TBD Meeting (2884-21)

Patients who receive the mRNA COVID-19 vaccines are experiencing a variety of skin rashes, a dermatologist told colleagues, and some lesions don’t appear until several days after an injection. The good news is that these side effects tend to be minor and vanish within a few days, Esther Freeman, MD, PhD, said in a presentation at the American Academy of Dermatology Virtual Meeting Experience.

“The reality is actually very reassuring,” Dr. Freeman said, especially in light of what is currently known about when the rashes occur and how anaphylaxis is extremely uncommon. Now, she added, dermatologists can tell patients who had reactions to their initial vaccination that “we know you had this big reaction, and we know that it was upsetting and uncomfortable. But it may not happen the second time around. And if it does, [the reaction is] probably going to be smaller.”

Dr. Freeman, associate professor of dermatology at Harvard Medical School, Boston, highlighted a study published in the Journal of the American Academy of Dermatology that she coauthored with dermatologists across the United States. The researchers tracked 414 cutaneous reactions to the Moderna (83%) and Pfizer (17%) COVID-19 vaccines in a group of patients, which was 90% female, 78% White, and mostly from the United States. Their average age was 44 years. The cases were reported to the AAD–International League of Dermatological Societies registry of COVID-19 cutaneous manifestations.

While most were women, “it’s a little hard to know if this is really going to end up being a true finding,” said Dr. Freeman, the registry’s principal investigator and a member of the AAD’s COVID-19 Ad Hoc Task Force. “If you think about who got vaccinated early, it was health care providers, and the American health care workforce is over 70% female. So I think there’s a little bit of bias here. There may also be a bias because women may be slightly more likely to report or go to their health care provider for a rash.”

Delayed large local reactions were the most common, accounting for 66% (175 cases) of the 267 skin reactions reported after the first Moderna vaccine dose and 30% (31 cases) of the 102 reactions reported after the second dose. These reactions represented 15% (5 cases) of the 34 skin reactions reported after the first Pfizer vaccine dose and 18% (7 cases) of the 40 reactions after the second dose.

There are two peaks with that first dose, Dr. Freeman said. “There’s a peak around day 2 or 3. And there’s another peak around day 7 or 8 with some of these reactions. Only 27% who had a reaction with the first dose had the same reaction with the second.” She added that these reactions “are not cellulitis and don’t require antibiotics.”

Other more common reactions included local injection-site reactions (swelling, erythema, and pain), urticaria (after 24 hours in almost all cases, occurring at a higher rate in patients who received the Pfizer vaccine), and morbilliform eruptions.

Dr. Freeman said that patients may experience redness and swelling in the hands and feet that can be “very uncomfortable.” She described one patient “who was having a hard time actually closing his fist, just because of the amount of swelling and redness in his hand. It did resolve, and it’s important to reassure your patients it will go away.”

According to this study, less common reports of other cutaneous findings with both vaccines included 9 reports of swelling at the site of cosmetic fillers, 8 reports of pernio/chilblains, 10 reports of varicella zoster, 4 reports of herpes simplex flares, 4 pityriasis rosea–like reactions, and 4 rashes in infants of vaccinated breastfeeding mothers.

The study noted that “patients responded well to topical corticosteroids, oral antihistamines, and/or pain-relieving medications. These reactions resolved after a median of 3-4 days.”

It’s important to understand that none of the patients developed anaphylaxis after the second dose even if they’d had a reaction to the first dose, Dr. Freeman said. “But I should point out that we’re talking about reactions that have started more than 4 hours after the vaccine. If a rash such as a urticaria specifically starts within 4 hours of vaccination, that’s in a different category. Those are considered more immediate allergic reactions, and those patients need to be seen by allergy before a second dose.”

Dr. Freeman added that “it’s really interesting to think about how our bodies are really reacting to the vaccine in a way that’s mimicking our body’s reactions to COVID-19.” For example, some patients who got vaccinated developed chilblains similar to the “COVID toes” described in infected patients, apparently as part of the body’s immune response to the virus. “We’ve seen this in patients who actually had COVID and had prior COVID toes and then actually got a flare with their vaccine. And then we’ve also seen it in patients who never had COVID.”

In regard to general advice for patients, she said, “I do still encourage my patients who previously had COVID to go ahead and get the vaccine even if they had a skin manifestation with COVID.”

Shari Lipner, MD, PhD, associate professor of clinical dermatology, Weill Cornell Medicine, New York, said she has have seen only a handful of cases of delayed large local reactions and local injection site reactions after COVID-19 vaccination. “I have seen a significant number of cases of acute urticaria following the first and second doses,” she said in an interview. “However, it is important to keep in mind that we cannot determine cause and effect for the cases of acute urticaria. They may or may not be vaccine related.”

Fortunately, none of the adverse effects she’s seen have been severe. “It is important that dermatologists educate the public and their patients that most people do not develop any skin reaction in response to the vaccine,” she said. In the minority who do, “reactions tend to be mild and are not life-threatening. Many of these skin reactions resolve on their own without treatment.”

She added that “patients with pernio/chilblains or herpes zoster following vaccination should be referred by a board-certified dermatologist for prompt treatment and to avoid sequelae.”


 

‘COVID vaccine arm’

Delayed local reactions to the Moderna vaccine were also described in a report published online on May 12, 2021, in JAMA Dermatology, after the AAD meeting, in 16 patients referred to the Yale New Haven (Conn.) Hospital Dermatology service who experienced delayed localized cutaneous hypersensitivity reactions a median of 7 days after receiving the vaccine (range, 2-12 days), from Jan. 20 to Feb. 12, 2021. No such cases were reported in Pfizer vaccine recipients.

Of the 16 patients, whose median age was 38 years and who were mostly women, 15 developed the reaction after the first dose, described as “pruritic and variably painful erythematous reactions near the injection site,” which lasted a median of 5 days (range, 1-21 days). After the second dose, 12 of the 16 patients developed injection-site reactions (including one patient who had no reaction after dose 1), a median of 2 days after the vaccine was administered (range, 0-5 days). Histologic results of a biopsy in one patient with a reaction to the second dose “ demonstrated mild predominantly perivascular and focal interstitial mixed infiltrate with lymphocytes and eosinophils consistent with a dermal hypersensitivity reaction,” wrote Alicia J. Little, MD, PhD, of the department of dermatology, Yale University, New Haven, and coauthors.

Compared with immediate hypersensitivity reactions, occurring within 4 hours of vaccination, such as anaphylaxis and urticaria, they concluded that “these delayed localized hypersensitivity reactions are not a contraindication to subsequent vaccination,” and they proposed that they be named “COVID vaccine arm.”

Dr. Freeman reported no disclosures. Dr. Lipner also had no relevant disclosures. Dr. Little reported receiving a grant from the National Center for Advancing Translational Science and a Women’s Health Career Development Award from the Dermatology Foundation while the study was conducted; another author reported equity in Johnson & Johnson in his spouse’s retirement fund outside the submitted work.
 

Patients who receive the mRNA COVID-19 vaccines are experiencing a variety of skin rashes, a dermatologist told colleagues, and some lesions don’t appear until several days after an injection. The good news is that these side effects tend to be minor and vanish within a few days, Esther Freeman, MD, PhD, said in a presentation at the American Academy of Dermatology Virtual Meeting Experience.

“The reality is actually very reassuring,” Dr. Freeman said, especially in light of what is currently known about when the rashes occur and how anaphylaxis is extremely uncommon. Now, she added, dermatologists can tell patients who had reactions to their initial vaccination that “we know you had this big reaction, and we know that it was upsetting and uncomfortable. But it may not happen the second time around. And if it does, [the reaction is] probably going to be smaller.”

Dr. Freeman, associate professor of dermatology at Harvard Medical School, Boston, highlighted a study published in the Journal of the American Academy of Dermatology that she coauthored with dermatologists across the United States. The researchers tracked 414 cutaneous reactions to the Moderna (83%) and Pfizer (17%) COVID-19 vaccines in a group of patients, which was 90% female, 78% White, and mostly from the United States. Their average age was 44 years. The cases were reported to the AAD–International League of Dermatological Societies registry of COVID-19 cutaneous manifestations.

While most were women, “it’s a little hard to know if this is really going to end up being a true finding,” said Dr. Freeman, the registry’s principal investigator and a member of the AAD’s COVID-19 Ad Hoc Task Force. “If you think about who got vaccinated early, it was health care providers, and the American health care workforce is over 70% female. So I think there’s a little bit of bias here. There may also be a bias because women may be slightly more likely to report or go to their health care provider for a rash.”

Delayed large local reactions were the most common, accounting for 66% (175 cases) of the 267 skin reactions reported after the first Moderna vaccine dose and 30% (31 cases) of the 102 reactions reported after the second dose. These reactions represented 15% (5 cases) of the 34 skin reactions reported after the first Pfizer vaccine dose and 18% (7 cases) of the 40 reactions after the second dose.

There are two peaks with that first dose, Dr. Freeman said. “There’s a peak around day 2 or 3. And there’s another peak around day 7 or 8 with some of these reactions. Only 27% who had a reaction with the first dose had the same reaction with the second.” She added that these reactions “are not cellulitis and don’t require antibiotics.”

Other more common reactions included local injection-site reactions (swelling, erythema, and pain), urticaria (after 24 hours in almost all cases, occurring at a higher rate in patients who received the Pfizer vaccine), and morbilliform eruptions.

Dr. Freeman said that patients may experience redness and swelling in the hands and feet that can be “very uncomfortable.” She described one patient “who was having a hard time actually closing his fist, just because of the amount of swelling and redness in his hand. It did resolve, and it’s important to reassure your patients it will go away.”

According to this study, less common reports of other cutaneous findings with both vaccines included 9 reports of swelling at the site of cosmetic fillers, 8 reports of pernio/chilblains, 10 reports of varicella zoster, 4 reports of herpes simplex flares, 4 pityriasis rosea–like reactions, and 4 rashes in infants of vaccinated breastfeeding mothers.

The study noted that “patients responded well to topical corticosteroids, oral antihistamines, and/or pain-relieving medications. These reactions resolved after a median of 3-4 days.”

It’s important to understand that none of the patients developed anaphylaxis after the second dose even if they’d had a reaction to the first dose, Dr. Freeman said. “But I should point out that we’re talking about reactions that have started more than 4 hours after the vaccine. If a rash such as a urticaria specifically starts within 4 hours of vaccination, that’s in a different category. Those are considered more immediate allergic reactions, and those patients need to be seen by allergy before a second dose.”

Dr. Freeman added that “it’s really interesting to think about how our bodies are really reacting to the vaccine in a way that’s mimicking our body’s reactions to COVID-19.” For example, some patients who got vaccinated developed chilblains similar to the “COVID toes” described in infected patients, apparently as part of the body’s immune response to the virus. “We’ve seen this in patients who actually had COVID and had prior COVID toes and then actually got a flare with their vaccine. And then we’ve also seen it in patients who never had COVID.”

In regard to general advice for patients, she said, “I do still encourage my patients who previously had COVID to go ahead and get the vaccine even if they had a skin manifestation with COVID.”

Shari Lipner, MD, PhD, associate professor of clinical dermatology, Weill Cornell Medicine, New York, said she has have seen only a handful of cases of delayed large local reactions and local injection site reactions after COVID-19 vaccination. “I have seen a significant number of cases of acute urticaria following the first and second doses,” she said in an interview. “However, it is important to keep in mind that we cannot determine cause and effect for the cases of acute urticaria. They may or may not be vaccine related.”

Fortunately, none of the adverse effects she’s seen have been severe. “It is important that dermatologists educate the public and their patients that most people do not develop any skin reaction in response to the vaccine,” she said. In the minority who do, “reactions tend to be mild and are not life-threatening. Many of these skin reactions resolve on their own without treatment.”

She added that “patients with pernio/chilblains or herpes zoster following vaccination should be referred by a board-certified dermatologist for prompt treatment and to avoid sequelae.”


 

‘COVID vaccine arm’

Delayed local reactions to the Moderna vaccine were also described in a report published online on May 12, 2021, in JAMA Dermatology, after the AAD meeting, in 16 patients referred to the Yale New Haven (Conn.) Hospital Dermatology service who experienced delayed localized cutaneous hypersensitivity reactions a median of 7 days after receiving the vaccine (range, 2-12 days), from Jan. 20 to Feb. 12, 2021. No such cases were reported in Pfizer vaccine recipients.

Of the 16 patients, whose median age was 38 years and who were mostly women, 15 developed the reaction after the first dose, described as “pruritic and variably painful erythematous reactions near the injection site,” which lasted a median of 5 days (range, 1-21 days). After the second dose, 12 of the 16 patients developed injection-site reactions (including one patient who had no reaction after dose 1), a median of 2 days after the vaccine was administered (range, 0-5 days). Histologic results of a biopsy in one patient with a reaction to the second dose “ demonstrated mild predominantly perivascular and focal interstitial mixed infiltrate with lymphocytes and eosinophils consistent with a dermal hypersensitivity reaction,” wrote Alicia J. Little, MD, PhD, of the department of dermatology, Yale University, New Haven, and coauthors.

Compared with immediate hypersensitivity reactions, occurring within 4 hours of vaccination, such as anaphylaxis and urticaria, they concluded that “these delayed localized hypersensitivity reactions are not a contraindication to subsequent vaccination,” and they proposed that they be named “COVID vaccine arm.”

Dr. Freeman reported no disclosures. Dr. Lipner also had no relevant disclosures. Dr. Little reported receiving a grant from the National Center for Advancing Translational Science and a Women’s Health Career Development Award from the Dermatology Foundation while the study was conducted; another author reported equity in Johnson & Johnson in his spouse’s retirement fund outside the submitted work.
 

Patients who receive the mRNA COVID-19 vaccines are experiencing a variety of skin rashes, a dermatologist told colleagues, and some lesions don’t appear until several days after an injection. The good news is that these side effects tend to be minor and vanish within a few days, Esther Freeman, MD, PhD, said in a presentation at the American Academy of Dermatology Virtual Meeting Experience.

“The reality is actually very reassuring,” Dr. Freeman said, especially in light of what is currently known about when the rashes occur and how anaphylaxis is extremely uncommon. Now, she added, dermatologists can tell patients who had reactions to their initial vaccination that “we know you had this big reaction, and we know that it was upsetting and uncomfortable. But it may not happen the second time around. And if it does, [the reaction is] probably going to be smaller.”

Dr. Freeman, associate professor of dermatology at Harvard Medical School, Boston, highlighted a study published in the Journal of the American Academy of Dermatology that she coauthored with dermatologists across the United States. The researchers tracked 414 cutaneous reactions to the Moderna (83%) and Pfizer (17%) COVID-19 vaccines in a group of patients, which was 90% female, 78% White, and mostly from the United States. Their average age was 44 years. The cases were reported to the AAD–International League of Dermatological Societies registry of COVID-19 cutaneous manifestations.

While most were women, “it’s a little hard to know if this is really going to end up being a true finding,” said Dr. Freeman, the registry’s principal investigator and a member of the AAD’s COVID-19 Ad Hoc Task Force. “If you think about who got vaccinated early, it was health care providers, and the American health care workforce is over 70% female. So I think there’s a little bit of bias here. There may also be a bias because women may be slightly more likely to report or go to their health care provider for a rash.”

Delayed large local reactions were the most common, accounting for 66% (175 cases) of the 267 skin reactions reported after the first Moderna vaccine dose and 30% (31 cases) of the 102 reactions reported after the second dose. These reactions represented 15% (5 cases) of the 34 skin reactions reported after the first Pfizer vaccine dose and 18% (7 cases) of the 40 reactions after the second dose.

There are two peaks with that first dose, Dr. Freeman said. “There’s a peak around day 2 or 3. And there’s another peak around day 7 or 8 with some of these reactions. Only 27% who had a reaction with the first dose had the same reaction with the second.” She added that these reactions “are not cellulitis and don’t require antibiotics.”

Other more common reactions included local injection-site reactions (swelling, erythema, and pain), urticaria (after 24 hours in almost all cases, occurring at a higher rate in patients who received the Pfizer vaccine), and morbilliform eruptions.

Dr. Freeman said that patients may experience redness and swelling in the hands and feet that can be “very uncomfortable.” She described one patient “who was having a hard time actually closing his fist, just because of the amount of swelling and redness in his hand. It did resolve, and it’s important to reassure your patients it will go away.”

According to this study, less common reports of other cutaneous findings with both vaccines included 9 reports of swelling at the site of cosmetic fillers, 8 reports of pernio/chilblains, 10 reports of varicella zoster, 4 reports of herpes simplex flares, 4 pityriasis rosea–like reactions, and 4 rashes in infants of vaccinated breastfeeding mothers.

The study noted that “patients responded well to topical corticosteroids, oral antihistamines, and/or pain-relieving medications. These reactions resolved after a median of 3-4 days.”

It’s important to understand that none of the patients developed anaphylaxis after the second dose even if they’d had a reaction to the first dose, Dr. Freeman said. “But I should point out that we’re talking about reactions that have started more than 4 hours after the vaccine. If a rash such as a urticaria specifically starts within 4 hours of vaccination, that’s in a different category. Those are considered more immediate allergic reactions, and those patients need to be seen by allergy before a second dose.”

Dr. Freeman added that “it’s really interesting to think about how our bodies are really reacting to the vaccine in a way that’s mimicking our body’s reactions to COVID-19.” For example, some patients who got vaccinated developed chilblains similar to the “COVID toes” described in infected patients, apparently as part of the body’s immune response to the virus. “We’ve seen this in patients who actually had COVID and had prior COVID toes and then actually got a flare with their vaccine. And then we’ve also seen it in patients who never had COVID.”

In regard to general advice for patients, she said, “I do still encourage my patients who previously had COVID to go ahead and get the vaccine even if they had a skin manifestation with COVID.”

Shari Lipner, MD, PhD, associate professor of clinical dermatology, Weill Cornell Medicine, New York, said she has have seen only a handful of cases of delayed large local reactions and local injection site reactions after COVID-19 vaccination. “I have seen a significant number of cases of acute urticaria following the first and second doses,” she said in an interview. “However, it is important to keep in mind that we cannot determine cause and effect for the cases of acute urticaria. They may or may not be vaccine related.”

Fortunately, none of the adverse effects she’s seen have been severe. “It is important that dermatologists educate the public and their patients that most people do not develop any skin reaction in response to the vaccine,” she said. In the minority who do, “reactions tend to be mild and are not life-threatening. Many of these skin reactions resolve on their own without treatment.”

She added that “patients with pernio/chilblains or herpes zoster following vaccination should be referred by a board-certified dermatologist for prompt treatment and to avoid sequelae.”


 

‘COVID vaccine arm’

Delayed local reactions to the Moderna vaccine were also described in a report published online on May 12, 2021, in JAMA Dermatology, after the AAD meeting, in 16 patients referred to the Yale New Haven (Conn.) Hospital Dermatology service who experienced delayed localized cutaneous hypersensitivity reactions a median of 7 days after receiving the vaccine (range, 2-12 days), from Jan. 20 to Feb. 12, 2021. No such cases were reported in Pfizer vaccine recipients.

Of the 16 patients, whose median age was 38 years and who were mostly women, 15 developed the reaction after the first dose, described as “pruritic and variably painful erythematous reactions near the injection site,” which lasted a median of 5 days (range, 1-21 days). After the second dose, 12 of the 16 patients developed injection-site reactions (including one patient who had no reaction after dose 1), a median of 2 days after the vaccine was administered (range, 0-5 days). Histologic results of a biopsy in one patient with a reaction to the second dose “ demonstrated mild predominantly perivascular and focal interstitial mixed infiltrate with lymphocytes and eosinophils consistent with a dermal hypersensitivity reaction,” wrote Alicia J. Little, MD, PhD, of the department of dermatology, Yale University, New Haven, and coauthors.

Compared with immediate hypersensitivity reactions, occurring within 4 hours of vaccination, such as anaphylaxis and urticaria, they concluded that “these delayed localized hypersensitivity reactions are not a contraindication to subsequent vaccination,” and they proposed that they be named “COVID vaccine arm.”

Dr. Freeman reported no disclosures. Dr. Lipner also had no relevant disclosures. Dr. Little reported receiving a grant from the National Center for Advancing Translational Science and a Women’s Health Career Development Award from the Dermatology Foundation while the study was conducted; another author reported equity in Johnson & Johnson in his spouse’s retirement fund outside the submitted work.
 

Genital skin exams in girls must be conducted with special care and alertness for signs of abuse, a dermatologist told colleagues at the American Academy of Dermatology Virtual Meeting Experience.

“One in four adult women report being childhood victims of sexual abuse, which is just a staggering number. This is an opportunity for us to identify these patients early and give them the terminology to be able to report what is happening to them,” said pediatric dermatologist Kalyani Marathe, MD, MPH, director of the division of dermatology at Cincinnati Children’s Hospital. “We also have the chance to give them a sense of agency over their bodies.”

Dr. Marathe offered the following recommendations when performing a genital skin exam:

• Make sure a “chaperone” is present. “Chaperones are a must when you’re examining children and teens,” she said. “Ask whom they prefer. For prepubertal children, you’re going to usually use the parent who’s there with them. If the parent is their father, they might ask him to step behind the curtain, in which case you can bring over your nurse or medical assistant.” Teens may ask either parent to step out of the room, she said. In that case, a nurse, medical assistant, resident, or trainee can fill in. “If you have male residents or trainees with you and the patient really does not want to be examined by a male, honor their request. Do not force them.”
• Explain why the exam is being performed. Make sure the patient understands why she is being seen, Dr. Marathe advised. For example, say something like “your pediatrician told us that you have an itchy area” or “your mom told us that there’s some loss of color in that area, that you’re having a problem there.” She added that it’s helpful to explain the type of doctor you are, with a comment such as the following: “We’re examining you because we’re doctors who specialize in skin. ... We want to help you feel better and make sure that your skin heals and is healthy.”
• Ask both the child and the parent for permission to perform the exam. While this may seem trivial, “it’s very, very important in setting the right tone for the encounter,” she said. “If the child says yes, we turn to the mom and say: ‘Mom, is it okay for us to do this exam today?’ You can see visible relief on the part of the parent, and as the parent relaxes, the child relaxes. Just saying those few things really makes the encounter so much smoother.” However, “if they say no, you have to honor the response. ... You say: ‘Okay, we’re not going to do the exam today,” and see the patient in a few weeks. If it’s urgent, an exam under anesthesia may be an option, she added.
• Talk to the child about the terms they use for private parts. It can be helpful to ask: “Do you have any terms for your private area?” According to Dr. Marathe, “this is a good chance to educate them on the terms vulva and vagina since they may be using other terminology. Making sure that they have the correct terms will actually help patients identify and report abuse earlier.” Dr. Marathe recalled that a colleague had a patient who’d been calling her private area “pound cake” and had been “reporting to her teacher that someone had been touching her ‘pound cake.’ Her teacher did not know what she meant by that, and this led to a great delay in her childhood abuse being reported.”
• Talk about what will happen during the exam. “I like to show them any instruments that we’re going to be using,” Dr. Marathe said. “If we’re using a flashlight, for example, I like to show them a picture [of a flashlight] or show them that flashlight. If we’re using a camera to do digital photography, show them that. If we’re going to be using a Q-tip or a swab to demonstrate anything or to take a culture, I like to show them that beforehand to make sure that they know what we’re doing.” In regard to photography, “make sure the parent and child know where the photos are going to go, who’s going to see them, what are they going to be used for. If they’re going to be used for educational purposes, make sure they have given explicit permission for that and they know they’ll be deidentified.”
• Make it clear that the exam won’t be painful. It’s important to put both the patient and the parent at ease on this front, Dr. Marathe said. “A lot of parents are concerned that we’re going to do a speculum exam in their prepubertal child. So make sure that it’s clarified ahead of time that we’re not going to be doing a speculum exam.”

Commenting on this topic, Tor Shwayder, MD, a pediatric dermatologist at Henry Ford Health System, Detroit, urged colleagues to take action if they feel suspicious about a possible sign of child abuse, even if they’re far from certain that anything is wrong. “Don’t ignore those feelings in the back of the brain,” he said in an interview.

Most states have child-abuse hotlines for medical professionals, and major hospitals will have child-abuse teams, Dr. Shwayder said. He urged dermatologists to take advantage of these resources when appropriate. “The professionals on the other side of the 800 number or at the hospital will help you. You don’t have to decide immediately whether this is child abuse. You just need to have a suspicion.”

Dr. Marathe and Dr. Shwayder report no disclosures.

Genital skin exams in girls must be conducted with special care and alertness for signs of abuse, a dermatologist told colleagues at the American Academy of Dermatology Virtual Meeting Experience.

“One in four adult women report being childhood victims of sexual abuse, which is just a staggering number. This is an opportunity for us to identify these patients early and give them the terminology to be able to report what is happening to them,” said pediatric dermatologist Kalyani Marathe, MD, MPH, director of the division of dermatology at Cincinnati Children’s Hospital. “We also have the chance to give them a sense of agency over their bodies.”

Dr. Marathe offered the following recommendations when performing a genital skin exam:

• Make sure a “chaperone” is present. “Chaperones are a must when you’re examining children and teens,” she said. “Ask whom they prefer. For prepubertal children, you’re going to usually use the parent who’s there with them. If the parent is their father, they might ask him to step behind the curtain, in which case you can bring over your nurse or medical assistant.” Teens may ask either parent to step out of the room, she said. In that case, a nurse, medical assistant, resident, or trainee can fill in. “If you have male residents or trainees with you and the patient really does not want to be examined by a male, honor their request. Do not force them.”
• Explain why the exam is being performed. Make sure the patient understands why she is being seen, Dr. Marathe advised. For example, say something like “your pediatrician told us that you have an itchy area” or “your mom told us that there’s some loss of color in that area, that you’re having a problem there.” She added that it’s helpful to explain the type of doctor you are, with a comment such as the following: “We’re examining you because we’re doctors who specialize in skin. ... We want to help you feel better and make sure that your skin heals and is healthy.”
• Ask both the child and the parent for permission to perform the exam. While this may seem trivial, “it’s very, very important in setting the right tone for the encounter,” she said. “If the child says yes, we turn to the mom and say: ‘Mom, is it okay for us to do this exam today?’ You can see visible relief on the part of the parent, and as the parent relaxes, the child relaxes. Just saying those few things really makes the encounter so much smoother.” However, “if they say no, you have to honor the response. ... You say: ‘Okay, we’re not going to do the exam today,” and see the patient in a few weeks. If it’s urgent, an exam under anesthesia may be an option, she added.
• Talk to the child about the terms they use for private parts. It can be helpful to ask: “Do you have any terms for your private area?” According to Dr. Marathe, “this is a good chance to educate them on the terms vulva and vagina since they may be using other terminology. Making sure that they have the correct terms will actually help patients identify and report abuse earlier.” Dr. Marathe recalled that a colleague had a patient who’d been calling her private area “pound cake” and had been “reporting to her teacher that someone had been touching her ‘pound cake.’ Her teacher did not know what she meant by that, and this led to a great delay in her childhood abuse being reported.”
• Talk about what will happen during the exam. “I like to show them any instruments that we’re going to be using,” Dr. Marathe said. “If we’re using a flashlight, for example, I like to show them a picture [of a flashlight] or show them that flashlight. If we’re using a camera to do digital photography, show them that. If we’re going to be using a Q-tip or a swab to demonstrate anything or to take a culture, I like to show them that beforehand to make sure that they know what we’re doing.” In regard to photography, “make sure the parent and child know where the photos are going to go, who’s going to see them, what are they going to be used for. If they’re going to be used for educational purposes, make sure they have given explicit permission for that and they know they’ll be deidentified.”
• Make it clear that the exam won’t be painful. It’s important to put both the patient and the parent at ease on this front, Dr. Marathe said. “A lot of parents are concerned that we’re going to do a speculum exam in their prepubertal child. So make sure that it’s clarified ahead of time that we’re not going to be doing a speculum exam.”

Commenting on this topic, Tor Shwayder, MD, a pediatric dermatologist at Henry Ford Health System, Detroit, urged colleagues to take action if they feel suspicious about a possible sign of child abuse, even if they’re far from certain that anything is wrong. “Don’t ignore those feelings in the back of the brain,” he said in an interview.

Most states have child-abuse hotlines for medical professionals, and major hospitals will have child-abuse teams, Dr. Shwayder said. He urged dermatologists to take advantage of these resources when appropriate. “The professionals on the other side of the 800 number or at the hospital will help you. You don’t have to decide immediately whether this is child abuse. You just need to have a suspicion.”

Dr. Marathe and Dr. Shwayder report no disclosures.

Genital skin exams in girls must be conducted with special care and alertness for signs of abuse, a dermatologist told colleagues at the American Academy of Dermatology Virtual Meeting Experience.

“One in four adult women report being childhood victims of sexual abuse, which is just a staggering number. This is an opportunity for us to identify these patients early and give them the terminology to be able to report what is happening to them,” said pediatric dermatologist Kalyani Marathe, MD, MPH, director of the division of dermatology at Cincinnati Children’s Hospital. “We also have the chance to give them a sense of agency over their bodies.”

Dr. Marathe offered the following recommendations when performing a genital skin exam:

• Make sure a “chaperone” is present. “Chaperones are a must when you’re examining children and teens,” she said. “Ask whom they prefer. For prepubertal children, you’re going to usually use the parent who’s there with them. If the parent is their father, they might ask him to step behind the curtain, in which case you can bring over your nurse or medical assistant.” Teens may ask either parent to step out of the room, she said. In that case, a nurse, medical assistant, resident, or trainee can fill in. “If you have male residents or trainees with you and the patient really does not want to be examined by a male, honor their request. Do not force them.”
• Explain why the exam is being performed. Make sure the patient understands why she is being seen, Dr. Marathe advised. For example, say something like “your pediatrician told us that you have an itchy area” or “your mom told us that there’s some loss of color in that area, that you’re having a problem there.” She added that it’s helpful to explain the type of doctor you are, with a comment such as the following: “We’re examining you because we’re doctors who specialize in skin. ... We want to help you feel better and make sure that your skin heals and is healthy.”
• Ask both the child and the parent for permission to perform the exam. While this may seem trivial, “it’s very, very important in setting the right tone for the encounter,” she said. “If the child says yes, we turn to the mom and say: ‘Mom, is it okay for us to do this exam today?’ You can see visible relief on the part of the parent, and as the parent relaxes, the child relaxes. Just saying those few things really makes the encounter so much smoother.” However, “if they say no, you have to honor the response. ... You say: ‘Okay, we’re not going to do the exam today,” and see the patient in a few weeks. If it’s urgent, an exam under anesthesia may be an option, she added.
• Talk to the child about the terms they use for private parts. It can be helpful to ask: “Do you have any terms for your private area?” According to Dr. Marathe, “this is a good chance to educate them on the terms vulva and vagina since they may be using other terminology. Making sure that they have the correct terms will actually help patients identify and report abuse earlier.” Dr. Marathe recalled that a colleague had a patient who’d been calling her private area “pound cake” and had been “reporting to her teacher that someone had been touching her ‘pound cake.’ Her teacher did not know what she meant by that, and this led to a great delay in her childhood abuse being reported.”
• Talk about what will happen during the exam. “I like to show them any instruments that we’re going to be using,” Dr. Marathe said. “If we’re using a flashlight, for example, I like to show them a picture [of a flashlight] or show them that flashlight. If we’re using a camera to do digital photography, show them that. If we’re going to be using a Q-tip or a swab to demonstrate anything or to take a culture, I like to show them that beforehand to make sure that they know what we’re doing.” In regard to photography, “make sure the parent and child know where the photos are going to go, who’s going to see them, what are they going to be used for. If they’re going to be used for educational purposes, make sure they have given explicit permission for that and they know they’ll be deidentified.”
• Make it clear that the exam won’t be painful. It’s important to put both the patient and the parent at ease on this front, Dr. Marathe said. “A lot of parents are concerned that we’re going to do a speculum exam in their prepubertal child. So make sure that it’s clarified ahead of time that we’re not going to be doing a speculum exam.”

Commenting on this topic, Tor Shwayder, MD, a pediatric dermatologist at Henry Ford Health System, Detroit, urged colleagues to take action if they feel suspicious about a possible sign of child abuse, even if they’re far from certain that anything is wrong. “Don’t ignore those feelings in the back of the brain,” he said in an interview.

Most states have child-abuse hotlines for medical professionals, and major hospitals will have child-abuse teams, Dr. Shwayder said. He urged dermatologists to take advantage of these resources when appropriate. “The professionals on the other side of the 800 number or at the hospital will help you. You don’t have to decide immediately whether this is child abuse. You just need to have a suspicion.”

Dr. Marathe and Dr. Shwayder report no disclosures.

Women had about a twofold higher risk than that of men of developing dermatologic adverse events while taking immune checkpoint inhibitors for metastatic melanoma in a review of 235 patients at Dana Farber Cancer Center, Boston.
 

Overall, 62.4% of the 93 women in the review and 48.6% of the 142 men experienced confirmed skin reactions, for an odds ratio (OR) of 2.11 for women compared with men (P = .01).

“Clinicians should consider these results in counseling female patients regarding an elevated risk of dermatologic adverse events” when taking checkpoint inhibitors, said investigators led by Harvard University medical student Jordan Said, who presented the results at the American Academy of Dermatology Virtual Meeting Experience.

Autoimmune-like adverse events are common with checkpoint inhibitors. Dermatologic side effects occur in about half of people receiving monotherapy and more than that among patients receiving combination therapy.

Skin reactions can include psoriasiform dermatitis, lichenoid reactions, vitiligo, and bullous pemphigoid and may require hospitalization and prolonged steroid treatment.

Not much is known about risk factors for these reactions. A higher incidence among women has been previously reported. A 2019 study found a higher risk for pneumonitis and endocrinopathy, including hypophysitis, among women who underwent treatment for non–small cell lung cancer or metastatic melanoma.

The 2019 study found that the risk was higher among premenopausal women than postmenopausal women, which led some to suggest that estrogen may play a role.

The results of the Dana Farber review argue against that notion. In their review, the investigators found that the risk was similarly elevated among the 27 premenopausal women (OR, 1.97; P = .40) and the 66 postmenopausal women (OR, 2.17, P = .05). In the study, women who were aged 52 years or older at the start of treatment were considered to be postmenopausal.

“This suggests that factors beyond sex hormones are likely contributory” to the difference in risk between men and women. It’s known that women are at higher risk for autoimmune disease overall, which might be related to the increased odds of autoimmune-like reactions, and it may be that sex-related differences in innate and adoptive immunity are at work, Mr. Said noted.

When asked for comment, Douglas Johnson, MD, assistant professor of hematology/oncology at Vanderbilt University, Nashville, Tenn., said that although some studies have reported a greater risk for side effects among women, others have not. “Additional research is needed to determine the interactions between sex and effects of immune checkpoint inhibitors, as well as many other possible triggers of immune-related adverse events,” he said.

“Continued work in this area will be so important to help determine how to best counsel women and to ensure early recognition and intervention for dermatologic side effects,” said Bernice Kwong, MD, director of the Supportive Dermato-Oncology Program at Stanford (Calif.) University.

The patients in the review were treated from 2011 to 2016 and underwent at least monthly evaluations by their medical teams. They were taking either nivolumab, pembrolizumab, or ipilimumab or a nivolumab/ipilimumab combination.

The median age of the men in the study was 65 years; the median age of women was 60 years. Almost 98% of the participants were White. The majority received one to three infusions, most commonly with pembrolizumab monotherapy.

No funding for the study was reported. Mr. Said has disclosed no relevant financial relationships.

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

Women had about a twofold higher risk than that of men of developing dermatologic adverse events while taking immune checkpoint inhibitors for metastatic melanoma in a review of 235 patients at Dana Farber Cancer Center, Boston.
 

Overall, 62.4% of the 93 women in the review and 48.6% of the 142 men experienced confirmed skin reactions, for an odds ratio (OR) of 2.11 for women compared with men (P = .01).

“Clinicians should consider these results in counseling female patients regarding an elevated risk of dermatologic adverse events” when taking checkpoint inhibitors, said investigators led by Harvard University medical student Jordan Said, who presented the results at the American Academy of Dermatology Virtual Meeting Experience.

Autoimmune-like adverse events are common with checkpoint inhibitors. Dermatologic side effects occur in about half of people receiving monotherapy and more than that among patients receiving combination therapy.

Skin reactions can include psoriasiform dermatitis, lichenoid reactions, vitiligo, and bullous pemphigoid and may require hospitalization and prolonged steroid treatment.

Not much is known about risk factors for these reactions. A higher incidence among women has been previously reported. A 2019 study found a higher risk for pneumonitis and endocrinopathy, including hypophysitis, among women who underwent treatment for non–small cell lung cancer or metastatic melanoma.

The 2019 study found that the risk was higher among premenopausal women than postmenopausal women, which led some to suggest that estrogen may play a role.

The results of the Dana Farber review argue against that notion. In their review, the investigators found that the risk was similarly elevated among the 27 premenopausal women (OR, 1.97; P = .40) and the 66 postmenopausal women (OR, 2.17, P = .05). In the study, women who were aged 52 years or older at the start of treatment were considered to be postmenopausal.

“This suggests that factors beyond sex hormones are likely contributory” to the difference in risk between men and women. It’s known that women are at higher risk for autoimmune disease overall, which might be related to the increased odds of autoimmune-like reactions, and it may be that sex-related differences in innate and adoptive immunity are at work, Mr. Said noted.

When asked for comment, Douglas Johnson, MD, assistant professor of hematology/oncology at Vanderbilt University, Nashville, Tenn., said that although some studies have reported a greater risk for side effects among women, others have not. “Additional research is needed to determine the interactions between sex and effects of immune checkpoint inhibitors, as well as many other possible triggers of immune-related adverse events,” he said.

“Continued work in this area will be so important to help determine how to best counsel women and to ensure early recognition and intervention for dermatologic side effects,” said Bernice Kwong, MD, director of the Supportive Dermato-Oncology Program at Stanford (Calif.) University.

The patients in the review were treated from 2011 to 2016 and underwent at least monthly evaluations by their medical teams. They were taking either nivolumab, pembrolizumab, or ipilimumab or a nivolumab/ipilimumab combination.

The median age of the men in the study was 65 years; the median age of women was 60 years. Almost 98% of the participants were White. The majority received one to three infusions, most commonly with pembrolizumab monotherapy.

No funding for the study was reported. Mr. Said has disclosed no relevant financial relationships.

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

Women had about a twofold higher risk than that of men of developing dermatologic adverse events while taking immune checkpoint inhibitors for metastatic melanoma in a review of 235 patients at Dana Farber Cancer Center, Boston.
 

Overall, 62.4% of the 93 women in the review and 48.6% of the 142 men experienced confirmed skin reactions, for an odds ratio (OR) of 2.11 for women compared with men (P = .01).

“Clinicians should consider these results in counseling female patients regarding an elevated risk of dermatologic adverse events” when taking checkpoint inhibitors, said investigators led by Harvard University medical student Jordan Said, who presented the results at the American Academy of Dermatology Virtual Meeting Experience.

Autoimmune-like adverse events are common with checkpoint inhibitors. Dermatologic side effects occur in about half of people receiving monotherapy and more than that among patients receiving combination therapy.

Skin reactions can include psoriasiform dermatitis, lichenoid reactions, vitiligo, and bullous pemphigoid and may require hospitalization and prolonged steroid treatment.

Not much is known about risk factors for these reactions. A higher incidence among women has been previously reported. A 2019 study found a higher risk for pneumonitis and endocrinopathy, including hypophysitis, among women who underwent treatment for non–small cell lung cancer or metastatic melanoma.

The 2019 study found that the risk was higher among premenopausal women than postmenopausal women, which led some to suggest that estrogen may play a role.

The results of the Dana Farber review argue against that notion. In their review, the investigators found that the risk was similarly elevated among the 27 premenopausal women (OR, 1.97; P = .40) and the 66 postmenopausal women (OR, 2.17, P = .05). In the study, women who were aged 52 years or older at the start of treatment were considered to be postmenopausal.

“This suggests that factors beyond sex hormones are likely contributory” to the difference in risk between men and women. It’s known that women are at higher risk for autoimmune disease overall, which might be related to the increased odds of autoimmune-like reactions, and it may be that sex-related differences in innate and adoptive immunity are at work, Mr. Said noted.

When asked for comment, Douglas Johnson, MD, assistant professor of hematology/oncology at Vanderbilt University, Nashville, Tenn., said that although some studies have reported a greater risk for side effects among women, others have not. “Additional research is needed to determine the interactions between sex and effects of immune checkpoint inhibitors, as well as many other possible triggers of immune-related adverse events,” he said.

“Continued work in this area will be so important to help determine how to best counsel women and to ensure early recognition and intervention for dermatologic side effects,” said Bernice Kwong, MD, director of the Supportive Dermato-Oncology Program at Stanford (Calif.) University.

The patients in the review were treated from 2011 to 2016 and underwent at least monthly evaluations by their medical teams. They were taking either nivolumab, pembrolizumab, or ipilimumab or a nivolumab/ipilimumab combination.

The median age of the men in the study was 65 years; the median age of women was 60 years. Almost 98% of the participants were White. The majority received one to three infusions, most commonly with pembrolizumab monotherapy.

No funding for the study was reported. Mr. Said has disclosed no relevant financial relationships.

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

In patients with newly diagnosed or relapsing pemphigus vulgaris, an update of the phase 2 BELIEVE study with the Bruton tyrosine kinase (BTK) inhibitor rilzabrutinib has raised hopes that the ongoing phase 3 trial will confirm that this drug is a breakthrough therapy, according to an investigator who presented the data at the American Academy of Dermatology Virtual Meeting Experience.

Among the highlights of the phase 2 data presented during a late-breaking research session was that a substantial minority of patients achieved a complete response within 12 weeks of starting treatment with rilzabrutinib. Treatment was associated with mostly mild and transient adverse events, according to Dedee F. Murrell, MD, director of dermatology, St. George Hospital, University of New South Wales, Sydney.

Many of the phase 2 results have been presented previously and the phase 3 trial, called PEGASUS, has now completed enrollment.

Focusing on part A of the BELIEVE study, Dr. Murrell reported that about one-third of the 27 patients enrolled had newly diagnosed pemphigus. The remaining patients had relapsing disease after a mean 8.9 years after diagnosis. The disease was judged moderate to severe in 59%. The daily oral dose of rilzabrutinib ranged from 400 mg to 600 mg twice daily.

For the primary endpoint of control of disease activity (CDA), meaning no formation of new lesions with diminishing activity of existing lesions, 52% had responded by week 4 and 70% had responded by week 12, which was the end of active treatment. Responses at both time points were comparable among patients with newly diagnosed disease (56% at week 4 and 67% at week 12) relapsing disease (50% and 72%, respectively), moderate disease severity at baseline (55% and 64%, respectively) and more severe disease (50% and 75%, respectively), Dr. Murrell noted.

“A complete response was achieved by 22% of patients at week 4 and nearly 30% by the end of the study,” she said.

These response rates were reflected in the Pemphigus Disease Area Index (PDAI) and the Autoimmune Bullous Disease Quality of Life (ABQOL) Score. From a baseline score of 20, the PDAI fell to 10 at 4 weeks and then to 6 at 12 weeks in the newly diagnosed cohort. In the relapsing cohort, the score fell from a baseline of 18 to 13 at week 4 and then to 7 at week 12.

“The improvement corresponded to a reduction in steroid doses,” Dr. Murrell reported. By the end of the study, the mean daily dose of corticosteroids fell to 10 mg from a baseline of 20 mg. In a 12-week follow-up, corticosteroid doses rose slowly and did not reach baseline levels until about eight weeks after rilzabrutinib was discontinued.

The ABQOL scores fell most rapidly in the newly diagnosed cohort. By week 12, there was about a 6.6-point reduction. In the relapsing group, the score fell by 3.7 points from a similar baseline level. Both reductions are considered highly clinically meaningful, according to Dr. Murrell. At the end of the 12 weeks of follow-up after the drug was discontinued, ABQOL scores had increased but remained below the baseline.

Nausea was reported by 15% of patients, making it the most commonly reported adverse event. All cases were grade 1 severity. Three patients had grade 2 abdominal pain. The only grade 3 event in this series was a case of cellulitis in a patient who had developed steroid-induced diabetes mellitus. With treatment, the cellulitis resolved, and the patient completed the study.

Data from part B of the BELIEVE study, which was similarly designed and enrolled 15 patients with newly diagnosed or relapsing pemphigus vulgaris, was not updated by Dr. Murrell at the meeting, but these data have been presented before and showed similar results, including achievement of CDA in the majority of patients accompanied by a reduction in corticosteroid doses.

“In summary, rilzabrutinib produced a rapid clinical effect with an overall favorable benefit-to-risk profile,” said Dr. Murrell, who reiterated that the improvement in quality of life underscored meaningful activity.

Three BTK inhibitors, ibrutinib, acalabrutinib, and zanubrutinib, have been approved for the treatment of hematologic malignancies. These have also been well tolerated. The shared mechanism of action of these drugs is a reduction in B-cell activity achieved by blocking BTK enzyme signaling. The autoimmune activity of pemphigus vulgaris is at least partially mediated by B cells.

“Rilzabrutinib is the first BTK inhibitor tried in pemphigus,” said Dr. Murrell, who cited evidence that pemphigus is at least partially mediated by B-cell activity. The proof-of-concept phase 2 study has increased expectations for the phase 3 PEGASUS trial, which is scheduled for completion in about 1 year, she said.

Dr. Murrell reports financial relationship with multiple pharmaceutical companies, including Principia Biopharma, a Sanofi subsidiary that is developing rilzabrutinib and sponsored the BELIEVE trial.


 

In patients with newly diagnosed or relapsing pemphigus vulgaris, an update of the phase 2 BELIEVE study with the Bruton tyrosine kinase (BTK) inhibitor rilzabrutinib has raised hopes that the ongoing phase 3 trial will confirm that this drug is a breakthrough therapy, according to an investigator who presented the data at the American Academy of Dermatology Virtual Meeting Experience.

Among the highlights of the phase 2 data presented during a late-breaking research session was that a substantial minority of patients achieved a complete response within 12 weeks of starting treatment with rilzabrutinib. Treatment was associated with mostly mild and transient adverse events, according to Dedee F. Murrell, MD, director of dermatology, St. George Hospital, University of New South Wales, Sydney.

Many of the phase 2 results have been presented previously and the phase 3 trial, called PEGASUS, has now completed enrollment.

Focusing on part A of the BELIEVE study, Dr. Murrell reported that about one-third of the 27 patients enrolled had newly diagnosed pemphigus. The remaining patients had relapsing disease after a mean 8.9 years after diagnosis. The disease was judged moderate to severe in 59%. The daily oral dose of rilzabrutinib ranged from 400 mg to 600 mg twice daily.

For the primary endpoint of control of disease activity (CDA), meaning no formation of new lesions with diminishing activity of existing lesions, 52% had responded by week 4 and 70% had responded by week 12, which was the end of active treatment. Responses at both time points were comparable among patients with newly diagnosed disease (56% at week 4 and 67% at week 12) relapsing disease (50% and 72%, respectively), moderate disease severity at baseline (55% and 64%, respectively) and more severe disease (50% and 75%, respectively), Dr. Murrell noted.

“A complete response was achieved by 22% of patients at week 4 and nearly 30% by the end of the study,” she said.

These response rates were reflected in the Pemphigus Disease Area Index (PDAI) and the Autoimmune Bullous Disease Quality of Life (ABQOL) Score. From a baseline score of 20, the PDAI fell to 10 at 4 weeks and then to 6 at 12 weeks in the newly diagnosed cohort. In the relapsing cohort, the score fell from a baseline of 18 to 13 at week 4 and then to 7 at week 12.

“The improvement corresponded to a reduction in steroid doses,” Dr. Murrell reported. By the end of the study, the mean daily dose of corticosteroids fell to 10 mg from a baseline of 20 mg. In a 12-week follow-up, corticosteroid doses rose slowly and did not reach baseline levels until about eight weeks after rilzabrutinib was discontinued.

The ABQOL scores fell most rapidly in the newly diagnosed cohort. By week 12, there was about a 6.6-point reduction. In the relapsing group, the score fell by 3.7 points from a similar baseline level. Both reductions are considered highly clinically meaningful, according to Dr. Murrell. At the end of the 12 weeks of follow-up after the drug was discontinued, ABQOL scores had increased but remained below the baseline.

Nausea was reported by 15% of patients, making it the most commonly reported adverse event. All cases were grade 1 severity. Three patients had grade 2 abdominal pain. The only grade 3 event in this series was a case of cellulitis in a patient who had developed steroid-induced diabetes mellitus. With treatment, the cellulitis resolved, and the patient completed the study.

Data from part B of the BELIEVE study, which was similarly designed and enrolled 15 patients with newly diagnosed or relapsing pemphigus vulgaris, was not updated by Dr. Murrell at the meeting, but these data have been presented before and showed similar results, including achievement of CDA in the majority of patients accompanied by a reduction in corticosteroid doses.

“In summary, rilzabrutinib produced a rapid clinical effect with an overall favorable benefit-to-risk profile,” said Dr. Murrell, who reiterated that the improvement in quality of life underscored meaningful activity.

Three BTK inhibitors, ibrutinib, acalabrutinib, and zanubrutinib, have been approved for the treatment of hematologic malignancies. These have also been well tolerated. The shared mechanism of action of these drugs is a reduction in B-cell activity achieved by blocking BTK enzyme signaling. The autoimmune activity of pemphigus vulgaris is at least partially mediated by B cells.

“Rilzabrutinib is the first BTK inhibitor tried in pemphigus,” said Dr. Murrell, who cited evidence that pemphigus is at least partially mediated by B-cell activity. The proof-of-concept phase 2 study has increased expectations for the phase 3 PEGASUS trial, which is scheduled for completion in about 1 year, she said.

Dr. Murrell reports financial relationship with multiple pharmaceutical companies, including Principia Biopharma, a Sanofi subsidiary that is developing rilzabrutinib and sponsored the BELIEVE trial.


 

In patients with newly diagnosed or relapsing pemphigus vulgaris, an update of the phase 2 BELIEVE study with the Bruton tyrosine kinase (BTK) inhibitor rilzabrutinib has raised hopes that the ongoing phase 3 trial will confirm that this drug is a breakthrough therapy, according to an investigator who presented the data at the American Academy of Dermatology Virtual Meeting Experience.

Among the highlights of the phase 2 data presented during a late-breaking research session was that a substantial minority of patients achieved a complete response within 12 weeks of starting treatment with rilzabrutinib. Treatment was associated with mostly mild and transient adverse events, according to Dedee F. Murrell, MD, director of dermatology, St. George Hospital, University of New South Wales, Sydney.

Many of the phase 2 results have been presented previously and the phase 3 trial, called PEGASUS, has now completed enrollment.

Focusing on part A of the BELIEVE study, Dr. Murrell reported that about one-third of the 27 patients enrolled had newly diagnosed pemphigus. The remaining patients had relapsing disease after a mean 8.9 years after diagnosis. The disease was judged moderate to severe in 59%. The daily oral dose of rilzabrutinib ranged from 400 mg to 600 mg twice daily.

For the primary endpoint of control of disease activity (CDA), meaning no formation of new lesions with diminishing activity of existing lesions, 52% had responded by week 4 and 70% had responded by week 12, which was the end of active treatment. Responses at both time points were comparable among patients with newly diagnosed disease (56% at week 4 and 67% at week 12) relapsing disease (50% and 72%, respectively), moderate disease severity at baseline (55% and 64%, respectively) and more severe disease (50% and 75%, respectively), Dr. Murrell noted.

“A complete response was achieved by 22% of patients at week 4 and nearly 30% by the end of the study,” she said.

These response rates were reflected in the Pemphigus Disease Area Index (PDAI) and the Autoimmune Bullous Disease Quality of Life (ABQOL) Score. From a baseline score of 20, the PDAI fell to 10 at 4 weeks and then to 6 at 12 weeks in the newly diagnosed cohort. In the relapsing cohort, the score fell from a baseline of 18 to 13 at week 4 and then to 7 at week 12.

“The improvement corresponded to a reduction in steroid doses,” Dr. Murrell reported. By the end of the study, the mean daily dose of corticosteroids fell to 10 mg from a baseline of 20 mg. In a 12-week follow-up, corticosteroid doses rose slowly and did not reach baseline levels until about eight weeks after rilzabrutinib was discontinued.

The ABQOL scores fell most rapidly in the newly diagnosed cohort. By week 12, there was about a 6.6-point reduction. In the relapsing group, the score fell by 3.7 points from a similar baseline level. Both reductions are considered highly clinically meaningful, according to Dr. Murrell. At the end of the 12 weeks of follow-up after the drug was discontinued, ABQOL scores had increased but remained below the baseline.

Nausea was reported by 15% of patients, making it the most commonly reported adverse event. All cases were grade 1 severity. Three patients had grade 2 abdominal pain. The only grade 3 event in this series was a case of cellulitis in a patient who had developed steroid-induced diabetes mellitus. With treatment, the cellulitis resolved, and the patient completed the study.

Data from part B of the BELIEVE study, which was similarly designed and enrolled 15 patients with newly diagnosed or relapsing pemphigus vulgaris, was not updated by Dr. Murrell at the meeting, but these data have been presented before and showed similar results, including achievement of CDA in the majority of patients accompanied by a reduction in corticosteroid doses.

“In summary, rilzabrutinib produced a rapid clinical effect with an overall favorable benefit-to-risk profile,” said Dr. Murrell, who reiterated that the improvement in quality of life underscored meaningful activity.

Three BTK inhibitors, ibrutinib, acalabrutinib, and zanubrutinib, have been approved for the treatment of hematologic malignancies. These have also been well tolerated. The shared mechanism of action of these drugs is a reduction in B-cell activity achieved by blocking BTK enzyme signaling. The autoimmune activity of pemphigus vulgaris is at least partially mediated by B cells.

“Rilzabrutinib is the first BTK inhibitor tried in pemphigus,” said Dr. Murrell, who cited evidence that pemphigus is at least partially mediated by B-cell activity. The proof-of-concept phase 2 study has increased expectations for the phase 3 PEGASUS trial, which is scheduled for completion in about 1 year, she said.

Dr. Murrell reports financial relationship with multiple pharmaceutical companies, including Principia Biopharma, a Sanofi subsidiary that is developing rilzabrutinib and sponsored the BELIEVE trial.


 

In the analysis of images for detecting potential pathology, artificial intelligence (AI) is showing enormous promise across multiple fields of medicine. But the technology in dermatology is bound to fail in skin of color if training does not specifically address these skin types, according to Adewole S. Adamson, MD, who outlined this issue at the American Academy of Dermatology Virtual Meeting Experience.

“Machine learning algorithms are only as good as the inputs through which they learn. Without representation from individuals with skin of color, we are at risk of creating a new source of racial disparity in patient care,” Dr. Adamson, assistant professor in the division of dermatology, department of internal medicine, University of Texas at Austin, said at the meeting.

Diagnostic algorithms using AI are typically based on deep learning, a subset of machine learning that depends on artificial neural networks. In the case of image processing, neural networks can “learn” to recognize objects, faces, or, in the realm of health care, disease, from exposure to multiple images.

There are many other variables that affect the accuracy of deep learning for diagnostic algorithms, including the depth of the layering through which the process distills multiple inputs of information, but the number of inputs is critical. In the case of skin lesions, machines cannot learn to recognize features of different skin types without exposure.

“There are studies demonstrating that dermatologists can be outperformed for detection of skin cancers by AI, so this is going to be an increasingly powerful tool,” Dr. Adamson said. The problem is that “there has been very little representation in darker skin types” in the algorithms developed so far.

The risk is that AI will exacerbate an existing problem. Skin cancer in darker skin is less common but already underdiagnosed, independent of AI. Per 100,000 males in the United States, the rate of melanoma is about 30-fold greater in White men than in Black men (33.0 vs. 1.0). Among females, the racial difference is smaller but still enormous (20.2 vs. 1.2 per 100,000 females), according to U.S. data.

For the low representation of darker skin in studies so far with AI, “one of the arguments is that skin cancer is not a big deal in darker skin types,” Dr. Adamson said.

It might be the other way around. The relative infrequency with which skin cancer occurs in the Black population in the United States might explain a low level of suspicion and ultimately delays in diagnosis, which, in turn, leads to worse outcomes. According to one analysis drawn from the Surveillance, Epidemiology and End-Result (SEER) database (1998-2011), the proportion of patients with regionally advanced or distant disease was nearly twice as great (11.6% vs. 6.0%; P < .05) in Black patients, relative to White patients.

Not surprisingly, given the importance of early diagnosis of cancers overall and skin cancer specifically, the mean survival for malignant melanoma in Black patients was almost 4 years lower than in White patients (10.8 vs. 14.6 years; P < .001) for nodular melanoma, the same study found.

In humans, bias is reasonably attributed in many cases to judgments made on a small sample size. The problem in AI is analogous. Dr. Adamson, who has published research on the potential for machine learning to contribute to health care disparities in dermatology, cited work done by Joy Buolamwini, a graduate researcher in the media lab at the Massachusetts Institute of Technology. In one study she conducted, the rate of AI facial recognition failure was 1% in White males, 7% in White females, 12% in skin-of-color males, and 35% in skin-of-color females. Fewer inputs of skin of color is the likely explanation, Dr. Adamson said.

The potential for racial bias from AI in the diagnosis of disease increases and becomes more complex when inputs beyond imaging, such as past medical history, are included. Dr. Adamson warned of the potential for “bias to creep in” when there is failure to account for societal, cultural, or other differences that distinguish one patient group from another. However, for skin cancer or other diseases based on images alone, he said there are solutions.

“We are in the early days, and there is time to change this,” Dr. Adamson said, referring to the low representation of skin of color in AI training sets. In addition to including more skin types to train recognition, creating AI algorithms specifically for dark skin is another potential approach.

However, his key point was the importance of recognizing the need for solutions.

“AI is the future, but we must apply the same rigor to AI as to other medical interventions to ensure that the technology is not applied in a biased fashion,” he said.

Susan M. Swetter, MD, professor of dermatology and director of the pigmented lesion and melanoma program at Stanford (Calif.) University Medical Center and Cancer Institute, agreed. As someone who has been following the progress of AI in the diagnosis of skin cancer, Dr. Swetter recognizes the potential for this technology to increase diagnostic efficiency and accuracy, but she also called for studies specific to skin of color.

In the analysis of images for detecting potential pathology, artificial intelligence (AI) is showing enormous promise across multiple fields of medicine. But the technology in dermatology is bound to fail in skin of color if training does not specifically address these skin types, according to Adewole S. Adamson, MD, who outlined this issue at the American Academy of Dermatology Virtual Meeting Experience.

“Machine learning algorithms are only as good as the inputs through which they learn. Without representation from individuals with skin of color, we are at risk of creating a new source of racial disparity in patient care,” Dr. Adamson, assistant professor in the division of dermatology, department of internal medicine, University of Texas at Austin, said at the meeting.

Diagnostic algorithms using AI are typically based on deep learning, a subset of machine learning that depends on artificial neural networks. In the case of image processing, neural networks can “learn” to recognize objects, faces, or, in the realm of health care, disease, from exposure to multiple images.

There are many other variables that affect the accuracy of deep learning for diagnostic algorithms, including the depth of the layering through which the process distills multiple inputs of information, but the number of inputs is critical. In the case of skin lesions, machines cannot learn to recognize features of different skin types without exposure.

“There are studies demonstrating that dermatologists can be outperformed for detection of skin cancers by AI, so this is going to be an increasingly powerful tool,” Dr. Adamson said. The problem is that “there has been very little representation in darker skin types” in the algorithms developed so far.

The risk is that AI will exacerbate an existing problem. Skin cancer in darker skin is less common but already underdiagnosed, independent of AI. Per 100,000 males in the United States, the rate of melanoma is about 30-fold greater in White men than in Black men (33.0 vs. 1.0). Among females, the racial difference is smaller but still enormous (20.2 vs. 1.2 per 100,000 females), according to U.S. data.

For the low representation of darker skin in studies so far with AI, “one of the arguments is that skin cancer is not a big deal in darker skin types,” Dr. Adamson said.

It might be the other way around. The relative infrequency with which skin cancer occurs in the Black population in the United States might explain a low level of suspicion and ultimately delays in diagnosis, which, in turn, leads to worse outcomes. According to one analysis drawn from the Surveillance, Epidemiology and End-Result (SEER) database (1998-2011), the proportion of patients with regionally advanced or distant disease was nearly twice as great (11.6% vs. 6.0%; P < .05) in Black patients, relative to White patients.

Not surprisingly, given the importance of early diagnosis of cancers overall and skin cancer specifically, the mean survival for malignant melanoma in Black patients was almost 4 years lower than in White patients (10.8 vs. 14.6 years; P < .001) for nodular melanoma, the same study found.

In humans, bias is reasonably attributed in many cases to judgments made on a small sample size. The problem in AI is analogous. Dr. Adamson, who has published research on the potential for machine learning to contribute to health care disparities in dermatology, cited work done by Joy Buolamwini, a graduate researcher in the media lab at the Massachusetts Institute of Technology. In one study she conducted, the rate of AI facial recognition failure was 1% in White males, 7% in White females, 12% in skin-of-color males, and 35% in skin-of-color females. Fewer inputs of skin of color is the likely explanation, Dr. Adamson said.

The potential for racial bias from AI in the diagnosis of disease increases and becomes more complex when inputs beyond imaging, such as past medical history, are included. Dr. Adamson warned of the potential for “bias to creep in” when there is failure to account for societal, cultural, or other differences that distinguish one patient group from another. However, for skin cancer or other diseases based on images alone, he said there are solutions.

“We are in the early days, and there is time to change this,” Dr. Adamson said, referring to the low representation of skin of color in AI training sets. In addition to including more skin types to train recognition, creating AI algorithms specifically for dark skin is another potential approach.

However, his key point was the importance of recognizing the need for solutions.

“AI is the future, but we must apply the same rigor to AI as to other medical interventions to ensure that the technology is not applied in a biased fashion,” he said.

Susan M. Swetter, MD, professor of dermatology and director of the pigmented lesion and melanoma program at Stanford (Calif.) University Medical Center and Cancer Institute, agreed. As someone who has been following the progress of AI in the diagnosis of skin cancer, Dr. Swetter recognizes the potential for this technology to increase diagnostic efficiency and accuracy, but she also called for studies specific to skin of color.

In the analysis of images for detecting potential pathology, artificial intelligence (AI) is showing enormous promise across multiple fields of medicine. But the technology in dermatology is bound to fail in skin of color if training does not specifically address these skin types, according to Adewole S. Adamson, MD, who outlined this issue at the American Academy of Dermatology Virtual Meeting Experience.

“Machine learning algorithms are only as good as the inputs through which they learn. Without representation from individuals with skin of color, we are at risk of creating a new source of racial disparity in patient care,” Dr. Adamson, assistant professor in the division of dermatology, department of internal medicine, University of Texas at Austin, said at the meeting.

Diagnostic algorithms using AI are typically based on deep learning, a subset of machine learning that depends on artificial neural networks. In the case of image processing, neural networks can “learn” to recognize objects, faces, or, in the realm of health care, disease, from exposure to multiple images.

There are many other variables that affect the accuracy of deep learning for diagnostic algorithms, including the depth of the layering through which the process distills multiple inputs of information, but the number of inputs is critical. In the case of skin lesions, machines cannot learn to recognize features of different skin types without exposure.

“There are studies demonstrating that dermatologists can be outperformed for detection of skin cancers by AI, so this is going to be an increasingly powerful tool,” Dr. Adamson said. The problem is that “there has been very little representation in darker skin types” in the algorithms developed so far.

The risk is that AI will exacerbate an existing problem. Skin cancer in darker skin is less common but already underdiagnosed, independent of AI. Per 100,000 males in the United States, the rate of melanoma is about 30-fold greater in White men than in Black men (33.0 vs. 1.0). Among females, the racial difference is smaller but still enormous (20.2 vs. 1.2 per 100,000 females), according to U.S. data.

For the low representation of darker skin in studies so far with AI, “one of the arguments is that skin cancer is not a big deal in darker skin types,” Dr. Adamson said.

It might be the other way around. The relative infrequency with which skin cancer occurs in the Black population in the United States might explain a low level of suspicion and ultimately delays in diagnosis, which, in turn, leads to worse outcomes. According to one analysis drawn from the Surveillance, Epidemiology and End-Result (SEER) database (1998-2011), the proportion of patients with regionally advanced or distant disease was nearly twice as great (11.6% vs. 6.0%; P < .05) in Black patients, relative to White patients.

Not surprisingly, given the importance of early diagnosis of cancers overall and skin cancer specifically, the mean survival for malignant melanoma in Black patients was almost 4 years lower than in White patients (10.8 vs. 14.6 years; P < .001) for nodular melanoma, the same study found.

In humans, bias is reasonably attributed in many cases to judgments made on a small sample size. The problem in AI is analogous. Dr. Adamson, who has published research on the potential for machine learning to contribute to health care disparities in dermatology, cited work done by Joy Buolamwini, a graduate researcher in the media lab at the Massachusetts Institute of Technology. In one study she conducted, the rate of AI facial recognition failure was 1% in White males, 7% in White females, 12% in skin-of-color males, and 35% in skin-of-color females. Fewer inputs of skin of color is the likely explanation, Dr. Adamson said.

The potential for racial bias from AI in the diagnosis of disease increases and becomes more complex when inputs beyond imaging, such as past medical history, are included. Dr. Adamson warned of the potential for “bias to creep in” when there is failure to account for societal, cultural, or other differences that distinguish one patient group from another. However, for skin cancer or other diseases based on images alone, he said there are solutions.

“We are in the early days, and there is time to change this,” Dr. Adamson said, referring to the low representation of skin of color in AI training sets. In addition to including more skin types to train recognition, creating AI algorithms specifically for dark skin is another potential approach.

However, his key point was the importance of recognizing the need for solutions.

“AI is the future, but we must apply the same rigor to AI as to other medical interventions to ensure that the technology is not applied in a biased fashion,” he said.

Susan M. Swetter, MD, professor of dermatology and director of the pigmented lesion and melanoma program at Stanford (Calif.) University Medical Center and Cancer Institute, agreed. As someone who has been following the progress of AI in the diagnosis of skin cancer, Dr. Swetter recognizes the potential for this technology to increase diagnostic efficiency and accuracy, but she also called for studies specific to skin of color.

Dermatologists cautioned colleagues to be aware of special hazards facing the LGBTQ community: A higher risk of skin cancer among gay men, possibly because of excess ultraviolet exposure, and acne in transgender people, who are especially vulnerable to acne because of hormone therapy.

The identities of sexual minorities “have a significant influence on many facets of health,” dermatologist Matthew Mansh, MD, of the University of Minnesota, Minneapolis, said in a presentation at the American Academy of Dermatology Virtual Meeting Experience.

In regard to skin cancer, he said, “there seems to be consistently higher rates of skin cancer and certain preventable risk behaviors like indoor tanning among sexual minority men.”

Dr. Mansh, codirector of the high-risk nonmelanoma skin cancer clinic at the University of Minnesota, highlighted a report, published in JAMA Dermatology in 2020, that used 2014-2018 U.S. survey data of over 870,000 adults to look at the association between sexual orientation and lifetime prevalence of skin cancer. The investigators found that gay and bisexual men had a higher lifetime prevalence of skin cancer compared with heterosexual men (adjusted odds ratio [aOR], 1.25; 95% confidence interval, 1.03-1.50; P = .02; and aOR, 1.46; 95% CI, 1.01-2.10; P = .04; for gay and bisexual men, respectively).

When compared with heterosexual women, risk among bisexual women was lower (aOR, 0.75; 95% CI, 0.60-0.95; P  = .02), but not among lesbian women (aOR, 1.01; 95% CI, 0.77-1.33; P = .95, respectively).

Other studies have reached similar conclusions, Dr. Mansh said, although there’s been fairly little research in this area. What could explain these differences? Factors such as smoking, age, and alcohol use affect skin cancer risk, he said, but these studies control for those variables. Instead, he noted, it’s useful to look at studies of ultraviolet exposure.

For example, he highlighted a study published in JAMA Dermatology in 2015, which examined 12-month indoor-tanning rates and skin cancer prevalence by sexual orientation, using data from California and national health interview surveys. The study found that compared with heterosexual men, “sexual minority men had higher rates of indoor tanning by roughly three- to sixfold,” said Dr. Mansh, the lead author. “And this was among respondents who were adults over age 18. People between the ages of 18 and 34 years are important from a skin cancer perspective as it’s well established that exposure to tanning beds at a younger age is most associated with an increased risk of skin cancer.”

Sexual minority men were also significantly more likely to report having skin cancer, compared with heterosexual men.

In the study, sexual minority women had about half the odds of engaging in indoor tanning compared with heterosexual women, and were less likely to report having been diagnosed with nonmelanoma skin cancer, he added.

Other studies suggest that gay and bisexual men live in neighborhoods with more indoor tanning salons and that they may spend more time in the sun outside too, he said. Some research suggests motivations for tanning include social pressure and the desire to improve appearance, he added.

Overall, “we may be able to use these data to add more appropriate screening and recommendations for these patients, which are sorely lacking in dermatology,” and to design targeted behavioral interventions, said Dr. Mansh, codirector of the dermatology gender care clinic at the University of Minnesota.

What can dermatologists do now? In an interview, dermatologist Jon Klint Peebles, MD, of the mid-Atlantic Permanente Medical Group, in Largo, Md., suggested that colleagues ask patients questions about indoor tanning frequency, the motivations for tanning, exposure to outdoor ultraviolet radiation, sunscreen use, and use of photoprotective clothing.

Hormone therapy and acne

In a related presentation at the meeting, Howa Yeung, MD, of the department of dermatology, Emory University, Atlanta, said that in transgender people, estrogen therapy can actually reduce sebum production and often improves acne, while testosterone therapy frequently has the opposite effect.

“We’ve seen some pretty tough cases of acne in transmasculine patients in my practice,” said Dr. Yeung, who highlighted a recently published study that tracked 988 transgender patients in Boston who underwent testosterone therapy. Nearly a third were diagnosed with acne, compared with 6% prior to hormone therapy, and those at the highest risk were aged 18-21.

The prevalence of acne was 25% 2 years after initiation of hormone therapy. “Acne remains a very common issue and not just at the beginning of treatment,” he said.

In 2020, Dr. Yeung and colleagues reported the results of a survey of 696 transgender patients in California and Georgia; most were treated with hormone therapy. They found that 14% of transmasculine patients reported currently having moderate to severe acne diagnosed by a physician, compared with 1% of transfeminine patients.

Dr. Yeung noted that another survey of transmasculine persons who had received testosterone found that those who had moderate to severe acne were more likely to suffer from depression and anxiety than were those who had never had acne (aOR, 2.4; 95% CI, 1.1-5.4; P = .001, for depression; and aOR, 2.7; 95% CI, 1.2-6.3; P = .002, for anxiety).

Acne treatments in transmasculine patients are complicated by the fact that hormone treatments for acne can have feminizing effects, Dr. Yeung said, adding that it’s not clear how clascoterone, a new anti-androgen topical therapy for acne, will affect them. For now, many patients will require isotretinoin for treating acne.

Dr. Peebles cautioned that with isotretinoin, “we still do not yet have solid data on the optimal dosing or duration in the context of testosterone-induced acne, as well as what individual factors may be predictive of treatment success or failure. It is also important to be aware of any planned surgical procedures, whether as part of gender-affirming care or otherwise, given that some surgeons may view isotretinoin as a barrier for some procedures, despite limited data to support this.”

Both Dr. Peebles and Dr. Yeung noted that the iPledge risk management program for isotretinoin patients who may become pregnant is problematic. “A trans man who is assigned female at birth and identifies as a man and has a uterus and ovaries must be registered as a female with reproductive potential,” Dr. Yeung said.

“While the program remains inherently discriminatory, it is important to have an honest conversation with patients about these issues in a sensitive way,” Dr. Peebles noted. “Luckily, there is substantial momentum building around modifying iPLEDGE to become more inclusive. While the mechanics are complicated and involve a variety of entities and advocacy initiatives, we are optimistic that major changes are in the pipeline.”

Dr. Mansh, Dr. Yeung, and Dr. Peebles reported no disclosures.

Dermatologists cautioned colleagues to be aware of special hazards facing the LGBTQ community: A higher risk of skin cancer among gay men, possibly because of excess ultraviolet exposure, and acne in transgender people, who are especially vulnerable to acne because of hormone therapy.

The identities of sexual minorities “have a significant influence on many facets of health,” dermatologist Matthew Mansh, MD, of the University of Minnesota, Minneapolis, said in a presentation at the American Academy of Dermatology Virtual Meeting Experience.

In regard to skin cancer, he said, “there seems to be consistently higher rates of skin cancer and certain preventable risk behaviors like indoor tanning among sexual minority men.”

Dr. Mansh, codirector of the high-risk nonmelanoma skin cancer clinic at the University of Minnesota, highlighted a report, published in JAMA Dermatology in 2020, that used 2014-2018 U.S. survey data of over 870,000 adults to look at the association between sexual orientation and lifetime prevalence of skin cancer. The investigators found that gay and bisexual men had a higher lifetime prevalence of skin cancer compared with heterosexual men (adjusted odds ratio [aOR], 1.25; 95% confidence interval, 1.03-1.50; P = .02; and aOR, 1.46; 95% CI, 1.01-2.10; P = .04; for gay and bisexual men, respectively).

When compared with heterosexual women, risk among bisexual women was lower (aOR, 0.75; 95% CI, 0.60-0.95; P  = .02), but not among lesbian women (aOR, 1.01; 95% CI, 0.77-1.33; P = .95, respectively).

Other studies have reached similar conclusions, Dr. Mansh said, although there’s been fairly little research in this area. What could explain these differences? Factors such as smoking, age, and alcohol use affect skin cancer risk, he said, but these studies control for those variables. Instead, he noted, it’s useful to look at studies of ultraviolet exposure.

For example, he highlighted a study published in JAMA Dermatology in 2015, which examined 12-month indoor-tanning rates and skin cancer prevalence by sexual orientation, using data from California and national health interview surveys. The study found that compared with heterosexual men, “sexual minority men had higher rates of indoor tanning by roughly three- to sixfold,” said Dr. Mansh, the lead author. “And this was among respondents who were adults over age 18. People between the ages of 18 and 34 years are important from a skin cancer perspective as it’s well established that exposure to tanning beds at a younger age is most associated with an increased risk of skin cancer.”

Sexual minority men were also significantly more likely to report having skin cancer, compared with heterosexual men.

In the study, sexual minority women had about half the odds of engaging in indoor tanning compared with heterosexual women, and were less likely to report having been diagnosed with nonmelanoma skin cancer, he added.

Other studies suggest that gay and bisexual men live in neighborhoods with more indoor tanning salons and that they may spend more time in the sun outside too, he said. Some research suggests motivations for tanning include social pressure and the desire to improve appearance, he added.

Overall, “we may be able to use these data to add more appropriate screening and recommendations for these patients, which are sorely lacking in dermatology,” and to design targeted behavioral interventions, said Dr. Mansh, codirector of the dermatology gender care clinic at the University of Minnesota.

What can dermatologists do now? In an interview, dermatologist Jon Klint Peebles, MD, of the mid-Atlantic Permanente Medical Group, in Largo, Md., suggested that colleagues ask patients questions about indoor tanning frequency, the motivations for tanning, exposure to outdoor ultraviolet radiation, sunscreen use, and use of photoprotective clothing.

Hormone therapy and acne

In a related presentation at the meeting, Howa Yeung, MD, of the department of dermatology, Emory University, Atlanta, said that in transgender people, estrogen therapy can actually reduce sebum production and often improves acne, while testosterone therapy frequently has the opposite effect.

“We’ve seen some pretty tough cases of acne in transmasculine patients in my practice,” said Dr. Yeung, who highlighted a recently published study that tracked 988 transgender patients in Boston who underwent testosterone therapy. Nearly a third were diagnosed with acne, compared with 6% prior to hormone therapy, and those at the highest risk were aged 18-21.

The prevalence of acne was 25% 2 years after initiation of hormone therapy. “Acne remains a very common issue and not just at the beginning of treatment,” he said.

In 2020, Dr. Yeung and colleagues reported the results of a survey of 696 transgender patients in California and Georgia; most were treated with hormone therapy. They found that 14% of transmasculine patients reported currently having moderate to severe acne diagnosed by a physician, compared with 1% of transfeminine patients.

Dr. Yeung noted that another survey of transmasculine persons who had received testosterone found that those who had moderate to severe acne were more likely to suffer from depression and anxiety than were those who had never had acne (aOR, 2.4; 95% CI, 1.1-5.4; P = .001, for depression; and aOR, 2.7; 95% CI, 1.2-6.3; P = .002, for anxiety).

Acne treatments in transmasculine patients are complicated by the fact that hormone treatments for acne can have feminizing effects, Dr. Yeung said, adding that it’s not clear how clascoterone, a new anti-androgen topical therapy for acne, will affect them. For now, many patients will require isotretinoin for treating acne.

Dr. Peebles cautioned that with isotretinoin, “we still do not yet have solid data on the optimal dosing or duration in the context of testosterone-induced acne, as well as what individual factors may be predictive of treatment success or failure. It is also important to be aware of any planned surgical procedures, whether as part of gender-affirming care or otherwise, given that some surgeons may view isotretinoin as a barrier for some procedures, despite limited data to support this.”

Both Dr. Peebles and Dr. Yeung noted that the iPledge risk management program for isotretinoin patients who may become pregnant is problematic. “A trans man who is assigned female at birth and identifies as a man and has a uterus and ovaries must be registered as a female with reproductive potential,” Dr. Yeung said.

“While the program remains inherently discriminatory, it is important to have an honest conversation with patients about these issues in a sensitive way,” Dr. Peebles noted. “Luckily, there is substantial momentum building around modifying iPLEDGE to become more inclusive. While the mechanics are complicated and involve a variety of entities and advocacy initiatives, we are optimistic that major changes are in the pipeline.”

Dr. Mansh, Dr. Yeung, and Dr. Peebles reported no disclosures.

Dermatologists cautioned colleagues to be aware of special hazards facing the LGBTQ community: A higher risk of skin cancer among gay men, possibly because of excess ultraviolet exposure, and acne in transgender people, who are especially vulnerable to acne because of hormone therapy.

The identities of sexual minorities “have a significant influence on many facets of health,” dermatologist Matthew Mansh, MD, of the University of Minnesota, Minneapolis, said in a presentation at the American Academy of Dermatology Virtual Meeting Experience.

In regard to skin cancer, he said, “there seems to be consistently higher rates of skin cancer and certain preventable risk behaviors like indoor tanning among sexual minority men.”

Dr. Mansh, codirector of the high-risk nonmelanoma skin cancer clinic at the University of Minnesota, highlighted a report, published in JAMA Dermatology in 2020, that used 2014-2018 U.S. survey data of over 870,000 adults to look at the association between sexual orientation and lifetime prevalence of skin cancer. The investigators found that gay and bisexual men had a higher lifetime prevalence of skin cancer compared with heterosexual men (adjusted odds ratio [aOR], 1.25; 95% confidence interval, 1.03-1.50; P = .02; and aOR, 1.46; 95% CI, 1.01-2.10; P = .04; for gay and bisexual men, respectively).

When compared with heterosexual women, risk among bisexual women was lower (aOR, 0.75; 95% CI, 0.60-0.95; P  = .02), but not among lesbian women (aOR, 1.01; 95% CI, 0.77-1.33; P = .95, respectively).

Other studies have reached similar conclusions, Dr. Mansh said, although there’s been fairly little research in this area. What could explain these differences? Factors such as smoking, age, and alcohol use affect skin cancer risk, he said, but these studies control for those variables. Instead, he noted, it’s useful to look at studies of ultraviolet exposure.

For example, he highlighted a study published in JAMA Dermatology in 2015, which examined 12-month indoor-tanning rates and skin cancer prevalence by sexual orientation, using data from California and national health interview surveys. The study found that compared with heterosexual men, “sexual minority men had higher rates of indoor tanning by roughly three- to sixfold,” said Dr. Mansh, the lead author. “And this was among respondents who were adults over age 18. People between the ages of 18 and 34 years are important from a skin cancer perspective as it’s well established that exposure to tanning beds at a younger age is most associated with an increased risk of skin cancer.”

Sexual minority men were also significantly more likely to report having skin cancer, compared with heterosexual men.

In the study, sexual minority women had about half the odds of engaging in indoor tanning compared with heterosexual women, and were less likely to report having been diagnosed with nonmelanoma skin cancer, he added.

Other studies suggest that gay and bisexual men live in neighborhoods with more indoor tanning salons and that they may spend more time in the sun outside too, he said. Some research suggests motivations for tanning include social pressure and the desire to improve appearance, he added.

Overall, “we may be able to use these data to add more appropriate screening and recommendations for these patients, which are sorely lacking in dermatology,” and to design targeted behavioral interventions, said Dr. Mansh, codirector of the dermatology gender care clinic at the University of Minnesota.

What can dermatologists do now? In an interview, dermatologist Jon Klint Peebles, MD, of the mid-Atlantic Permanente Medical Group, in Largo, Md., suggested that colleagues ask patients questions about indoor tanning frequency, the motivations for tanning, exposure to outdoor ultraviolet radiation, sunscreen use, and use of photoprotective clothing.

Hormone therapy and acne

In a related presentation at the meeting, Howa Yeung, MD, of the department of dermatology, Emory University, Atlanta, said that in transgender people, estrogen therapy can actually reduce sebum production and often improves acne, while testosterone therapy frequently has the opposite effect.

“We’ve seen some pretty tough cases of acne in transmasculine patients in my practice,” said Dr. Yeung, who highlighted a recently published study that tracked 988 transgender patients in Boston who underwent testosterone therapy. Nearly a third were diagnosed with acne, compared with 6% prior to hormone therapy, and those at the highest risk were aged 18-21.

The prevalence of acne was 25% 2 years after initiation of hormone therapy. “Acne remains a very common issue and not just at the beginning of treatment,” he said.

In 2020, Dr. Yeung and colleagues reported the results of a survey of 696 transgender patients in California and Georgia; most were treated with hormone therapy. They found that 14% of transmasculine patients reported currently having moderate to severe acne diagnosed by a physician, compared with 1% of transfeminine patients.

Dr. Yeung noted that another survey of transmasculine persons who had received testosterone found that those who had moderate to severe acne were more likely to suffer from depression and anxiety than were those who had never had acne (aOR, 2.4; 95% CI, 1.1-5.4; P = .001, for depression; and aOR, 2.7; 95% CI, 1.2-6.3; P = .002, for anxiety).

Acne treatments in transmasculine patients are complicated by the fact that hormone treatments for acne can have feminizing effects, Dr. Yeung said, adding that it’s not clear how clascoterone, a new anti-androgen topical therapy for acne, will affect them. For now, many patients will require isotretinoin for treating acne.

Dr. Peebles cautioned that with isotretinoin, “we still do not yet have solid data on the optimal dosing or duration in the context of testosterone-induced acne, as well as what individual factors may be predictive of treatment success or failure. It is also important to be aware of any planned surgical procedures, whether as part of gender-affirming care or otherwise, given that some surgeons may view isotretinoin as a barrier for some procedures, despite limited data to support this.”

Both Dr. Peebles and Dr. Yeung noted that the iPledge risk management program for isotretinoin patients who may become pregnant is problematic. “A trans man who is assigned female at birth and identifies as a man and has a uterus and ovaries must be registered as a female with reproductive potential,” Dr. Yeung said.

“While the program remains inherently discriminatory, it is important to have an honest conversation with patients about these issues in a sensitive way,” Dr. Peebles noted. “Luckily, there is substantial momentum building around modifying iPLEDGE to become more inclusive. While the mechanics are complicated and involve a variety of entities and advocacy initiatives, we are optimistic that major changes are in the pipeline.”

Dr. Mansh, Dr. Yeung, and Dr. Peebles reported no disclosures.

People with psoriasis have a higher risk of infection with COVID-19 than the general population, but some systemic treatments appear to lower risk in patients, compared with those on topical therapy, a new study finds.

“Our study results suggest that psoriasis is an independent risk factor for COVID-19 illness,” study coauthor Jeffrey Liu, a medical student at the University of Southern California, Los Angeles, said in an interview after he presented the findings at the American Academy of Dermatology Virtual Meeting Experience. “And our findings are consistent with the hypothesis that certain systemic agents may confer a protective effect against COVID-19 illness.”

Mr. Liu and coinvestigators used a Symphony Health dataset to analyze the health records of 167,027 U.S. patients diagnosed with psoriasis and a control group of 1,002,162 patients. The participants, all at least 20 years old, had been treated for psoriasis or psoriatic arthritis from May 2019 through Jan. 1, 2020, and were tracked until Nov. 11, 2020.

The ages and races of peoples in the two groups were roughly similar. Overall, 55% were women and 75% were White, and their average age was 58 years. Type 2 diabetes was more common in the psoriasis group than the control group (23% vs. 16%), as was obesity (27% vs. 15%). Of the patients with psoriasis, 60% were on topical treatments, 19% were on oral therapies, and 22% were on biologic therapy, with only a few taking both oral and biologic therapies.

After adjustment for age and gender, patients with psoriasis were 33% more likely than the control group to develop COVID-19 (adjusted incidence rate ratio, 1.33; 95% confidence interval, 1.23-1.38; P < .0001).

In a separate analysis, the gap persisted after adjustment for demographics and comorbidities: Patients with psoriasis had a higher rate of COVID-19 infection vs. controls (adjusted odds ratio, 1.18; 95% CI, 1.13-1.23; P < .0001). Among all patients, non-White race, older age, and comorbidities were all linked to higher risk of COVID-19 (all P < .0001).

Psoriasis might make patients more vulnerable to COVID-19 because the presence of up-regulated genes in psoriatic skin “may lead to systemic hyperinflammation and sensitization of patients with psoriasis to proinflammatory cytokine storm,” Mr. Liu said. This, in turn, may trigger more severe symptomatic disease that requires medical treatment, he said.

Reduced risk, compared with topical therapies

After adjustment for age and gender, those treated with TNF-alpha inhibitors, methotrexate, and apremilast (Otezla) all had statistically lower risks of COVID-19 vs. those on topical therapy (aIRR, 0.82; 95% CI, 0.69-0.95; P < .0029 for TNF-alpha inhibitors; aIRR, 0.75; 95% CI, 0.67-0.86; P < .0001 for methotrexate; and aIRR, 0.69; 95% CI, 0.55-0.85; P < .0006 for apremilast).

Reduced risk held true for those in the separate analysis after adjustment for comorbidities and demographics (respectively, aOR, 0.87; 95% CI, 0.77-1.00; P < .0469; aOR, 0.81; 95% CI, 0.71-0.92; P < .0011; and aOR, 0.70; 95% CI, 0.57-0.87; P < .0014).

Apremilast and methotrexate may boost protection against COVID-19 by inhibiting the body’s production of cytokines, Mr. Liu said.

One message of the study is that “dermatologists should not be scared of prescribing biologics or oral therapies for psoriasis,” the study’s lead author Jashin J. Wu, MD, of the Dermatology Research and Education Foundation in Irvine, Calif., said in an interview.

However, the results on the effects of systemic therapies were not all positive. Interleukin (IL)–17 inhibitors were an outlier: After adjustment for age and gender, patients treated with this class of drugs were 36% more likely to develop COVID-19 than those on oral agents (aIRR, 1.36; 95% CI, 1.13-1.63; P < .0009).

Among patients on biologics, those taking IL-17 inhibitors had the highest risk of COVID-19, Mr. Liu said. “The risk was higher in this class regardless of reference group – general population, the topical cohort, and the oral cohort,” he said. “This may relate to the observation that this biologic class exerts more broad immunosuppressive effects on antiviral host immunity. Notably, large meta-estimates of pivotal trials have observed increased risk of respiratory tract infections for patients on IL-17 inhibitors.”

In an interview, Erica Dommasch, MD, MPH, of the department of dermatology at Beth Israel Deaconess Medical Center, Boston, cautioned that “the data from this study is very hard to interpret.”

It’s likely that some patients with psoriasis on systemic medications “may have been the most careful about limiting exposures,” she said. “Thus, it’s hard to account for behavioral changes in individuals that may have led to the decreased incidence in psoriasis in patients on systemic agents versus topical therapy alone.”

Patients with psoriasis may also be tested more often for COVID-19, and unmeasured comorbidities like chronic kidney disease may play a role too, she said. Still, she added, “it’s reassuring that the authors did not find an increased rate of COVID among psoriasis patients on systemic agents versus topicals alone.” And she agreed with Dr. Wu about the importance of treating psoriasis with therapy beyond topical treatments during the pandemic: “Providers should feel comfortable prescribing systemic medications to psoriasis patients when otherwise appropriate.”

As for the next steps, Dr. Wu said, “we will be exploring more about the prognosis of COVID-19 infection in psoriasis patients. In addition, we will be exploring the relationship of COVID-19 infection with other inflammatory skin diseases, such as atopic dermatitis.”

No study funding is reported. Dr. Wu discloses investigator, consultant, or speaker relationships with AbbVie, Almirall, Amgen, Arcutis, Aristea Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Dr. Reddy’s Laboratories, Eli Lilly, Galderma, Janssen, LEO Pharma, Mindera, Novartis, Regeneron, Sanofi Genzyme, Solius, Sun Pharmaceutical, UCB, Valeant Pharmaceuticals North America, and Zerigo Health. Mr. Liu and Dr. Dommasch have no disclosures.

People with psoriasis have a higher risk of infection with COVID-19 than the general population, but some systemic treatments appear to lower risk in patients, compared with those on topical therapy, a new study finds.

“Our study results suggest that psoriasis is an independent risk factor for COVID-19 illness,” study coauthor Jeffrey Liu, a medical student at the University of Southern California, Los Angeles, said in an interview after he presented the findings at the American Academy of Dermatology Virtual Meeting Experience. “And our findings are consistent with the hypothesis that certain systemic agents may confer a protective effect against COVID-19 illness.”

Mr. Liu and coinvestigators used a Symphony Health dataset to analyze the health records of 167,027 U.S. patients diagnosed with psoriasis and a control group of 1,002,162 patients. The participants, all at least 20 years old, had been treated for psoriasis or psoriatic arthritis from May 2019 through Jan. 1, 2020, and were tracked until Nov. 11, 2020.

The ages and races of peoples in the two groups were roughly similar. Overall, 55% were women and 75% were White, and their average age was 58 years. Type 2 diabetes was more common in the psoriasis group than the control group (23% vs. 16%), as was obesity (27% vs. 15%). Of the patients with psoriasis, 60% were on topical treatments, 19% were on oral therapies, and 22% were on biologic therapy, with only a few taking both oral and biologic therapies.

After adjustment for age and gender, patients with psoriasis were 33% more likely than the control group to develop COVID-19 (adjusted incidence rate ratio, 1.33; 95% confidence interval, 1.23-1.38; P < .0001).

In a separate analysis, the gap persisted after adjustment for demographics and comorbidities: Patients with psoriasis had a higher rate of COVID-19 infection vs. controls (adjusted odds ratio, 1.18; 95% CI, 1.13-1.23; P < .0001). Among all patients, non-White race, older age, and comorbidities were all linked to higher risk of COVID-19 (all P < .0001).

Psoriasis might make patients more vulnerable to COVID-19 because the presence of up-regulated genes in psoriatic skin “may lead to systemic hyperinflammation and sensitization of patients with psoriasis to proinflammatory cytokine storm,” Mr. Liu said. This, in turn, may trigger more severe symptomatic disease that requires medical treatment, he said.

Reduced risk, compared with topical therapies

After adjustment for age and gender, those treated with TNF-alpha inhibitors, methotrexate, and apremilast (Otezla) all had statistically lower risks of COVID-19 vs. those on topical therapy (aIRR, 0.82; 95% CI, 0.69-0.95; P < .0029 for TNF-alpha inhibitors; aIRR, 0.75; 95% CI, 0.67-0.86; P < .0001 for methotrexate; and aIRR, 0.69; 95% CI, 0.55-0.85; P < .0006 for apremilast).

Reduced risk held true for those in the separate analysis after adjustment for comorbidities and demographics (respectively, aOR, 0.87; 95% CI, 0.77-1.00; P < .0469; aOR, 0.81; 95% CI, 0.71-0.92; P < .0011; and aOR, 0.70; 95% CI, 0.57-0.87; P < .0014).

Apremilast and methotrexate may boost protection against COVID-19 by inhibiting the body’s production of cytokines, Mr. Liu said.

One message of the study is that “dermatologists should not be scared of prescribing biologics or oral therapies for psoriasis,” the study’s lead author Jashin J. Wu, MD, of the Dermatology Research and Education Foundation in Irvine, Calif., said in an interview.

However, the results on the effects of systemic therapies were not all positive. Interleukin (IL)–17 inhibitors were an outlier: After adjustment for age and gender, patients treated with this class of drugs were 36% more likely to develop COVID-19 than those on oral agents (aIRR, 1.36; 95% CI, 1.13-1.63; P < .0009).

Among patients on biologics, those taking IL-17 inhibitors had the highest risk of COVID-19, Mr. Liu said. “The risk was higher in this class regardless of reference group – general population, the topical cohort, and the oral cohort,” he said. “This may relate to the observation that this biologic class exerts more broad immunosuppressive effects on antiviral host immunity. Notably, large meta-estimates of pivotal trials have observed increased risk of respiratory tract infections for patients on IL-17 inhibitors.”

In an interview, Erica Dommasch, MD, MPH, of the department of dermatology at Beth Israel Deaconess Medical Center, Boston, cautioned that “the data from this study is very hard to interpret.”

It’s likely that some patients with psoriasis on systemic medications “may have been the most careful about limiting exposures,” she said. “Thus, it’s hard to account for behavioral changes in individuals that may have led to the decreased incidence in psoriasis in patients on systemic agents versus topical therapy alone.”

Patients with psoriasis may also be tested more often for COVID-19, and unmeasured comorbidities like chronic kidney disease may play a role too, she said. Still, she added, “it’s reassuring that the authors did not find an increased rate of COVID among psoriasis patients on systemic agents versus topicals alone.” And she agreed with Dr. Wu about the importance of treating psoriasis with therapy beyond topical treatments during the pandemic: “Providers should feel comfortable prescribing systemic medications to psoriasis patients when otherwise appropriate.”

As for the next steps, Dr. Wu said, “we will be exploring more about the prognosis of COVID-19 infection in psoriasis patients. In addition, we will be exploring the relationship of COVID-19 infection with other inflammatory skin diseases, such as atopic dermatitis.”

No study funding is reported. Dr. Wu discloses investigator, consultant, or speaker relationships with AbbVie, Almirall, Amgen, Arcutis, Aristea Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Dr. Reddy’s Laboratories, Eli Lilly, Galderma, Janssen, LEO Pharma, Mindera, Novartis, Regeneron, Sanofi Genzyme, Solius, Sun Pharmaceutical, UCB, Valeant Pharmaceuticals North America, and Zerigo Health. Mr. Liu and Dr. Dommasch have no disclosures.

People with psoriasis have a higher risk of infection with COVID-19 than the general population, but some systemic treatments appear to lower risk in patients, compared with those on topical therapy, a new study finds.

“Our study results suggest that psoriasis is an independent risk factor for COVID-19 illness,” study coauthor Jeffrey Liu, a medical student at the University of Southern California, Los Angeles, said in an interview after he presented the findings at the American Academy of Dermatology Virtual Meeting Experience. “And our findings are consistent with the hypothesis that certain systemic agents may confer a protective effect against COVID-19 illness.”

Mr. Liu and coinvestigators used a Symphony Health dataset to analyze the health records of 167,027 U.S. patients diagnosed with psoriasis and a control group of 1,002,162 patients. The participants, all at least 20 years old, had been treated for psoriasis or psoriatic arthritis from May 2019 through Jan. 1, 2020, and were tracked until Nov. 11, 2020.

The ages and races of peoples in the two groups were roughly similar. Overall, 55% were women and 75% were White, and their average age was 58 years. Type 2 diabetes was more common in the psoriasis group than the control group (23% vs. 16%), as was obesity (27% vs. 15%). Of the patients with psoriasis, 60% were on topical treatments, 19% were on oral therapies, and 22% were on biologic therapy, with only a few taking both oral and biologic therapies.

After adjustment for age and gender, patients with psoriasis were 33% more likely than the control group to develop COVID-19 (adjusted incidence rate ratio, 1.33; 95% confidence interval, 1.23-1.38; P < .0001).

In a separate analysis, the gap persisted after adjustment for demographics and comorbidities: Patients with psoriasis had a higher rate of COVID-19 infection vs. controls (adjusted odds ratio, 1.18; 95% CI, 1.13-1.23; P < .0001). Among all patients, non-White race, older age, and comorbidities were all linked to higher risk of COVID-19 (all P < .0001).

Psoriasis might make patients more vulnerable to COVID-19 because the presence of up-regulated genes in psoriatic skin “may lead to systemic hyperinflammation and sensitization of patients with psoriasis to proinflammatory cytokine storm,” Mr. Liu said. This, in turn, may trigger more severe symptomatic disease that requires medical treatment, he said.

Reduced risk, compared with topical therapies

After adjustment for age and gender, those treated with TNF-alpha inhibitors, methotrexate, and apremilast (Otezla) all had statistically lower risks of COVID-19 vs. those on topical therapy (aIRR, 0.82; 95% CI, 0.69-0.95; P < .0029 for TNF-alpha inhibitors; aIRR, 0.75; 95% CI, 0.67-0.86; P < .0001 for methotrexate; and aIRR, 0.69; 95% CI, 0.55-0.85; P < .0006 for apremilast).

Reduced risk held true for those in the separate analysis after adjustment for comorbidities and demographics (respectively, aOR, 0.87; 95% CI, 0.77-1.00; P < .0469; aOR, 0.81; 95% CI, 0.71-0.92; P < .0011; and aOR, 0.70; 95% CI, 0.57-0.87; P < .0014).

Apremilast and methotrexate may boost protection against COVID-19 by inhibiting the body’s production of cytokines, Mr. Liu said.

One message of the study is that “dermatologists should not be scared of prescribing biologics or oral therapies for psoriasis,” the study’s lead author Jashin J. Wu, MD, of the Dermatology Research and Education Foundation in Irvine, Calif., said in an interview.

However, the results on the effects of systemic therapies were not all positive. Interleukin (IL)–17 inhibitors were an outlier: After adjustment for age and gender, patients treated with this class of drugs were 36% more likely to develop COVID-19 than those on oral agents (aIRR, 1.36; 95% CI, 1.13-1.63; P < .0009).

Among patients on biologics, those taking IL-17 inhibitors had the highest risk of COVID-19, Mr. Liu said. “The risk was higher in this class regardless of reference group – general population, the topical cohort, and the oral cohort,” he said. “This may relate to the observation that this biologic class exerts more broad immunosuppressive effects on antiviral host immunity. Notably, large meta-estimates of pivotal trials have observed increased risk of respiratory tract infections for patients on IL-17 inhibitors.”

In an interview, Erica Dommasch, MD, MPH, of the department of dermatology at Beth Israel Deaconess Medical Center, Boston, cautioned that “the data from this study is very hard to interpret.”

It’s likely that some patients with psoriasis on systemic medications “may have been the most careful about limiting exposures,” she said. “Thus, it’s hard to account for behavioral changes in individuals that may have led to the decreased incidence in psoriasis in patients on systemic agents versus topical therapy alone.”

Patients with psoriasis may also be tested more often for COVID-19, and unmeasured comorbidities like chronic kidney disease may play a role too, she said. Still, she added, “it’s reassuring that the authors did not find an increased rate of COVID among psoriasis patients on systemic agents versus topicals alone.” And she agreed with Dr. Wu about the importance of treating psoriasis with therapy beyond topical treatments during the pandemic: “Providers should feel comfortable prescribing systemic medications to psoriasis patients when otherwise appropriate.”

As for the next steps, Dr. Wu said, “we will be exploring more about the prognosis of COVID-19 infection in psoriasis patients. In addition, we will be exploring the relationship of COVID-19 infection with other inflammatory skin diseases, such as atopic dermatitis.”

No study funding is reported. Dr. Wu discloses investigator, consultant, or speaker relationships with AbbVie, Almirall, Amgen, Arcutis, Aristea Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Dr. Reddy’s Laboratories, Eli Lilly, Galderma, Janssen, LEO Pharma, Mindera, Novartis, Regeneron, Sanofi Genzyme, Solius, Sun Pharmaceutical, UCB, Valeant Pharmaceuticals North America, and Zerigo Health. Mr. Liu and Dr. Dommasch have no disclosures.

The remarkable efficacy of biologics for moderate to severe psoriasis has led some to ask if biologics should be used for milder cases.

The issue was tackled in a debate at the American Academy of Dermatology Virtual Meeting Experience.

Taking the con side, Kenneth Gordon, MD, professor and chair of dermatology at the Medical College of Wisconsin, Milwaukee, argued that, with the high cost of biologics, availability of many alternatives, and other issues, “we should just say no. ... There is no good reason that we need to expand the use of biologics in patients with limited disease.”

On the pro side, Richard Langley, MD, professor of dermatology at Dalhousie University Halifax, N.S, argued for a nuanced approach. He noted that patients with smaller patches of disease can be just as miserable as patients who hit traditional benchmarks of increased severity, such as high body surface area involvement – especially if those small areas are in sensitive locations like the scalp, palms, or genitals.

The decision to use a biologic should hinge on how badly patients and their quality of life are affected, not on “some artificial and limiting definition” of severity, Dr. Langley said.

Dr. Gordon didn’t disagree, noting that current use criteria include objective measures as well as disease in sensitive areas and failure of alternative treatments.

Rather, he was concerned about “expanding the definition of who is eligible beyond these criteria ... to chase every last bit of” disease. “I don’t think we have” a good rationale for that approach, he said.

Cost is the most important issue, Dr. Gordon said.

With more biologics on the way and prices continuing to go up, “there is going to a be a huge challenge to our use of these expensive medicines over the next few years” from payers. “It is important that we use them smartly in order to make sure we are able to use them for people with severe disease” who really need them. If “we start using biologics for all our patients with psoriasis,” it will be a “cost disaster,” Dr. Gordon said.

In addition, topicals and home phototherapy can be effective as long as patients adhere to them, as can alternative systemic agents, such as methotrexate and apremilast.

Often with biologics, “the issue is mainly convenience” rather than a fundamental problem with the alternatives, and despite the good safety record in trials, “chasing the last bit” of psoriasis with a biologic “is not necessarily” without risk for the patient, Dr. Gordon said.

Still, there can be a “pretty significant disconnect” between how patients perceive their psoriasis and “what physicians are thinking and prescribing” for it based on objective measures, Dr. Langley noted. Sometimes patients who have limited disease but are in significant distress aren’t even receiving treatment or are only given another cream to add to their collection of ones that haven’t worked.

One problem with traditional severity classifications is that they don’t generally take patients’ subjective experience into account, he added. There’s also been a lack of standardization to the point that dermatologists, researchers, and payers can sometimes disagree over severity in a given patient.

There’s movement toward better incorporation of patient experience into severity considerations, but for now at least, a designation of mild psoriasis can underestimate the true severity of disease, Dr. Langley said.

Dr. Gordon and Dr. Langley reported receiving honoraria and/or research support from many pharmaceutical companies, including AbbVie, Pfizer, and Lilly.

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

The remarkable efficacy of biologics for moderate to severe psoriasis has led some to ask if biologics should be used for milder cases.

The issue was tackled in a debate at the American Academy of Dermatology Virtual Meeting Experience.

Taking the con side, Kenneth Gordon, MD, professor and chair of dermatology at the Medical College of Wisconsin, Milwaukee, argued that, with the high cost of biologics, availability of many alternatives, and other issues, “we should just say no. ... There is no good reason that we need to expand the use of biologics in patients with limited disease.”

On the pro side, Richard Langley, MD, professor of dermatology at Dalhousie University Halifax, N.S, argued for a nuanced approach. He noted that patients with smaller patches of disease can be just as miserable as patients who hit traditional benchmarks of increased severity, such as high body surface area involvement – especially if those small areas are in sensitive locations like the scalp, palms, or genitals.

The decision to use a biologic should hinge on how badly patients and their quality of life are affected, not on “some artificial and limiting definition” of severity, Dr. Langley said.

Dr. Gordon didn’t disagree, noting that current use criteria include objective measures as well as disease in sensitive areas and failure of alternative treatments.

Rather, he was concerned about “expanding the definition of who is eligible beyond these criteria ... to chase every last bit of” disease. “I don’t think we have” a good rationale for that approach, he said.

Cost is the most important issue, Dr. Gordon said.

With more biologics on the way and prices continuing to go up, “there is going to a be a huge challenge to our use of these expensive medicines over the next few years” from payers. “It is important that we use them smartly in order to make sure we are able to use them for people with severe disease” who really need them. If “we start using biologics for all our patients with psoriasis,” it will be a “cost disaster,” Dr. Gordon said.

In addition, topicals and home phototherapy can be effective as long as patients adhere to them, as can alternative systemic agents, such as methotrexate and apremilast.

Often with biologics, “the issue is mainly convenience” rather than a fundamental problem with the alternatives, and despite the good safety record in trials, “chasing the last bit” of psoriasis with a biologic “is not necessarily” without risk for the patient, Dr. Gordon said.

Still, there can be a “pretty significant disconnect” between how patients perceive their psoriasis and “what physicians are thinking and prescribing” for it based on objective measures, Dr. Langley noted. Sometimes patients who have limited disease but are in significant distress aren’t even receiving treatment or are only given another cream to add to their collection of ones that haven’t worked.

One problem with traditional severity classifications is that they don’t generally take patients’ subjective experience into account, he added. There’s also been a lack of standardization to the point that dermatologists, researchers, and payers can sometimes disagree over severity in a given patient.

There’s movement toward better incorporation of patient experience into severity considerations, but for now at least, a designation of mild psoriasis can underestimate the true severity of disease, Dr. Langley said.

Dr. Gordon and Dr. Langley reported receiving honoraria and/or research support from many pharmaceutical companies, including AbbVie, Pfizer, and Lilly.

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

The remarkable efficacy of biologics for moderate to severe psoriasis has led some to ask if biologics should be used for milder cases.

The issue was tackled in a debate at the American Academy of Dermatology Virtual Meeting Experience.

Taking the con side, Kenneth Gordon, MD, professor and chair of dermatology at the Medical College of Wisconsin, Milwaukee, argued that, with the high cost of biologics, availability of many alternatives, and other issues, “we should just say no. ... There is no good reason that we need to expand the use of biologics in patients with limited disease.”

On the pro side, Richard Langley, MD, professor of dermatology at Dalhousie University Halifax, N.S, argued for a nuanced approach. He noted that patients with smaller patches of disease can be just as miserable as patients who hit traditional benchmarks of increased severity, such as high body surface area involvement – especially if those small areas are in sensitive locations like the scalp, palms, or genitals.

The decision to use a biologic should hinge on how badly patients and their quality of life are affected, not on “some artificial and limiting definition” of severity, Dr. Langley said.

Dr. Gordon didn’t disagree, noting that current use criteria include objective measures as well as disease in sensitive areas and failure of alternative treatments.

Rather, he was concerned about “expanding the definition of who is eligible beyond these criteria ... to chase every last bit of” disease. “I don’t think we have” a good rationale for that approach, he said.

Cost is the most important issue, Dr. Gordon said.

With more biologics on the way and prices continuing to go up, “there is going to a be a huge challenge to our use of these expensive medicines over the next few years” from payers. “It is important that we use them smartly in order to make sure we are able to use them for people with severe disease” who really need them. If “we start using biologics for all our patients with psoriasis,” it will be a “cost disaster,” Dr. Gordon said.

In addition, topicals and home phototherapy can be effective as long as patients adhere to them, as can alternative systemic agents, such as methotrexate and apremilast.

Often with biologics, “the issue is mainly convenience” rather than a fundamental problem with the alternatives, and despite the good safety record in trials, “chasing the last bit” of psoriasis with a biologic “is not necessarily” without risk for the patient, Dr. Gordon said.

Still, there can be a “pretty significant disconnect” between how patients perceive their psoriasis and “what physicians are thinking and prescribing” for it based on objective measures, Dr. Langley noted. Sometimes patients who have limited disease but are in significant distress aren’t even receiving treatment or are only given another cream to add to their collection of ones that haven’t worked.

One problem with traditional severity classifications is that they don’t generally take patients’ subjective experience into account, he added. There’s also been a lack of standardization to the point that dermatologists, researchers, and payers can sometimes disagree over severity in a given patient.

There’s movement toward better incorporation of patient experience into severity considerations, but for now at least, a designation of mild psoriasis can underestimate the true severity of disease, Dr. Langley said.

Dr. Gordon and Dr. Langley reported receiving honoraria and/or research support from many pharmaceutical companies, including AbbVie, Pfizer, and Lilly.

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

Researchers are reporting impressive results in a small, open-label trial of the JAK inhibitor tofacitinib in cutaneous sarcoidosis: 6 of 10 patients improved so much that they reached a disease activity level of zero, and all patients improved by an average of 83% via a scoring system.

“Not only did patients get better, but they were in many cases able to come off their baseline immunosuppressive regimen, including prednisone and methotrexate. They’d get off prednisone entirely or, in some cases, decrease it substantially,” study investigator William Damsky, MD, PhD, reported at the American Academy of Dermatology Virtual Meeting Experience.

Sarcoidosis is a common disease that affects an estimated 1 in 25 Black women and is believed to contribute to the deaths of about 4,000 people in the United States each year, noted Dr. Damsky of the department of dermatology, Yale University, New Haven, Conn. One famous patient is comedian Bernie Mac, who died from the condition in 2008.

“Approximately one third of patients have cutaneous involvement,” Dr. Damsky said, and skin may be the only manifestation of the disease. There is no Food and Drug Administration-approved therapy for cutaneous sarcoidosis, he added. Prednisone, the first-line therapy in skin manifestations, is approved only for pulmonary sarcoidosis.


“Oftentimes, there’s an attempt to transition either partially or fully to other therapies, including methotrexate and TNF-alpha blockers. But there’s been mixed success in doing that,” he said. This is not always possible, “so a lot of patients end up on prednisone.”

Earlier, a team at Yale prescribed 5 mg tofacitinib (Xeljanz) for several patients with severe cutaneous sarcoidosis and saw impressive results, Dr. Damsky said, including a patient with pulmonary sarcoidosis that also improved. He noted that there are case reports in the medical literature with similar findings.

Those positive results inspired the new study. Researchers recruited 10 patients with cutaneous sarcoidosis (9 with internal organ involvement) with a Cutaneous Sarcoidosis Activity and Morphology Instrument ( CSAMI ) score of 10 or higher. Nine patients were in their 50s, one was aged 63 years, and five were men. Skin colors of the patients ranged from Fitzpatrick skin types I to VI, and all had been taking at least two medications, typically methotrexate and prednisone.

The patients received 5 mg of tofacitinib twice a day for 6 months. “Everyone got better during the study, and six patients had a complete response, which we defined as a CSAMI score of zero activity,” Dr. Damsky said. “It’s really quite remarkable to see that.” Overall, the patients saw an 83% improvement in CSAMI scores.

In regard to safety, “all patients completed the study,” he said. “Tofacitinib was well tolerated, and there were no serious adverse effects or events.”

Tofacitinib is approved for treating rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, and polyarticular course juvenile idiopathic arthritis.

A month’s supply of twice-daily 5 mg tofacitinib pills would cost $4,900-$5,100 with free coupons, according to information accessed on April 24, 2021, on GoodRx.com. Generics are not available.

In an interview, Sotonye Imadojemu, MD, of the department of dermatology, Brigham and Women’s Hospital, Boston, praised the study, and said “tofacitinib is a reasonable treatment for treatment-refractory or extensive cutaneous sarcoidosis,” although it will be helpful to get results from randomized-controlled trials.

She cautioned that the drug “is a powerful immunosuppressant, so the risk of infection must be discussed with patients before prescribing. Screening for chronic infections such as viral hepatitis, tuberculosis, and HIV should be completed prior to treatment initiation. Blood counts, liver function, and lipid panels should be regularly monitored. The vaccines necessary for those who are immunosuppressed should be administered as able, and age-appropriate cancer screening must be kept up to date.”

The study was funded by Pfizer, the Dermatology Foundation, and the Yale Department of Dermatology. Dr. Damsky disclosed research support (Pfizer), consulting fees (Eli Lilly, Pfizer, TWi Biotechnology), and licensing fees (EMD Millipore/MillporeSigma). Dr. Imadojemu has no disclosures.

This article was updated 5/5/21.

Researchers are reporting impressive results in a small, open-label trial of the JAK inhibitor tofacitinib in cutaneous sarcoidosis: 6 of 10 patients improved so much that they reached a disease activity level of zero, and all patients improved by an average of 83% via a scoring system.

“Not only did patients get better, but they were in many cases able to come off their baseline immunosuppressive regimen, including prednisone and methotrexate. They’d get off prednisone entirely or, in some cases, decrease it substantially,” study investigator William Damsky, MD, PhD, reported at the American Academy of Dermatology Virtual Meeting Experience.

Sarcoidosis is a common disease that affects an estimated 1 in 25 Black women and is believed to contribute to the deaths of about 4,000 people in the United States each year, noted Dr. Damsky of the department of dermatology, Yale University, New Haven, Conn. One famous patient is comedian Bernie Mac, who died from the condition in 2008.

“Approximately one third of patients have cutaneous involvement,” Dr. Damsky said, and skin may be the only manifestation of the disease. There is no Food and Drug Administration-approved therapy for cutaneous sarcoidosis, he added. Prednisone, the first-line therapy in skin manifestations, is approved only for pulmonary sarcoidosis.


“Oftentimes, there’s an attempt to transition either partially or fully to other therapies, including methotrexate and TNF-alpha blockers. But there’s been mixed success in doing that,” he said. This is not always possible, “so a lot of patients end up on prednisone.”

Earlier, a team at Yale prescribed 5 mg tofacitinib (Xeljanz) for several patients with severe cutaneous sarcoidosis and saw impressive results, Dr. Damsky said, including a patient with pulmonary sarcoidosis that also improved. He noted that there are case reports in the medical literature with similar findings.

Those positive results inspired the new study. Researchers recruited 10 patients with cutaneous sarcoidosis (9 with internal organ involvement) with a Cutaneous Sarcoidosis Activity and Morphology Instrument ( CSAMI ) score of 10 or higher. Nine patients were in their 50s, one was aged 63 years, and five were men. Skin colors of the patients ranged from Fitzpatrick skin types I to VI, and all had been taking at least two medications, typically methotrexate and prednisone.

The patients received 5 mg of tofacitinib twice a day for 6 months. “Everyone got better during the study, and six patients had a complete response, which we defined as a CSAMI score of zero activity,” Dr. Damsky said. “It’s really quite remarkable to see that.” Overall, the patients saw an 83% improvement in CSAMI scores.

In regard to safety, “all patients completed the study,” he said. “Tofacitinib was well tolerated, and there were no serious adverse effects or events.”

Tofacitinib is approved for treating rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, and polyarticular course juvenile idiopathic arthritis.

A month’s supply of twice-daily 5 mg tofacitinib pills would cost $4,900-$5,100 with free coupons, according to information accessed on April 24, 2021, on GoodRx.com. Generics are not available.

In an interview, Sotonye Imadojemu, MD, of the department of dermatology, Brigham and Women’s Hospital, Boston, praised the study, and said “tofacitinib is a reasonable treatment for treatment-refractory or extensive cutaneous sarcoidosis,” although it will be helpful to get results from randomized-controlled trials.

She cautioned that the drug “is a powerful immunosuppressant, so the risk of infection must be discussed with patients before prescribing. Screening for chronic infections such as viral hepatitis, tuberculosis, and HIV should be completed prior to treatment initiation. Blood counts, liver function, and lipid panels should be regularly monitored. The vaccines necessary for those who are immunosuppressed should be administered as able, and age-appropriate cancer screening must be kept up to date.”

The study was funded by Pfizer, the Dermatology Foundation, and the Yale Department of Dermatology. Dr. Damsky disclosed research support (Pfizer), consulting fees (Eli Lilly, Pfizer, TWi Biotechnology), and licensing fees (EMD Millipore/MillporeSigma). Dr. Imadojemu has no disclosures.

This article was updated 5/5/21.

Researchers are reporting impressive results in a small, open-label trial of the JAK inhibitor tofacitinib in cutaneous sarcoidosis: 6 of 10 patients improved so much that they reached a disease activity level of zero, and all patients improved by an average of 83% via a scoring system.

“Not only did patients get better, but they were in many cases able to come off their baseline immunosuppressive regimen, including prednisone and methotrexate. They’d get off prednisone entirely or, in some cases, decrease it substantially,” study investigator William Damsky, MD, PhD, reported at the American Academy of Dermatology Virtual Meeting Experience.

Sarcoidosis is a common disease that affects an estimated 1 in 25 Black women and is believed to contribute to the deaths of about 4,000 people in the United States each year, noted Dr. Damsky of the department of dermatology, Yale University, New Haven, Conn. One famous patient is comedian Bernie Mac, who died from the condition in 2008.

“Approximately one third of patients have cutaneous involvement,” Dr. Damsky said, and skin may be the only manifestation of the disease. There is no Food and Drug Administration-approved therapy for cutaneous sarcoidosis, he added. Prednisone, the first-line therapy in skin manifestations, is approved only for pulmonary sarcoidosis.


“Oftentimes, there’s an attempt to transition either partially or fully to other therapies, including methotrexate and TNF-alpha blockers. But there’s been mixed success in doing that,” he said. This is not always possible, “so a lot of patients end up on prednisone.”

Earlier, a team at Yale prescribed 5 mg tofacitinib (Xeljanz) for several patients with severe cutaneous sarcoidosis and saw impressive results, Dr. Damsky said, including a patient with pulmonary sarcoidosis that also improved. He noted that there are case reports in the medical literature with similar findings.

Those positive results inspired the new study. Researchers recruited 10 patients with cutaneous sarcoidosis (9 with internal organ involvement) with a Cutaneous Sarcoidosis Activity and Morphology Instrument ( CSAMI ) score of 10 or higher. Nine patients were in their 50s, one was aged 63 years, and five were men. Skin colors of the patients ranged from Fitzpatrick skin types I to VI, and all had been taking at least two medications, typically methotrexate and prednisone.

The patients received 5 mg of tofacitinib twice a day for 6 months. “Everyone got better during the study, and six patients had a complete response, which we defined as a CSAMI score of zero activity,” Dr. Damsky said. “It’s really quite remarkable to see that.” Overall, the patients saw an 83% improvement in CSAMI scores.

In regard to safety, “all patients completed the study,” he said. “Tofacitinib was well tolerated, and there were no serious adverse effects or events.”

Tofacitinib is approved for treating rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, and polyarticular course juvenile idiopathic arthritis.

A month’s supply of twice-daily 5 mg tofacitinib pills would cost $4,900-$5,100 with free coupons, according to information accessed on April 24, 2021, on GoodRx.com. Generics are not available.

In an interview, Sotonye Imadojemu, MD, of the department of dermatology, Brigham and Women’s Hospital, Boston, praised the study, and said “tofacitinib is a reasonable treatment for treatment-refractory or extensive cutaneous sarcoidosis,” although it will be helpful to get results from randomized-controlled trials.

She cautioned that the drug “is a powerful immunosuppressant, so the risk of infection must be discussed with patients before prescribing. Screening for chronic infections such as viral hepatitis, tuberculosis, and HIV should be completed prior to treatment initiation. Blood counts, liver function, and lipid panels should be regularly monitored. The vaccines necessary for those who are immunosuppressed should be administered as able, and age-appropriate cancer screening must be kept up to date.”

The study was funded by Pfizer, the Dermatology Foundation, and the Yale Department of Dermatology. Dr. Damsky disclosed research support (Pfizer), consulting fees (Eli Lilly, Pfizer, TWi Biotechnology), and licensing fees (EMD Millipore/MillporeSigma). Dr. Imadojemu has no disclosures.

This article was updated 5/5/21.

Sofpironium bromide, a new topical anticholinergic agent, appears to be a safer version of glycopyrrolate for the treatment of axillary hyperhidrosis, according to 48-week safety and outcome data.

Koldunov/Thinkstock

A structural analogue of glycopyrrolate working through the same mechanism, sofpironium bromide was developed as a retrometabolic agent. This means it is rapidly transformed into an inactive metabolite after application, reducing risk of systemic effects, study investigator Stacy Smith, MD, explained in the late-breaking research session at the American Academy of Dermatology Virtual Meeting Experience.

The anticholinergic glycopyrrolate, which currently is the most commonly used therapy for hyperhidrosis, is absorbed through the skin and excreted through the urine. The systemic exposure to the active agent after topical application explains the substantial risk of adverse effects, said Dr. Smith, a clinician and researcher affiliated with the California Dermatology and Clinical Research Institute, Encinitas.

In contrast,“sofpironium bromide is the ideal topical medication, because it has strong activity at the application site but then reduced systemic activity due to the retrometabolism,” Dr. Smith said.

The 52-week data from the open-label, phase 3 trial supports the premise. In this study of 299 patients randomized to the 5% (102 patients) or 15% (197 patients) topical sofpironium bromide gel formulations, most anticholinergic adverse events were mild or moderate and transient, with complaints concentrated in the first 3 months of the trial.

“The retrometabolic pathway seems to work,” Dr. Smith said. He acknowledged that the treatment-naive patients who entered the study “had to get used to the drug over time,” but the data “show they did.”

The phase 3 trial of sofpironium bromide, which is already approved to treat axillary hyperhidrosis in Japan, did not have a placebo control. It was focused primarily on safety, but outcomes were assessed with the Hyperhidrosis Disease Severity Measure–Axillary (HDSM-Ax).

At least a 1-point improvement in the 7-point HDSM-Ax scale, which is considered clinically meaningful, was achieved by 86.1% and 85.8% of those treated with the 5% and 15% gels, respectively. A 2-point or greater improvement at the end of the study was observed in 69.4% and 61.9%, respectively.

“The medication works well and there was improved efficacy over time. About two-thirds of the patients had at least a 2-point improvement in the HDSM-Ax score at the end of 48 weeks,” Dr. Smith reported.

While response rates climbed over the course of the study, rates of adverse events fell markedly.

After 2 weeks of treatment, the proportions of patients with a treatment-related adverse event were 6% and just under 15% for the 5% and 15% topical-gel groups, respectively. At each 2-week interval when reassessed, the rates fell. By week 12, the rates were less than 2% and about 4% in the two groups, respectively.

The discontinuation rates overall for anticholinergic side effects were 3% and 8.1% for the lower and higher doses. Blurred vision accounted for the vast majority of these discontinuations in both groups. The other discontinuations, which included those for dry mouth, urinary retention, and mydriasis, occurred in one patient each. Again, discontinuations were most common in the first few months of the study.

For the total study population, mild (10.8% vs. 24%) and moderate (10.8% vs. 20.3%) side effects accounted for almost all side effects with the lower and higher doses of the topical drug. Only one patient in the low-dose group had a severe adverse event. At 6.1%, the proportion of the high-dose group with a severe adverse event was higher, but none of the adverse events were considered serious. All were transient.

These rates of adverse events are lower than those reported historically with effective doses of glycopyrrolate, Dr. Smith said.

The data presented by Dr. Smith are part of a phase 3 pivotal trials program designed to gain FDA approval. Going forward, these trials, which are enrolling patients as young as 9 years old, are expected to focus on clinical development of the 15% gel, he added.

The gel is delivered with a metered-dose pump that has an applicator, according to Brickell Biotech, the company developing the treatment in the United States. The 5% formulation was approved in Japan in September 2020, for the treatment of primary axillary hyperhidrosis.

In an interview, David M. Pariser, MD, professor of dermatology, Eastern Virginia Medical School, Norfolk, said that he believes that this drug has could be helpful if the pivotal studies confirm efficacy with a lower risk of adverse events relative to glycopyrrolate. “If it is true that, in phase 3, placebo-controlled trials, there are fewer systemic anticholinergic effects, then this drug will be very useful,” said Dr. Pariser, cofounder of the International Hyperhidrosis Society and an investigator on a previously published dose-ranging, phase 2 study of sofpironium bromide.

The trial was sponsored by Brickell Biotech, which compensated Dr. Smith and other coauthors for their participation. Dr. Pariser has financial relationships with multiple pharmaceutical companies with dermatologic products, including Brickell Biotech.

This article was updated 4/26/21.

Sofpironium bromide, a new topical anticholinergic agent, appears to be a safer version of glycopyrrolate for the treatment of axillary hyperhidrosis, according to 48-week safety and outcome data.

Koldunov/Thinkstock

A structural analogue of glycopyrrolate working through the same mechanism, sofpironium bromide was developed as a retrometabolic agent. This means it is rapidly transformed into an inactive metabolite after application, reducing risk of systemic effects, study investigator Stacy Smith, MD, explained in the late-breaking research session at the American Academy of Dermatology Virtual Meeting Experience.

The anticholinergic glycopyrrolate, which currently is the most commonly used therapy for hyperhidrosis, is absorbed through the skin and excreted through the urine. The systemic exposure to the active agent after topical application explains the substantial risk of adverse effects, said Dr. Smith, a clinician and researcher affiliated with the California Dermatology and Clinical Research Institute, Encinitas.

In contrast,“sofpironium bromide is the ideal topical medication, because it has strong activity at the application site but then reduced systemic activity due to the retrometabolism,” Dr. Smith said.

The 52-week data from the open-label, phase 3 trial supports the premise. In this study of 299 patients randomized to the 5% (102 patients) or 15% (197 patients) topical sofpironium bromide gel formulations, most anticholinergic adverse events were mild or moderate and transient, with complaints concentrated in the first 3 months of the trial.

“The retrometabolic pathway seems to work,” Dr. Smith said. He acknowledged that the treatment-naive patients who entered the study “had to get used to the drug over time,” but the data “show they did.”

The phase 3 trial of sofpironium bromide, which is already approved to treat axillary hyperhidrosis in Japan, did not have a placebo control. It was focused primarily on safety, but outcomes were assessed with the Hyperhidrosis Disease Severity Measure–Axillary (HDSM-Ax).

At least a 1-point improvement in the 7-point HDSM-Ax scale, which is considered clinically meaningful, was achieved by 86.1% and 85.8% of those treated with the 5% and 15% gels, respectively. A 2-point or greater improvement at the end of the study was observed in 69.4% and 61.9%, respectively.

“The medication works well and there was improved efficacy over time. About two-thirds of the patients had at least a 2-point improvement in the HDSM-Ax score at the end of 48 weeks,” Dr. Smith reported.

While response rates climbed over the course of the study, rates of adverse events fell markedly.

After 2 weeks of treatment, the proportions of patients with a treatment-related adverse event were 6% and just under 15% for the 5% and 15% topical-gel groups, respectively. At each 2-week interval when reassessed, the rates fell. By week 12, the rates were less than 2% and about 4% in the two groups, respectively.

The discontinuation rates overall for anticholinergic side effects were 3% and 8.1% for the lower and higher doses. Blurred vision accounted for the vast majority of these discontinuations in both groups. The other discontinuations, which included those for dry mouth, urinary retention, and mydriasis, occurred in one patient each. Again, discontinuations were most common in the first few months of the study.

For the total study population, mild (10.8% vs. 24%) and moderate (10.8% vs. 20.3%) side effects accounted for almost all side effects with the lower and higher doses of the topical drug. Only one patient in the low-dose group had a severe adverse event. At 6.1%, the proportion of the high-dose group with a severe adverse event was higher, but none of the adverse events were considered serious. All were transient.

These rates of adverse events are lower than those reported historically with effective doses of glycopyrrolate, Dr. Smith said.

The data presented by Dr. Smith are part of a phase 3 pivotal trials program designed to gain FDA approval. Going forward, these trials, which are enrolling patients as young as 9 years old, are expected to focus on clinical development of the 15% gel, he added.

The gel is delivered with a metered-dose pump that has an applicator, according to Brickell Biotech, the company developing the treatment in the United States. The 5% formulation was approved in Japan in September 2020, for the treatment of primary axillary hyperhidrosis.

In an interview, David M. Pariser, MD, professor of dermatology, Eastern Virginia Medical School, Norfolk, said that he believes that this drug has could be helpful if the pivotal studies confirm efficacy with a lower risk of adverse events relative to glycopyrrolate. “If it is true that, in phase 3, placebo-controlled trials, there are fewer systemic anticholinergic effects, then this drug will be very useful,” said Dr. Pariser, cofounder of the International Hyperhidrosis Society and an investigator on a previously published dose-ranging, phase 2 study of sofpironium bromide.

The trial was sponsored by Brickell Biotech, which compensated Dr. Smith and other coauthors for their participation. Dr. Pariser has financial relationships with multiple pharmaceutical companies with dermatologic products, including Brickell Biotech.

This article was updated 4/26/21.

Sofpironium bromide, a new topical anticholinergic agent, appears to be a safer version of glycopyrrolate for the treatment of axillary hyperhidrosis, according to 48-week safety and outcome data.

Koldunov/Thinkstock

A structural analogue of glycopyrrolate working through the same mechanism, sofpironium bromide was developed as a retrometabolic agent. This means it is rapidly transformed into an inactive metabolite after application, reducing risk of systemic effects, study investigator Stacy Smith, MD, explained in the late-breaking research session at the American Academy of Dermatology Virtual Meeting Experience.

The anticholinergic glycopyrrolate, which currently is the most commonly used therapy for hyperhidrosis, is absorbed through the skin and excreted through the urine. The systemic exposure to the active agent after topical application explains the substantial risk of adverse effects, said Dr. Smith, a clinician and researcher affiliated with the California Dermatology and Clinical Research Institute, Encinitas.

In contrast,“sofpironium bromide is the ideal topical medication, because it has strong activity at the application site but then reduced systemic activity due to the retrometabolism,” Dr. Smith said.

The 52-week data from the open-label, phase 3 trial supports the premise. In this study of 299 patients randomized to the 5% (102 patients) or 15% (197 patients) topical sofpironium bromide gel formulations, most anticholinergic adverse events were mild or moderate and transient, with complaints concentrated in the first 3 months of the trial.

“The retrometabolic pathway seems to work,” Dr. Smith said. He acknowledged that the treatment-naive patients who entered the study “had to get used to the drug over time,” but the data “show they did.”

The phase 3 trial of sofpironium bromide, which is already approved to treat axillary hyperhidrosis in Japan, did not have a placebo control. It was focused primarily on safety, but outcomes were assessed with the Hyperhidrosis Disease Severity Measure–Axillary (HDSM-Ax).

At least a 1-point improvement in the 7-point HDSM-Ax scale, which is considered clinically meaningful, was achieved by 86.1% and 85.8% of those treated with the 5% and 15% gels, respectively. A 2-point or greater improvement at the end of the study was observed in 69.4% and 61.9%, respectively.

“The medication works well and there was improved efficacy over time. About two-thirds of the patients had at least a 2-point improvement in the HDSM-Ax score at the end of 48 weeks,” Dr. Smith reported.

While response rates climbed over the course of the study, rates of adverse events fell markedly.

After 2 weeks of treatment, the proportions of patients with a treatment-related adverse event were 6% and just under 15% for the 5% and 15% topical-gel groups, respectively. At each 2-week interval when reassessed, the rates fell. By week 12, the rates were less than 2% and about 4% in the two groups, respectively.

The discontinuation rates overall for anticholinergic side effects were 3% and 8.1% for the lower and higher doses. Blurred vision accounted for the vast majority of these discontinuations in both groups. The other discontinuations, which included those for dry mouth, urinary retention, and mydriasis, occurred in one patient each. Again, discontinuations were most common in the first few months of the study.

For the total study population, mild (10.8% vs. 24%) and moderate (10.8% vs. 20.3%) side effects accounted for almost all side effects with the lower and higher doses of the topical drug. Only one patient in the low-dose group had a severe adverse event. At 6.1%, the proportion of the high-dose group with a severe adverse event was higher, but none of the adverse events were considered serious. All were transient.

These rates of adverse events are lower than those reported historically with effective doses of glycopyrrolate, Dr. Smith said.

The data presented by Dr. Smith are part of a phase 3 pivotal trials program designed to gain FDA approval. Going forward, these trials, which are enrolling patients as young as 9 years old, are expected to focus on clinical development of the 15% gel, he added.

The gel is delivered with a metered-dose pump that has an applicator, according to Brickell Biotech, the company developing the treatment in the United States. The 5% formulation was approved in Japan in September 2020, for the treatment of primary axillary hyperhidrosis.

In an interview, David M. Pariser, MD, professor of dermatology, Eastern Virginia Medical School, Norfolk, said that he believes that this drug has could be helpful if the pivotal studies confirm efficacy with a lower risk of adverse events relative to glycopyrrolate. “If it is true that, in phase 3, placebo-controlled trials, there are fewer systemic anticholinergic effects, then this drug will be very useful,” said Dr. Pariser, cofounder of the International Hyperhidrosis Society and an investigator on a previously published dose-ranging, phase 2 study of sofpironium bromide.

The trial was sponsored by Brickell Biotech, which compensated Dr. Smith and other coauthors for their participation. Dr. Pariser has financial relationships with multiple pharmaceutical companies with dermatologic products, including Brickell Biotech.

This article was updated 4/26/21.