients. If [FMT provides] a 30% improvement over that, that would be great, but it’s hard to extrapolate from such small numbers.”
 

 

 

Positive results in an Israeli study

Results from a similar, smaller phase 1 trial of 2 FMT donors and 10 recipients with metastatic melanoma who had progressed on anti-PD-1 therapy, from the Ella Lemelbaum Institute for Immuno-Oncology at Sheba Medical Center in Tel HaShomer, Israel, yielded similar results. The FMT protocol in this study included colonoscopy and oral stool capsules, followed by the reintroduction of anti–PD-1 therapy with nivolumab. The two FMT donors had previously been treated with anti–PD-1 monotherapy for metastatic melanoma and had achieved a clinical response for at least 1 year. Of the 10 FMT recipients, 1 had a complete response and 2 had a partial response.

Dr. Erez Baruch

“We expected changes in the immune system but did not expect that 3 out of the 10 patients in our study would be turned from nonresponders to responders,” the study’s lead author, Erez N. Baruch, MD, PhD, told this news organization. “Since this was a first-in-human study, we were aiming to assess safety and not clinical responses. [We found] that microbiota modulation can change the immune infiltration within melanoma tumors and by this affect response to immunotherapy.”

Dr. Baruch, an internal medicine resident in the physician-scientist track program at the University of Texas, Houston, said that the findings create a potential new therapeutic paradigm, or a new “playing ground” for drug development that can support existing immunotherapies. “It is important for dermatologists to understand that disruptions of the gut microbiota, mainly by antibiotics, may be harmful to melanoma patients,” he said. “Antibiotics in cancer patients should be used judiciously but of course should not be avoided when there’s an indication.”

As for next steps, Dr. Zarour and colleagues are recruiting more patients to boost their sample size and conducting sequential analysis of the microbiome of study participants “to better determine what the good and bad bugs are,” he said. “There are so many variables, including diet and geography. We need more data.” The hope is to develop a “microbiome signature” to identify patients likely to respond to FMT, and maybe one day, a probiotic capsule that patients take to optimize their response to immunotherapy.

“We don’t want to say that the microbiome is responsible for everything, but it’s responsible for some of the response and some of the resistance to treatment,” Dr. Zarour said. “So, we want to identify what candidate nonresponders are more likely to respond to FMT and be able to stick the right stool in the donor. This goes to better education of the microbiome signature. We are working hard on that.”

Dr. Baruch added that performing FMT for melanoma patients requires tight collaborations between oncologists, dermatologists, GI, and infectious disease experts. “These usually can be done in the setting of large cancer centers and will probably not be available in any hospital,” he said. “This is why understanding the mechanisms and developing an FMT-like drug is important. We are focusing on studying the mechanisms behind the clinical effect in order to develop a drug with an FMT-like effect without the safety and logistic issues related to FMTs.”

Dr. Tamia A. Harris-Tyron


Tamia A. Harris-Tryon, MD, PhD, whose lab at the University of Texas Southwestern Medical Center at Dallas is studying how diet and the microbiota impact skin immunity, underscored the importance of evaluating the characteristics of the diet of patients as trials of FMT in melanoma patients carry on. “We know that the diet impacts the repertoire of microbes that colonize the gut,” said Dr. Harris-Tryon, assistant professor in the department of dermatology at the medical center. “The diet of the recipient likely has an impact” on the success of donor FMT.

She also noted that other skin conditions have been linked to a disrupted gut microbiome, such as psoriasis. “Given the safety of FMT in both of these studies, trials of FMT in psoriasis and other systemic skin conditions should be considered,” she said.

According to Dr. Zarour, mounting data from separate studies show that some gut microbiota play a role in adverse events experienced by melanoma patients on immunotherapy. “That is very important, especially with combination therapy,” he said. “There are also microbes involved in resistance to treatment, so the idea would be to identify these microbes.”

Studies raise more questions

In the opinion of Dr. Greiling, results from these two studies raise more questions than they answer. “The big question ... is why and how does FMT work, and how can we make the response better?” she said. “Is there one particular gene product from one microbe that is the key magic ingredient, and we can harness this as a drug? More likely it’s a complex interplay between multiple bacterial species needed to direct the immune response. Is there a group of microbes that is the same from person to person, or is it more complex?”

Then there are pending regulatory concerns. “We know that FMT works for [Clostridioides] difficile colitis but it’s not officially [Food and Drug Administration] approved,” Dr. Greiling said. “The FDA is really struggling with how to approve or regulate using bacteria as a drug. Where is that crossover? That inhibits things moving forward, for good reason. You want to balance safety with live microbes.”

The UPMC clinical trial was supported by Merck. Dr. Zarour disclosed that he is supported by grants from the National Cancer Institute and the James W. and Frances G. McGlothlin Chair in Melanoma Immunotherapy Research at UPMC. The Israeli study was funded by the Ella Lemelbaum Institute for Immuno-Oncology. Dr. Baruch was supported by the Allen Berg Fund for Excellence in Immuno-Oncology Research. Dr. Greiling and Dr. Harris-Tryon reported having no relevant financial disclosures.

Publications
Topics
Sections

In the fall of 2020, Hassane M. Zarour, MD, and colleagues began to pore over raw data from their phase 1 clinical trial designed to determine if fecal microbiota transplantation (FMT) could reprogram the gut microbiome in advanced melanoma patients who failed to respond to anti–programmed death 1immunotherapy.

Dr. Hassane M. Zarour

Preclinical mouse studies have demonstrated that the gut microbiota could influence the response of tumors to anti–PD-1 immunotherapy, but FMT had not been previously evaluated in human patients with malignant melanoma whose disease persisted or progressed after medical therapy. Only 30%-40% of melanoma patients respond to anti–PD-1 immunotherapy, so the researchers’ sense of anticipation was palpable. “It’s a high-risk, high-reward study, so you never know,” Dr. Zarour, a dermatologist and immunologist who is coleader of the melanoma program at the University of Pittsburgh Medical Center’s Hillman Cancer Center, said in an interview.

For the study, which was funded by the National Institutes of Health and published in Science, Dr. Zarour and a team of colleagues, including Diwakar Davar, MD, a medical oncologist/hematologist at UPMC and Giorgio Trinchieri, MD, head of the cancer immunology section at the National Cancer Institute, enrolled 16 patients with advanced melanoma whose disease had persisted or progressed with anti-PD-1 drugs; donors were 7 patients with advanced melanoma who had responded to pembrolizumab, 4 with a complete response and 3 with a partial response, with a median progression-free survival of 56 months.

After donors and patients underwent serial stool sampling and studies to stamp out the potential for transmitting infectious agents, the researchers administered the donor-derived FMT to patients via colonoscopy every 14 days for 3 weeks, followed by pembrolizumab. To their delight, 6 of the 15 evaluable recipients responded to treatment, with a reduction in tumor or long-term disease stabilization. Moreover, responders also showed increased abundance of taxa that were previously associated with response to immunotherapy, increased activation of CD8+ T cells, and decreased frequency of interleukin-8–expressing myeloid cells.

“This opens new doors for the future,” Dr. Zarour said. “It’s very encouraging, but I don’t want to overstate the data. It’s a small, nonrandomized trial, but one has to keep in mind that people were skeptical about this work; they didn’t think FMT would work. Now we see many people coming into the field to investigate the role of the microbiome as a therapeutic tool, which is great.”

Dr. Teri Greiling

Teri Greiling, MD, characterized the finding as a key development in understanding the microbiome’s potential to influence the course of melanoma and other diseases. “What’s emerging over the last decade of research is that our immune system has a close, back-and-forth relationship with our microbiota,” said Dr. Greiling, associate professor of dermatology at Oregon Health & Science University, Portland. “From day 1 of birth, we’re colonized by microbes that train our immune system how to function. In response, your immune system keeps those microbes in check and shapes which ones are allowed to colonize, and which ones are a target for attack. Thus, inflammatory responses are generated. Similarly, the goal of immunotherapy is to activate the immune system to fight cancer. This study shows that the immune system continues to need the colonizing microbes in our body to function optimally.”

Immunotherapy with checkpoint inhibitors was not an option for malignant melanoma patients until 2011, she noted, so the potential for FMT to further improve outcomes is welcome news for patients and their families. “We went from a less than 5% chance of survival with metastatic melanoma to now, with the right combination of checkpoint inhibitors, we’re up over 50%, which is amazing in a decade,” Dr. Greiling said. “Still, we’re losing half of our patients. If [FMT provides] a 30% improvement over that, that would be great, but it’s hard to extrapolate from such small numbers.”
 

 

 

Positive results in an Israeli study

Results from a similar, smaller phase 1 trial of 2 FMT donors and 10 recipients with metastatic melanoma who had progressed on anti-PD-1 therapy, from the Ella Lemelbaum Institute for Immuno-Oncology at Sheba Medical Center in Tel HaShomer, Israel, yielded similar results. The FMT protocol in this study included colonoscopy and oral stool capsules, followed by the reintroduction of anti–PD-1 therapy with nivolumab. The two FMT donors had previously been treated with anti–PD-1 monotherapy for metastatic melanoma and had achieved a clinical response for at least 1 year. Of the 10 FMT recipients, 1 had a complete response and 2 had a partial response.

Dr. Erez Baruch

“We expected changes in the immune system but did not expect that 3 out of the 10 patients in our study would be turned from nonresponders to responders,” the study’s lead author, Erez N. Baruch, MD, PhD, told this news organization. “Since this was a first-in-human study, we were aiming to assess safety and not clinical responses. [We found] that microbiota modulation can change the immune infiltration within melanoma tumors and by this affect response to immunotherapy.”

Dr. Baruch, an internal medicine resident in the physician-scientist track program at the University of Texas, Houston, said that the findings create a potential new therapeutic paradigm, or a new “playing ground” for drug development that can support existing immunotherapies. “It is important for dermatologists to understand that disruptions of the gut microbiota, mainly by antibiotics, may be harmful to melanoma patients,” he said. “Antibiotics in cancer patients should be used judiciously but of course should not be avoided when there’s an indication.”

As for next steps, Dr. Zarour and colleagues are recruiting more patients to boost their sample size and conducting sequential analysis of the microbiome of study participants “to better determine what the good and bad bugs are,” he said. “There are so many variables, including diet and geography. We need more data.” The hope is to develop a “microbiome signature” to identify patients likely to respond to FMT, and maybe one day, a probiotic capsule that patients take to optimize their response to immunotherapy.

“We don’t want to say that the microbiome is responsible for everything, but it’s responsible for some of the response and some of the resistance to treatment,” Dr. Zarour said. “So, we want to identify what candidate nonresponders are more likely to respond to FMT and be able to stick the right stool in the donor. This goes to better education of the microbiome signature. We are working hard on that.”

Dr. Baruch added that performing FMT for melanoma patients requires tight collaborations between oncologists, dermatologists, GI, and infectious disease experts. “These usually can be done in the setting of large cancer centers and will probably not be available in any hospital,” he said. “This is why understanding the mechanisms and developing an FMT-like drug is important. We are focusing on studying the mechanisms behind the clinical effect in order to develop a drug with an FMT-like effect without the safety and logistic issues related to FMTs.”

Dr. Tamia A. Harris-Tyron


Tamia A. Harris-Tryon, MD, PhD, whose lab at the University of Texas Southwestern Medical Center at Dallas is studying how diet and the microbiota impact skin immunity, underscored the importance of evaluating the characteristics of the diet of patients as trials of FMT in melanoma patients carry on. “We know that the diet impacts the repertoire of microbes that colonize the gut,” said Dr. Harris-Tryon, assistant professor in the department of dermatology at the medical center. “The diet of the recipient likely has an impact” on the success of donor FMT.

She also noted that other skin conditions have been linked to a disrupted gut microbiome, such as psoriasis. “Given the safety of FMT in both of these studies, trials of FMT in psoriasis and other systemic skin conditions should be considered,” she said.

According to Dr. Zarour, mounting data from separate studies show that some gut microbiota play a role in adverse events experienced by melanoma patients on immunotherapy. “That is very important, especially with combination therapy,” he said. “There are also microbes involved in resistance to treatment, so the idea would be to identify these microbes.”

Studies raise more questions

In the opinion of Dr. Greiling, results from these two studies raise more questions than they answer. “The big question ... is why and how does FMT work, and how can we make the response better?” she said. “Is there one particular gene product from one microbe that is the key magic ingredient, and we can harness this as a drug? More likely it’s a complex interplay between multiple bacterial species needed to direct the immune response. Is there a group of microbes that is the same from person to person, or is it more complex?”

Then there are pending regulatory concerns. “We know that FMT works for [Clostridioides] difficile colitis but it’s not officially [Food and Drug Administration] approved,” Dr. Greiling said. “The FDA is really struggling with how to approve or regulate using bacteria as a drug. Where is that crossover? That inhibits things moving forward, for good reason. You want to balance safety with live microbes.”

The UPMC clinical trial was supported by Merck. Dr. Zarour disclosed that he is supported by grants from the National Cancer Institute and the James W. and Frances G. McGlothlin Chair in Melanoma Immunotherapy Research at UPMC. The Israeli study was funded by the Ella Lemelbaum Institute for Immuno-Oncology. Dr. Baruch was supported by the Allen Berg Fund for Excellence in Immuno-Oncology Research. Dr. Greiling and Dr. Harris-Tryon reported having no relevant financial disclosures.

In the fall of 2020, Hassane M. Zarour, MD, and colleagues began to pore over raw data from their phase 1 clinical trial designed to determine if fecal microbiota transplantation (FMT) could reprogram the gut microbiome in advanced melanoma patients who failed to respond to anti–programmed death 1immunotherapy.

Dr. Hassane M. Zarour

Preclinical mouse studies have demonstrated that the gut microbiota could influence the response of tumors to anti–PD-1 immunotherapy, but FMT had not been previously evaluated in human patients with malignant melanoma whose disease persisted or progressed after medical therapy. Only 30%-40% of melanoma patients respond to anti–PD-1 immunotherapy, so the researchers’ sense of anticipation was palpable. “It’s a high-risk, high-reward study, so you never know,” Dr. Zarour, a dermatologist and immunologist who is coleader of the melanoma program at the University of Pittsburgh Medical Center’s Hillman Cancer Center, said in an interview.

For the study, which was funded by the National Institutes of Health and published in Science, Dr. Zarour and a team of colleagues, including Diwakar Davar, MD, a medical oncologist/hematologist at UPMC and Giorgio Trinchieri, MD, head of the cancer immunology section at the National Cancer Institute, enrolled 16 patients with advanced melanoma whose disease had persisted or progressed with anti-PD-1 drugs; donors were 7 patients with advanced melanoma who had responded to pembrolizumab, 4 with a complete response and 3 with a partial response, with a median progression-free survival of 56 months.

After donors and patients underwent serial stool sampling and studies to stamp out the potential for transmitting infectious agents, the researchers administered the donor-derived FMT to patients via colonoscopy every 14 days for 3 weeks, followed by pembrolizumab. To their delight, 6 of the 15 evaluable recipients responded to treatment, with a reduction in tumor or long-term disease stabilization. Moreover, responders also showed increased abundance of taxa that were previously associated with response to immunotherapy, increased activation of CD8+ T cells, and decreased frequency of interleukin-8–expressing myeloid cells.

“This opens new doors for the future,” Dr. Zarour said. “It’s very encouraging, but I don’t want to overstate the data. It’s a small, nonrandomized trial, but one has to keep in mind that people were skeptical about this work; they didn’t think FMT would work. Now we see many people coming into the field to investigate the role of the microbiome as a therapeutic tool, which is great.”

Dr. Teri Greiling

Teri Greiling, MD, characterized the finding as a key development in understanding the microbiome’s potential to influence the course of melanoma and other diseases. “What’s emerging over the last decade of research is that our immune system has a close, back-and-forth relationship with our microbiota,” said Dr. Greiling, associate professor of dermatology at Oregon Health & Science University, Portland. “From day 1 of birth, we’re colonized by microbes that train our immune system how to function. In response, your immune system keeps those microbes in check and shapes which ones are allowed to colonize, and which ones are a target for attack. Thus, inflammatory responses are generated. Similarly, the goal of immunotherapy is to activate the immune system to fight cancer. This study shows that the immune system continues to need the colonizing microbes in our body to function optimally.”

Immunotherapy with checkpoint inhibitors was not an option for malignant melanoma patients until 2011, she noted, so the potential for FMT to further improve outcomes is welcome news for patients and their families. “We went from a less than 5% chance of survival with metastatic melanoma to now, with the right combination of checkpoint inhibitors, we’re up over 50%, which is amazing in a decade,” Dr. Greiling said. “Still, we’re losing half of our patients. If [FMT provides] a 30% improvement over that, that would be great, but it’s hard to extrapolate from such small numbers.”
 

 

 

Positive results in an Israeli study

Results from a similar, smaller phase 1 trial of 2 FMT donors and 10 recipients with metastatic melanoma who had progressed on anti-PD-1 therapy, from the Ella Lemelbaum Institute for Immuno-Oncology at Sheba Medical Center in Tel HaShomer, Israel, yielded similar results. The FMT protocol in this study included colonoscopy and oral stool capsules, followed by the reintroduction of anti–PD-1 therapy with nivolumab. The two FMT donors had previously been treated with anti–PD-1 monotherapy for metastatic melanoma and had achieved a clinical response for at least 1 year. Of the 10 FMT recipients, 1 had a complete response and 2 had a partial response.

Dr. Erez Baruch

“We expected changes in the immune system but did not expect that 3 out of the 10 patients in our study would be turned from nonresponders to responders,” the study’s lead author, Erez N. Baruch, MD, PhD, told this news organization. “Since this was a first-in-human study, we were aiming to assess safety and not clinical responses. [We found] that microbiota modulation can change the immune infiltration within melanoma tumors and by this affect response to immunotherapy.”

Dr. Baruch, an internal medicine resident in the physician-scientist track program at the University of Texas, Houston, said that the findings create a potential new therapeutic paradigm, or a new “playing ground” for drug development that can support existing immunotherapies. “It is important for dermatologists to understand that disruptions of the gut microbiota, mainly by antibiotics, may be harmful to melanoma patients,” he said. “Antibiotics in cancer patients should be used judiciously but of course should not be avoided when there’s an indication.”

As for next steps, Dr. Zarour and colleagues are recruiting more patients to boost their sample size and conducting sequential analysis of the microbiome of study participants “to better determine what the good and bad bugs are,” he said. “There are so many variables, including diet and geography. We need more data.” The hope is to develop a “microbiome signature” to identify patients likely to respond to FMT, and maybe one day, a probiotic capsule that patients take to optimize their response to immunotherapy.

“We don’t want to say that the microbiome is responsible for everything, but it’s responsible for some of the response and some of the resistance to treatment,” Dr. Zarour said. “So, we want to identify what candidate nonresponders are more likely to respond to FMT and be able to stick the right stool in the donor. This goes to better education of the microbiome signature. We are working hard on that.”

Dr. Baruch added that performing FMT for melanoma patients requires tight collaborations between oncologists, dermatologists, GI, and infectious disease experts. “These usually can be done in the setting of large cancer centers and will probably not be available in any hospital,” he said. “This is why understanding the mechanisms and developing an FMT-like drug is important. We are focusing on studying the mechanisms behind the clinical effect in order to develop a drug with an FMT-like effect without the safety and logistic issues related to FMTs.”

Dr. Tamia A. Harris-Tyron


Tamia A. Harris-Tryon, MD, PhD, whose lab at the University of Texas Southwestern Medical Center at Dallas is studying how diet and the microbiota impact skin immunity, underscored the importance of evaluating the characteristics of the diet of patients as trials of FMT in melanoma patients carry on. “We know that the diet impacts the repertoire of microbes that colonize the gut,” said Dr. Harris-Tryon, assistant professor in the department of dermatology at the medical center. “The diet of the recipient likely has an impact” on the success of donor FMT.

She also noted that other skin conditions have been linked to a disrupted gut microbiome, such as psoriasis. “Given the safety of FMT in both of these studies, trials of FMT in psoriasis and other systemic skin conditions should be considered,” she said.

According to Dr. Zarour, mounting data from separate studies show that some gut microbiota play a role in adverse events experienced by melanoma patients on immunotherapy. “That is very important, especially with combination therapy,” he said. “There are also microbes involved in resistance to treatment, so the idea would be to identify these microbes.”

Studies raise more questions

In the opinion of Dr. Greiling, results from these two studies raise more questions than they answer. “The big question ... is why and how does FMT work, and how can we make the response better?” she said. “Is there one particular gene product from one microbe that is the key magic ingredient, and we can harness this as a drug? More likely it’s a complex interplay between multiple bacterial species needed to direct the immune response. Is there a group of microbes that is the same from person to person, or is it more complex?”

Then there are pending regulatory concerns. “We know that FMT works for [Clostridioides] difficile colitis but it’s not officially [Food and Drug Administration] approved,” Dr. Greiling said. “The FDA is really struggling with how to approve or regulate using bacteria as a drug. Where is that crossover? That inhibits things moving forward, for good reason. You want to balance safety with live microbes.”

The UPMC clinical trial was supported by Merck. Dr. Zarour disclosed that he is supported by grants from the National Cancer Institute and the James W. and Frances G. McGlothlin Chair in Melanoma Immunotherapy Research at UPMC. The Israeli study was funded by the Ella Lemelbaum Institute for Immuno-Oncology. Dr. Baruch was supported by the Allen Berg Fund for Excellence in Immuno-Oncology Research. Dr. Greiling and Dr. Harris-Tryon reported having no relevant financial disclosures.

Publications
Publications
Topics
Article Type
Sections
Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME
Disqus Comments
Default
Use ProPublica
Hide sidebar & use full width
render the right sidebar.
Conference Recap Checkbox
Not Conference Recap
Clinical Edge
Display the Slideshow in this Article
Medscape Article
Display survey writer
Reuters content
Disable Inline Native ads
WebMD Article

FDA OKs iPLEDGE change for gender-neutral language

Article Type
Changed
Wed, 10/13/2021 - 15:15

The Food and Drug Administration has approved a modification to the isotretinoin risk-mitigation program to make it more inclusive for transgender patients.

Beginning on Dec. 13, 2021, patients prescribed isotretinoin for acne will be assigned to one of two risk categories – those who can get pregnant and those who cannot for the iPLEDGE Risk Evaluation and Mitigation Strategy (REMS). Previously, there were three risk categories: females of reproductive potential, females not of reproductive potential, and males.

In recent years, dermatologists and others have advocated for the change, hoping to make the process more inclusive and less intrusive for their transgender patients.

Isotretinoin (Accutane, Absorica, Amnesteem, Claravis, others) has a high risk of severe birth defects, and has been linked with other health issues, making it crucial for those with the ability to become pregnant to take contraceptive precautions while on the medication. Under the iPLEDGE program, physicians, patients, and pharmacies prescribing, using, or dispensing the drug must all be registered, with requirements that include the use of two forms of an effective contraceptive and regular pregnancy testing for patients who can become pregnant.

The FDA had given notification in June 2018 that the REMS modification and labeling change would be required, replacing the gender-specific language with gender-neutral language, according to an FDA spokesperson. The change was based on feedback that the gender-specific language can be a barrier to access for some patients. The FDA approved the modification on Oct. 8.
 

Expert reactions

“This is an exciting and welcome change from the FDA on iPLEDGE that many dermatologists, myself included, have advocated for quite a few years,” Howa Yeung, MD, MSc, assistant professor of dermatology at Emory University, Atlanta, said in an interview.

In a report on the dermatologic care for lesbian, gay, bisexual, and transgender persons published in the Journal of the American Academy of Dermatology, Dr. Yeung and his colleagues noted that more than 10 million lesbian, gay, bisexual and transgender people live in the United States and that improving their health is a public health priority.

“For cisgender patients, nothing has changed – patients will continue to receive appropriate educational material related to isotretinoin based on their pregnancy potential,” Dr. Yeung said. “For transgender and gender diverse patients, this is a huge step forward.”



Under the previous system, doctors were asked to register patients using gender binary categories, “which were confusing when they did not reflect reality” for these patients, Dr. Yeung said. The new system, Dr. Yeung added, “will make my job easier. I no longer have to struggle between respecting the patient’s gender identity and providing medically necessary care for patients with severe acne.”

“The new terminology is not just respectful, it also is simpler and makes more sense,” agreed Joshua D. Safer, MD, executive director of the Center for Transgender Medicine and Surgery at Mount Sinai Health System and professor of medicine at the Icahn School of Medicine at Mount Sinai, New York. “As it stood, a transgender man with his uterus and ovaries in place might be missed in the pregnancy surveillance system because he could simply be labeled a man and not followed further. At the same time, both transgender women and cisgender women who were at no risk of pregnancy could be subject to more medical scrutiny that might have been consider intrusive.”

The change “validates the important point that pregnancy potential is not exclusively defined by sociocultural constructs of gender and allow dermatologists to focus purely on what matters when prescribing isotretinoin – whether an individual is able to become pregnant or not, regardless of their gender identity,” Klint Peebles, MD, a dermatologist at Kaiser Permanente in Washington, D.C., and suburban Maryland, who has also advocated for the change, said in an interview.

 

 

 

FDA elaborates

The modification includes important changes for doctors, pharmacists, and patients alike, according to the FDA.

Health care providers must assign and confirm their currently enrolled patient’s risk category when they first log in to the IPLEDGE REMS website on or after Dec. 13, the effective date. They should be sure any patient whose prescription RMA (iPLEDGE authorization) expires on Dec. 11-12 is told to obtain their prescription before midnight, Eastern time, Dec. 10.

Pharmacists will be affected, too, since the iPLEDGE REMS changed to a new platform vendor and the current “switch” pharmacy management system will be removed as a method to verify authorization to dispense isotretinoin. With these changes, as of Dec. 13, pharmacists can’t use the switch system to obtain a predispense authorization, or RMA (risk management authorization). They will need to obtain an RMA online by accessing the iPLEDGE REMS website or via telephone to the PLEDGE REMS center, 866-495-0654, before dispensing the prescription.

Patients, beginning Dec. 13, will have the option of presenting a unique QR code at the pharmacy on their smartphone rather than providing the iPLEDGE identification number. The code can be accessed by logging into their account on the iPLEDGE REMS website.

Patients with an isotretinoin prescription RMA that expires Dec. 11-12, must obtain the prescription before 11:59 p.m. Eastern time on Dec. 10. If the RMA expires before the prescription is picked up, the patient must begin the authorization process all over again.

Dr. Safer, Dr. Yeung, and Dr. Peebles have no relevant disclosures.

More information on the update and the isotretinoin REMS program is available on the FDA website.

Publications
Topics
Sections

The Food and Drug Administration has approved a modification to the isotretinoin risk-mitigation program to make it more inclusive for transgender patients.

Beginning on Dec. 13, 2021, patients prescribed isotretinoin for acne will be assigned to one of two risk categories – those who can get pregnant and those who cannot for the iPLEDGE Risk Evaluation and Mitigation Strategy (REMS). Previously, there were three risk categories: females of reproductive potential, females not of reproductive potential, and males.

In recent years, dermatologists and others have advocated for the change, hoping to make the process more inclusive and less intrusive for their transgender patients.

Isotretinoin (Accutane, Absorica, Amnesteem, Claravis, others) has a high risk of severe birth defects, and has been linked with other health issues, making it crucial for those with the ability to become pregnant to take contraceptive precautions while on the medication. Under the iPLEDGE program, physicians, patients, and pharmacies prescribing, using, or dispensing the drug must all be registered, with requirements that include the use of two forms of an effective contraceptive and regular pregnancy testing for patients who can become pregnant.

The FDA had given notification in June 2018 that the REMS modification and labeling change would be required, replacing the gender-specific language with gender-neutral language, according to an FDA spokesperson. The change was based on feedback that the gender-specific language can be a barrier to access for some patients. The FDA approved the modification on Oct. 8.
 

Expert reactions

“This is an exciting and welcome change from the FDA on iPLEDGE that many dermatologists, myself included, have advocated for quite a few years,” Howa Yeung, MD, MSc, assistant professor of dermatology at Emory University, Atlanta, said in an interview.

In a report on the dermatologic care for lesbian, gay, bisexual, and transgender persons published in the Journal of the American Academy of Dermatology, Dr. Yeung and his colleagues noted that more than 10 million lesbian, gay, bisexual and transgender people live in the United States and that improving their health is a public health priority.

“For cisgender patients, nothing has changed – patients will continue to receive appropriate educational material related to isotretinoin based on their pregnancy potential,” Dr. Yeung said. “For transgender and gender diverse patients, this is a huge step forward.”



Under the previous system, doctors were asked to register patients using gender binary categories, “which were confusing when they did not reflect reality” for these patients, Dr. Yeung said. The new system, Dr. Yeung added, “will make my job easier. I no longer have to struggle between respecting the patient’s gender identity and providing medically necessary care for patients with severe acne.”

“The new terminology is not just respectful, it also is simpler and makes more sense,” agreed Joshua D. Safer, MD, executive director of the Center for Transgender Medicine and Surgery at Mount Sinai Health System and professor of medicine at the Icahn School of Medicine at Mount Sinai, New York. “As it stood, a transgender man with his uterus and ovaries in place might be missed in the pregnancy surveillance system because he could simply be labeled a man and not followed further. At the same time, both transgender women and cisgender women who were at no risk of pregnancy could be subject to more medical scrutiny that might have been consider intrusive.”

The change “validates the important point that pregnancy potential is not exclusively defined by sociocultural constructs of gender and allow dermatologists to focus purely on what matters when prescribing isotretinoin – whether an individual is able to become pregnant or not, regardless of their gender identity,” Klint Peebles, MD, a dermatologist at Kaiser Permanente in Washington, D.C., and suburban Maryland, who has also advocated for the change, said in an interview.

 

 

 

FDA elaborates

The modification includes important changes for doctors, pharmacists, and patients alike, according to the FDA.

Health care providers must assign and confirm their currently enrolled patient’s risk category when they first log in to the IPLEDGE REMS website on or after Dec. 13, the effective date. They should be sure any patient whose prescription RMA (iPLEDGE authorization) expires on Dec. 11-12 is told to obtain their prescription before midnight, Eastern time, Dec. 10.

Pharmacists will be affected, too, since the iPLEDGE REMS changed to a new platform vendor and the current “switch” pharmacy management system will be removed as a method to verify authorization to dispense isotretinoin. With these changes, as of Dec. 13, pharmacists can’t use the switch system to obtain a predispense authorization, or RMA (risk management authorization). They will need to obtain an RMA online by accessing the iPLEDGE REMS website or via telephone to the PLEDGE REMS center, 866-495-0654, before dispensing the prescription.

Patients, beginning Dec. 13, will have the option of presenting a unique QR code at the pharmacy on their smartphone rather than providing the iPLEDGE identification number. The code can be accessed by logging into their account on the iPLEDGE REMS website.

Patients with an isotretinoin prescription RMA that expires Dec. 11-12, must obtain the prescription before 11:59 p.m. Eastern time on Dec. 10. If the RMA expires before the prescription is picked up, the patient must begin the authorization process all over again.

Dr. Safer, Dr. Yeung, and Dr. Peebles have no relevant disclosures.

More information on the update and the isotretinoin REMS program is available on the FDA website.

The Food and Drug Administration has approved a modification to the isotretinoin risk-mitigation program to make it more inclusive for transgender patients.

Beginning on Dec. 13, 2021, patients prescribed isotretinoin for acne will be assigned to one of two risk categories – those who can get pregnant and those who cannot for the iPLEDGE Risk Evaluation and Mitigation Strategy (REMS). Previously, there were three risk categories: females of reproductive potential, females not of reproductive potential, and males.

In recent years, dermatologists and others have advocated for the change, hoping to make the process more inclusive and less intrusive for their transgender patients.

Isotretinoin (Accutane, Absorica, Amnesteem, Claravis, others) has a high risk of severe birth defects, and has been linked with other health issues, making it crucial for those with the ability to become pregnant to take contraceptive precautions while on the medication. Under the iPLEDGE program, physicians, patients, and pharmacies prescribing, using, or dispensing the drug must all be registered, with requirements that include the use of two forms of an effective contraceptive and regular pregnancy testing for patients who can become pregnant.

The FDA had given notification in June 2018 that the REMS modification and labeling change would be required, replacing the gender-specific language with gender-neutral language, according to an FDA spokesperson. The change was based on feedback that the gender-specific language can be a barrier to access for some patients. The FDA approved the modification on Oct. 8.
 

Expert reactions

“This is an exciting and welcome change from the FDA on iPLEDGE that many dermatologists, myself included, have advocated for quite a few years,” Howa Yeung, MD, MSc, assistant professor of dermatology at Emory University, Atlanta, said in an interview.

In a report on the dermatologic care for lesbian, gay, bisexual, and transgender persons published in the Journal of the American Academy of Dermatology, Dr. Yeung and his colleagues noted that more than 10 million lesbian, gay, bisexual and transgender people live in the United States and that improving their health is a public health priority.

“For cisgender patients, nothing has changed – patients will continue to receive appropriate educational material related to isotretinoin based on their pregnancy potential,” Dr. Yeung said. “For transgender and gender diverse patients, this is a huge step forward.”



Under the previous system, doctors were asked to register patients using gender binary categories, “which were confusing when they did not reflect reality” for these patients, Dr. Yeung said. The new system, Dr. Yeung added, “will make my job easier. I no longer have to struggle between respecting the patient’s gender identity and providing medically necessary care for patients with severe acne.”

“The new terminology is not just respectful, it also is simpler and makes more sense,” agreed Joshua D. Safer, MD, executive director of the Center for Transgender Medicine and Surgery at Mount Sinai Health System and professor of medicine at the Icahn School of Medicine at Mount Sinai, New York. “As it stood, a transgender man with his uterus and ovaries in place might be missed in the pregnancy surveillance system because he could simply be labeled a man and not followed further. At the same time, both transgender women and cisgender women who were at no risk of pregnancy could be subject to more medical scrutiny that might have been consider intrusive.”

The change “validates the important point that pregnancy potential is not exclusively defined by sociocultural constructs of gender and allow dermatologists to focus purely on what matters when prescribing isotretinoin – whether an individual is able to become pregnant or not, regardless of their gender identity,” Klint Peebles, MD, a dermatologist at Kaiser Permanente in Washington, D.C., and suburban Maryland, who has also advocated for the change, said in an interview.

 

 

 

FDA elaborates

The modification includes important changes for doctors, pharmacists, and patients alike, according to the FDA.

Health care providers must assign and confirm their currently enrolled patient’s risk category when they first log in to the IPLEDGE REMS website on or after Dec. 13, the effective date. They should be sure any patient whose prescription RMA (iPLEDGE authorization) expires on Dec. 11-12 is told to obtain their prescription before midnight, Eastern time, Dec. 10.

Pharmacists will be affected, too, since the iPLEDGE REMS changed to a new platform vendor and the current “switch” pharmacy management system will be removed as a method to verify authorization to dispense isotretinoin. With these changes, as of Dec. 13, pharmacists can’t use the switch system to obtain a predispense authorization, or RMA (risk management authorization). They will need to obtain an RMA online by accessing the iPLEDGE REMS website or via telephone to the PLEDGE REMS center, 866-495-0654, before dispensing the prescription.

Patients, beginning Dec. 13, will have the option of presenting a unique QR code at the pharmacy on their smartphone rather than providing the iPLEDGE identification number. The code can be accessed by logging into their account on the iPLEDGE REMS website.

Patients with an isotretinoin prescription RMA that expires Dec. 11-12, must obtain the prescription before 11:59 p.m. Eastern time on Dec. 10. If the RMA expires before the prescription is picked up, the patient must begin the authorization process all over again.

Dr. Safer, Dr. Yeung, and Dr. Peebles have no relevant disclosures.

More information on the update and the isotretinoin REMS program is available on the FDA website.

Publications
Publications
Topics
Article Type
Sections
Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME
Disqus Comments
Default
Use ProPublica
Hide sidebar & use full width
render the right sidebar.
Conference Recap Checkbox
Not Conference Recap
Clinical Edge
Display the Slideshow in this Article
Medscape Article
Display survey writer
Reuters content
Disable Inline Native ads
WebMD Article

9-step ladder may kids with allergies return to eggs

Article Type
Changed
Thu, 10/14/2021 - 13:23

For many children in the process of outgrowing egg allergy, the step-wise reintroduction of foods that contain eggs can be achieved at home using a nine-rung laddered approach, according to updated guidelines from the British Society for Allergy and Clinical Immunology (BSACI).

Attempts to reintroduce egg into the child’s diet can start at the age of 12 months or 6 months from the last reaction, as long as past reactions have been mild to moderate and the child does not have asthma, according to guidelines from the BSACI, which represents allergists, pediatricians, and other health care practitioners.

According to the guidelines, the reintroduction needs to be guided by a specialist allergy service for children who have had severe reactions to egg or who have asthma.

Susan C. Leech, MB BChir, DCH, first author of the guidelines and a consultant in pediatric allergy with the Department of Child Health at Kings College Hospital, London, told this news organization that home reintroduction should begin slowly with small amounts of baked egg, starting with a pea-sized piece of cake, and should proceed gradually.

“Parents can be reassured that it’s a relatively safe thing to do as long as it’s done with caution,” said Dr. Leech.

The expanded guidelines include a new nine-step reintroduction ladder. It builds on a three-stage classification of egg-containing foods that was first introduced in BSACI guidelines in 2010.

On the bottom four rungs, children work their way through small but increasing amounts of fairy cakes (cupcakes), biscuits (cookies), and other foods containing baked eggs.

The next three rungs involve hard-boiled eggs, quiche, and other well-cooked egg products.

At the eighth rung, children can have small mouthfuls of runny scrambled eggs, mayonnaise, and other less-cooked or raw egg-containing products. At the top rung, children can have increasing amounts of those products as well as licks of cake batter.

The guidelines were published online September 29 in Clinical and Experimental Allergy along with a supplement that includes a series of examples showing how the guidelines apply to specific patient cases.

“These are examples only,” the guideline authors caution in the appendix. “Clinical judgment of severity is important as risk assessment is not always easy.”

Anna Nowak-Wegrzyn, MD, PhD, a professor of pediatrics at NYU Grossman School of Medicine and chief of pediatric allergy and immunology for Hassenfeld Children’s Hospital at NYU Langone, who was not involved in the BSACI guidelines, described the egg ladder as a “proactive” strategy that deserves further study and consideration.

“I think that this may be a valid approach,” said Dr. Nowak-Wegrzyn in an interview. “Eggs have good nutritional value, and they are present in a lot of foods, so avoidance creates logistical challenges.”

Using the egg ladder for home-based reintroduction may be especially suited in resource-poor areas where access to an allergist may be difficult, she said. It may also be suited for families that can’t visit the office because of pandemic-related restrictions.

“If the child had a severe reaction or if they have asthma, then it’s a no-go,” she added, “but if you have a patient who has a really mild reaction and you think that overall the risk of a significant reaction or bad symptoms is low, then it may be worth doing.”

Dr. Leech and Dr. Nowak-Wegrzyn have disclosed no relevant financial relationships.

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

Publications
Topics
Sections

For many children in the process of outgrowing egg allergy, the step-wise reintroduction of foods that contain eggs can be achieved at home using a nine-rung laddered approach, according to updated guidelines from the British Society for Allergy and Clinical Immunology (BSACI).

Attempts to reintroduce egg into the child’s diet can start at the age of 12 months or 6 months from the last reaction, as long as past reactions have been mild to moderate and the child does not have asthma, according to guidelines from the BSACI, which represents allergists, pediatricians, and other health care practitioners.

According to the guidelines, the reintroduction needs to be guided by a specialist allergy service for children who have had severe reactions to egg or who have asthma.

Susan C. Leech, MB BChir, DCH, first author of the guidelines and a consultant in pediatric allergy with the Department of Child Health at Kings College Hospital, London, told this news organization that home reintroduction should begin slowly with small amounts of baked egg, starting with a pea-sized piece of cake, and should proceed gradually.

“Parents can be reassured that it’s a relatively safe thing to do as long as it’s done with caution,” said Dr. Leech.

The expanded guidelines include a new nine-step reintroduction ladder. It builds on a three-stage classification of egg-containing foods that was first introduced in BSACI guidelines in 2010.

On the bottom four rungs, children work their way through small but increasing amounts of fairy cakes (cupcakes), biscuits (cookies), and other foods containing baked eggs.

The next three rungs involve hard-boiled eggs, quiche, and other well-cooked egg products.

At the eighth rung, children can have small mouthfuls of runny scrambled eggs, mayonnaise, and other less-cooked or raw egg-containing products. At the top rung, children can have increasing amounts of those products as well as licks of cake batter.

The guidelines were published online September 29 in Clinical and Experimental Allergy along with a supplement that includes a series of examples showing how the guidelines apply to specific patient cases.

“These are examples only,” the guideline authors caution in the appendix. “Clinical judgment of severity is important as risk assessment is not always easy.”

Anna Nowak-Wegrzyn, MD, PhD, a professor of pediatrics at NYU Grossman School of Medicine and chief of pediatric allergy and immunology for Hassenfeld Children’s Hospital at NYU Langone, who was not involved in the BSACI guidelines, described the egg ladder as a “proactive” strategy that deserves further study and consideration.

“I think that this may be a valid approach,” said Dr. Nowak-Wegrzyn in an interview. “Eggs have good nutritional value, and they are present in a lot of foods, so avoidance creates logistical challenges.”

Using the egg ladder for home-based reintroduction may be especially suited in resource-poor areas where access to an allergist may be difficult, she said. It may also be suited for families that can’t visit the office because of pandemic-related restrictions.

“If the child had a severe reaction or if they have asthma, then it’s a no-go,” she added, “but if you have a patient who has a really mild reaction and you think that overall the risk of a significant reaction or bad symptoms is low, then it may be worth doing.”

Dr. Leech and Dr. Nowak-Wegrzyn have disclosed no relevant financial relationships.

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

For many children in the process of outgrowing egg allergy, the step-wise reintroduction of foods that contain eggs can be achieved at home using a nine-rung laddered approach, according to updated guidelines from the British Society for Allergy and Clinical Immunology (BSACI).

Attempts to reintroduce egg into the child’s diet can start at the age of 12 months or 6 months from the last reaction, as long as past reactions have been mild to moderate and the child does not have asthma, according to guidelines from the BSACI, which represents allergists, pediatricians, and other health care practitioners.

According to the guidelines, the reintroduction needs to be guided by a specialist allergy service for children who have had severe reactions to egg or who have asthma.

Susan C. Leech, MB BChir, DCH, first author of the guidelines and a consultant in pediatric allergy with the Department of Child Health at Kings College Hospital, London, told this news organization that home reintroduction should begin slowly with small amounts of baked egg, starting with a pea-sized piece of cake, and should proceed gradually.

“Parents can be reassured that it’s a relatively safe thing to do as long as it’s done with caution,” said Dr. Leech.

The expanded guidelines include a new nine-step reintroduction ladder. It builds on a three-stage classification of egg-containing foods that was first introduced in BSACI guidelines in 2010.

On the bottom four rungs, children work their way through small but increasing amounts of fairy cakes (cupcakes), biscuits (cookies), and other foods containing baked eggs.

The next three rungs involve hard-boiled eggs, quiche, and other well-cooked egg products.

At the eighth rung, children can have small mouthfuls of runny scrambled eggs, mayonnaise, and other less-cooked or raw egg-containing products. At the top rung, children can have increasing amounts of those products as well as licks of cake batter.

The guidelines were published online September 29 in Clinical and Experimental Allergy along with a supplement that includes a series of examples showing how the guidelines apply to specific patient cases.

“These are examples only,” the guideline authors caution in the appendix. “Clinical judgment of severity is important as risk assessment is not always easy.”

Anna Nowak-Wegrzyn, MD, PhD, a professor of pediatrics at NYU Grossman School of Medicine and chief of pediatric allergy and immunology for Hassenfeld Children’s Hospital at NYU Langone, who was not involved in the BSACI guidelines, described the egg ladder as a “proactive” strategy that deserves further study and consideration.

“I think that this may be a valid approach,” said Dr. Nowak-Wegrzyn in an interview. “Eggs have good nutritional value, and they are present in a lot of foods, so avoidance creates logistical challenges.”

Using the egg ladder for home-based reintroduction may be especially suited in resource-poor areas where access to an allergist may be difficult, she said. It may also be suited for families that can’t visit the office because of pandemic-related restrictions.

“If the child had a severe reaction or if they have asthma, then it’s a no-go,” she added, “but if you have a patient who has a really mild reaction and you think that overall the risk of a significant reaction or bad symptoms is low, then it may be worth doing.”

Dr. Leech and Dr. Nowak-Wegrzyn have disclosed no relevant financial relationships.

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

Publications
Publications
Topics
Article Type
Sections
Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME
Disqus Comments
Default
Use ProPublica
Hide sidebar & use full width
render the right sidebar.
Conference Recap Checkbox
Not Conference Recap
Clinical Edge
Display the Slideshow in this Article
Medscape Article
Display survey writer
Reuters content
Disable Inline Native ads
WebMD Article

Omega-3s tame inflammation in elderly COVID-19 patients

Article Type
Changed
Fri, 10/15/2021 - 09:37

In frail elderly adults with COVID-19 infections, treatment with omega-3 fatty acids may improve lipid responses and decrease levels of proinflammatory lipid mediators, results of a small randomized controlled trial suggest.

Results of the study, which included 22 patients with multiple comorbidities, were presented at the European Geriatric Medicine Society annual congress, a hybrid live and online meeting.

The patients, who had a median age of 81 years, were randomized to receive an intravenous infusion of an omega-3 polyunsaturated fatty acid (PUFA) emulsion containing 10 g of fish oil per 100 mL or a saline placebo.

Those who received the intravenous infusion had significant decreases from baseline to end of treatment in the neutrophil-to-lymphocyte ratio (NLR), indicating marked reductions in systemic inflammation.

In contrast, patients randomized to a saline placebo had no significant improvements in NLR, Magnus Bäck, MD, PhD, from the Karolinska Institute in Stockholm reported at the meeting.

“Our lipidomic analysis also showed that omega-3 treatment skewed the lipid response, with reduced levels of proinflammatory lipid mediators, and increased levels of proresolving mediators,” according to a late-breaking abstract, which Dr. Bäck presented during the session.

Omega-3 treatment was not significantly associated with reduction in either C-reactive protein (CRP) or the proinflammatory cytokine interleukin-6, however.
 

‘Eicosanoid storm’

In a review article published in January 2021 in the open-access journal Frontiers in Physiology, Dr. Bäck and colleagues outlined the rationale for their randomized trial.

“Excessive inflammation has been reported in severe cases with respiratory failure and cardiovascular complications,” they wrote. “In addition to the release of cytokines, referred to as cytokine release syndrome or ‘cytokine storm,’ increased proinflammatory lipid mediators derived from the omega-6 polyunsaturated fatty acid (PUFA) arachidonic acid may cause an ‘eicosanoid storm,’ which contributes to the uncontrolled systemic inflammation.”

Omega-3 PUFA contains proresolving mediators that can limit inflammatory reactions, suggesting the possibility of an inflammation-resolving benefit in patients with COVID-19 without concerns about immunosuppression, the authors hypothesized.
 

Trial details

In the trial, COVID-Omega-F, they enrolled patients with a COVID-19 diagnosis requiring hospitalization. Patients with an allergy to fish oil or who had contraindications to intravenous PUFA administration (for example, risk for bleeding, shock, or emboli) were excluded.

Ten patients were randomly assigned to receive infusions of the omega-3 PUFA and 12 were assigned to receive infusions of the placebo, once daily for 5 days. The primary outcome measure was change in inflammatory biomarkers, including white blood cell counts, CRP, cytokines, and lipid mediators.

Baseline demographic and clinical characteristics were similar between the two study arms, with a median of about 7 days since the onset of symptoms, and 3.5 days since a diagnosis of COVID-19.

All patients had low lymphocyte responses reflected by a high NLR, a prognostic measure for worse outcomes in patients with COVID-19 infections, Dr. Bäck said.

Inflammation was moderate, with a CRP of 65 mg/L in the placebo group and 62 mg/L in the omega-3 group.

Seven patients in each study arm received concomitant corticoid treatment. Two patients in each arm died in hospital, but there were no serious treatment-related adverse events.
 

 

 

Inflammatory markers improve

As noted before, there was a significant decline in NLR from baseline among patients randomized to omega-3 (P = .02) but no corresponding decrease in patients assigned to placebo infusions.

“The significant decrease was largely driven by an increase in the lymphocyte count in the omega-3 treated group (P = .004), whereas lymphocytes did not significantly change,” Dr. Bäck said.

As expected, patients in the omega-3 group had pronounced increases in omega-3 fatty acids, including eicosapentaenoic acid and docosahexaenoic acid.

The metabolism of fatty acids also differed markedly between the groups, with a significant decrease in the omega-3 group but not the placebo group in proinflammatory mediators, and an increase in precursors to proresolving mediators, Dr. Bäck noted.
 

AFib concerns

In a question-and-answer part of the session, a physician who identified herself as “Senya from Russia” questioned the safety of omega-3 treatment in this population, “because recently there was a meta-analysis which showed that omega-3 fatty acids will increase the risk of atrial fibrillation in older adults especially.”

The systematic review and meta-analysis she referred to, published in Circulation and reported on by this news organization, showed that, among 81,210 patients with a mean age of 65 enrolled in seven randomized controlled trials, omega-3 fatty acid supplementation was associated with a 25% increase in risk for atrial fibrillation. This risk appeared to be higher in trials testing doses greater than 1 g/day, according to the paper.

“This was not monitored in this study,” Dr. Bäck replied. “It is true that the meta-analysis showed an increased incidence of atrial fibrillation, so it would be something to monitor in case this trial would be expanded to a larger population.”

The study was supported by the Karolinska Institute. Dr. Bäck disclosed no relevant financial relationships.

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

Meeting/Event
Publications
Topics
Sections
Meeting/Event
Meeting/Event

In frail elderly adults with COVID-19 infections, treatment with omega-3 fatty acids may improve lipid responses and decrease levels of proinflammatory lipid mediators, results of a small randomized controlled trial suggest.

Results of the study, which included 22 patients with multiple comorbidities, were presented at the European Geriatric Medicine Society annual congress, a hybrid live and online meeting.

The patients, who had a median age of 81 years, were randomized to receive an intravenous infusion of an omega-3 polyunsaturated fatty acid (PUFA) emulsion containing 10 g of fish oil per 100 mL or a saline placebo.

Those who received the intravenous infusion had significant decreases from baseline to end of treatment in the neutrophil-to-lymphocyte ratio (NLR), indicating marked reductions in systemic inflammation.

In contrast, patients randomized to a saline placebo had no significant improvements in NLR, Magnus Bäck, MD, PhD, from the Karolinska Institute in Stockholm reported at the meeting.

“Our lipidomic analysis also showed that omega-3 treatment skewed the lipid response, with reduced levels of proinflammatory lipid mediators, and increased levels of proresolving mediators,” according to a late-breaking abstract, which Dr. Bäck presented during the session.

Omega-3 treatment was not significantly associated with reduction in either C-reactive protein (CRP) or the proinflammatory cytokine interleukin-6, however.
 

‘Eicosanoid storm’

In a review article published in January 2021 in the open-access journal Frontiers in Physiology, Dr. Bäck and colleagues outlined the rationale for their randomized trial.

“Excessive inflammation has been reported in severe cases with respiratory failure and cardiovascular complications,” they wrote. “In addition to the release of cytokines, referred to as cytokine release syndrome or ‘cytokine storm,’ increased proinflammatory lipid mediators derived from the omega-6 polyunsaturated fatty acid (PUFA) arachidonic acid may cause an ‘eicosanoid storm,’ which contributes to the uncontrolled systemic inflammation.”

Omega-3 PUFA contains proresolving mediators that can limit inflammatory reactions, suggesting the possibility of an inflammation-resolving benefit in patients with COVID-19 without concerns about immunosuppression, the authors hypothesized.
 

Trial details

In the trial, COVID-Omega-F, they enrolled patients with a COVID-19 diagnosis requiring hospitalization. Patients with an allergy to fish oil or who had contraindications to intravenous PUFA administration (for example, risk for bleeding, shock, or emboli) were excluded.

Ten patients were randomly assigned to receive infusions of the omega-3 PUFA and 12 were assigned to receive infusions of the placebo, once daily for 5 days. The primary outcome measure was change in inflammatory biomarkers, including white blood cell counts, CRP, cytokines, and lipid mediators.

Baseline demographic and clinical characteristics were similar between the two study arms, with a median of about 7 days since the onset of symptoms, and 3.5 days since a diagnosis of COVID-19.

All patients had low lymphocyte responses reflected by a high NLR, a prognostic measure for worse outcomes in patients with COVID-19 infections, Dr. Bäck said.

Inflammation was moderate, with a CRP of 65 mg/L in the placebo group and 62 mg/L in the omega-3 group.

Seven patients in each study arm received concomitant corticoid treatment. Two patients in each arm died in hospital, but there were no serious treatment-related adverse events.
 

 

 

Inflammatory markers improve

As noted before, there was a significant decline in NLR from baseline among patients randomized to omega-3 (P = .02) but no corresponding decrease in patients assigned to placebo infusions.

“The significant decrease was largely driven by an increase in the lymphocyte count in the omega-3 treated group (P = .004), whereas lymphocytes did not significantly change,” Dr. Bäck said.

As expected, patients in the omega-3 group had pronounced increases in omega-3 fatty acids, including eicosapentaenoic acid and docosahexaenoic acid.

The metabolism of fatty acids also differed markedly between the groups, with a significant decrease in the omega-3 group but not the placebo group in proinflammatory mediators, and an increase in precursors to proresolving mediators, Dr. Bäck noted.
 

AFib concerns

In a question-and-answer part of the session, a physician who identified herself as “Senya from Russia” questioned the safety of omega-3 treatment in this population, “because recently there was a meta-analysis which showed that omega-3 fatty acids will increase the risk of atrial fibrillation in older adults especially.”

The systematic review and meta-analysis she referred to, published in Circulation and reported on by this news organization, showed that, among 81,210 patients with a mean age of 65 enrolled in seven randomized controlled trials, omega-3 fatty acid supplementation was associated with a 25% increase in risk for atrial fibrillation. This risk appeared to be higher in trials testing doses greater than 1 g/day, according to the paper.

“This was not monitored in this study,” Dr. Bäck replied. “It is true that the meta-analysis showed an increased incidence of atrial fibrillation, so it would be something to monitor in case this trial would be expanded to a larger population.”

The study was supported by the Karolinska Institute. Dr. Bäck disclosed no relevant financial relationships.

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

In frail elderly adults with COVID-19 infections, treatment with omega-3 fatty acids may improve lipid responses and decrease levels of proinflammatory lipid mediators, results of a small randomized controlled trial suggest.

Results of the study, which included 22 patients with multiple comorbidities, were presented at the European Geriatric Medicine Society annual congress, a hybrid live and online meeting.

The patients, who had a median age of 81 years, were randomized to receive an intravenous infusion of an omega-3 polyunsaturated fatty acid (PUFA) emulsion containing 10 g of fish oil per 100 mL or a saline placebo.

Those who received the intravenous infusion had significant decreases from baseline to end of treatment in the neutrophil-to-lymphocyte ratio (NLR), indicating marked reductions in systemic inflammation.

In contrast, patients randomized to a saline placebo had no significant improvements in NLR, Magnus Bäck, MD, PhD, from the Karolinska Institute in Stockholm reported at the meeting.

“Our lipidomic analysis also showed that omega-3 treatment skewed the lipid response, with reduced levels of proinflammatory lipid mediators, and increased levels of proresolving mediators,” according to a late-breaking abstract, which Dr. Bäck presented during the session.

Omega-3 treatment was not significantly associated with reduction in either C-reactive protein (CRP) or the proinflammatory cytokine interleukin-6, however.
 

‘Eicosanoid storm’

In a review article published in January 2021 in the open-access journal Frontiers in Physiology, Dr. Bäck and colleagues outlined the rationale for their randomized trial.

“Excessive inflammation has been reported in severe cases with respiratory failure and cardiovascular complications,” they wrote. “In addition to the release of cytokines, referred to as cytokine release syndrome or ‘cytokine storm,’ increased proinflammatory lipid mediators derived from the omega-6 polyunsaturated fatty acid (PUFA) arachidonic acid may cause an ‘eicosanoid storm,’ which contributes to the uncontrolled systemic inflammation.”

Omega-3 PUFA contains proresolving mediators that can limit inflammatory reactions, suggesting the possibility of an inflammation-resolving benefit in patients with COVID-19 without concerns about immunosuppression, the authors hypothesized.
 

Trial details

In the trial, COVID-Omega-F, they enrolled patients with a COVID-19 diagnosis requiring hospitalization. Patients with an allergy to fish oil or who had contraindications to intravenous PUFA administration (for example, risk for bleeding, shock, or emboli) were excluded.

Ten patients were randomly assigned to receive infusions of the omega-3 PUFA and 12 were assigned to receive infusions of the placebo, once daily for 5 days. The primary outcome measure was change in inflammatory biomarkers, including white blood cell counts, CRP, cytokines, and lipid mediators.

Baseline demographic and clinical characteristics were similar between the two study arms, with a median of about 7 days since the onset of symptoms, and 3.5 days since a diagnosis of COVID-19.

All patients had low lymphocyte responses reflected by a high NLR, a prognostic measure for worse outcomes in patients with COVID-19 infections, Dr. Bäck said.

Inflammation was moderate, with a CRP of 65 mg/L in the placebo group and 62 mg/L in the omega-3 group.

Seven patients in each study arm received concomitant corticoid treatment. Two patients in each arm died in hospital, but there were no serious treatment-related adverse events.
 

 

 

Inflammatory markers improve

As noted before, there was a significant decline in NLR from baseline among patients randomized to omega-3 (P = .02) but no corresponding decrease in patients assigned to placebo infusions.

“The significant decrease was largely driven by an increase in the lymphocyte count in the omega-3 treated group (P = .004), whereas lymphocytes did not significantly change,” Dr. Bäck said.

As expected, patients in the omega-3 group had pronounced increases in omega-3 fatty acids, including eicosapentaenoic acid and docosahexaenoic acid.

The metabolism of fatty acids also differed markedly between the groups, with a significant decrease in the omega-3 group but not the placebo group in proinflammatory mediators, and an increase in precursors to proresolving mediators, Dr. Bäck noted.
 

AFib concerns

In a question-and-answer part of the session, a physician who identified herself as “Senya from Russia” questioned the safety of omega-3 treatment in this population, “because recently there was a meta-analysis which showed that omega-3 fatty acids will increase the risk of atrial fibrillation in older adults especially.”

The systematic review and meta-analysis she referred to, published in Circulation and reported on by this news organization, showed that, among 81,210 patients with a mean age of 65 enrolled in seven randomized controlled trials, omega-3 fatty acid supplementation was associated with a 25% increase in risk for atrial fibrillation. This risk appeared to be higher in trials testing doses greater than 1 g/day, according to the paper.

“This was not monitored in this study,” Dr. Bäck replied. “It is true that the meta-analysis showed an increased incidence of atrial fibrillation, so it would be something to monitor in case this trial would be expanded to a larger population.”

The study was supported by the Karolinska Institute. Dr. Bäck disclosed no relevant financial relationships.

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

Publications
Publications
Topics
Article Type
Sections
Article Source

FROM EUGMS

Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME
Disqus Comments
Default
Use ProPublica
Hide sidebar & use full width
render the right sidebar.
Conference Recap Checkbox
Not Conference Recap
Clinical Edge
Display the Slideshow in this Article
Medscape Article
Display survey writer
Reuters content
Disable Inline Native ads
WebMD Article

Study of biologics’ impact on psoriasis-to-PsA transition contradicts previous findings

Article Type
Changed
Tue, 02/07/2023 - 16:44

Data source likely contributes biases

A new study has found that patients with psoriasis who were treated with biologics were more likely to develop psoriatic arthritis (PsA) than those treated with phototherapy, oral therapy, or no therapy at all, although the authors cautioned readers to consider potential biases when reviewing their findings.

“We do not suggest that these results should be interpreted causally; in other words, biologics likely do not cause PsA,” Elana Meer of the University of Pennsylvania, Philadelphia, and coauthors wrote. The study was published in Annals of the Rheumatic Diseases.

Three studies in dermatology clinic-based populations published this past summer – one from Italy, one from Argentina, and one from Israel – suggested that biologics can decrease a psoriasis patient’s risk of developing PsA. To further assess the impact of treatment with biologics, Ms. Meer and associates retrospectively examined the health records of thousands of patients with psoriasis between the ages of 16 and 90 who were initiating therapy. All told, data from 193,709 patients with psoriasis and without PsA who were treated between 2006 and 2017 were gathered from the OptumInsights Electronic Health Record Database.



A total of 14,569 patients from that cohort initiated biologic therapy while 20,321 patients initiated either oral therapy or phototherapy. The mean age in the biologics group was 45.9 years, compared with 49.8 years in the oral and phototherapy group.

The incidence of PsA across all patients was 9.75 cases per 1,000 person-years, compared with 77.26 among the biologic group, 61.99 among the oral therapy group, 26.11 among the phototherapy group, and 5.85 among those who did not receive therapy. After a multivariable adjustment in which biologics were a time-varying exposure, receiving biologics was associated with a higher incidence of PsA (hazard ratio, 4.48; 95% confidence interval, 4.23-4.75). In a model where time starts at the first use of biologics, the incidence was lower – but still notable – after multivariable adjustment (HR, 2.14; 95% CI, 2.00-2.28) and propensity score matching (HR, 2.17; 95% CI, 2.03-2.33).

Bias likely plays a large role in retrospective PsA study

“We’ve been struggling for the last several years to find a database that allows us to really address this question retrospectively,” study coauthor Christopher T. Ritchlin, MD, of the University of Rochester (N.Y.), said in an interview. “It looks like the model you use for a retrospective analysis heavily influences what you come out with.”

Dr. Christopher T. Ritchlin

He described the potential biases they identified, including the possibility of protopathic bias indicating that patients being treated with biologics who then report joint pain have developed PsA – and are coded accordingly after visiting a rheumatologist.

“This has convinced us that you have to do a prospective study,” he said. “We’ve known that there were flaws with previous studies in this area. We tried to overcome them with our methodology, but there’s no way you can overcome a coding issue when you’re looking at such a large database.”

He noted another likely bias: The patients who are more likely to develop PsA are the ones with severe psoriasis, and they are also the patients most likely to be prescribed biologics.

Courtesy Dr. Joel M. Gelfand
Dr. Joel M. Gelfand

“In my clinical experience, I have seen many patients develop psoriatic arthritis while on biologics for their psoriasis,” coauthor Joel M. Gelfand, MD, of the University of Pennsylvania, added in an interview. “Currently, we do not have adequate data to recommend treating psoriasis with a particular modality in order to prevent psoriatic arthritis. This question, however, is very important to patients and clinicians and ultimately is best answered with a large-scale pragmatic trial.”

Dr. Ritchlin reported that a prospective study in which “patients with psoriasis who do not have arthritis but do have certain risk factors and abnormal findings on musculoskeletal ultrasounds” will be treated with either biologic agents or placebo is about to begin, with a goal of “either attenuating or preventing the onset of PsA.”



The authors recognized their study’s additional limitations, including electronic health records being used as the primary data source and the possibility that medications were prescribed but never filled. That said, they did attempt to address the latter by using two prescriptions for a given therapy as the primary analysis, “suggesting a refill was initiated.”

The authors said that no commercial entities provided support for the study. Two of the authors acknowledged receiving funding from the National Psoriasis Foundation, and several authors declared potential conflicts of interests that included consulting and receiving honoraria from various pharmaceutical companies.

Publications
Topics
Sections

Data source likely contributes biases

Data source likely contributes biases

A new study has found that patients with psoriasis who were treated with biologics were more likely to develop psoriatic arthritis (PsA) than those treated with phototherapy, oral therapy, or no therapy at all, although the authors cautioned readers to consider potential biases when reviewing their findings.

“We do not suggest that these results should be interpreted causally; in other words, biologics likely do not cause PsA,” Elana Meer of the University of Pennsylvania, Philadelphia, and coauthors wrote. The study was published in Annals of the Rheumatic Diseases.

Three studies in dermatology clinic-based populations published this past summer – one from Italy, one from Argentina, and one from Israel – suggested that biologics can decrease a psoriasis patient’s risk of developing PsA. To further assess the impact of treatment with biologics, Ms. Meer and associates retrospectively examined the health records of thousands of patients with psoriasis between the ages of 16 and 90 who were initiating therapy. All told, data from 193,709 patients with psoriasis and without PsA who were treated between 2006 and 2017 were gathered from the OptumInsights Electronic Health Record Database.



A total of 14,569 patients from that cohort initiated biologic therapy while 20,321 patients initiated either oral therapy or phototherapy. The mean age in the biologics group was 45.9 years, compared with 49.8 years in the oral and phototherapy group.

The incidence of PsA across all patients was 9.75 cases per 1,000 person-years, compared with 77.26 among the biologic group, 61.99 among the oral therapy group, 26.11 among the phototherapy group, and 5.85 among those who did not receive therapy. After a multivariable adjustment in which biologics were a time-varying exposure, receiving biologics was associated with a higher incidence of PsA (hazard ratio, 4.48; 95% confidence interval, 4.23-4.75). In a model where time starts at the first use of biologics, the incidence was lower – but still notable – after multivariable adjustment (HR, 2.14; 95% CI, 2.00-2.28) and propensity score matching (HR, 2.17; 95% CI, 2.03-2.33).

Bias likely plays a large role in retrospective PsA study

“We’ve been struggling for the last several years to find a database that allows us to really address this question retrospectively,” study coauthor Christopher T. Ritchlin, MD, of the University of Rochester (N.Y.), said in an interview. “It looks like the model you use for a retrospective analysis heavily influences what you come out with.”

Dr. Christopher T. Ritchlin

He described the potential biases they identified, including the possibility of protopathic bias indicating that patients being treated with biologics who then report joint pain have developed PsA – and are coded accordingly after visiting a rheumatologist.

“This has convinced us that you have to do a prospective study,” he said. “We’ve known that there were flaws with previous studies in this area. We tried to overcome them with our methodology, but there’s no way you can overcome a coding issue when you’re looking at such a large database.”

He noted another likely bias: The patients who are more likely to develop PsA are the ones with severe psoriasis, and they are also the patients most likely to be prescribed biologics.

Courtesy Dr. Joel M. Gelfand
Dr. Joel M. Gelfand

“In my clinical experience, I have seen many patients develop psoriatic arthritis while on biologics for their psoriasis,” coauthor Joel M. Gelfand, MD, of the University of Pennsylvania, added in an interview. “Currently, we do not have adequate data to recommend treating psoriasis with a particular modality in order to prevent psoriatic arthritis. This question, however, is very important to patients and clinicians and ultimately is best answered with a large-scale pragmatic trial.”

Dr. Ritchlin reported that a prospective study in which “patients with psoriasis who do not have arthritis but do have certain risk factors and abnormal findings on musculoskeletal ultrasounds” will be treated with either biologic agents or placebo is about to begin, with a goal of “either attenuating or preventing the onset of PsA.”



The authors recognized their study’s additional limitations, including electronic health records being used as the primary data source and the possibility that medications were prescribed but never filled. That said, they did attempt to address the latter by using two prescriptions for a given therapy as the primary analysis, “suggesting a refill was initiated.”

The authors said that no commercial entities provided support for the study. Two of the authors acknowledged receiving funding from the National Psoriasis Foundation, and several authors declared potential conflicts of interests that included consulting and receiving honoraria from various pharmaceutical companies.

A new study has found that patients with psoriasis who were treated with biologics were more likely to develop psoriatic arthritis (PsA) than those treated with phototherapy, oral therapy, or no therapy at all, although the authors cautioned readers to consider potential biases when reviewing their findings.

“We do not suggest that these results should be interpreted causally; in other words, biologics likely do not cause PsA,” Elana Meer of the University of Pennsylvania, Philadelphia, and coauthors wrote. The study was published in Annals of the Rheumatic Diseases.

Three studies in dermatology clinic-based populations published this past summer – one from Italy, one from Argentina, and one from Israel – suggested that biologics can decrease a psoriasis patient’s risk of developing PsA. To further assess the impact of treatment with biologics, Ms. Meer and associates retrospectively examined the health records of thousands of patients with psoriasis between the ages of 16 and 90 who were initiating therapy. All told, data from 193,709 patients with psoriasis and without PsA who were treated between 2006 and 2017 were gathered from the OptumInsights Electronic Health Record Database.



A total of 14,569 patients from that cohort initiated biologic therapy while 20,321 patients initiated either oral therapy or phototherapy. The mean age in the biologics group was 45.9 years, compared with 49.8 years in the oral and phototherapy group.

The incidence of PsA across all patients was 9.75 cases per 1,000 person-years, compared with 77.26 among the biologic group, 61.99 among the oral therapy group, 26.11 among the phototherapy group, and 5.85 among those who did not receive therapy. After a multivariable adjustment in which biologics were a time-varying exposure, receiving biologics was associated with a higher incidence of PsA (hazard ratio, 4.48; 95% confidence interval, 4.23-4.75). In a model where time starts at the first use of biologics, the incidence was lower – but still notable – after multivariable adjustment (HR, 2.14; 95% CI, 2.00-2.28) and propensity score matching (HR, 2.17; 95% CI, 2.03-2.33).

Bias likely plays a large role in retrospective PsA study

“We’ve been struggling for the last several years to find a database that allows us to really address this question retrospectively,” study coauthor Christopher T. Ritchlin, MD, of the University of Rochester (N.Y.), said in an interview. “It looks like the model you use for a retrospective analysis heavily influences what you come out with.”

Dr. Christopher T. Ritchlin

He described the potential biases they identified, including the possibility of protopathic bias indicating that patients being treated with biologics who then report joint pain have developed PsA – and are coded accordingly after visiting a rheumatologist.

“This has convinced us that you have to do a prospective study,” he said. “We’ve known that there were flaws with previous studies in this area. We tried to overcome them with our methodology, but there’s no way you can overcome a coding issue when you’re looking at such a large database.”

He noted another likely bias: The patients who are more likely to develop PsA are the ones with severe psoriasis, and they are also the patients most likely to be prescribed biologics.

Courtesy Dr. Joel M. Gelfand
Dr. Joel M. Gelfand

“In my clinical experience, I have seen many patients develop psoriatic arthritis while on biologics for their psoriasis,” coauthor Joel M. Gelfand, MD, of the University of Pennsylvania, added in an interview. “Currently, we do not have adequate data to recommend treating psoriasis with a particular modality in order to prevent psoriatic arthritis. This question, however, is very important to patients and clinicians and ultimately is best answered with a large-scale pragmatic trial.”

Dr. Ritchlin reported that a prospective study in which “patients with psoriasis who do not have arthritis but do have certain risk factors and abnormal findings on musculoskeletal ultrasounds” will be treated with either biologic agents or placebo is about to begin, with a goal of “either attenuating or preventing the onset of PsA.”



The authors recognized their study’s additional limitations, including electronic health records being used as the primary data source and the possibility that medications were prescribed but never filled. That said, they did attempt to address the latter by using two prescriptions for a given therapy as the primary analysis, “suggesting a refill was initiated.”

The authors said that no commercial entities provided support for the study. Two of the authors acknowledged receiving funding from the National Psoriasis Foundation, and several authors declared potential conflicts of interests that included consulting and receiving honoraria from various pharmaceutical companies.

Publications
Publications
Topics
Article Type
Sections
Article Source

FROM ANNALS OF THE RHEUMATIC DISEASES

Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME
Disqus Comments
Default
Use ProPublica
Hide sidebar & use full width
render the right sidebar.
Conference Recap Checkbox
Not Conference Recap
Clinical Edge
Display the Slideshow in this Article
Medscape Article
Display survey writer
Reuters content
Disable Inline Native ads
WebMD Article

Lupus may confer higher risk of death from COVID-19

Article Type
Changed
Tue, 10/19/2021 - 15:53

There is a significantly increased risk for acute respiratory distress syndrome (ARDS)–related death from COVID-19 among people with systemic lupus erythematous (SLE), compared with the general population, according to data collected in Brazil in 2020.

“Special care is therefore necessary for these patients, as well as reinforcement of the importance of preventive measures during a pandemic for this population,” said Eloisa Bonfá, MD, PhD, at the 14th International Congress on Systemic Lupus Erythematosus, which was held together with the 6th International Congress on Controversies in Rheumatology and Autoimmunity.

“We know that lupus patients have an increased susceptibility to infections due to autoimmune dysregulation and use of immunosuppressive therapy,” explained Dr. Bonfá, who is clinical director of the largest tertiary referral center for autoimmune rheumatic diseases in Latin America, the University of São Paulo Faculty of Medicine Hospital Clinics.

“Our study demonstrates for the first time that lupus patients have an increased ARDS severity,” she added.

Prior to the meeting, the study was published in ACR Open Rheumatology.
 

Collating the evidence

Since the COVID-19 pandemic began, there have been more than 20 million confirmed cases of SARS-CoV-2 infection in Brazil and more than half a million deaths.

Dr. Bonfá presented the results of a cross-sectional study that was part of the country’s national Influenza Epidemiological Reporting Surveillance System. Data from 2020 were used, which included just over 252,000 individuals who had polymerase chain reaction–confirmed SARS-CoV-2 infection. Of these individuals, there were 319 consecutively recruited patients with SLE.

The aim was to look at the effect of being hospitalized for COVID-19–related ARDS on outcomes in people with SLE versus the general population.

ARDS was defined as a positive polymerase chain reaction test and accompanying flu-like symptoms with dyspnea, respiratory discomfort, persistent pressure in the chest, or desaturation less than 95% in room air or having a bluish tinge to the lips or face.

Other telling signs of a serious respiratory infection that were evaluated, but not mandatory for study eligibility, were loss of smell, impaired taste, typical CT findings, or having had contact with a confirmed COVID-19 case in the preceding 2 weeks.
 

Key findings

The risk for death from COVID-19–related ARDS was “more than double” in patients with SLE, compared with the general population, Dr. Bonfá reported. The relative risk in the fully adjusted, propensity-scored analysis was approximately 2.25.

That analysis did not account for other comorbidities but was fully adjusted for individuals’ age, sex, and region of Brazil where they lived. The latter was important, Dr. Bonfá said, because “we have a high disparity regarding health access and treatment among regions.”

Comorbidities considered as part of the analyses included arterial hypertension, diabetes, malignancies, neurologic disease, and diseases affecting the heart, lung, liver, and kidneys. Researchers also adjusted for smoking, alcohol intake, body weight, pregnancy, and transplantation.

SLE had a greater impact on individuals’ outcomes than all other comorbidities considered.

“We evaluated lupus as one comorbidity compared to all other comorbidities,” Dr. Bonfá explained.

SLE “more than doubled the chances” of dying from ARDS, she said. “This is [a] very impressive finding.”

They found that SLE was associated with an RR for death of 1.73, compared with non-SLE patients, when propensity-score matching without adjustment for comorbidities was used. The RR for death dropped to 1.40 but was still significant when researchers included comorbidities.

Dr. Bonfá and her team also looked at a combined endpoint of death, ICU admission, and need for mechanical ventilation. They found an increased risk in patients with SLE versus the general population in all their analyses, ranging from 1.70 if comorbidities were included in the model to 1.27 if they weren’t to 1.39 if propensity-score matching alone was used.  
 

 

 

Got lupus? ‘Get vaccinated’

“The data we have are in nonvaccinated patients,” Dr. Bonfá said. “We didn’t have vaccines in 2020.”

Whether being vaccinated might make a different to the risks found in this study is an “interesting question,” and one that may be examined in the future.

Certainly, other work Dr. Bonfá has been involved in seems to point to a likely benefit of vaccination in patients with autoimmune diseases in terms of reducing mortality from COVID-19, even when rates of infection may be on the rise.  

“There’s considerable vaccine hesitancy in SLE patients,” Chi-Chiu Mok, MD, of Tuen Mun Hospital in Hong Kong, observed in a separate presentation at the congress.

This may be for several reasons, such as worry that their disease may flare or the vaccine might compromise their drug treatment or result in uncommon complications.

However, “we should encourage our SLE patients to receive COVID-19 vaccination at a time of clinical remission or low disease activity state,” Dr. Mok advised.

“Physical distancing, protective masks, and personal hygiene [measures]” should also continue.

The bottom line for those with SLE is to get vaccinated, stressed Sandra Navarra, MD, of the University of Santo Tomas Hospital in Manila, the Philippines, during the discussion.

“There’s still so much out there that we do not know about,” she said. “Just get yourself vaccinated.”

The study had no outside funding. Dr. Bonfá, Dr. Mok, and Dr. Navarra reported no relevant financial relationships.

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

Meeting/Event
Publications
Topics
Sections
Meeting/Event
Meeting/Event

There is a significantly increased risk for acute respiratory distress syndrome (ARDS)–related death from COVID-19 among people with systemic lupus erythematous (SLE), compared with the general population, according to data collected in Brazil in 2020.

“Special care is therefore necessary for these patients, as well as reinforcement of the importance of preventive measures during a pandemic for this population,” said Eloisa Bonfá, MD, PhD, at the 14th International Congress on Systemic Lupus Erythematosus, which was held together with the 6th International Congress on Controversies in Rheumatology and Autoimmunity.

“We know that lupus patients have an increased susceptibility to infections due to autoimmune dysregulation and use of immunosuppressive therapy,” explained Dr. Bonfá, who is clinical director of the largest tertiary referral center for autoimmune rheumatic diseases in Latin America, the University of São Paulo Faculty of Medicine Hospital Clinics.

“Our study demonstrates for the first time that lupus patients have an increased ARDS severity,” she added.

Prior to the meeting, the study was published in ACR Open Rheumatology.
 

Collating the evidence

Since the COVID-19 pandemic began, there have been more than 20 million confirmed cases of SARS-CoV-2 infection in Brazil and more than half a million deaths.

Dr. Bonfá presented the results of a cross-sectional study that was part of the country’s national Influenza Epidemiological Reporting Surveillance System. Data from 2020 were used, which included just over 252,000 individuals who had polymerase chain reaction–confirmed SARS-CoV-2 infection. Of these individuals, there were 319 consecutively recruited patients with SLE.

The aim was to look at the effect of being hospitalized for COVID-19–related ARDS on outcomes in people with SLE versus the general population.

ARDS was defined as a positive polymerase chain reaction test and accompanying flu-like symptoms with dyspnea, respiratory discomfort, persistent pressure in the chest, or desaturation less than 95% in room air or having a bluish tinge to the lips or face.

Other telling signs of a serious respiratory infection that were evaluated, but not mandatory for study eligibility, were loss of smell, impaired taste, typical CT findings, or having had contact with a confirmed COVID-19 case in the preceding 2 weeks.
 

Key findings

The risk for death from COVID-19–related ARDS was “more than double” in patients with SLE, compared with the general population, Dr. Bonfá reported. The relative risk in the fully adjusted, propensity-scored analysis was approximately 2.25.

That analysis did not account for other comorbidities but was fully adjusted for individuals’ age, sex, and region of Brazil where they lived. The latter was important, Dr. Bonfá said, because “we have a high disparity regarding health access and treatment among regions.”

Comorbidities considered as part of the analyses included arterial hypertension, diabetes, malignancies, neurologic disease, and diseases affecting the heart, lung, liver, and kidneys. Researchers also adjusted for smoking, alcohol intake, body weight, pregnancy, and transplantation.

SLE had a greater impact on individuals’ outcomes than all other comorbidities considered.

“We evaluated lupus as one comorbidity compared to all other comorbidities,” Dr. Bonfá explained.

SLE “more than doubled the chances” of dying from ARDS, she said. “This is [a] very impressive finding.”

They found that SLE was associated with an RR for death of 1.73, compared with non-SLE patients, when propensity-score matching without adjustment for comorbidities was used. The RR for death dropped to 1.40 but was still significant when researchers included comorbidities.

Dr. Bonfá and her team also looked at a combined endpoint of death, ICU admission, and need for mechanical ventilation. They found an increased risk in patients with SLE versus the general population in all their analyses, ranging from 1.70 if comorbidities were included in the model to 1.27 if they weren’t to 1.39 if propensity-score matching alone was used.  
 

 

 

Got lupus? ‘Get vaccinated’

“The data we have are in nonvaccinated patients,” Dr. Bonfá said. “We didn’t have vaccines in 2020.”

Whether being vaccinated might make a different to the risks found in this study is an “interesting question,” and one that may be examined in the future.

Certainly, other work Dr. Bonfá has been involved in seems to point to a likely benefit of vaccination in patients with autoimmune diseases in terms of reducing mortality from COVID-19, even when rates of infection may be on the rise.  

“There’s considerable vaccine hesitancy in SLE patients,” Chi-Chiu Mok, MD, of Tuen Mun Hospital in Hong Kong, observed in a separate presentation at the congress.

This may be for several reasons, such as worry that their disease may flare or the vaccine might compromise their drug treatment or result in uncommon complications.

However, “we should encourage our SLE patients to receive COVID-19 vaccination at a time of clinical remission or low disease activity state,” Dr. Mok advised.

“Physical distancing, protective masks, and personal hygiene [measures]” should also continue.

The bottom line for those with SLE is to get vaccinated, stressed Sandra Navarra, MD, of the University of Santo Tomas Hospital in Manila, the Philippines, during the discussion.

“There’s still so much out there that we do not know about,” she said. “Just get yourself vaccinated.”

The study had no outside funding. Dr. Bonfá, Dr. Mok, and Dr. Navarra reported no relevant financial relationships.

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

There is a significantly increased risk for acute respiratory distress syndrome (ARDS)–related death from COVID-19 among people with systemic lupus erythematous (SLE), compared with the general population, according to data collected in Brazil in 2020.

“Special care is therefore necessary for these patients, as well as reinforcement of the importance of preventive measures during a pandemic for this population,” said Eloisa Bonfá, MD, PhD, at the 14th International Congress on Systemic Lupus Erythematosus, which was held together with the 6th International Congress on Controversies in Rheumatology and Autoimmunity.

“We know that lupus patients have an increased susceptibility to infections due to autoimmune dysregulation and use of immunosuppressive therapy,” explained Dr. Bonfá, who is clinical director of the largest tertiary referral center for autoimmune rheumatic diseases in Latin America, the University of São Paulo Faculty of Medicine Hospital Clinics.

“Our study demonstrates for the first time that lupus patients have an increased ARDS severity,” she added.

Prior to the meeting, the study was published in ACR Open Rheumatology.
 

Collating the evidence

Since the COVID-19 pandemic began, there have been more than 20 million confirmed cases of SARS-CoV-2 infection in Brazil and more than half a million deaths.

Dr. Bonfá presented the results of a cross-sectional study that was part of the country’s national Influenza Epidemiological Reporting Surveillance System. Data from 2020 were used, which included just over 252,000 individuals who had polymerase chain reaction–confirmed SARS-CoV-2 infection. Of these individuals, there were 319 consecutively recruited patients with SLE.

The aim was to look at the effect of being hospitalized for COVID-19–related ARDS on outcomes in people with SLE versus the general population.

ARDS was defined as a positive polymerase chain reaction test and accompanying flu-like symptoms with dyspnea, respiratory discomfort, persistent pressure in the chest, or desaturation less than 95% in room air or having a bluish tinge to the lips or face.

Other telling signs of a serious respiratory infection that were evaluated, but not mandatory for study eligibility, were loss of smell, impaired taste, typical CT findings, or having had contact with a confirmed COVID-19 case in the preceding 2 weeks.
 

Key findings

The risk for death from COVID-19–related ARDS was “more than double” in patients with SLE, compared with the general population, Dr. Bonfá reported. The relative risk in the fully adjusted, propensity-scored analysis was approximately 2.25.

That analysis did not account for other comorbidities but was fully adjusted for individuals’ age, sex, and region of Brazil where they lived. The latter was important, Dr. Bonfá said, because “we have a high disparity regarding health access and treatment among regions.”

Comorbidities considered as part of the analyses included arterial hypertension, diabetes, malignancies, neurologic disease, and diseases affecting the heart, lung, liver, and kidneys. Researchers also adjusted for smoking, alcohol intake, body weight, pregnancy, and transplantation.

SLE had a greater impact on individuals’ outcomes than all other comorbidities considered.

“We evaluated lupus as one comorbidity compared to all other comorbidities,” Dr. Bonfá explained.

SLE “more than doubled the chances” of dying from ARDS, she said. “This is [a] very impressive finding.”

They found that SLE was associated with an RR for death of 1.73, compared with non-SLE patients, when propensity-score matching without adjustment for comorbidities was used. The RR for death dropped to 1.40 but was still significant when researchers included comorbidities.

Dr. Bonfá and her team also looked at a combined endpoint of death, ICU admission, and need for mechanical ventilation. They found an increased risk in patients with SLE versus the general population in all their analyses, ranging from 1.70 if comorbidities were included in the model to 1.27 if they weren’t to 1.39 if propensity-score matching alone was used.  
 

 

 

Got lupus? ‘Get vaccinated’

“The data we have are in nonvaccinated patients,” Dr. Bonfá said. “We didn’t have vaccines in 2020.”

Whether being vaccinated might make a different to the risks found in this study is an “interesting question,” and one that may be examined in the future.

Certainly, other work Dr. Bonfá has been involved in seems to point to a likely benefit of vaccination in patients with autoimmune diseases in terms of reducing mortality from COVID-19, even when rates of infection may be on the rise.  

“There’s considerable vaccine hesitancy in SLE patients,” Chi-Chiu Mok, MD, of Tuen Mun Hospital in Hong Kong, observed in a separate presentation at the congress.

This may be for several reasons, such as worry that their disease may flare or the vaccine might compromise their drug treatment or result in uncommon complications.

However, “we should encourage our SLE patients to receive COVID-19 vaccination at a time of clinical remission or low disease activity state,” Dr. Mok advised.

“Physical distancing, protective masks, and personal hygiene [measures]” should also continue.

The bottom line for those with SLE is to get vaccinated, stressed Sandra Navarra, MD, of the University of Santo Tomas Hospital in Manila, the Philippines, during the discussion.

“There’s still so much out there that we do not know about,” she said. “Just get yourself vaccinated.”

The study had no outside funding. Dr. Bonfá, Dr. Mok, and Dr. Navarra reported no relevant financial relationships.

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

Publications
Publications
Topics
Article Type
Sections
Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME
Disqus Comments
Default
Use ProPublica
Hide sidebar & use full width
render the right sidebar.
Conference Recap Checkbox
Not Conference Recap
Clinical Edge
Display the Slideshow in this Article
Medscape Article
Display survey writer
Reuters content
Disable Inline Native ads
WebMD Article

Soft Nodule on the Forearm

Article Type
Changed
Fri, 10/15/2021 - 07:34
Display Headline
Soft Nodule on the Forearm

The Diagnosis: Schwannoma

Schwannoma, also known as neurilemmoma, is a benign encapsulated neoplasm of the peripheral nerve sheath that presents as a subcutaneous nodule.1 It also may present in the retroperitoneum, mediastinum, and viscera (eg, gastrointestinal tract, bone, upper respiratory tract, lymph nodes). It may occur as multiple lesions when associated with certain syndromes. It usually is an asymptomatic indolent tumor with neurologic symptoms, such as pain and tenderness, in the lesions that are deeper, larger, or closer in proximity to nearby structures.2,3

Histologically, a schwannoma is encapsulated by the perineurium of the nerve bundle from which it originates (quiz image [top]). The tumor consists of hypercellular (Antoni type A) and hypocellular (Antoni type B) areas. Antoni type A areas consist of tightly packed, spindleshaped cells with elongated wavy nuclei and indistinct cytoplasmic borders. These nuclei tend to align into parallel rows with intervening anuclear zones forming Verocay bodies (quiz image [bottom]).4 Verocay bodies are not seen in all schwannomas, and similar formations may be seen in other tumors as well. Solitary circumscribed neuromas also have Verocay bodies, whereas dermatofibromas and leiomyomas have Verocay-like bodies. Antoni type B areas have scattered spindled or ovoid cells in an edematous or myxoid matrix interspersed with inflammatory cells such as lymphocytes and histiocytes. Vessels with thick hyalinized walls are a helpful feature in diagnosis.2 Schwann cells of a schwannoma stain diffusely positive with S-100 protein. The capsule stains positively with epithelial membrane antigen due to the presence of perineurial cells.2

The morphologic variants of this entity include conventional (common, solitary), cellular, plexiform, ancient, melanotic, epithelioid, pseudoglandular, neuroblastomalike, and microcystic/reticular schwannomas. There are additional variants that are associated with genetic syndromes, such as multiple cutaneous plexiform schwannomas linked with neurofibromatosis type 2, psammomatous melanotic schwannoma presenting in Carney complex, schwannomatosis, and segmental schwannomatosis (a distinct form of neurofibromatosis characterized by multiple schwannomas localized to one limb). Either presentation may have alteration or deletion of the neurofibromatosis type 2 gene, NF2, on chromosome 22.2,5

Nodular fasciitis is a benign tumor of fibroblasts and myofibroblasts that usually arises in the subcutaneous tissues. It most commonly occurs in the upper extremities, trunk, head, and neck. It presents as a single, often painful, rapidly growing, subcutaneous nodule. Histologically, lesions mostly are well circumscribed yet unencapsulated, in contrast to schwannomas. They may be hypocellular or hypercellular and are composed of uniform spindle cells with a feathery or fascicular (tissue culture–like) appearance in a loose, myxoid to collagenous stroma. There may be foci of hemorrhage and conspicuous mitoses but not atypical figures (Figure 1). Immunohistochemically, the cells stain positively for smooth muscle actin and negatively for S-100 protein, which sets it apart from a schwannoma. Most cases contain fusion genes, with myosin heavy chain 9 ubiquitin-specific peptidase 6, MYH9-USP6, being the most common fusion product.6

FIGURE 1. Nodular fasciitis. Uniform spindle cells with a tissue culture–like appearance in a loose, myxoid to collagenous stroma (H&E, original magnification ×100).

Solitary circumscribed neuroma (palisaded encapsulated neuroma) is a benign, usually solitary dermal lesion. It most commonly occurs in middle-aged to elderly adults as a small (<1 cm), firm, flesh-colored to pink papule on the face (ie, cheeks, nose, nasolabial folds) and less commonly in the oral and acral regions and on the eyelids and penis. The lesion usually is unilobular; however, other growth patterns such as plexiform, multilobular, and fungating variants have been identified. Histologically, it is a well-circumscribed nodule with a thin capsule of perineurium that is composed of interlacing bundles of Schwann cells with a characteristic clefting artifact (Figure 2). Cells have wavy dark nuclei with scant cytoplasm that occasionally form palisades or Verocay bodies causing these lesions to be confused with schwannomas. Immunohistochemically, the Schwann cells stain positively with S-100 protein, and the perineurium stains positively with epithelial membrane antigen, Claudin-1, and Glut-1. Neurofilament protein stains axons throughout neuromas, whereas in schwannoma, the expression often is limited to entrapped axons at the periphery of the tumor.7

FIGURE 2. Solitary circumscribed neuroma. Interlacing bundles of spindle cells with a characteristic clefting artifact (H&E, original magnification ×40).

Angioleiomyoma is an uncommon, benign, smooth muscle neoplasm of the skin and subcutaneous tissue that originates from vascular smooth muscle. It most commonly presents in adult females aged 30 to 60 years, with a predilection for the lower limbs. These tumors typically are solitary, slow growing, and less than 2 cm in diameter and may be painful upon compression. Similar to schwannoma, angioleiomyoma is an encapsulated lesion composed of interlacing, uniform, smooth muscle bundles distributed around vessels (Figure 3). Smooth muscle cells have oval- or cigar-shaped nuclei with a small perinuclear vacuole of glycogen. Immunohistochemically, there is strong diffuse staining for smooth muscle actin and h-caldesmon. Recurrence after excision is rare.2,8

FIGURE 3. Angioleiomyoma. Interlacing, uniform, smooth muscle bundles distributed around vessels (H&E, original magnification ×40).

Neurofibroma is a common, mostly sporadic, benign tumor of nerve sheath origin. The solitary type may be localized (well circumscribed, unencapsulated) or diffuse. The presence of multiple, deep, and plexiform lesions is associated with neurofibromatosis type 1 (von Recklinghausen disease) that is caused by germline mutations in the NF1 gene. Histologically, the tumor is composed of Schwann cells, fibroblasts, perineurial cells, and nerve axons within an extracellular myxoid to collagenous matrix (Figure 4). The diffuse type is an ill-defined proliferation that entraps adnexal structures. The plexiform type is defined by multinodular serpentine fascicles. Immunohistochemically, the Schwann cells stain positive for S-100 protein and SOX10 (SRY-Box Transcription Factor 10). Epithelial membrane antigen stains admixed perineurial cells. Neurofilament protein highlights intratumoral axons, which generally are not found throughout schwannomas. Transformation to a malignant peripheral nerve sheath tumor occurs in up to 10% of patients with neurofibromatosis type 1, usually in plexiform neurofibromas, and is characterized by increased cellularity, atypia, mitotic activity, and necrosis.9

FIGURE 4. Neurofibroma. Loosely arranged spindle cells in a haphazard arrangement with small, hyperchromatic, wavy nuclei in a myxoid to collagenous matrix (H&E, original magnification ×40).

References
  1. Ritter SE, Elston DM. Cutaneous schwannoma of the foot. Cutis. 2001;67:127-129.
  2. Calonje E, Damaskou V, Lazar AJ. Connective tissue tumors. In: Calonje E, Brenn T, Lazar AJ, et al, eds. McKee’s Pathology of the Skin. 5th ed. Vol 2. Elsevier Saunders; 2020:1698-1894.
  3. Knight DM, Birch R, Pringle J. Benign solitary schwannomas: a review of 234 cases. J Bone Joint Surg Br. 2007;89:382-387.
  4. Lespi PJ, Smit R. Verocay body—prominent cutaneous leiomyoma. Am J Dermatopathol. 1999;21:110-111.
  5. Kurtkaya-Yapicier O, Scheithauer B, Woodruff JM. The pathobiologic spectrum of schwannomas. Histol Histopathol. 2003;18:925-934.
  6. Erickson-Johnson MR, Chou MM, Evers BR, et al. Nodular fasciitis: a novel model of transient neoplasia induced by MYH9-USP6 gene fusion. Lab Invest. 2011;91:1427-1433.
  7. Leblebici C, Savli TC, Yeni B, et al. Palisaded encapsulated (solitary circumscribed) neuroma: a review of 30 cases. Int J Surg Pathol. 2019;27:506-514.
  8. Yeung CM, Moore L, Lans J, et al. Angioleiomyoma of the hand: a case series and review of the literature. Arch Bone Jt Surg. 2020; 8:373-377.
  9. Skovronsky DM, Oberholtzer JC. Pathologic classification of peripheral nerve tumors. Neurosurg Clin North Am. 2004;15:157-166.
Article PDF
Author and Disclosure Information

From the Department of Pathology, Geisinger Medical Center, Danville, Pennsylvania. Dr. Ferringer also is from the Department of Dermatology.

The authors report no conflict of interest.

Correspondence: Syeda F. Absar, MD, MPH, Department of Pathology, Geisinger Medical Center, 100 N Academy Ave, Mailstop 19-20, Danville, PA 17822 ([email protected]).

Issue
Cutis - 108(4)
Publications
Topics
Page Number
180,187-188
Sections
Author and Disclosure Information

From the Department of Pathology, Geisinger Medical Center, Danville, Pennsylvania. Dr. Ferringer also is from the Department of Dermatology.

The authors report no conflict of interest.

Correspondence: Syeda F. Absar, MD, MPH, Department of Pathology, Geisinger Medical Center, 100 N Academy Ave, Mailstop 19-20, Danville, PA 17822 ([email protected]).

Author and Disclosure Information

From the Department of Pathology, Geisinger Medical Center, Danville, Pennsylvania. Dr. Ferringer also is from the Department of Dermatology.

The authors report no conflict of interest.

Correspondence: Syeda F. Absar, MD, MPH, Department of Pathology, Geisinger Medical Center, 100 N Academy Ave, Mailstop 19-20, Danville, PA 17822 ([email protected]).

Article PDF
Article PDF

The Diagnosis: Schwannoma

Schwannoma, also known as neurilemmoma, is a benign encapsulated neoplasm of the peripheral nerve sheath that presents as a subcutaneous nodule.1 It also may present in the retroperitoneum, mediastinum, and viscera (eg, gastrointestinal tract, bone, upper respiratory tract, lymph nodes). It may occur as multiple lesions when associated with certain syndromes. It usually is an asymptomatic indolent tumor with neurologic symptoms, such as pain and tenderness, in the lesions that are deeper, larger, or closer in proximity to nearby structures.2,3

Histologically, a schwannoma is encapsulated by the perineurium of the nerve bundle from which it originates (quiz image [top]). The tumor consists of hypercellular (Antoni type A) and hypocellular (Antoni type B) areas. Antoni type A areas consist of tightly packed, spindleshaped cells with elongated wavy nuclei and indistinct cytoplasmic borders. These nuclei tend to align into parallel rows with intervening anuclear zones forming Verocay bodies (quiz image [bottom]).4 Verocay bodies are not seen in all schwannomas, and similar formations may be seen in other tumors as well. Solitary circumscribed neuromas also have Verocay bodies, whereas dermatofibromas and leiomyomas have Verocay-like bodies. Antoni type B areas have scattered spindled or ovoid cells in an edematous or myxoid matrix interspersed with inflammatory cells such as lymphocytes and histiocytes. Vessels with thick hyalinized walls are a helpful feature in diagnosis.2 Schwann cells of a schwannoma stain diffusely positive with S-100 protein. The capsule stains positively with epithelial membrane antigen due to the presence of perineurial cells.2

The morphologic variants of this entity include conventional (common, solitary), cellular, plexiform, ancient, melanotic, epithelioid, pseudoglandular, neuroblastomalike, and microcystic/reticular schwannomas. There are additional variants that are associated with genetic syndromes, such as multiple cutaneous plexiform schwannomas linked with neurofibromatosis type 2, psammomatous melanotic schwannoma presenting in Carney complex, schwannomatosis, and segmental schwannomatosis (a distinct form of neurofibromatosis characterized by multiple schwannomas localized to one limb). Either presentation may have alteration or deletion of the neurofibromatosis type 2 gene, NF2, on chromosome 22.2,5

Nodular fasciitis is a benign tumor of fibroblasts and myofibroblasts that usually arises in the subcutaneous tissues. It most commonly occurs in the upper extremities, trunk, head, and neck. It presents as a single, often painful, rapidly growing, subcutaneous nodule. Histologically, lesions mostly are well circumscribed yet unencapsulated, in contrast to schwannomas. They may be hypocellular or hypercellular and are composed of uniform spindle cells with a feathery or fascicular (tissue culture–like) appearance in a loose, myxoid to collagenous stroma. There may be foci of hemorrhage and conspicuous mitoses but not atypical figures (Figure 1). Immunohistochemically, the cells stain positively for smooth muscle actin and negatively for S-100 protein, which sets it apart from a schwannoma. Most cases contain fusion genes, with myosin heavy chain 9 ubiquitin-specific peptidase 6, MYH9-USP6, being the most common fusion product.6

FIGURE 1. Nodular fasciitis. Uniform spindle cells with a tissue culture–like appearance in a loose, myxoid to collagenous stroma (H&E, original magnification ×100).

Solitary circumscribed neuroma (palisaded encapsulated neuroma) is a benign, usually solitary dermal lesion. It most commonly occurs in middle-aged to elderly adults as a small (<1 cm), firm, flesh-colored to pink papule on the face (ie, cheeks, nose, nasolabial folds) and less commonly in the oral and acral regions and on the eyelids and penis. The lesion usually is unilobular; however, other growth patterns such as plexiform, multilobular, and fungating variants have been identified. Histologically, it is a well-circumscribed nodule with a thin capsule of perineurium that is composed of interlacing bundles of Schwann cells with a characteristic clefting artifact (Figure 2). Cells have wavy dark nuclei with scant cytoplasm that occasionally form palisades or Verocay bodies causing these lesions to be confused with schwannomas. Immunohistochemically, the Schwann cells stain positively with S-100 protein, and the perineurium stains positively with epithelial membrane antigen, Claudin-1, and Glut-1. Neurofilament protein stains axons throughout neuromas, whereas in schwannoma, the expression often is limited to entrapped axons at the periphery of the tumor.7

FIGURE 2. Solitary circumscribed neuroma. Interlacing bundles of spindle cells with a characteristic clefting artifact (H&E, original magnification ×40).

Angioleiomyoma is an uncommon, benign, smooth muscle neoplasm of the skin and subcutaneous tissue that originates from vascular smooth muscle. It most commonly presents in adult females aged 30 to 60 years, with a predilection for the lower limbs. These tumors typically are solitary, slow growing, and less than 2 cm in diameter and may be painful upon compression. Similar to schwannoma, angioleiomyoma is an encapsulated lesion composed of interlacing, uniform, smooth muscle bundles distributed around vessels (Figure 3). Smooth muscle cells have oval- or cigar-shaped nuclei with a small perinuclear vacuole of glycogen. Immunohistochemically, there is strong diffuse staining for smooth muscle actin and h-caldesmon. Recurrence after excision is rare.2,8

FIGURE 3. Angioleiomyoma. Interlacing, uniform, smooth muscle bundles distributed around vessels (H&E, original magnification ×40).

Neurofibroma is a common, mostly sporadic, benign tumor of nerve sheath origin. The solitary type may be localized (well circumscribed, unencapsulated) or diffuse. The presence of multiple, deep, and plexiform lesions is associated with neurofibromatosis type 1 (von Recklinghausen disease) that is caused by germline mutations in the NF1 gene. Histologically, the tumor is composed of Schwann cells, fibroblasts, perineurial cells, and nerve axons within an extracellular myxoid to collagenous matrix (Figure 4). The diffuse type is an ill-defined proliferation that entraps adnexal structures. The plexiform type is defined by multinodular serpentine fascicles. Immunohistochemically, the Schwann cells stain positive for S-100 protein and SOX10 (SRY-Box Transcription Factor 10). Epithelial membrane antigen stains admixed perineurial cells. Neurofilament protein highlights intratumoral axons, which generally are not found throughout schwannomas. Transformation to a malignant peripheral nerve sheath tumor occurs in up to 10% of patients with neurofibromatosis type 1, usually in plexiform neurofibromas, and is characterized by increased cellularity, atypia, mitotic activity, and necrosis.9

FIGURE 4. Neurofibroma. Loosely arranged spindle cells in a haphazard arrangement with small, hyperchromatic, wavy nuclei in a myxoid to collagenous matrix (H&E, original magnification ×40).

The Diagnosis: Schwannoma

Schwannoma, also known as neurilemmoma, is a benign encapsulated neoplasm of the peripheral nerve sheath that presents as a subcutaneous nodule.1 It also may present in the retroperitoneum, mediastinum, and viscera (eg, gastrointestinal tract, bone, upper respiratory tract, lymph nodes). It may occur as multiple lesions when associated with certain syndromes. It usually is an asymptomatic indolent tumor with neurologic symptoms, such as pain and tenderness, in the lesions that are deeper, larger, or closer in proximity to nearby structures.2,3

Histologically, a schwannoma is encapsulated by the perineurium of the nerve bundle from which it originates (quiz image [top]). The tumor consists of hypercellular (Antoni type A) and hypocellular (Antoni type B) areas. Antoni type A areas consist of tightly packed, spindleshaped cells with elongated wavy nuclei and indistinct cytoplasmic borders. These nuclei tend to align into parallel rows with intervening anuclear zones forming Verocay bodies (quiz image [bottom]).4 Verocay bodies are not seen in all schwannomas, and similar formations may be seen in other tumors as well. Solitary circumscribed neuromas also have Verocay bodies, whereas dermatofibromas and leiomyomas have Verocay-like bodies. Antoni type B areas have scattered spindled or ovoid cells in an edematous or myxoid matrix interspersed with inflammatory cells such as lymphocytes and histiocytes. Vessels with thick hyalinized walls are a helpful feature in diagnosis.2 Schwann cells of a schwannoma stain diffusely positive with S-100 protein. The capsule stains positively with epithelial membrane antigen due to the presence of perineurial cells.2

The morphologic variants of this entity include conventional (common, solitary), cellular, plexiform, ancient, melanotic, epithelioid, pseudoglandular, neuroblastomalike, and microcystic/reticular schwannomas. There are additional variants that are associated with genetic syndromes, such as multiple cutaneous plexiform schwannomas linked with neurofibromatosis type 2, psammomatous melanotic schwannoma presenting in Carney complex, schwannomatosis, and segmental schwannomatosis (a distinct form of neurofibromatosis characterized by multiple schwannomas localized to one limb). Either presentation may have alteration or deletion of the neurofibromatosis type 2 gene, NF2, on chromosome 22.2,5

Nodular fasciitis is a benign tumor of fibroblasts and myofibroblasts that usually arises in the subcutaneous tissues. It most commonly occurs in the upper extremities, trunk, head, and neck. It presents as a single, often painful, rapidly growing, subcutaneous nodule. Histologically, lesions mostly are well circumscribed yet unencapsulated, in contrast to schwannomas. They may be hypocellular or hypercellular and are composed of uniform spindle cells with a feathery or fascicular (tissue culture–like) appearance in a loose, myxoid to collagenous stroma. There may be foci of hemorrhage and conspicuous mitoses but not atypical figures (Figure 1). Immunohistochemically, the cells stain positively for smooth muscle actin and negatively for S-100 protein, which sets it apart from a schwannoma. Most cases contain fusion genes, with myosin heavy chain 9 ubiquitin-specific peptidase 6, MYH9-USP6, being the most common fusion product.6

FIGURE 1. Nodular fasciitis. Uniform spindle cells with a tissue culture–like appearance in a loose, myxoid to collagenous stroma (H&E, original magnification ×100).

Solitary circumscribed neuroma (palisaded encapsulated neuroma) is a benign, usually solitary dermal lesion. It most commonly occurs in middle-aged to elderly adults as a small (<1 cm), firm, flesh-colored to pink papule on the face (ie, cheeks, nose, nasolabial folds) and less commonly in the oral and acral regions and on the eyelids and penis. The lesion usually is unilobular; however, other growth patterns such as plexiform, multilobular, and fungating variants have been identified. Histologically, it is a well-circumscribed nodule with a thin capsule of perineurium that is composed of interlacing bundles of Schwann cells with a characteristic clefting artifact (Figure 2). Cells have wavy dark nuclei with scant cytoplasm that occasionally form palisades or Verocay bodies causing these lesions to be confused with schwannomas. Immunohistochemically, the Schwann cells stain positively with S-100 protein, and the perineurium stains positively with epithelial membrane antigen, Claudin-1, and Glut-1. Neurofilament protein stains axons throughout neuromas, whereas in schwannoma, the expression often is limited to entrapped axons at the periphery of the tumor.7

FIGURE 2. Solitary circumscribed neuroma. Interlacing bundles of spindle cells with a characteristic clefting artifact (H&E, original magnification ×40).

Angioleiomyoma is an uncommon, benign, smooth muscle neoplasm of the skin and subcutaneous tissue that originates from vascular smooth muscle. It most commonly presents in adult females aged 30 to 60 years, with a predilection for the lower limbs. These tumors typically are solitary, slow growing, and less than 2 cm in diameter and may be painful upon compression. Similar to schwannoma, angioleiomyoma is an encapsulated lesion composed of interlacing, uniform, smooth muscle bundles distributed around vessels (Figure 3). Smooth muscle cells have oval- or cigar-shaped nuclei with a small perinuclear vacuole of glycogen. Immunohistochemically, there is strong diffuse staining for smooth muscle actin and h-caldesmon. Recurrence after excision is rare.2,8

FIGURE 3. Angioleiomyoma. Interlacing, uniform, smooth muscle bundles distributed around vessels (H&E, original magnification ×40).

Neurofibroma is a common, mostly sporadic, benign tumor of nerve sheath origin. The solitary type may be localized (well circumscribed, unencapsulated) or diffuse. The presence of multiple, deep, and plexiform lesions is associated with neurofibromatosis type 1 (von Recklinghausen disease) that is caused by germline mutations in the NF1 gene. Histologically, the tumor is composed of Schwann cells, fibroblasts, perineurial cells, and nerve axons within an extracellular myxoid to collagenous matrix (Figure 4). The diffuse type is an ill-defined proliferation that entraps adnexal structures. The plexiform type is defined by multinodular serpentine fascicles. Immunohistochemically, the Schwann cells stain positive for S-100 protein and SOX10 (SRY-Box Transcription Factor 10). Epithelial membrane antigen stains admixed perineurial cells. Neurofilament protein highlights intratumoral axons, which generally are not found throughout schwannomas. Transformation to a malignant peripheral nerve sheath tumor occurs in up to 10% of patients with neurofibromatosis type 1, usually in plexiform neurofibromas, and is characterized by increased cellularity, atypia, mitotic activity, and necrosis.9

FIGURE 4. Neurofibroma. Loosely arranged spindle cells in a haphazard arrangement with small, hyperchromatic, wavy nuclei in a myxoid to collagenous matrix (H&E, original magnification ×40).

References
  1. Ritter SE, Elston DM. Cutaneous schwannoma of the foot. Cutis. 2001;67:127-129.
  2. Calonje E, Damaskou V, Lazar AJ. Connective tissue tumors. In: Calonje E, Brenn T, Lazar AJ, et al, eds. McKee’s Pathology of the Skin. 5th ed. Vol 2. Elsevier Saunders; 2020:1698-1894.
  3. Knight DM, Birch R, Pringle J. Benign solitary schwannomas: a review of 234 cases. J Bone Joint Surg Br. 2007;89:382-387.
  4. Lespi PJ, Smit R. Verocay body—prominent cutaneous leiomyoma. Am J Dermatopathol. 1999;21:110-111.
  5. Kurtkaya-Yapicier O, Scheithauer B, Woodruff JM. The pathobiologic spectrum of schwannomas. Histol Histopathol. 2003;18:925-934.
  6. Erickson-Johnson MR, Chou MM, Evers BR, et al. Nodular fasciitis: a novel model of transient neoplasia induced by MYH9-USP6 gene fusion. Lab Invest. 2011;91:1427-1433.
  7. Leblebici C, Savli TC, Yeni B, et al. Palisaded encapsulated (solitary circumscribed) neuroma: a review of 30 cases. Int J Surg Pathol. 2019;27:506-514.
  8. Yeung CM, Moore L, Lans J, et al. Angioleiomyoma of the hand: a case series and review of the literature. Arch Bone Jt Surg. 2020; 8:373-377.
  9. Skovronsky DM, Oberholtzer JC. Pathologic classification of peripheral nerve tumors. Neurosurg Clin North Am. 2004;15:157-166.
References
  1. Ritter SE, Elston DM. Cutaneous schwannoma of the foot. Cutis. 2001;67:127-129.
  2. Calonje E, Damaskou V, Lazar AJ. Connective tissue tumors. In: Calonje E, Brenn T, Lazar AJ, et al, eds. McKee’s Pathology of the Skin. 5th ed. Vol 2. Elsevier Saunders; 2020:1698-1894.
  3. Knight DM, Birch R, Pringle J. Benign solitary schwannomas: a review of 234 cases. J Bone Joint Surg Br. 2007;89:382-387.
  4. Lespi PJ, Smit R. Verocay body—prominent cutaneous leiomyoma. Am J Dermatopathol. 1999;21:110-111.
  5. Kurtkaya-Yapicier O, Scheithauer B, Woodruff JM. The pathobiologic spectrum of schwannomas. Histol Histopathol. 2003;18:925-934.
  6. Erickson-Johnson MR, Chou MM, Evers BR, et al. Nodular fasciitis: a novel model of transient neoplasia induced by MYH9-USP6 gene fusion. Lab Invest. 2011;91:1427-1433.
  7. Leblebici C, Savli TC, Yeni B, et al. Palisaded encapsulated (solitary circumscribed) neuroma: a review of 30 cases. Int J Surg Pathol. 2019;27:506-514.
  8. Yeung CM, Moore L, Lans J, et al. Angioleiomyoma of the hand: a case series and review of the literature. Arch Bone Jt Surg. 2020; 8:373-377.
  9. Skovronsky DM, Oberholtzer JC. Pathologic classification of peripheral nerve tumors. Neurosurg Clin North Am. 2004;15:157-166.
Issue
Cutis - 108(4)
Issue
Cutis - 108(4)
Page Number
180,187-188
Page Number
180,187-188
Publications
Publications
Topics
Article Type
Display Headline
Soft Nodule on the Forearm
Display Headline
Soft Nodule on the Forearm
Sections
Questionnaire Body

H&E, original magnification ×40.

H&E, original magnification ×100.

A 54-year-old woman presented with an enlarging mass on the right volar forearm. Physical examination revealed a 1-cm, soft, mobile, subcutaneous nodule. Excision revealed tan-pink, indurated, fibrous, nodular tissue.

Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME
Disqus Comments
Default
Gate On Date
Wed, 10/13/2021 - 08:45
Un-Gate On Date
Wed, 10/13/2021 - 08:45
Use ProPublica
CFC Schedule Remove Status
Wed, 10/13/2021 - 08:45
Hide sidebar & use full width
render the right sidebar.
Conference Recap Checkbox
Not Conference Recap
Clinical Edge
Display the Slideshow in this Article
Medscape Article
Display survey writer
Reuters content
Disable Inline Native ads
WebMD Article
Article PDF Media