MDedge Dermatology

PORTLAND, ORE. – The recurrent boils, abscesses, and nodules of the chronic inflammatory skin condition hidradenitis suppurativa (HS) may improve during pregnancy for a subset of women, but for many, pregnancy does not change the disease course and may worsen symptoms.

In addition, HS appears to be a risk factor for adverse pregnancy and maternal outcomes.

“This is relevant, because in the United States, HS disproportionately impacts women compared with men by a ratio of about 3:1,” Jennifer Hsiao, MD, said at the annual meeting of the Pacific Dermatologic Association.

“It’s at the beginning of the third trimester that the placental transfer of antibodies picks up,” she said. “At that point in time, you can have a discussion with the patient: do you want to stay on treatment and treat through, or do you want to consider being taken off the medication? I think this is a discussion that needs to be had, because let’s say you peel off adalimumab or infliximab and they have severe HS flares. I’m not sure that leads to a better outcome. I usually treat through for my pregnant patients.”

To better understand clinician practice patterns on the management of HS in pregnancy, Dr. Hsiao and Erin Collier, MD, MPH, of University of California, Los Angeles, and colleagues distributed an online survey to HS specialists in North America. They reported the findings in the International Journal of Women’s Dermatology.

Of the 49 respondents, 36 (73%) directed an HS specialty clinic and 29 (59%) reported having prescribed or continued a biologic agent in a pregnant HS patient. The top three biologics prescribed were adalimumab (90%), infliximab (41%), and certolizumab pegol (34%). Dr. Hsiao noted that certolizumab pegol is a pegylated anti-TNF, so it lacks an Fc region on the medication.

“This means that it cannot be actively transported by the neonatal Fc receptor on the placenta, thus resulting in minimal placental transmission,” she said. “The main issue is that there is little data on its efficacy in HS, but it’s a reasonable option to consider in a pregnant patient, especially in a patient with severe HS who asks, ‘what’s the safest biologic that I can go on?’ But you’d have to discuss with the patient that in terms of efficacy data, there is much less in the literature compared to adalimumab or infliximab.”

Breastfeeding while on anti–TNF-alpha biologics is considered safe. “There are minimal amounts of medication in breast milk,” she said. “If any gets through, infant gastric digestion is thought to take care of the rest. Of note, babies born to mothers who are continually treated with biologic agents should not be given live vaccinations for 6 months after birth.”

In a single-center study, Dr. Hsiao and colleagues retrospectively examined pregnancy complications, pregnancy outcomes, and neonatal outcomes in patients with HS. The study population included 202 pregnancies in 127 HS patients. Of 134 babies born to mothers with HS, 74% were breastfed and 24% were bottle-fed, and presence of HS lesions on the breast was significantly associated with not breastfeeding.

“So, when we see these patients, if moms decide to breastfeed and they have lesions on the breast, it would be helpful to discuss expectations and perhaps treat HS breast lesions early, so the breastfeeding process may go more smoothly for them after they deliver,” said Dr. Hsiao, who is one of the editors of the textbook “A Comprehensive Guide to Hidradenitis Suppurativa” (Elsevier, 2021). Safety-related resources that she recommends for clinicians include Mother to Baby and the Drugs and Lactation Database (LactMed).

Dr. Hsiao concluded her presentation by spotlighting the influence of pregnancy on HS comorbidities. Patients with HS already have a higher prevalence of depression and anxiety compared to controls. “Pregnancy can exacerbate underlying mood disorders in patients,” she said. “That’s why monitoring the patient’s mood and coordinating mental health care with the patient’s primary care physician and ob.gyn. is important.”

In addition, pregnancy-related changes in body mass index, blood pressure, lipid metabolism, and glucose tolerance trend toward changes seen in metabolic syndrome, she said, and HS patients are already at higher risk of metabolic syndrome compared with the general population.

HS may also compromise a patient’s ability to have a healthy pregnancy. Dr. Hsiao worked with Amit Garg, MD, and colleagues on a study that drew from the IBM MarketScan Commercial Claims Database to evaluate adverse pregnancy and maternal outcomes in women with HS between Jan. 1, 2011, and Sept. 30, 2015.

After the researchers adjusted for age, race, smoking status, and other comorbidities, they found that HS pregnancies were independently associated with spontaneous abortion (odds ratio, 1.20), gestational diabetes (OR, 1.26), and cesarean section (OR, 1.09). The findings were published in the Journal of the American Academy of Dermatology.

A separate study that used the same database found comparable results, also published in the Journal of the American Academy of Dermatology. “What I say to patients right now is, ‘there are many women with HS who have healthy pregnancies and deliver healthy babies, but HS could be a risk factor for a higher-risk pregnancy.’ It’s important that these patients are established with an ob.gyn. and are closely monitored to make sure that we optimize their care and give them the best outcome possible for mom and baby.”

Dr. Hsiao disclosed that she is on the board of directors for the Hidradenitis Suppurativa Foundation. She has also served as an advisor for Novartis, UCB, and Boehringer Ingelheim and as a speaker and advisor for AbbVie.

PORTLAND, ORE. – The recurrent boils, abscesses, and nodules of the chronic inflammatory skin condition hidradenitis suppurativa (HS) may improve during pregnancy for a subset of women, but for many, pregnancy does not change the disease course and may worsen symptoms.

In addition, HS appears to be a risk factor for adverse pregnancy and maternal outcomes.

“This is relevant, because in the United States, HS disproportionately impacts women compared with men by a ratio of about 3:1,” Jennifer Hsiao, MD, said at the annual meeting of the Pacific Dermatologic Association.

“It’s at the beginning of the third trimester that the placental transfer of antibodies picks up,” she said. “At that point in time, you can have a discussion with the patient: do you want to stay on treatment and treat through, or do you want to consider being taken off the medication? I think this is a discussion that needs to be had, because let’s say you peel off adalimumab or infliximab and they have severe HS flares. I’m not sure that leads to a better outcome. I usually treat through for my pregnant patients.”

To better understand clinician practice patterns on the management of HS in pregnancy, Dr. Hsiao and Erin Collier, MD, MPH, of University of California, Los Angeles, and colleagues distributed an online survey to HS specialists in North America. They reported the findings in the International Journal of Women’s Dermatology.

Of the 49 respondents, 36 (73%) directed an HS specialty clinic and 29 (59%) reported having prescribed or continued a biologic agent in a pregnant HS patient. The top three biologics prescribed were adalimumab (90%), infliximab (41%), and certolizumab pegol (34%). Dr. Hsiao noted that certolizumab pegol is a pegylated anti-TNF, so it lacks an Fc region on the medication.

“This means that it cannot be actively transported by the neonatal Fc receptor on the placenta, thus resulting in minimal placental transmission,” she said. “The main issue is that there is little data on its efficacy in HS, but it’s a reasonable option to consider in a pregnant patient, especially in a patient with severe HS who asks, ‘what’s the safest biologic that I can go on?’ But you’d have to discuss with the patient that in terms of efficacy data, there is much less in the literature compared to adalimumab or infliximab.”

Breastfeeding while on anti–TNF-alpha biologics is considered safe. “There are minimal amounts of medication in breast milk,” she said. “If any gets through, infant gastric digestion is thought to take care of the rest. Of note, babies born to mothers who are continually treated with biologic agents should not be given live vaccinations for 6 months after birth.”

In a single-center study, Dr. Hsiao and colleagues retrospectively examined pregnancy complications, pregnancy outcomes, and neonatal outcomes in patients with HS. The study population included 202 pregnancies in 127 HS patients. Of 134 babies born to mothers with HS, 74% were breastfed and 24% were bottle-fed, and presence of HS lesions on the breast was significantly associated with not breastfeeding.

“So, when we see these patients, if moms decide to breastfeed and they have lesions on the breast, it would be helpful to discuss expectations and perhaps treat HS breast lesions early, so the breastfeeding process may go more smoothly for them after they deliver,” said Dr. Hsiao, who is one of the editors of the textbook “A Comprehensive Guide to Hidradenitis Suppurativa” (Elsevier, 2021). Safety-related resources that she recommends for clinicians include Mother to Baby and the Drugs and Lactation Database (LactMed).

Dr. Hsiao concluded her presentation by spotlighting the influence of pregnancy on HS comorbidities. Patients with HS already have a higher prevalence of depression and anxiety compared to controls. “Pregnancy can exacerbate underlying mood disorders in patients,” she said. “That’s why monitoring the patient’s mood and coordinating mental health care with the patient’s primary care physician and ob.gyn. is important.”

In addition, pregnancy-related changes in body mass index, blood pressure, lipid metabolism, and glucose tolerance trend toward changes seen in metabolic syndrome, she said, and HS patients are already at higher risk of metabolic syndrome compared with the general population.

HS may also compromise a patient’s ability to have a healthy pregnancy. Dr. Hsiao worked with Amit Garg, MD, and colleagues on a study that drew from the IBM MarketScan Commercial Claims Database to evaluate adverse pregnancy and maternal outcomes in women with HS between Jan. 1, 2011, and Sept. 30, 2015.

After the researchers adjusted for age, race, smoking status, and other comorbidities, they found that HS pregnancies were independently associated with spontaneous abortion (odds ratio, 1.20), gestational diabetes (OR, 1.26), and cesarean section (OR, 1.09). The findings were published in the Journal of the American Academy of Dermatology.

A separate study that used the same database found comparable results, also published in the Journal of the American Academy of Dermatology. “What I say to patients right now is, ‘there are many women with HS who have healthy pregnancies and deliver healthy babies, but HS could be a risk factor for a higher-risk pregnancy.’ It’s important that these patients are established with an ob.gyn. and are closely monitored to make sure that we optimize their care and give them the best outcome possible for mom and baby.”

Dr. Hsiao disclosed that she is on the board of directors for the Hidradenitis Suppurativa Foundation. She has also served as an advisor for Novartis, UCB, and Boehringer Ingelheim and as a speaker and advisor for AbbVie.

PORTLAND, ORE. – The recurrent boils, abscesses, and nodules of the chronic inflammatory skin condition hidradenitis suppurativa (HS) may improve during pregnancy for a subset of women, but for many, pregnancy does not change the disease course and may worsen symptoms.

In addition, HS appears to be a risk factor for adverse pregnancy and maternal outcomes.

“This is relevant, because in the United States, HS disproportionately impacts women compared with men by a ratio of about 3:1,” Jennifer Hsiao, MD, said at the annual meeting of the Pacific Dermatologic Association.

“It’s at the beginning of the third trimester that the placental transfer of antibodies picks up,” she said. “At that point in time, you can have a discussion with the patient: do you want to stay on treatment and treat through, or do you want to consider being taken off the medication? I think this is a discussion that needs to be had, because let’s say you peel off adalimumab or infliximab and they have severe HS flares. I’m not sure that leads to a better outcome. I usually treat through for my pregnant patients.”

To better understand clinician practice patterns on the management of HS in pregnancy, Dr. Hsiao and Erin Collier, MD, MPH, of University of California, Los Angeles, and colleagues distributed an online survey to HS specialists in North America. They reported the findings in the International Journal of Women’s Dermatology.

Of the 49 respondents, 36 (73%) directed an HS specialty clinic and 29 (59%) reported having prescribed or continued a biologic agent in a pregnant HS patient. The top three biologics prescribed were adalimumab (90%), infliximab (41%), and certolizumab pegol (34%). Dr. Hsiao noted that certolizumab pegol is a pegylated anti-TNF, so it lacks an Fc region on the medication.

“This means that it cannot be actively transported by the neonatal Fc receptor on the placenta, thus resulting in minimal placental transmission,” she said. “The main issue is that there is little data on its efficacy in HS, but it’s a reasonable option to consider in a pregnant patient, especially in a patient with severe HS who asks, ‘what’s the safest biologic that I can go on?’ But you’d have to discuss with the patient that in terms of efficacy data, there is much less in the literature compared to adalimumab or infliximab.”

Breastfeeding while on anti–TNF-alpha biologics is considered safe. “There are minimal amounts of medication in breast milk,” she said. “If any gets through, infant gastric digestion is thought to take care of the rest. Of note, babies born to mothers who are continually treated with biologic agents should not be given live vaccinations for 6 months after birth.”

In a single-center study, Dr. Hsiao and colleagues retrospectively examined pregnancy complications, pregnancy outcomes, and neonatal outcomes in patients with HS. The study population included 202 pregnancies in 127 HS patients. Of 134 babies born to mothers with HS, 74% were breastfed and 24% were bottle-fed, and presence of HS lesions on the breast was significantly associated with not breastfeeding.

“So, when we see these patients, if moms decide to breastfeed and they have lesions on the breast, it would be helpful to discuss expectations and perhaps treat HS breast lesions early, so the breastfeeding process may go more smoothly for them after they deliver,” said Dr. Hsiao, who is one of the editors of the textbook “A Comprehensive Guide to Hidradenitis Suppurativa” (Elsevier, 2021). Safety-related resources that she recommends for clinicians include Mother to Baby and the Drugs and Lactation Database (LactMed).

Dr. Hsiao concluded her presentation by spotlighting the influence of pregnancy on HS comorbidities. Patients with HS already have a higher prevalence of depression and anxiety compared to controls. “Pregnancy can exacerbate underlying mood disorders in patients,” she said. “That’s why monitoring the patient’s mood and coordinating mental health care with the patient’s primary care physician and ob.gyn. is important.”

In addition, pregnancy-related changes in body mass index, blood pressure, lipid metabolism, and glucose tolerance trend toward changes seen in metabolic syndrome, she said, and HS patients are already at higher risk of metabolic syndrome compared with the general population.

HS may also compromise a patient’s ability to have a healthy pregnancy. Dr. Hsiao worked with Amit Garg, MD, and colleagues on a study that drew from the IBM MarketScan Commercial Claims Database to evaluate adverse pregnancy and maternal outcomes in women with HS between Jan. 1, 2011, and Sept. 30, 2015.

After the researchers adjusted for age, race, smoking status, and other comorbidities, they found that HS pregnancies were independently associated with spontaneous abortion (odds ratio, 1.20), gestational diabetes (OR, 1.26), and cesarean section (OR, 1.09). The findings were published in the Journal of the American Academy of Dermatology.

A separate study that used the same database found comparable results, also published in the Journal of the American Academy of Dermatology. “What I say to patients right now is, ‘there are many women with HS who have healthy pregnancies and deliver healthy babies, but HS could be a risk factor for a higher-risk pregnancy.’ It’s important that these patients are established with an ob.gyn. and are closely monitored to make sure that we optimize their care and give them the best outcome possible for mom and baby.”

Dr. Hsiao disclosed that she is on the board of directors for the Hidradenitis Suppurativa Foundation. She has also served as an advisor for Novartis, UCB, and Boehringer Ingelheim and as a speaker and advisor for AbbVie.

Stress, meet weight gain. Weight gain, meet stress

You’re not eating differently and you’re keeping active, but your waistline is expanding. How is that happening? Since eating healthy and exercising shouldn’t make you gain weight, there may be a hidden factor getting in your way. Stress. The one thing that can have a grip on your circadian rhythm stronger than any bodybuilder.

Francesca Bellini/iStock/Getty Images

Investigators at Weill Cornell Medicine published two mouse studies that suggest stress and other factors that throw the body’s circadian clocks out of rhythm may contribute to weight gain.

In the first study, the researchers imitated disruptive condition effects like high cortisol exposure and chronic stress by implanting pellets under the skin that released glucocorticoid at a constant rate for 21 days. Mice that received the pellets had twice as much white and brown fat, as well as much higher insulin levels, regardless of their unchanged and still-healthy diet.

In the second study, they used tagged proteins as markers to monitor the daily fluctuations of a protein that regulates fat cell production and circadian gene expression in mouse fat cell precursors. The results showed “that fat cell precursors commit to becoming fat cells only during the circadian cycle phase corresponding to evening in humans,” they said in a written statement.

“Every cell in our body has an intrinsic cell clock, just like the fat cells, and we have a master clock in our brain, which controls hormone secretion,” said senior author Mary Teruel of Cornell University. “A lot of forces are working against a healthy metabolism when we are out of circadian rhythm. The more we understand, the more likely we will be able to do something about it.”

So if you’re stressing out that the scale is or isn’t moving in the direction you want, you could be standing in your own way. Take a chill pill.
 

Who can smell cancer? The locust nose

If you need to smell some gas, there’s nothing better than a nose. Just ask a scientist: “Noses are still state of the art,” said Debajit Saha, PhD, of Michigan State University. “There’s really nothing like them when it comes to gas sensing.”

Derrick L. Turner

And when it comes to noses, dogs are best, right? After all, there’s a reason we don’t have bomb-sniffing wombats and drug-sniffing ostriches. Dogs are better. Better, but not perfect. And if they’re not perfect, then human technology can do better.

Enter the electronic nose. Which is better than dogs … except that it isn’t. “People have been working on ‘electronic noses’ for more than 15 years, but they’re still not close to achieving what biology can do seamlessly,” Dr. Saha explained in a statement from the university.

Which brings us back to dogs. If you want to detect early-stage cancer using smell, you go to the dogs, right? Nope.

Here’s Christopher Contag, PhD, also of Michigan State, who recruited Dr. Saha to the university: “I told him, ‘When you come here, we’ll detect cancer. I’m sure your locusts can do it.’ ”

Yes, locusts. Dr. Contag and his research team were looking at mouth cancers and noticed that different cell lines had different appearances. Then they discovered that those different-looking cell lines produced different metabolites, some of which were volatile.

Enter Dr. Saha’s locusts. They were able to tell the difference between normal cells and cancer cells and could even distinguish between the different cell lines. And how they were able to share this information? Not voluntarily, that’s for sure. The researchers attached electrodes to the insects’ brains and recorded their responses to gas samples from both healthy and cancer cells. Those brain signals were then used to create chemical profiles of the different cells. Piece of cake.

The whole getting-electrodes-attached-to-their-brains thing seemed at least a bit ethically ambiguous, so we contacted the locusts’ PR office, which offered some positive spin: “Humans get their early cancer detection and we get that whole swarms-that-devour-entire-countrysides thing off our backs. Win win.”
 

Bad news for vampires everywhere

Pop culture has been extraordinarily kind to the vampire. A few hundred years ago, vampires were demon-possessed, often-inhuman monsters. Now? They’re suave, sophisticated, beautiful, and oh-so dramatic and angst-filled about their “curse.” Drink a little human blood, live and look young forever. Such monsters they are.

eakkachaister/Thinkstock

It does make sense in a morbid sort of way. An old person receiving the blood of the young does seem like a good idea for rejuvenation, right? A team of Ukrainian researchers sought to find out, conducting a study in which older mice were linked with young mice via heterochronic parabiosis. For 3 months, old-young mice pairs were surgically connected and shared blood. After 3 months, the mice were disconnected from each other and the effects of the blood link were studied.

For all the vampire enthusiasts out there, we have bad news and worse news. The bad news first: The older mice received absolutely no benefit from heterochronic parabiosis. No youthfulness, no increased lifespan, nothing. The worse news is that the younger mice were adversely affected by the older blood. They aged more and experienced a shortened lifespan, even after the connection was severed. The old blood, according to the investigators, contains factors capable of inducing aging in younger mice, but the opposite is not true. Further research into aging, they added, should focus on suppressing the aging factors in older blood.

Of note, the paper was written by doctors who are currently refugees, fleeing the war in Ukraine. We don’t want to speculate on the true cause of the war, but we’re onto you, Putin. We know you wanted the vampire research for yourself, but it won’t work. Your dream of becoming Vlad “Dracula” Putin will never come to pass.
 

Hearing is not always believing

Have you ever heard yourself on a voice mail, or from a recording you did at work? No matter how good you sound, you still might feel like the recording sounds nothing like you. It may even cause low self-esteem for those who don’t like how their voice sounds or don’t recognize it when it’s played back to them.

Hiroshi Imamizu, University of Tokyo

Since one possible symptom of schizophrenia is not recognizing one’s own speech and having a false sense of control over actions, and those with schizophrenia may hallucinate or hear voices, not being able to recognize their own voices may be alarming.

A recent study on the sense of agency, or sense of control, involved having volunteers speak with different pitches in their voices and then having it played back to them to gauge their reactions.

“Our results demonstrate that hearing one’s own voice is a critical factor to increased self-agency over speech. In other words, we do not strongly feel that ‘I’ am generating the speech if we hear someone else’s voice as an outcome of the speech. Our study provides empirical evidence of the tight link between the sense of agency and self-voice identity,” lead author Ryu Ohata, PhD, of the University of Tokyo, said in a written statement.

As social interaction becomes more digital through platforms such as FaceTime, Zoom, and voicemail, especially since the pandemic has promoted social distancing, it makes sense that people may be more aware and more surprised by how they sound on recordings.

So, if you ever promised someone something that you don’t want to do, and they play it back to you from the recording you made, maybe you can just say you don’t recognize the voice. And if it’s not you, then you don’t have to do it.
 

Stress, meet weight gain. Weight gain, meet stress

You’re not eating differently and you’re keeping active, but your waistline is expanding. How is that happening? Since eating healthy and exercising shouldn’t make you gain weight, there may be a hidden factor getting in your way. Stress. The one thing that can have a grip on your circadian rhythm stronger than any bodybuilder.

Francesca Bellini/iStock/Getty Images

Investigators at Weill Cornell Medicine published two mouse studies that suggest stress and other factors that throw the body’s circadian clocks out of rhythm may contribute to weight gain.

In the first study, the researchers imitated disruptive condition effects like high cortisol exposure and chronic stress by implanting pellets under the skin that released glucocorticoid at a constant rate for 21 days. Mice that received the pellets had twice as much white and brown fat, as well as much higher insulin levels, regardless of their unchanged and still-healthy diet.

In the second study, they used tagged proteins as markers to monitor the daily fluctuations of a protein that regulates fat cell production and circadian gene expression in mouse fat cell precursors. The results showed “that fat cell precursors commit to becoming fat cells only during the circadian cycle phase corresponding to evening in humans,” they said in a written statement.

“Every cell in our body has an intrinsic cell clock, just like the fat cells, and we have a master clock in our brain, which controls hormone secretion,” said senior author Mary Teruel of Cornell University. “A lot of forces are working against a healthy metabolism when we are out of circadian rhythm. The more we understand, the more likely we will be able to do something about it.”

So if you’re stressing out that the scale is or isn’t moving in the direction you want, you could be standing in your own way. Take a chill pill.
 

Who can smell cancer? The locust nose

If you need to smell some gas, there’s nothing better than a nose. Just ask a scientist: “Noses are still state of the art,” said Debajit Saha, PhD, of Michigan State University. “There’s really nothing like them when it comes to gas sensing.”

Derrick L. Turner

And when it comes to noses, dogs are best, right? After all, there’s a reason we don’t have bomb-sniffing wombats and drug-sniffing ostriches. Dogs are better. Better, but not perfect. And if they’re not perfect, then human technology can do better.

Enter the electronic nose. Which is better than dogs … except that it isn’t. “People have been working on ‘electronic noses’ for more than 15 years, but they’re still not close to achieving what biology can do seamlessly,” Dr. Saha explained in a statement from the university.

Which brings us back to dogs. If you want to detect early-stage cancer using smell, you go to the dogs, right? Nope.

Here’s Christopher Contag, PhD, also of Michigan State, who recruited Dr. Saha to the university: “I told him, ‘When you come here, we’ll detect cancer. I’m sure your locusts can do it.’ ”

Yes, locusts. Dr. Contag and his research team were looking at mouth cancers and noticed that different cell lines had different appearances. Then they discovered that those different-looking cell lines produced different metabolites, some of which were volatile.

Enter Dr. Saha’s locusts. They were able to tell the difference between normal cells and cancer cells and could even distinguish between the different cell lines. And how they were able to share this information? Not voluntarily, that’s for sure. The researchers attached electrodes to the insects’ brains and recorded their responses to gas samples from both healthy and cancer cells. Those brain signals were then used to create chemical profiles of the different cells. Piece of cake.

The whole getting-electrodes-attached-to-their-brains thing seemed at least a bit ethically ambiguous, so we contacted the locusts’ PR office, which offered some positive spin: “Humans get their early cancer detection and we get that whole swarms-that-devour-entire-countrysides thing off our backs. Win win.”
 

Bad news for vampires everywhere

Pop culture has been extraordinarily kind to the vampire. A few hundred years ago, vampires were demon-possessed, often-inhuman monsters. Now? They’re suave, sophisticated, beautiful, and oh-so dramatic and angst-filled about their “curse.” Drink a little human blood, live and look young forever. Such monsters they are.

eakkachaister/Thinkstock

It does make sense in a morbid sort of way. An old person receiving the blood of the young does seem like a good idea for rejuvenation, right? A team of Ukrainian researchers sought to find out, conducting a study in which older mice were linked with young mice via heterochronic parabiosis. For 3 months, old-young mice pairs were surgically connected and shared blood. After 3 months, the mice were disconnected from each other and the effects of the blood link were studied.

For all the vampire enthusiasts out there, we have bad news and worse news. The bad news first: The older mice received absolutely no benefit from heterochronic parabiosis. No youthfulness, no increased lifespan, nothing. The worse news is that the younger mice were adversely affected by the older blood. They aged more and experienced a shortened lifespan, even after the connection was severed. The old blood, according to the investigators, contains factors capable of inducing aging in younger mice, but the opposite is not true. Further research into aging, they added, should focus on suppressing the aging factors in older blood.

Of note, the paper was written by doctors who are currently refugees, fleeing the war in Ukraine. We don’t want to speculate on the true cause of the war, but we’re onto you, Putin. We know you wanted the vampire research for yourself, but it won’t work. Your dream of becoming Vlad “Dracula” Putin will never come to pass.
 

Hearing is not always believing

Have you ever heard yourself on a voice mail, or from a recording you did at work? No matter how good you sound, you still might feel like the recording sounds nothing like you. It may even cause low self-esteem for those who don’t like how their voice sounds or don’t recognize it when it’s played back to them.

Hiroshi Imamizu, University of Tokyo

Since one possible symptom of schizophrenia is not recognizing one’s own speech and having a false sense of control over actions, and those with schizophrenia may hallucinate or hear voices, not being able to recognize their own voices may be alarming.

A recent study on the sense of agency, or sense of control, involved having volunteers speak with different pitches in their voices and then having it played back to them to gauge their reactions.

“Our results demonstrate that hearing one’s own voice is a critical factor to increased self-agency over speech. In other words, we do not strongly feel that ‘I’ am generating the speech if we hear someone else’s voice as an outcome of the speech. Our study provides empirical evidence of the tight link between the sense of agency and self-voice identity,” lead author Ryu Ohata, PhD, of the University of Tokyo, said in a written statement.

As social interaction becomes more digital through platforms such as FaceTime, Zoom, and voicemail, especially since the pandemic has promoted social distancing, it makes sense that people may be more aware and more surprised by how they sound on recordings.

So, if you ever promised someone something that you don’t want to do, and they play it back to you from the recording you made, maybe you can just say you don’t recognize the voice. And if it’s not you, then you don’t have to do it.
 

Stress, meet weight gain. Weight gain, meet stress

You’re not eating differently and you’re keeping active, but your waistline is expanding. How is that happening? Since eating healthy and exercising shouldn’t make you gain weight, there may be a hidden factor getting in your way. Stress. The one thing that can have a grip on your circadian rhythm stronger than any bodybuilder.

Francesca Bellini/iStock/Getty Images

Investigators at Weill Cornell Medicine published two mouse studies that suggest stress and other factors that throw the body’s circadian clocks out of rhythm may contribute to weight gain.

In the first study, the researchers imitated disruptive condition effects like high cortisol exposure and chronic stress by implanting pellets under the skin that released glucocorticoid at a constant rate for 21 days. Mice that received the pellets had twice as much white and brown fat, as well as much higher insulin levels, regardless of their unchanged and still-healthy diet.

In the second study, they used tagged proteins as markers to monitor the daily fluctuations of a protein that regulates fat cell production and circadian gene expression in mouse fat cell precursors. The results showed “that fat cell precursors commit to becoming fat cells only during the circadian cycle phase corresponding to evening in humans,” they said in a written statement.

“Every cell in our body has an intrinsic cell clock, just like the fat cells, and we have a master clock in our brain, which controls hormone secretion,” said senior author Mary Teruel of Cornell University. “A lot of forces are working against a healthy metabolism when we are out of circadian rhythm. The more we understand, the more likely we will be able to do something about it.”

So if you’re stressing out that the scale is or isn’t moving in the direction you want, you could be standing in your own way. Take a chill pill.
 

Who can smell cancer? The locust nose

If you need to smell some gas, there’s nothing better than a nose. Just ask a scientist: “Noses are still state of the art,” said Debajit Saha, PhD, of Michigan State University. “There’s really nothing like them when it comes to gas sensing.”

Derrick L. Turner

And when it comes to noses, dogs are best, right? After all, there’s a reason we don’t have bomb-sniffing wombats and drug-sniffing ostriches. Dogs are better. Better, but not perfect. And if they’re not perfect, then human technology can do better.

Enter the electronic nose. Which is better than dogs … except that it isn’t. “People have been working on ‘electronic noses’ for more than 15 years, but they’re still not close to achieving what biology can do seamlessly,” Dr. Saha explained in a statement from the university.

Which brings us back to dogs. If you want to detect early-stage cancer using smell, you go to the dogs, right? Nope.

Here’s Christopher Contag, PhD, also of Michigan State, who recruited Dr. Saha to the university: “I told him, ‘When you come here, we’ll detect cancer. I’m sure your locusts can do it.’ ”

Yes, locusts. Dr. Contag and his research team were looking at mouth cancers and noticed that different cell lines had different appearances. Then they discovered that those different-looking cell lines produced different metabolites, some of which were volatile.

Enter Dr. Saha’s locusts. They were able to tell the difference between normal cells and cancer cells and could even distinguish between the different cell lines. And how they were able to share this information? Not voluntarily, that’s for sure. The researchers attached electrodes to the insects’ brains and recorded their responses to gas samples from both healthy and cancer cells. Those brain signals were then used to create chemical profiles of the different cells. Piece of cake.

The whole getting-electrodes-attached-to-their-brains thing seemed at least a bit ethically ambiguous, so we contacted the locusts’ PR office, which offered some positive spin: “Humans get their early cancer detection and we get that whole swarms-that-devour-entire-countrysides thing off our backs. Win win.”
 

Bad news for vampires everywhere

Pop culture has been extraordinarily kind to the vampire. A few hundred years ago, vampires were demon-possessed, often-inhuman monsters. Now? They’re suave, sophisticated, beautiful, and oh-so dramatic and angst-filled about their “curse.” Drink a little human blood, live and look young forever. Such monsters they are.

eakkachaister/Thinkstock

It does make sense in a morbid sort of way. An old person receiving the blood of the young does seem like a good idea for rejuvenation, right? A team of Ukrainian researchers sought to find out, conducting a study in which older mice were linked with young mice via heterochronic parabiosis. For 3 months, old-young mice pairs were surgically connected and shared blood. After 3 months, the mice were disconnected from each other and the effects of the blood link were studied.

For all the vampire enthusiasts out there, we have bad news and worse news. The bad news first: The older mice received absolutely no benefit from heterochronic parabiosis. No youthfulness, no increased lifespan, nothing. The worse news is that the younger mice were adversely affected by the older blood. They aged more and experienced a shortened lifespan, even after the connection was severed. The old blood, according to the investigators, contains factors capable of inducing aging in younger mice, but the opposite is not true. Further research into aging, they added, should focus on suppressing the aging factors in older blood.

Of note, the paper was written by doctors who are currently refugees, fleeing the war in Ukraine. We don’t want to speculate on the true cause of the war, but we’re onto you, Putin. We know you wanted the vampire research for yourself, but it won’t work. Your dream of becoming Vlad “Dracula” Putin will never come to pass.
 

Hearing is not always believing

Have you ever heard yourself on a voice mail, or from a recording you did at work? No matter how good you sound, you still might feel like the recording sounds nothing like you. It may even cause low self-esteem for those who don’t like how their voice sounds or don’t recognize it when it’s played back to them.

Hiroshi Imamizu, University of Tokyo

Since one possible symptom of schizophrenia is not recognizing one’s own speech and having a false sense of control over actions, and those with schizophrenia may hallucinate or hear voices, not being able to recognize their own voices may be alarming.

A recent study on the sense of agency, or sense of control, involved having volunteers speak with different pitches in their voices and then having it played back to them to gauge their reactions.

“Our results demonstrate that hearing one’s own voice is a critical factor to increased self-agency over speech. In other words, we do not strongly feel that ‘I’ am generating the speech if we hear someone else’s voice as an outcome of the speech. Our study provides empirical evidence of the tight link between the sense of agency and self-voice identity,” lead author Ryu Ohata, PhD, of the University of Tokyo, said in a written statement.

As social interaction becomes more digital through platforms such as FaceTime, Zoom, and voicemail, especially since the pandemic has promoted social distancing, it makes sense that people may be more aware and more surprised by how they sound on recordings.

So, if you ever promised someone something that you don’t want to do, and they play it back to you from the recording you made, maybe you can just say you don’t recognize the voice. And if it’s not you, then you don’t have to do it.
 

Acute generalized pustular psoriasis (GPP) is a rare severe variant of psoriasis characterized by the sudden widespread eruption of sterile pustules.^1,2 The cutaneous manifestations of GPP also may be accompanied by signs of systemic inflammation, including fever, malaise, and leukocytosis.² Complications are common and may be life-threatening, especially in older patients with comorbid diseases.³ Generalized pustular psoriasis most commonly occurs in patients with a preceding history of psoriasis, but it also may occur de novo.⁴ Generalized pustular psoriasis is associated with notable morbidity and mortality, and relapses are common.^3,4 Many triggers of GPP have been identified, including initiation and withdrawal of various medications, infections, pregnancy, and other conditions.^5,6 Although GPP most often occurs in adults, it also may arise in children and infants.³ In pregnancy, GPP is referred to as impetigo herpetiformis, despite having no etiologic ties with either herpes simplex virus or staphylococcal or streptococcal infection. Impetigo herpetiformis is considered one of the most dangerous dermatoses of pregnancy because of high rates of associated maternal and fetal morbidity.^6,7

Acute GPP has proven to be a challenging disease to treat due to the rarity and relapsing-remitting nature of the disease; additionally, there are relatively few randomized controlled trials investigating the efficacy and safety of treatments for GPP. This review summarizes the features of GPP, including the pathophysiology of the disease, clinical and histological manifestations, and recommendations for management based on a PubMed search of articles indexed for MEDLINE using MeSH terms pertaining to the disease, including generalized pustular psoriasis, impetigo herpetiformis, and von Zumbusch psoriasis.

Pathophysiology

The pathophysiology of GPP is only partially understood, but it is thought to have a distinct pattern of immune activation compared with plaque psoriasis.⁸ Although there is a considerable amount of overlap and cross-talk among cytokine pathways, GPP generally is driven by innate immunity and unrestrained IL-36 cytokine activity. In contrast, adaptive immune responses—namely the tumor necrosis factor (TNF) α, IL-23, IL-17, and IL-22 axes—underlie plaque psoriasis.^8-10

Proinflammatory IL-36 cytokines α, β, and γ, which are all part of the IL-1 superfamily, bind to the IL-36 receptor (IL-36R) to recruit and activate immune cells via various mediators, including IL-1β; IL-8; and chemokines CXCL1, CXCL2, and CXCL8.³ The IL-36 receptor antagonist (IL-36ra) acts to inhibit this inflammatory cascade.^3,8 Microarray analyses of skin biopsy samples have shown that overexpression of IL-17A, TNF-α, IL-1, and IL-36 are seen in both GPP and plaque psoriasis lesions, but GPP lesions had higher expression of IL-1β, IL-36α, and IL-36γ and elevated neutrophil chemokines—CXCL1, CXCL2, and CXCL8—compared with plaque psoriasis lesions.⁸

Gene Mutations Associated With GPP

There are 3 gene mutations that have been associated with pustular variants of psoriasis, though these mutations account for a minority of cases of GPP.⁴ Genetic screenings are not routinely indicated in patients with GPP, but they may be warranted in severe cases when a familial pattern of inheritance is suspected.⁴

IL36RN—The gene IL36RN codes the anti-inflammatory IL-36ra. Loss-of-function mutations in IL36RN lead to impairment of IL-36ra and consequently hyperactivity of the proinflammatory responses triggered by IL-36.³ Homozygous and heterozygous mutations in IL36RN have been observed in both familial and sporadic cases of GPP.^11-13 Subsequent retrospective analyses have identified the presence of IL36RN mutations in patients with GPP with frequencies ranging from 23% to 37%.^14-17IL36RN mutations are thought to be more common in patients without concomitant plaque psoriasis and have been associated with severe disease and early disease onset.¹⁵

CARD14—A gain-of-function mutation in CARD14 results in overactivation of the proinflammatory nuclear factor κB pathway and has been implicated in cases of GPP with concurrent psoriasis vulgaris. Interestingly, this may suggest distinct etiologies underlying GPP de novo and GPP in patients with a history of psoriasis.^18,19

AP1S3—A loss-of-function mutation in AP1S3 results in abnormal endosomal trafficking and autophagy as well as increased expression of IL-36α.^20,21

Clinical Presentation and DiagnosisCutaneous Manifestations of GPP

Generalized pustular psoriasis is characterized by the onset of widespread 2- to 3-mm sterile pustules on erythematous skin or within psoriasiform plaques⁴ (Figure). In patients with skin of color, the erythema may appear less obvious or perhaps slightly violaceous compared to White skin. Pustules may coalesce to form “lakes” of pus.⁵ Cutaneous symptoms include pain, burning, and pruritus. Associated mucosal findings may include cheilitis, geographic tongue, conjunctivitis, and uveitis.⁴

The severity of symptoms can vary greatly among patients as well as between flares within the same patient.^2,3 Four distinct patterns of GPP have been described. The von Zumbusch pattern is characterized by a rapid, generalized, painful, erythematous and pustular eruption accompanied by fever and asthenia. The pustules usually resolve after several days with extensive scaling. The annular pattern is characterized by annular, erythematous, scaly lesions with pustules present centrifugally. The lesions enlarge by centrifugal expansion over a period of hours to days, while healing occurs centrally. The exanthematic type is an acute eruption of small pustules that abruptly appear and disappear within a few days, usually from infection or medication initiation. Sometimes pustules appear within or at the edge of existing psoriatic plaques in a localized pattern—the fourth pattern—often following the exposure to irritants (eg, tars, anthralin).⁵

Impetigo Herpetiformis—Impetigo herpetiformis is a form of GPP associated with pregnancy. It generally presents early in the third trimester with symmetric erythematous plaques in flexural and intertriginous areas with pustules present at lesion margins. Lesions expand centrifugally, with pustulation present at the advancing edge.^6,7 Patients often are acutely ill with fever, delirium, vomiting, and tetany. Mucous membranes, including the tongue, mouth, and esophagus, also may be involved. The eruption typically resolves after delivery, though it often recurs with subsequent pregnancies, with the morbidity risk rising with each successive pregnancy.⁷

Systemic and Extracutaneous Manifestations of GPP

Although the severity of GPP is highly variable, skin manifestations often are accompanied by systemic manifestations of inflammation, including fever and malaise. Common laboratory abnormalities include leukocytosis with peripheral neutrophilia, a high serum C-reactive protein level, hypocalcemia, and hypoalbuminemia.²² Abnormal liver enzymes often are present and result from neutrophilic cholangitis, with alternating strictures and dilations of biliary ducts observed on magnetic resonance imaging.²³ Additional laboratory abnormalities are provided in Table 2. Other extracutaneous findings associated with GPP include arthralgia, edema, and characteristic psoriatic nail changes.⁴ Fatal complications include acute respiratory distress syndrome, renal dysfunction, cardiovascular shock, and sepsis.^24,25

Histologic Features

Given the potential for the skin manifestations of GPP to mimic other disorders, a skin biopsy is warranted to confirm the diagnosis. Generalized pustular psoriasis is histologically characterized by the presence of subcorneal macropustules (ie, spongiform pustules of Kogoj) formed by neutrophil infiltration into the spongelike network of the epidermis.⁶ Otherwise, the architecture of the epithelium in GPP is similar to that seen with plaque psoriasis, with parakeratosis, acanthosis, rete-ridge elongation, diminished stratum granulosum, and thinning of the suprapapillary epidermis, though the inflammatory cell infiltrate and edema are markedly more severe in GPP than plaque psoriasis.^3,4

Differential Diagnosis

There are many other cutaneous pustular diagnoses that must be ruled out when evaluating a patient with GPP (Table 1).²⁶ Acute generalized exanthematous pustulosis (AGEP) is a common mimicker of GPP that is differentiated histologically by the presence of eosinophils and necrotic keratinocytes.⁴ In addition to its distinct histopathologic findings, AGEP is classically associated with recent initiation of certain medications, most commonly penicillins, macrolides, quinolones, sulfonamides, terbinafine, and diltiazem.²⁷ In contrast, GPP more commonly is related to withdrawal of corticosteroids as well as initiation of some biologic medications, including anti-TNF agents.³ Generalized pustular psoriasis should be suspected over AGEP in patients with a personal or family history of psoriasis, though GPP may arise in patients with or without a history of psoriasis. Acute generalized exanthematous pustulosis usually is more abrupt in both onset and resolution compared with GPP, with clearance of pustules within a few days to weeks following cessation of the triggering factor.⁴

Other pustular variants of psoriasis (eg, palmoplantar pustular psoriasis, acrodermatitis continua of Hallopeau) are differentiated from GPP by their chronicity and localization to palmoplantar and/or ungual surfaces.⁵ Other differential diagnoses are listed in Table 1.

Diagnostic Criteria for GPP

Diagnostic criteria have been proposed for GPP (Table 2), including (1) the presence of sterile pustules, (2) systemic signs of inflammation, (3) laboratory abnormalities, (4) histopathologic confirmation of spongiform pustules of Kogoj, and (5) recurrence of symptoms.²² To definitively diagnose GPP, all 5 criteria must be met. To rule out mimickers, it may be worthwhile to perform Gram staining, potassium hydroxide preparation, in vitro cultures, and/or immunofluorescence testing.⁶

Treatment

Given the high potential for mortality associated with GPP, the most essential component of management is to ensure adequate supportive care. Any temperature, fluid, or electrolyte imbalances should be corrected as they arise. Secondary infections also must be identified and treated, if present, to reduce the risk for fatal complications, including systemic infection and sepsis. Precautions must be taken to ensure that serious end-organ damage, including hepatic, renal, and respiratory dysfunction, is avoided.

Adjunctive topical intervention often is initiated with bland emollients, corticosteroids, calcineurin inhibitors, and/or vitamin D derivatives to help soothe skin symptoms, but treatment with systemic therapies usually is warranted to achieve symptom control.^2,25 Importantly, there are no systemic or topical agents that have specifically been approved for the treatment of GPP in Europe or the United States.³ Given the absence of universally accepted treatment guidelines, therapeutic agents for GPP usually are selected based on clinical experience while also taking the extent of involvement and disease severity into consideration.³

Treatment Recommendations for Adults

Oral Systemic Agents—Treatment guidelines set forth by the National Psoriasis Foundation (NPF) in 2012 proposed that first-line therapies for GPP should be acitretin, cyclosporine, methotrexate, and infliximab.²⁸ However, since those guidelines were established, many new biologic therapies have been approved for the treatment of psoriasis and often are considered in the treatment of psoriasis subtypes, including GPP.²⁹ Although retinoids previously were considered to be a preferred first-line therapy, they are associated with a high incidence of adverse effects and must be used with caution in women of childbearing age.⁶ Oral acitretin at a dosage of 0.75 to 1.0 mg/kg/d has been shown to result in clinical improvement within 1 to 2 weeks, and a maintenance dosage of 0.125 to 0.25 mg/kg/d is required for several months to prevent recurrence.³⁰ Methotrexate—5.0 to 15.0 mg/wk, or perhaps higher in patients with refractory disease, increased by 2.5-mg intervals until symptoms improve—is recommended by the NPF in patients who are unresponsive or cannot tolerate retinoids, though close monitoring for hematologic abnormalities is required. Cyclosporine 2.5 to 5.0 mg/kg/d is considered an alternative to methotrexate and retinoids; it has a faster onset of action, with improvement reported as early as 2 weeks after initiation of therapy.^1,28 Although cyclosporine may be effective in the acute phase, especially in severe cases of GPP, long-term use of cyclosporine is not recommended because of the potential for renal dysfunction and hypertension.³¹

Biologic Agents—More recent evidence has accumulated supporting the efficacy of anti-TNF agents in the treatment of GPP, suggesting the positioning of these agents as first line. A number of case series have shown dramatic and rapid improvement of GPP with intravenous infliximab 3 to 5 mg/kg, with results observed hours to days after the first infusion.^32-37 Thus, infliximab is recommended as first-line treatment in severe acute cases, though its efficacy as a maintenance therapy has not been sufficiently investigated.⁶ Case reports and case series document the safety and efficacy of adalimumab 40 to 80 mg every 1 to 2 weeks^38,39 and etanercept 25 to 50 mg twice weekly^40-42 in patients with recalcitrantGPP. Therefore, these anti-TNF agents may be considered in patients who are nonresponsive to treatment with infliximab.

Rarely, there have been reports of paradoxical induction of GPP with the use of some anti-TNF agents,^43-45 which may be due to a cytokine imbalance characterized by unopposed IFN-α activation.⁶ In patients with a history of GPP after initiation of a biologic, treatment with agents from within the offending class should be avoided.

The IL-17A monoclonal antibodies secukinumab, ixekizumab, and brodalumab have been shown in open-label phase 3 studies to result in disease remission at 12 weeks.^46-48 Treatment with guselkumab, an IL-23 monoclonal antibody, also has demonstrated efficacy in patients with GPP.⁴⁹ Ustekinumab, an IL-12/23 inhibitor, in combination with acitretin also has been shown to be successful in achieving disease remission after a few weeks of treatment.⁵⁰

More recent case reports have shown the efficacy of IL-1 inhibitors including gevokizumab, canakinumab, and anakinra in achieving GPP clearance, though more prospective studies are needed to evaluate their efficacy.^51-53 Given the etiologic association between IL-1 disinhibition and GPP, future investigations of these therapies as well as those that target the IL-36 pathway may prove to be particularly interesting.

Phototherapy and Combination Therapies—Phototherapy may be considered as maintenance therapy after disease control is achieved, though it is not considered appropriate for acute cases.²⁸ Combination therapies with a biologic plus a nonbiologic systemic agent or alternating among various biologics may allow physicians to maximize benefits and minimize adverse effects in the long term, though there is insufficient evidence to suggest any specific combination treatment algorithm for GPP.²⁸

Treatment Recommendations for Pediatric Patients

Based on a small number of case series and case reports, the first-line treatment strategy for children with GPP is similar to adults. Given the notable adverse events of most oral systemic agents, biologic therapies may emerge as first-line therapy in the pediatric population as more evidence accumulates.²⁸

Treatment Recommendations for Pregnant Patients

Systemic corticosteroids are widely considered to be the first-line treatments for the management of impetigo herpetiformis.⁷ Low-dose prednisone (15–30 mg/d) usually is effective, but severe cases may require increasing the dosage to 60 mg/d.⁶ Given the potential for rebound flares upon withdrawal of systemic corticosteroids, these agents must be gradually tapered after the resolution of symptoms.

Certolizumab pegol also is an attractive option in pregnant patients with impetigo herpetiformis because of its favorable safety profile and negligible mother-to-infant transfer through the placenta or breast milk. It has been shown to be effective in treating GPP and impetigo herpetiformis during pregnancy in recently published case reports.^54,55 In refractory cases, other TNF-α inhibitors (eg, adalimumab, infliximab, etanercept) or cyclosporine may be considered. However, cautious medical monitoring is warranted, as little is known about the potential adverse effects of these agents to the mother and fetus.^28,56 Data from transplant recipients along with several case reports indicate that cyclosporine is not associated with an increased risk for adverse effects during pregnancy at a dose of 2 to 3 mg/kg.^57-59 Both methotrexate and retinoids are known teratogens and are therefore contraindicated in pregnant patients.⁵⁶

If pustules do not resolve in the postpartum period, patients should be treated with standard GPP therapies. However, long-term and population studies are lacking regarding the potential for infant exposure to systemic agents in breast milk. Therefore, the NPF recommends avoiding breastfeeding while taking systemic medications, if possible.⁵⁶

Limitations of Treatment Recommendations

The ability to generate an evidence-based treatment strategy for GPP is limited by a lack of high-quality studies investigating the efficacy and safety of treatments in patients with GPP due to the rarity and relapsing-remitting nature of the disease, which makes randomized controlled trials difficult to conduct. The quality of the available research is further limited by the lack of validated outcome measures to specifically assess improvements in patients with GPP, such that results are difficult to synthesize and compare among studies.³¹

Conclusion

Although limited, the available research suggests that treatment with various biologics, especially infliximab, is effective in achieving rapid clearance in patients with GPP. In general, biologics may be the most appropriate treatment option in patients with GPP given their relatively favorable safety profiles. Other oral systemic agents, including acitretin, cyclosporine, and methotrexate, have limited evidence to support their use in the acute phase, but their safety profiles often limit their utility in the long-term. Emerging evidence regarding the association of GPP with IL36RN mutations suggests a unique role for agents targeting the IL-36 or IL-1 pathways, though this has yet to be thoroughly investigated.

Acute generalized pustular psoriasis (GPP) is a rare severe variant of psoriasis characterized by the sudden widespread eruption of sterile pustules.^1,2 The cutaneous manifestations of GPP also may be accompanied by signs of systemic inflammation, including fever, malaise, and leukocytosis.² Complications are common and may be life-threatening, especially in older patients with comorbid diseases.³ Generalized pustular psoriasis most commonly occurs in patients with a preceding history of psoriasis, but it also may occur de novo.⁴ Generalized pustular psoriasis is associated with notable morbidity and mortality, and relapses are common.^3,4 Many triggers of GPP have been identified, including initiation and withdrawal of various medications, infections, pregnancy, and other conditions.^5,6 Although GPP most often occurs in adults, it also may arise in children and infants.³ In pregnancy, GPP is referred to as impetigo herpetiformis, despite having no etiologic ties with either herpes simplex virus or staphylococcal or streptococcal infection. Impetigo herpetiformis is considered one of the most dangerous dermatoses of pregnancy because of high rates of associated maternal and fetal morbidity.^6,7

Acute GPP has proven to be a challenging disease to treat due to the rarity and relapsing-remitting nature of the disease; additionally, there are relatively few randomized controlled trials investigating the efficacy and safety of treatments for GPP. This review summarizes the features of GPP, including the pathophysiology of the disease, clinical and histological manifestations, and recommendations for management based on a PubMed search of articles indexed for MEDLINE using MeSH terms pertaining to the disease, including generalized pustular psoriasis, impetigo herpetiformis, and von Zumbusch psoriasis.

Pathophysiology

The pathophysiology of GPP is only partially understood, but it is thought to have a distinct pattern of immune activation compared with plaque psoriasis.⁸ Although there is a considerable amount of overlap and cross-talk among cytokine pathways, GPP generally is driven by innate immunity and unrestrained IL-36 cytokine activity. In contrast, adaptive immune responses—namely the tumor necrosis factor (TNF) α, IL-23, IL-17, and IL-22 axes—underlie plaque psoriasis.^8-10

Proinflammatory IL-36 cytokines α, β, and γ, which are all part of the IL-1 superfamily, bind to the IL-36 receptor (IL-36R) to recruit and activate immune cells via various mediators, including IL-1β; IL-8; and chemokines CXCL1, CXCL2, and CXCL8.³ The IL-36 receptor antagonist (IL-36ra) acts to inhibit this inflammatory cascade.^3,8 Microarray analyses of skin biopsy samples have shown that overexpression of IL-17A, TNF-α, IL-1, and IL-36 are seen in both GPP and plaque psoriasis lesions, but GPP lesions had higher expression of IL-1β, IL-36α, and IL-36γ and elevated neutrophil chemokines—CXCL1, CXCL2, and CXCL8—compared with plaque psoriasis lesions.⁸

Gene Mutations Associated With GPP

There are 3 gene mutations that have been associated with pustular variants of psoriasis, though these mutations account for a minority of cases of GPP.⁴ Genetic screenings are not routinely indicated in patients with GPP, but they may be warranted in severe cases when a familial pattern of inheritance is suspected.⁴

IL36RN—The gene IL36RN codes the anti-inflammatory IL-36ra. Loss-of-function mutations in IL36RN lead to impairment of IL-36ra and consequently hyperactivity of the proinflammatory responses triggered by IL-36.³ Homozygous and heterozygous mutations in IL36RN have been observed in both familial and sporadic cases of GPP.^11-13 Subsequent retrospective analyses have identified the presence of IL36RN mutations in patients with GPP with frequencies ranging from 23% to 37%.^14-17IL36RN mutations are thought to be more common in patients without concomitant plaque psoriasis and have been associated with severe disease and early disease onset.¹⁵

CARD14—A gain-of-function mutation in CARD14 results in overactivation of the proinflammatory nuclear factor κB pathway and has been implicated in cases of GPP with concurrent psoriasis vulgaris. Interestingly, this may suggest distinct etiologies underlying GPP de novo and GPP in patients with a history of psoriasis.^18,19

AP1S3—A loss-of-function mutation in AP1S3 results in abnormal endosomal trafficking and autophagy as well as increased expression of IL-36α.^20,21

Clinical Presentation and DiagnosisCutaneous Manifestations of GPP

Generalized pustular psoriasis is characterized by the onset of widespread 2- to 3-mm sterile pustules on erythematous skin or within psoriasiform plaques⁴ (Figure). In patients with skin of color, the erythema may appear less obvious or perhaps slightly violaceous compared to White skin. Pustules may coalesce to form “lakes” of pus.⁵ Cutaneous symptoms include pain, burning, and pruritus. Associated mucosal findings may include cheilitis, geographic tongue, conjunctivitis, and uveitis.⁴

The severity of symptoms can vary greatly among patients as well as between flares within the same patient.^2,3 Four distinct patterns of GPP have been described. The von Zumbusch pattern is characterized by a rapid, generalized, painful, erythematous and pustular eruption accompanied by fever and asthenia. The pustules usually resolve after several days with extensive scaling. The annular pattern is characterized by annular, erythematous, scaly lesions with pustules present centrifugally. The lesions enlarge by centrifugal expansion over a period of hours to days, while healing occurs centrally. The exanthematic type is an acute eruption of small pustules that abruptly appear and disappear within a few days, usually from infection or medication initiation. Sometimes pustules appear within or at the edge of existing psoriatic plaques in a localized pattern—the fourth pattern—often following the exposure to irritants (eg, tars, anthralin).⁵

Impetigo Herpetiformis—Impetigo herpetiformis is a form of GPP associated with pregnancy. It generally presents early in the third trimester with symmetric erythematous plaques in flexural and intertriginous areas with pustules present at lesion margins. Lesions expand centrifugally, with pustulation present at the advancing edge.^6,7 Patients often are acutely ill with fever, delirium, vomiting, and tetany. Mucous membranes, including the tongue, mouth, and esophagus, also may be involved. The eruption typically resolves after delivery, though it often recurs with subsequent pregnancies, with the morbidity risk rising with each successive pregnancy.⁷

Systemic and Extracutaneous Manifestations of GPP

Although the severity of GPP is highly variable, skin manifestations often are accompanied by systemic manifestations of inflammation, including fever and malaise. Common laboratory abnormalities include leukocytosis with peripheral neutrophilia, a high serum C-reactive protein level, hypocalcemia, and hypoalbuminemia.²² Abnormal liver enzymes often are present and result from neutrophilic cholangitis, with alternating strictures and dilations of biliary ducts observed on magnetic resonance imaging.²³ Additional laboratory abnormalities are provided in Table 2. Other extracutaneous findings associated with GPP include arthralgia, edema, and characteristic psoriatic nail changes.⁴ Fatal complications include acute respiratory distress syndrome, renal dysfunction, cardiovascular shock, and sepsis.^24,25

Histologic Features

Given the potential for the skin manifestations of GPP to mimic other disorders, a skin biopsy is warranted to confirm the diagnosis. Generalized pustular psoriasis is histologically characterized by the presence of subcorneal macropustules (ie, spongiform pustules of Kogoj) formed by neutrophil infiltration into the spongelike network of the epidermis.⁶ Otherwise, the architecture of the epithelium in GPP is similar to that seen with plaque psoriasis, with parakeratosis, acanthosis, rete-ridge elongation, diminished stratum granulosum, and thinning of the suprapapillary epidermis, though the inflammatory cell infiltrate and edema are markedly more severe in GPP than plaque psoriasis.^3,4

Differential Diagnosis

There are many other cutaneous pustular diagnoses that must be ruled out when evaluating a patient with GPP (Table 1).²⁶ Acute generalized exanthematous pustulosis (AGEP) is a common mimicker of GPP that is differentiated histologically by the presence of eosinophils and necrotic keratinocytes.⁴ In addition to its distinct histopathologic findings, AGEP is classically associated with recent initiation of certain medications, most commonly penicillins, macrolides, quinolones, sulfonamides, terbinafine, and diltiazem.²⁷ In contrast, GPP more commonly is related to withdrawal of corticosteroids as well as initiation of some biologic medications, including anti-TNF agents.³ Generalized pustular psoriasis should be suspected over AGEP in patients with a personal or family history of psoriasis, though GPP may arise in patients with or without a history of psoriasis. Acute generalized exanthematous pustulosis usually is more abrupt in both onset and resolution compared with GPP, with clearance of pustules within a few days to weeks following cessation of the triggering factor.⁴

Other pustular variants of psoriasis (eg, palmoplantar pustular psoriasis, acrodermatitis continua of Hallopeau) are differentiated from GPP by their chronicity and localization to palmoplantar and/or ungual surfaces.⁵ Other differential diagnoses are listed in Table 1.

Diagnostic Criteria for GPP

Diagnostic criteria have been proposed for GPP (Table 2), including (1) the presence of sterile pustules, (2) systemic signs of inflammation, (3) laboratory abnormalities, (4) histopathologic confirmation of spongiform pustules of Kogoj, and (5) recurrence of symptoms.²² To definitively diagnose GPP, all 5 criteria must be met. To rule out mimickers, it may be worthwhile to perform Gram staining, potassium hydroxide preparation, in vitro cultures, and/or immunofluorescence testing.⁶

Treatment

Given the high potential for mortality associated with GPP, the most essential component of management is to ensure adequate supportive care. Any temperature, fluid, or electrolyte imbalances should be corrected as they arise. Secondary infections also must be identified and treated, if present, to reduce the risk for fatal complications, including systemic infection and sepsis. Precautions must be taken to ensure that serious end-organ damage, including hepatic, renal, and respiratory dysfunction, is avoided.

Adjunctive topical intervention often is initiated with bland emollients, corticosteroids, calcineurin inhibitors, and/or vitamin D derivatives to help soothe skin symptoms, but treatment with systemic therapies usually is warranted to achieve symptom control.^2,25 Importantly, there are no systemic or topical agents that have specifically been approved for the treatment of GPP in Europe or the United States.³ Given the absence of universally accepted treatment guidelines, therapeutic agents for GPP usually are selected based on clinical experience while also taking the extent of involvement and disease severity into consideration.³

Treatment Recommendations for Adults

Oral Systemic Agents—Treatment guidelines set forth by the National Psoriasis Foundation (NPF) in 2012 proposed that first-line therapies for GPP should be acitretin, cyclosporine, methotrexate, and infliximab.²⁸ However, since those guidelines were established, many new biologic therapies have been approved for the treatment of psoriasis and often are considered in the treatment of psoriasis subtypes, including GPP.²⁹ Although retinoids previously were considered to be a preferred first-line therapy, they are associated with a high incidence of adverse effects and must be used with caution in women of childbearing age.⁶ Oral acitretin at a dosage of 0.75 to 1.0 mg/kg/d has been shown to result in clinical improvement within 1 to 2 weeks, and a maintenance dosage of 0.125 to 0.25 mg/kg/d is required for several months to prevent recurrence.³⁰ Methotrexate—5.0 to 15.0 mg/wk, or perhaps higher in patients with refractory disease, increased by 2.5-mg intervals until symptoms improve—is recommended by the NPF in patients who are unresponsive or cannot tolerate retinoids, though close monitoring for hematologic abnormalities is required. Cyclosporine 2.5 to 5.0 mg/kg/d is considered an alternative to methotrexate and retinoids; it has a faster onset of action, with improvement reported as early as 2 weeks after initiation of therapy.^1,28 Although cyclosporine may be effective in the acute phase, especially in severe cases of GPP, long-term use of cyclosporine is not recommended because of the potential for renal dysfunction and hypertension.³¹

Biologic Agents—More recent evidence has accumulated supporting the efficacy of anti-TNF agents in the treatment of GPP, suggesting the positioning of these agents as first line. A number of case series have shown dramatic and rapid improvement of GPP with intravenous infliximab 3 to 5 mg/kg, with results observed hours to days after the first infusion.^32-37 Thus, infliximab is recommended as first-line treatment in severe acute cases, though its efficacy as a maintenance therapy has not been sufficiently investigated.⁶ Case reports and case series document the safety and efficacy of adalimumab 40 to 80 mg every 1 to 2 weeks^38,39 and etanercept 25 to 50 mg twice weekly^40-42 in patients with recalcitrantGPP. Therefore, these anti-TNF agents may be considered in patients who are nonresponsive to treatment with infliximab.

Rarely, there have been reports of paradoxical induction of GPP with the use of some anti-TNF agents,^43-45 which may be due to a cytokine imbalance characterized by unopposed IFN-α activation.⁶ In patients with a history of GPP after initiation of a biologic, treatment with agents from within the offending class should be avoided.

The IL-17A monoclonal antibodies secukinumab, ixekizumab, and brodalumab have been shown in open-label phase 3 studies to result in disease remission at 12 weeks.^46-48 Treatment with guselkumab, an IL-23 monoclonal antibody, also has demonstrated efficacy in patients with GPP.⁴⁹ Ustekinumab, an IL-12/23 inhibitor, in combination with acitretin also has been shown to be successful in achieving disease remission after a few weeks of treatment.⁵⁰

More recent case reports have shown the efficacy of IL-1 inhibitors including gevokizumab, canakinumab, and anakinra in achieving GPP clearance, though more prospective studies are needed to evaluate their efficacy.^51-53 Given the etiologic association between IL-1 disinhibition and GPP, future investigations of these therapies as well as those that target the IL-36 pathway may prove to be particularly interesting.

Phototherapy and Combination Therapies—Phototherapy may be considered as maintenance therapy after disease control is achieved, though it is not considered appropriate for acute cases.²⁸ Combination therapies with a biologic plus a nonbiologic systemic agent or alternating among various biologics may allow physicians to maximize benefits and minimize adverse effects in the long term, though there is insufficient evidence to suggest any specific combination treatment algorithm for GPP.²⁸

Treatment Recommendations for Pediatric Patients

Based on a small number of case series and case reports, the first-line treatment strategy for children with GPP is similar to adults. Given the notable adverse events of most oral systemic agents, biologic therapies may emerge as first-line therapy in the pediatric population as more evidence accumulates.²⁸

Treatment Recommendations for Pregnant Patients

Systemic corticosteroids are widely considered to be the first-line treatments for the management of impetigo herpetiformis.⁷ Low-dose prednisone (15–30 mg/d) usually is effective, but severe cases may require increasing the dosage to 60 mg/d.⁶ Given the potential for rebound flares upon withdrawal of systemic corticosteroids, these agents must be gradually tapered after the resolution of symptoms.

Certolizumab pegol also is an attractive option in pregnant patients with impetigo herpetiformis because of its favorable safety profile and negligible mother-to-infant transfer through the placenta or breast milk. It has been shown to be effective in treating GPP and impetigo herpetiformis during pregnancy in recently published case reports.^54,55 In refractory cases, other TNF-α inhibitors (eg, adalimumab, infliximab, etanercept) or cyclosporine may be considered. However, cautious medical monitoring is warranted, as little is known about the potential adverse effects of these agents to the mother and fetus.^28,56 Data from transplant recipients along with several case reports indicate that cyclosporine is not associated with an increased risk for adverse effects during pregnancy at a dose of 2 to 3 mg/kg.^57-59 Both methotrexate and retinoids are known teratogens and are therefore contraindicated in pregnant patients.⁵⁶

If pustules do not resolve in the postpartum period, patients should be treated with standard GPP therapies. However, long-term and population studies are lacking regarding the potential for infant exposure to systemic agents in breast milk. Therefore, the NPF recommends avoiding breastfeeding while taking systemic medications, if possible.⁵⁶

Limitations of Treatment Recommendations

The ability to generate an evidence-based treatment strategy for GPP is limited by a lack of high-quality studies investigating the efficacy and safety of treatments in patients with GPP due to the rarity and relapsing-remitting nature of the disease, which makes randomized controlled trials difficult to conduct. The quality of the available research is further limited by the lack of validated outcome measures to specifically assess improvements in patients with GPP, such that results are difficult to synthesize and compare among studies.³¹

Conclusion

Although limited, the available research suggests that treatment with various biologics, especially infliximab, is effective in achieving rapid clearance in patients with GPP. In general, biologics may be the most appropriate treatment option in patients with GPP given their relatively favorable safety profiles. Other oral systemic agents, including acitretin, cyclosporine, and methotrexate, have limited evidence to support their use in the acute phase, but their safety profiles often limit their utility in the long-term. Emerging evidence regarding the association of GPP with IL36RN mutations suggests a unique role for agents targeting the IL-36 or IL-1 pathways, though this has yet to be thoroughly investigated.

Acute generalized pustular psoriasis (GPP) is a rare severe variant of psoriasis characterized by the sudden widespread eruption of sterile pustules.^1,2 The cutaneous manifestations of GPP also may be accompanied by signs of systemic inflammation, including fever, malaise, and leukocytosis.² Complications are common and may be life-threatening, especially in older patients with comorbid diseases.³ Generalized pustular psoriasis most commonly occurs in patients with a preceding history of psoriasis, but it also may occur de novo.⁴ Generalized pustular psoriasis is associated with notable morbidity and mortality, and relapses are common.^3,4 Many triggers of GPP have been identified, including initiation and withdrawal of various medications, infections, pregnancy, and other conditions.^5,6 Although GPP most often occurs in adults, it also may arise in children and infants.³ In pregnancy, GPP is referred to as impetigo herpetiformis, despite having no etiologic ties with either herpes simplex virus or staphylococcal or streptococcal infection. Impetigo herpetiformis is considered one of the most dangerous dermatoses of pregnancy because of high rates of associated maternal and fetal morbidity.^6,7

Acute GPP has proven to be a challenging disease to treat due to the rarity and relapsing-remitting nature of the disease; additionally, there are relatively few randomized controlled trials investigating the efficacy and safety of treatments for GPP. This review summarizes the features of GPP, including the pathophysiology of the disease, clinical and histological manifestations, and recommendations for management based on a PubMed search of articles indexed for MEDLINE using MeSH terms pertaining to the disease, including generalized pustular psoriasis, impetigo herpetiformis, and von Zumbusch psoriasis.

Pathophysiology

The pathophysiology of GPP is only partially understood, but it is thought to have a distinct pattern of immune activation compared with plaque psoriasis.⁸ Although there is a considerable amount of overlap and cross-talk among cytokine pathways, GPP generally is driven by innate immunity and unrestrained IL-36 cytokine activity. In contrast, adaptive immune responses—namely the tumor necrosis factor (TNF) α, IL-23, IL-17, and IL-22 axes—underlie plaque psoriasis.^8-10

Proinflammatory IL-36 cytokines α, β, and γ, which are all part of the IL-1 superfamily, bind to the IL-36 receptor (IL-36R) to recruit and activate immune cells via various mediators, including IL-1β; IL-8; and chemokines CXCL1, CXCL2, and CXCL8.³ The IL-36 receptor antagonist (IL-36ra) acts to inhibit this inflammatory cascade.^3,8 Microarray analyses of skin biopsy samples have shown that overexpression of IL-17A, TNF-α, IL-1, and IL-36 are seen in both GPP and plaque psoriasis lesions, but GPP lesions had higher expression of IL-1β, IL-36α, and IL-36γ and elevated neutrophil chemokines—CXCL1, CXCL2, and CXCL8—compared with plaque psoriasis lesions.⁸

Gene Mutations Associated With GPP

There are 3 gene mutations that have been associated with pustular variants of psoriasis, though these mutations account for a minority of cases of GPP.⁴ Genetic screenings are not routinely indicated in patients with GPP, but they may be warranted in severe cases when a familial pattern of inheritance is suspected.⁴

IL36RN—The gene IL36RN codes the anti-inflammatory IL-36ra. Loss-of-function mutations in IL36RN lead to impairment of IL-36ra and consequently hyperactivity of the proinflammatory responses triggered by IL-36.³ Homozygous and heterozygous mutations in IL36RN have been observed in both familial and sporadic cases of GPP.^11-13 Subsequent retrospective analyses have identified the presence of IL36RN mutations in patients with GPP with frequencies ranging from 23% to 37%.^14-17IL36RN mutations are thought to be more common in patients without concomitant plaque psoriasis and have been associated with severe disease and early disease onset.¹⁵

CARD14—A gain-of-function mutation in CARD14 results in overactivation of the proinflammatory nuclear factor κB pathway and has been implicated in cases of GPP with concurrent psoriasis vulgaris. Interestingly, this may suggest distinct etiologies underlying GPP de novo and GPP in patients with a history of psoriasis.^18,19

AP1S3—A loss-of-function mutation in AP1S3 results in abnormal endosomal trafficking and autophagy as well as increased expression of IL-36α.^20,21

Clinical Presentation and DiagnosisCutaneous Manifestations of GPP

Generalized pustular psoriasis is characterized by the onset of widespread 2- to 3-mm sterile pustules on erythematous skin or within psoriasiform plaques⁴ (Figure). In patients with skin of color, the erythema may appear less obvious or perhaps slightly violaceous compared to White skin. Pustules may coalesce to form “lakes” of pus.⁵ Cutaneous symptoms include pain, burning, and pruritus. Associated mucosal findings may include cheilitis, geographic tongue, conjunctivitis, and uveitis.⁴

The severity of symptoms can vary greatly among patients as well as between flares within the same patient.^2,3 Four distinct patterns of GPP have been described. The von Zumbusch pattern is characterized by a rapid, generalized, painful, erythematous and pustular eruption accompanied by fever and asthenia. The pustules usually resolve after several days with extensive scaling. The annular pattern is characterized by annular, erythematous, scaly lesions with pustules present centrifugally. The lesions enlarge by centrifugal expansion over a period of hours to days, while healing occurs centrally. The exanthematic type is an acute eruption of small pustules that abruptly appear and disappear within a few days, usually from infection or medication initiation. Sometimes pustules appear within or at the edge of existing psoriatic plaques in a localized pattern—the fourth pattern—often following the exposure to irritants (eg, tars, anthralin).⁵

Impetigo Herpetiformis—Impetigo herpetiformis is a form of GPP associated with pregnancy. It generally presents early in the third trimester with symmetric erythematous plaques in flexural and intertriginous areas with pustules present at lesion margins. Lesions expand centrifugally, with pustulation present at the advancing edge.^6,7 Patients often are acutely ill with fever, delirium, vomiting, and tetany. Mucous membranes, including the tongue, mouth, and esophagus, also may be involved. The eruption typically resolves after delivery, though it often recurs with subsequent pregnancies, with the morbidity risk rising with each successive pregnancy.⁷

Systemic and Extracutaneous Manifestations of GPP

Although the severity of GPP is highly variable, skin manifestations often are accompanied by systemic manifestations of inflammation, including fever and malaise. Common laboratory abnormalities include leukocytosis with peripheral neutrophilia, a high serum C-reactive protein level, hypocalcemia, and hypoalbuminemia.²² Abnormal liver enzymes often are present and result from neutrophilic cholangitis, with alternating strictures and dilations of biliary ducts observed on magnetic resonance imaging.²³ Additional laboratory abnormalities are provided in Table 2. Other extracutaneous findings associated with GPP include arthralgia, edema, and characteristic psoriatic nail changes.⁴ Fatal complications include acute respiratory distress syndrome, renal dysfunction, cardiovascular shock, and sepsis.^24,25

Histologic Features

Given the potential for the skin manifestations of GPP to mimic other disorders, a skin biopsy is warranted to confirm the diagnosis. Generalized pustular psoriasis is histologically characterized by the presence of subcorneal macropustules (ie, spongiform pustules of Kogoj) formed by neutrophil infiltration into the spongelike network of the epidermis.⁶ Otherwise, the architecture of the epithelium in GPP is similar to that seen with plaque psoriasis, with parakeratosis, acanthosis, rete-ridge elongation, diminished stratum granulosum, and thinning of the suprapapillary epidermis, though the inflammatory cell infiltrate and edema are markedly more severe in GPP than plaque psoriasis.^3,4

Differential Diagnosis

There are many other cutaneous pustular diagnoses that must be ruled out when evaluating a patient with GPP (Table 1).²⁶ Acute generalized exanthematous pustulosis (AGEP) is a common mimicker of GPP that is differentiated histologically by the presence of eosinophils and necrotic keratinocytes.⁴ In addition to its distinct histopathologic findings, AGEP is classically associated with recent initiation of certain medications, most commonly penicillins, macrolides, quinolones, sulfonamides, terbinafine, and diltiazem.²⁷ In contrast, GPP more commonly is related to withdrawal of corticosteroids as well as initiation of some biologic medications, including anti-TNF agents.³ Generalized pustular psoriasis should be suspected over AGEP in patients with a personal or family history of psoriasis, though GPP may arise in patients with or without a history of psoriasis. Acute generalized exanthematous pustulosis usually is more abrupt in both onset and resolution compared with GPP, with clearance of pustules within a few days to weeks following cessation of the triggering factor.⁴

Other pustular variants of psoriasis (eg, palmoplantar pustular psoriasis, acrodermatitis continua of Hallopeau) are differentiated from GPP by their chronicity and localization to palmoplantar and/or ungual surfaces.⁵ Other differential diagnoses are listed in Table 1.

Diagnostic Criteria for GPP

Diagnostic criteria have been proposed for GPP (Table 2), including (1) the presence of sterile pustules, (2) systemic signs of inflammation, (3) laboratory abnormalities, (4) histopathologic confirmation of spongiform pustules of Kogoj, and (5) recurrence of symptoms.²² To definitively diagnose GPP, all 5 criteria must be met. To rule out mimickers, it may be worthwhile to perform Gram staining, potassium hydroxide preparation, in vitro cultures, and/or immunofluorescence testing.⁶

Treatment

Given the high potential for mortality associated with GPP, the most essential component of management is to ensure adequate supportive care. Any temperature, fluid, or electrolyte imbalances should be corrected as they arise. Secondary infections also must be identified and treated, if present, to reduce the risk for fatal complications, including systemic infection and sepsis. Precautions must be taken to ensure that serious end-organ damage, including hepatic, renal, and respiratory dysfunction, is avoided.

Adjunctive topical intervention often is initiated with bland emollients, corticosteroids, calcineurin inhibitors, and/or vitamin D derivatives to help soothe skin symptoms, but treatment with systemic therapies usually is warranted to achieve symptom control.^2,25 Importantly, there are no systemic or topical agents that have specifically been approved for the treatment of GPP in Europe or the United States.³ Given the absence of universally accepted treatment guidelines, therapeutic agents for GPP usually are selected based on clinical experience while also taking the extent of involvement and disease severity into consideration.³

Treatment Recommendations for Adults

Oral Systemic Agents—Treatment guidelines set forth by the National Psoriasis Foundation (NPF) in 2012 proposed that first-line therapies for GPP should be acitretin, cyclosporine, methotrexate, and infliximab.²⁸ However, since those guidelines were established, many new biologic therapies have been approved for the treatment of psoriasis and often are considered in the treatment of psoriasis subtypes, including GPP.²⁹ Although retinoids previously were considered to be a preferred first-line therapy, they are associated with a high incidence of adverse effects and must be used with caution in women of childbearing age.⁶ Oral acitretin at a dosage of 0.75 to 1.0 mg/kg/d has been shown to result in clinical improvement within 1 to 2 weeks, and a maintenance dosage of 0.125 to 0.25 mg/kg/d is required for several months to prevent recurrence.³⁰ Methotrexate—5.0 to 15.0 mg/wk, or perhaps higher in patients with refractory disease, increased by 2.5-mg intervals until symptoms improve—is recommended by the NPF in patients who are unresponsive or cannot tolerate retinoids, though close monitoring for hematologic abnormalities is required. Cyclosporine 2.5 to 5.0 mg/kg/d is considered an alternative to methotrexate and retinoids; it has a faster onset of action, with improvement reported as early as 2 weeks after initiation of therapy.^1,28 Although cyclosporine may be effective in the acute phase, especially in severe cases of GPP, long-term use of cyclosporine is not recommended because of the potential for renal dysfunction and hypertension.³¹

Biologic Agents—More recent evidence has accumulated supporting the efficacy of anti-TNF agents in the treatment of GPP, suggesting the positioning of these agents as first line. A number of case series have shown dramatic and rapid improvement of GPP with intravenous infliximab 3 to 5 mg/kg, with results observed hours to days after the first infusion.^32-37 Thus, infliximab is recommended as first-line treatment in severe acute cases, though its efficacy as a maintenance therapy has not been sufficiently investigated.⁶ Case reports and case series document the safety and efficacy of adalimumab 40 to 80 mg every 1 to 2 weeks^38,39 and etanercept 25 to 50 mg twice weekly^40-42 in patients with recalcitrantGPP. Therefore, these anti-TNF agents may be considered in patients who are nonresponsive to treatment with infliximab.

Rarely, there have been reports of paradoxical induction of GPP with the use of some anti-TNF agents,^43-45 which may be due to a cytokine imbalance characterized by unopposed IFN-α activation.⁶ In patients with a history of GPP after initiation of a biologic, treatment with agents from within the offending class should be avoided.

The IL-17A monoclonal antibodies secukinumab, ixekizumab, and brodalumab have been shown in open-label phase 3 studies to result in disease remission at 12 weeks.^46-48 Treatment with guselkumab, an IL-23 monoclonal antibody, also has demonstrated efficacy in patients with GPP.⁴⁹ Ustekinumab, an IL-12/23 inhibitor, in combination with acitretin also has been shown to be successful in achieving disease remission after a few weeks of treatment.⁵⁰

More recent case reports have shown the efficacy of IL-1 inhibitors including gevokizumab, canakinumab, and anakinra in achieving GPP clearance, though more prospective studies are needed to evaluate their efficacy.^51-53 Given the etiologic association between IL-1 disinhibition and GPP, future investigations of these therapies as well as those that target the IL-36 pathway may prove to be particularly interesting.

Phototherapy and Combination Therapies—Phototherapy may be considered as maintenance therapy after disease control is achieved, though it is not considered appropriate for acute cases.²⁸ Combination therapies with a biologic plus a nonbiologic systemic agent or alternating among various biologics may allow physicians to maximize benefits and minimize adverse effects in the long term, though there is insufficient evidence to suggest any specific combination treatment algorithm for GPP.²⁸

Treatment Recommendations for Pediatric Patients

Based on a small number of case series and case reports, the first-line treatment strategy for children with GPP is similar to adults. Given the notable adverse events of most oral systemic agents, biologic therapies may emerge as first-line therapy in the pediatric population as more evidence accumulates.²⁸

Treatment Recommendations for Pregnant Patients

Systemic corticosteroids are widely considered to be the first-line treatments for the management of impetigo herpetiformis.⁷ Low-dose prednisone (15–30 mg/d) usually is effective, but severe cases may require increasing the dosage to 60 mg/d.⁶ Given the potential for rebound flares upon withdrawal of systemic corticosteroids, these agents must be gradually tapered after the resolution of symptoms.

Certolizumab pegol also is an attractive option in pregnant patients with impetigo herpetiformis because of its favorable safety profile and negligible mother-to-infant transfer through the placenta or breast milk. It has been shown to be effective in treating GPP and impetigo herpetiformis during pregnancy in recently published case reports.^54,55 In refractory cases, other TNF-α inhibitors (eg, adalimumab, infliximab, etanercept) or cyclosporine may be considered. However, cautious medical monitoring is warranted, as little is known about the potential adverse effects of these agents to the mother and fetus.^28,56 Data from transplant recipients along with several case reports indicate that cyclosporine is not associated with an increased risk for adverse effects during pregnancy at a dose of 2 to 3 mg/kg.^57-59 Both methotrexate and retinoids are known teratogens and are therefore contraindicated in pregnant patients.⁵⁶

If pustules do not resolve in the postpartum period, patients should be treated with standard GPP therapies. However, long-term and population studies are lacking regarding the potential for infant exposure to systemic agents in breast milk. Therefore, the NPF recommends avoiding breastfeeding while taking systemic medications, if possible.⁵⁶

Limitations of Treatment Recommendations

The ability to generate an evidence-based treatment strategy for GPP is limited by a lack of high-quality studies investigating the efficacy and safety of treatments in patients with GPP due to the rarity and relapsing-remitting nature of the disease, which makes randomized controlled trials difficult to conduct. The quality of the available research is further limited by the lack of validated outcome measures to specifically assess improvements in patients with GPP, such that results are difficult to synthesize and compare among studies.³¹

Conclusion

Although limited, the available research suggests that treatment with various biologics, especially infliximab, is effective in achieving rapid clearance in patients with GPP. In general, biologics may be the most appropriate treatment option in patients with GPP given their relatively favorable safety profiles. Other oral systemic agents, including acitretin, cyclosporine, and methotrexate, have limited evidence to support their use in the acute phase, but their safety profiles often limit their utility in the long-term. Emerging evidence regarding the association of GPP with IL36RN mutations suggests a unique role for agents targeting the IL-36 or IL-1 pathways, though this has yet to be thoroughly investigated.

To the Editor:

Psoriasis affects 2% to 3% of the US population and is one of the more commonly diagnosed dermatologic conditions.^1-3 Experts agree that common cutaneous diseases such as psoriasis present differently in patients with skin of color (SOC) compared to non-SOC patients.^3,4 Despite the prevalence of psoriasis, data on these morphologic differences are limited.^3-5 We performed a retrospective chart review comparing characteristics of psoriasis in SOC and non-SOC patients.

Through a search of electronic health records, we identified patients with an International Classification of Diseases, 10th Revision, diagnosis of psoriasis who were 18 years or older and were evaluated in the dermatology department between August 2015 and June 2020 at University Medical Center, an academic institution in New Orleans, Louisiana. Photographs and descriptions of lesions from these patients were reviewed. Patient data collected included age, sex, psoriasis classification, insurance status, self-identified race and ethnicity, location of lesion(s), biopsy, final diagnosis, and average number of visits or days required for accurate diagnosis. Self-identified SOC race and ethnicity categories included Black or African American, Hispanic, Asian, American Indian and Alaskan Native, Native Hawaiian and Other Pacific Islander, and “other.”

All analyses were conducted using R-4.0.1 statistics software. Categorical variables were compared in SOC and non-SOC groups using Fisher exact tests. Continuous covariates were conducted using a Wilcoxon rank sum test.

In total, we reviewed 557 charts. Four patients who declined to identify their race or ethnicity were excluded, yielding 286 SOC and 267 non-SOC patients (N=553). A total of 276 patients (131 SOC; 145 non-SOC) with a prior diagnosis of psoriasis were excluded in the days to diagnosis analysis. Twenty patients (15, SOC; 5, non-SOC) were given a diagnosis of a disease other than psoriasis when evaluated in the dermatology department.

Distributions between racial groups differed for insurance status, sex, psoriasis classification, biopsy status, and days between first dermatology visit and diagnosis. Skin of color patients had significantly longer days between initial presentation to dermatology and final diagnosis vs non-SOC patients (180.11 and 60.27 days, respectively; P=.001). Skin of color patients had a higher rate of palmoplantar psoriasis and severe plaque psoriasis (ie, >10% body surface area involvement) at presentation.

Several multivariable regression analyses were performed. Skin of color patients had significantly higher odds of biopsy compared to non-SOC patients (adjusted odds ratio [95% CI]=4 [2.05-7.82]; P<.001)(Figure 1). There were no significant predictors for severe plaque psoriasis involving more than 10% body surface area. Skin of color patients had a significantly longer time to diagnosis than non-SOC patients (P=.006)(Figure 2). On average, patients with SOC waited 3.23 times longer for a diagnosis than their non-SOC counterparts (95% CI, 1.42-7.36).

Our data reveal striking racial disparities in psoriasis care. Worse outcomes for patients with SOC compared to non-SOC patients may result from physicians’ inadequate familiarity with diverse presentations of psoriasis, including more frequent involvement of special body sites in SOC. Other likely contributing factors that we did not evaluate include socioeconomic barriers to health care, lack of physician diversity, missed appointments, and a paucity of literature on the topic of differentiating morphologies of psoriasis in SOC and non-SOC patients. Our study did not examine the effects of sex, tobacco use, or prior or current therapy, and it excluded pediatric patients.

To improve dermatologic outcomes for our increasingly diverse patient population, more studies must be undertaken to elucidate and document disparities in care for SOC populations.

To the Editor:

Psoriasis affects 2% to 3% of the US population and is one of the more commonly diagnosed dermatologic conditions.^1-3 Experts agree that common cutaneous diseases such as psoriasis present differently in patients with skin of color (SOC) compared to non-SOC patients.^3,4 Despite the prevalence of psoriasis, data on these morphologic differences are limited.^3-5 We performed a retrospective chart review comparing characteristics of psoriasis in SOC and non-SOC patients.

Through a search of electronic health records, we identified patients with an International Classification of Diseases, 10th Revision, diagnosis of psoriasis who were 18 years or older and were evaluated in the dermatology department between August 2015 and June 2020 at University Medical Center, an academic institution in New Orleans, Louisiana. Photographs and descriptions of lesions from these patients were reviewed. Patient data collected included age, sex, psoriasis classification, insurance status, self-identified race and ethnicity, location of lesion(s), biopsy, final diagnosis, and average number of visits or days required for accurate diagnosis. Self-identified SOC race and ethnicity categories included Black or African American, Hispanic, Asian, American Indian and Alaskan Native, Native Hawaiian and Other Pacific Islander, and “other.”

All analyses were conducted using R-4.0.1 statistics software. Categorical variables were compared in SOC and non-SOC groups using Fisher exact tests. Continuous covariates were conducted using a Wilcoxon rank sum test.

In total, we reviewed 557 charts. Four patients who declined to identify their race or ethnicity were excluded, yielding 286 SOC and 267 non-SOC patients (N=553). A total of 276 patients (131 SOC; 145 non-SOC) with a prior diagnosis of psoriasis were excluded in the days to diagnosis analysis. Twenty patients (15, SOC; 5, non-SOC) were given a diagnosis of a disease other than psoriasis when evaluated in the dermatology department.

Distributions between racial groups differed for insurance status, sex, psoriasis classification, biopsy status, and days between first dermatology visit and diagnosis. Skin of color patients had significantly longer days between initial presentation to dermatology and final diagnosis vs non-SOC patients (180.11 and 60.27 days, respectively; P=.001). Skin of color patients had a higher rate of palmoplantar psoriasis and severe plaque psoriasis (ie, >10% body surface area involvement) at presentation.

Several multivariable regression analyses were performed. Skin of color patients had significantly higher odds of biopsy compared to non-SOC patients (adjusted odds ratio [95% CI]=4 [2.05-7.82]; P<.001)(Figure 1). There were no significant predictors for severe plaque psoriasis involving more than 10% body surface area. Skin of color patients had a significantly longer time to diagnosis than non-SOC patients (P=.006)(Figure 2). On average, patients with SOC waited 3.23 times longer for a diagnosis than their non-SOC counterparts (95% CI, 1.42-7.36).

Our data reveal striking racial disparities in psoriasis care. Worse outcomes for patients with SOC compared to non-SOC patients may result from physicians’ inadequate familiarity with diverse presentations of psoriasis, including more frequent involvement of special body sites in SOC. Other likely contributing factors that we did not evaluate include socioeconomic barriers to health care, lack of physician diversity, missed appointments, and a paucity of literature on the topic of differentiating morphologies of psoriasis in SOC and non-SOC patients. Our study did not examine the effects of sex, tobacco use, or prior or current therapy, and it excluded pediatric patients.

To improve dermatologic outcomes for our increasingly diverse patient population, more studies must be undertaken to elucidate and document disparities in care for SOC populations.

To the Editor:

Psoriasis affects 2% to 3% of the US population and is one of the more commonly diagnosed dermatologic conditions.^1-3 Experts agree that common cutaneous diseases such as psoriasis present differently in patients with skin of color (SOC) compared to non-SOC patients.^3,4 Despite the prevalence of psoriasis, data on these morphologic differences are limited.^3-5 We performed a retrospective chart review comparing characteristics of psoriasis in SOC and non-SOC patients.

Through a search of electronic health records, we identified patients with an International Classification of Diseases, 10th Revision, diagnosis of psoriasis who were 18 years or older and were evaluated in the dermatology department between August 2015 and June 2020 at University Medical Center, an academic institution in New Orleans, Louisiana. Photographs and descriptions of lesions from these patients were reviewed. Patient data collected included age, sex, psoriasis classification, insurance status, self-identified race and ethnicity, location of lesion(s), biopsy, final diagnosis, and average number of visits or days required for accurate diagnosis. Self-identified SOC race and ethnicity categories included Black or African American, Hispanic, Asian, American Indian and Alaskan Native, Native Hawaiian and Other Pacific Islander, and “other.”

All analyses were conducted using R-4.0.1 statistics software. Categorical variables were compared in SOC and non-SOC groups using Fisher exact tests. Continuous covariates were conducted using a Wilcoxon rank sum test.

In total, we reviewed 557 charts. Four patients who declined to identify their race or ethnicity were excluded, yielding 286 SOC and 267 non-SOC patients (N=553). A total of 276 patients (131 SOC; 145 non-SOC) with a prior diagnosis of psoriasis were excluded in the days to diagnosis analysis. Twenty patients (15, SOC; 5, non-SOC) were given a diagnosis of a disease other than psoriasis when evaluated in the dermatology department.

Distributions between racial groups differed for insurance status, sex, psoriasis classification, biopsy status, and days between first dermatology visit and diagnosis. Skin of color patients had significantly longer days between initial presentation to dermatology and final diagnosis vs non-SOC patients (180.11 and 60.27 days, respectively; P=.001). Skin of color patients had a higher rate of palmoplantar psoriasis and severe plaque psoriasis (ie, >10% body surface area involvement) at presentation.

Several multivariable regression analyses were performed. Skin of color patients had significantly higher odds of biopsy compared to non-SOC patients (adjusted odds ratio [95% CI]=4 [2.05-7.82]; P<.001)(Figure 1). There were no significant predictors for severe plaque psoriasis involving more than 10% body surface area. Skin of color patients had a significantly longer time to diagnosis than non-SOC patients (P=.006)(Figure 2). On average, patients with SOC waited 3.23 times longer for a diagnosis than their non-SOC counterparts (95% CI, 1.42-7.36).

Our data reveal striking racial disparities in psoriasis care. Worse outcomes for patients with SOC compared to non-SOC patients may result from physicians’ inadequate familiarity with diverse presentations of psoriasis, including more frequent involvement of special body sites in SOC. Other likely contributing factors that we did not evaluate include socioeconomic barriers to health care, lack of physician diversity, missed appointments, and a paucity of literature on the topic of differentiating morphologies of psoriasis in SOC and non-SOC patients. Our study did not examine the effects of sex, tobacco use, or prior or current therapy, and it excluded pediatric patients.

To improve dermatologic outcomes for our increasingly diverse patient population, more studies must be undertaken to elucidate and document disparities in care for SOC populations.

Psoriasis is a chronic inflammatory skin disease characterized by erythematous scaly plaques that can invoke substantial pain, pruritus, and quality-of-life disturbance in patients. Topical therapies are the most commonly used medications for treating psoriasis, with one study (N = 128,308) showing that more than 85% of patients with psoriasis were managed solely with topical medications. ¹ For patients with mild to moderate psoriasis, topical agents alone may be able to control disease completely. For those with more severe disease, topical agents are used adjunctively with systemic or biologic agents to optimize disease control in localized areas.

The American Academy of Dermatology (AAD) and National Psoriasis Foundation (NPF) published guidelines in 2020 for managing psoriasis with topical agents in adults.² This review presents the most up-to-date clinical recommendations for topical agent use in adult patients with psoriasis and elaborates on each drug’s pharmacologic and safety profile. Specifically, evidence-based treatment recommendations for topical steroids, calcineurin inhibitors (CNIs), vitamin D analogues, retinoids (tazarotene), emollients, keratolytics (salicylic acid), anthracenes (anthralin), and keratoplastics (coal tar) will be addressed (Table 1). Recommendations for combination therapy with other treatment modalities including UVB light therapy, biologics, and systemic nonbiologic agents also will be discussed.

Selecting a Topical Agent Based on Disease Localization

When treating patients with psoriasis with topical therapies, clinicians should take into consideration drug potency, as it determines how effective a treatment will be in penetrating the skin barrier. Plaque characteristics, such as distribution (localized vs widespread), anatomical localization (flexural, scalp, palms/soles/nails), size (large vs small), and thickness (thick vs thin), not only influence treatment effectiveness but also the incidence of drug-related adverse events. Furthermore, preferred topical therapies are tailored to each patient based on disease characteristics and activity. Coal tar and anthralin have been used less frequently than other topical therapies for psoriasis because of their undesirable side-effect profiles (Table 1).³

Face and Intertriginous Regions—The face and intertriginous areas are sensitive because skin tends to be thin in these regions. Emollients are recommended for disease in these locations given their safety and flexibility in use for most areas. Conversely, anthralin should be avoided on the face, intertriginous areas, and even highly visible locations because of the potential for skin staining. Low-potency corticosteroids also have utility in psoriasis distributed on the face and intertriginous regions. Additionally, application of steroids around the eyes should be cautioned because topical steroids can induce ocular complications such as glaucoma and cataracts in rare circumstances.⁴

Off-label use of CNIs for psoriasis on the face and intertriginous areas also is effective. Currently, there is a level B recommendation for off-label use of 0.1% tacrolimus for up to 8 weeks for inverse psoriasis or psoriasis on the face. Off-label use of pimecrolimus for 4 to 8 weeks also can be considered for inverse psoriasis. Combination therapy consisting of hydrocortisone with calcipotriol ointment is another effective regimen.⁵ One study also suggested that use of crisaborole for 4 to 8 weeks in intertriginous psoriasis can be effective and well tolerated.⁶

Scalp—The vehicle of medication administration is especially important in hair-bearing areas such as the scalp, as these areas are challenging for medication application and patient adherence. Thus, patient preferences for the vehicle must be considered. Several studies have been conducted to assess preference for various vehicles in scalp psoriasis. A foam or solution may be preferable to ointments, gels, or creams.⁷ Gels may be preferred over ointments.⁸ There is a level A recommendation supporting the use of class 1 to 7 topical steroids for a minimum of 4 weeks as initial and maintenance treatment of scalp psoriasis. The highest level of evidence (level A) also supports the use of calcipotriol foam or combination therapy of calcipotriol–betamethasone dipropionate gel for 4 to 12 weeks as treatment of mild to moderate scalp psoriasis.

Nails—Several options for topical medications have been recommended for the treatment of nail psoriasis. Currently, there is a level B recommendation for the use of tazarotene for the treatment of nail psoriasis. Another effective regimen is combination therapy with vitamin D analogues and betamethasone dipropionate.⁹ Topical steroid use for nail psoriasis should be limited to 12 weeks because of the risk for bone atrophy with chronic steroid use.

Palmoplantar—The palms and soles have a thicker epidermal layer than other areas of the body. As a result, class 1 corticosteroids can be used for palmoplantar psoriasis for more than 4 weeks with vigilant monitoring for adverse effects such as skin atrophy, tachyphylaxis, or tinea infection. Tazarotene also has been shown to be helpful in treating palmoplantar psoriasis.

Resistant Disease—Intralesional steroids are beneficial treatment options for recalcitrant psoriasis in glabrous areas, as well as for palmoplantar, nail, and scalp psoriasis. Up to 10 mg/mL of triamcinolone acetonide used every 3 to 4 weeks is an effective regimen.¹⁰Pregnancy/Breastfeeding—Women of childbearing potential have additional safety precautions that should be considered during medication selection. Emollients have been shown to be safe during pregnancy and lactation. Currently, there is little known about CNI use during pregnancy. During lactation, CNIs can be used by breastfeeding mothers in most areas, excluding the breasts. Evaluation of the safety of anthralin and vitamin D analogues during pregnancy and lactation have not been studied. For these agents, dermatologists need to use their clinical judgment to weigh the risks and benefits of medication, particularly in patients requiring occlusion, higher medication doses, or treatment over a large surface area. Salicylic acid should be used with caution in pregnant and breastfeeding mothers because it is a pregnancy category C drug. Lower-potency corticosteroids may be used with caution during pregnancy and breastfeeding. More potent corticosteroids and coal tar, however, should be avoided. Similarly, tazarotene use is contraindicated in pregnancy. According to the US Food and Drug Administration labels for all forms of topical tazarotene, a pregnancy test must be obtained 2 weeks prior to tazarotene treatment initiation in women of childbearing potential because of the risk for serious fetal malformations and toxicity.

Recommendations, Risks, and Benefits of Topical Therapy for the Management of Psoriasis

Topical Corticosteroids—Topical corticosteroids (TCs) are widely used for inflammatory skin conditions and are available in a variety of strengths (Table 2). They are thought to exert their action by regulating the gene transcription of proinflammatory mediators. For psoriasis, steroids are recommended for 2 to 4 weeks, depending on disease severity. Although potent and superpotent steroids are more effective than mild- to moderate-strength TCs, use of lower-potency TCs may be warranted depending on disease distribution and localization.¹¹ For treatment of psoriasis with no involvement of the intertriginous areas, use of class 1 to 5 TCs for up to 4 weeks is recommended.

For moderate to severe psoriasis with 20% or less body surface area (BSA) affected, combination therapy consisting of mometasone and salicylic acid has been shown to be more effective than mometasone alone.^12,13 There currently is a level A recommendation for the use of combination therapy with class 1 TCs and etanercept for 12 weeks in patients with moderate to severe psoriasis who require both systemic and topical therapies for disease control. Similarly, combination therapy with infliximab and high-potency TCs has a level B recommendation to enhance efficacy for the treatment of moderate to severe psoriasis.¹⁴ High-quality studies on the use of TCs with anti–IL-12/IL-23, anti–IL-23, and anti–IL-17 currently are unavailable, but the combination is not expected to be unsafe.^14,15 Combination therapy of betamethasone dipropionate ointment and low-dose cyclosporine is an alternative regimen with a level B recommendation.

The most common adverse effects with use of TCs are skin thinning and atrophy, telangiectasia, and striae (Table 1). With clinical improvement of disease, it is recommended that clinicians taper TCs to prevent rebound effect. To decrease TC-related adverse effects, clinicians should use combination therapy with steroid-sparing agents for disease maintenance, transition to lower-potency corticosteroids, or use intermittent steroid therapy. Systemic effects of TC use include hypothalamic-pituitary-adrenal axis suppression, Cushing syndrome, and osteonecrosis of the femoral head.^16-18 These systemic effects with TC use are rare unless treatment is for disease involving greater than 20% BSA or occlusion for more than 4 weeks.

Calcineurin Inhibitors—Calcineurin inhibitors inhibit calcineurin phosphorylation and T-cell activation, subsequently decreasing the expression of proinflammatory cytokines. Currently, they are not approved by the US Food and Drug Administration to treat psoriasis but have demonstrated efficacy in randomized control trials (RCTs) for facial and intertriginous psoriasis. In RCTs, 71% of patients using pimecrolimus cream 0.1% twice daily for 8 weeks achieved an investigator global assessment score of clear (0) or almost clear (1) compared with 21% of placebo-treated patients (N=57).¹⁹ Other trials have shown that 65% of patients receiving tacrolimus ointment 0.1% for 8 weeks achieved an investigator global assessment score of 0 or 1 compared with 31% of placebo-treated patients (N=167).²⁰ Because of their efficacy in RCTs, CNIs commonly are used off label to treat psoriasis.

The most common adverse effects with CNI use are burning, pruritus, and flushing with alcohol ingestion (Table 1). Additionally, CNIs have a black box warning that use may increase the risk for malignancy, but this risk has not been demonstrated with topical use in humans.²¹Vitamin D Analogues—The class of vitamin D analogues—calcipotriol/calcipotriene and calcitriol—frequently are used to treat psoriasis. Vitamin D analogues exert their beneficial effects by inhibiting keratinocyte proliferation and enhancing keratinocyte differentiation. They also are ideal for long-term use (up to 52 weeks) in mild to moderate psoriasis and can be used in combination with class 2 and 3 TCs. There is a level A recommendation that supports the use of combination therapy with calcipotriol and TCs for the treatment of mild to moderate psoriasis.

For severe psoriasis, many studies have investigated the efficacy of combination therapy with vitamin D analogues and systemic treatments. Combination therapy with calcipotriol and methotrexate or calcipotriol and acitretin are effective treatment regimens with level A recommendations. Calcipotriol–betamethasone dipropionate ointment in combination with low-dose cyclosporine is an alternative option with a level B recommendation. Because vitamin D analogues are inactivated by UVA and UVB radiation, clinicians should advise their patients to use vitamin D analogues after receiving UVB phototherapy.²²

Common adverse effects of vitamin D analogues include burning, pruritus, erythema, and dryness (Table 1). Hypercalcemia and parathyroid hormone suppression are extremely rare unless treatment occurs over a large surface area (>30% BSA) or the patient has concurrent renal disease or impairments in calcium metabolism.

Tazarotene—Tazarotene is a topical retinoid that acts by decreasing keratinocyte proliferation, facilitating keratinocyte differentiation, and inhibiting inflammation. Patients with mild to moderate psoriasis are recommended to receive tazarotene treatment for 8 to 12 weeks. In several RCTs, tazarotene gel 0.1% and tazarotene cream 0.1% and 0.05% achieved treatment success in treating plaque psoriasis.^23,24

For increased efficacy, clinicians can recommend combination therapy with tazarotene and a TC. Combination therapy with tazarotene and a mid- or high-potency TC for 8 to 16 weeks has been shown to be more effective than treatment with tazarotene alone.²⁵ Thus, there is a level A recommendation for use of this combination to treat mild to moderate psoriasis. Agents used in combination therapy work synergistically to decrease the length of treatment and increase the duration of remission. The frequency of adverse effects, such as irritation from tazarotene and skin atrophy from TCs, also are reduced.²⁶ Combination therapy with tazarotene and narrowband UVB (NB-UVB) is another effective option that requires less UV radiation than NB-UVB alone because of the synergistic effects of both treatment modalities.²⁷ Clinicians should counsel patients on the adverse effects of tazarotene, which include local irritation, burning, pruritus, and erythema (Table 1).

Emollients—Emollients are nonmedicated moisturizers that decrease the amount of transepidermal water loss. There is a level B recommendation for use of emollients and TCs in combination for 4 to 8 weeks to treat psoriasis. In fact, combination therapy with mometasone and emollients has demonstrated greater improvement in symptoms of palmoplantar psoriasis (ie, erythema, desquamation, infiltration, BSA involvement) than mometasone alone.²⁸ Emollients are safe options that can be used on all areas of the body and during pregnancy and lactation. Although adverse effects of emollients are rare, clinicians should counsel patients on the risk for contact dermatitis if specific allergies to ingredients/fragrances exist (Table 1).

Salicylic Acid—Salicylic acid is a topical keratolytic that can be used to treat psoriatic plaques. Use of salicylic acid for 8 to 16 weeks has been shown to be effective for mild to moderate psoriasis. Combination therapy of salicylic acid and TCs in patients with 20% or less BSA affected is a safe and effective option with a level B recommendation. Combination therapy with salicylic acid and calcipotriene, however, should be avoided because calcipotriene is inactivated by salicylic acid. It also is recommended that salicylic acid application follow phototherapy when both treatment modalities are used in combination.^29,30 Clinicians should be cautious about using salicylic acid in patients with renal or hepatic disease because of the increased risk for salicylate toxicity (Table 1).

Anthralin—Anthralin is a synthetic hydrocarbon derivative that has been shown to reduce inflammation and normalize keratinocyte proliferation through an unknown mechanism. It is recommended that patients with mild to moderate psoriasis receive anthralin treatment for 8 to 12 weeks, with a maximum application time of 2 hours per day. Combination therapy of excimer laser and anthralin has been shown to be more effective in treating psoriasis than anthralin alone.³¹ Therefore, clinicians have the option of including excimer laser therapy for additional disease control. Anthralin should be avoided on the face, flexural regions, and highly visible areas because of potential skin staining (Table 1). Other adverse effects include application-site burning and erythema.

Coal Tar—Coal tar is a heterogenous mixture of aromatic hydrocarbons that is an effective treatment of psoriasis because of its inherent anti-inflammatory and keratoplastic properties. There is high-quality evidence supporting a level A recommendation for coal tar use in mild to moderate psoriasis. Combination therapy with NB-UVB and coal tar (also known as Goeckerman therapy) is a recommended treatment option with a quicker onset of action and improved outcomes compared with NB-UVB therapy alone.^32,33 Adverse events of coal tar include application-site irritation, folliculitis, contact dermatitis, phototoxicity, and skin pigmentation (Table 1).

Conclusion

Topical medications are versatile treatment options that can be utilized as monotherapy or adjunct therapy for mild to severe psoriasis. Benefits of topical agents include minimal required monitoring, few contraindications, and direct localized effect on plaques. Therefore, side effects with topical agent use rarely are systemic. Medication interactions are less of a concern with topical therapies; thus, they have better safety profiles compared with systemic therapies. This clinical review summarizes the recently published evidence-based guidelines from the AAD and NPF on the use of topical agents in psoriasis and may be a useful guiding framework for clinicians in their everyday practice.

Psoriasis is a chronic inflammatory skin disease characterized by erythematous scaly plaques that can invoke substantial pain, pruritus, and quality-of-life disturbance in patients. Topical therapies are the most commonly used medications for treating psoriasis, with one study (N = 128,308) showing that more than 85% of patients with psoriasis were managed solely with topical medications. ¹ For patients with mild to moderate psoriasis, topical agents alone may be able to control disease completely. For those with more severe disease, topical agents are used adjunctively with systemic or biologic agents to optimize disease control in localized areas.

The American Academy of Dermatology (AAD) and National Psoriasis Foundation (NPF) published guidelines in 2020 for managing psoriasis with topical agents in adults.² This review presents the most up-to-date clinical recommendations for topical agent use in adult patients with psoriasis and elaborates on each drug’s pharmacologic and safety profile. Specifically, evidence-based treatment recommendations for topical steroids, calcineurin inhibitors (CNIs), vitamin D analogues, retinoids (tazarotene), emollients, keratolytics (salicylic acid), anthracenes (anthralin), and keratoplastics (coal tar) will be addressed (Table 1). Recommendations for combination therapy with other treatment modalities including UVB light therapy, biologics, and systemic nonbiologic agents also will be discussed.

Selecting a Topical Agent Based on Disease Localization

When treating patients with psoriasis with topical therapies, clinicians should take into consideration drug potency, as it determines how effective a treatment will be in penetrating the skin barrier. Plaque characteristics, such as distribution (localized vs widespread), anatomical localization (flexural, scalp, palms/soles/nails), size (large vs small), and thickness (thick vs thin), not only influence treatment effectiveness but also the incidence of drug-related adverse events. Furthermore, preferred topical therapies are tailored to each patient based on disease characteristics and activity. Coal tar and anthralin have been used less frequently than other topical therapies for psoriasis because of their undesirable side-effect profiles (Table 1).³

Face and Intertriginous Regions—The face and intertriginous areas are sensitive because skin tends to be thin in these regions. Emollients are recommended for disease in these locations given their safety and flexibility in use for most areas. Conversely, anthralin should be avoided on the face, intertriginous areas, and even highly visible locations because of the potential for skin staining. Low-potency corticosteroids also have utility in psoriasis distributed on the face and intertriginous regions. Additionally, application of steroids around the eyes should be cautioned because topical steroids can induce ocular complications such as glaucoma and cataracts in rare circumstances.⁴

Off-label use of CNIs for psoriasis on the face and intertriginous areas also is effective. Currently, there is a level B recommendation for off-label use of 0.1% tacrolimus for up to 8 weeks for inverse psoriasis or psoriasis on the face. Off-label use of pimecrolimus for 4 to 8 weeks also can be considered for inverse psoriasis. Combination therapy consisting of hydrocortisone with calcipotriol ointment is another effective regimen.⁵ One study also suggested that use of crisaborole for 4 to 8 weeks in intertriginous psoriasis can be effective and well tolerated.⁶

Scalp—The vehicle of medication administration is especially important in hair-bearing areas such as the scalp, as these areas are challenging for medication application and patient adherence. Thus, patient preferences for the vehicle must be considered. Several studies have been conducted to assess preference for various vehicles in scalp psoriasis. A foam or solution may be preferable to ointments, gels, or creams.⁷ Gels may be preferred over ointments.⁸ There is a level A recommendation supporting the use of class 1 to 7 topical steroids for a minimum of 4 weeks as initial and maintenance treatment of scalp psoriasis. The highest level of evidence (level A) also supports the use of calcipotriol foam or combination therapy of calcipotriol–betamethasone dipropionate gel for 4 to 12 weeks as treatment of mild to moderate scalp psoriasis.

Nails—Several options for topical medications have been recommended for the treatment of nail psoriasis. Currently, there is a level B recommendation for the use of tazarotene for the treatment of nail psoriasis. Another effective regimen is combination therapy with vitamin D analogues and betamethasone dipropionate.⁹ Topical steroid use for nail psoriasis should be limited to 12 weeks because of the risk for bone atrophy with chronic steroid use.

Palmoplantar—The palms and soles have a thicker epidermal layer than other areas of the body. As a result, class 1 corticosteroids can be used for palmoplantar psoriasis for more than 4 weeks with vigilant monitoring for adverse effects such as skin atrophy, tachyphylaxis, or tinea infection. Tazarotene also has been shown to be helpful in treating palmoplantar psoriasis.

Resistant Disease—Intralesional steroids are beneficial treatment options for recalcitrant psoriasis in glabrous areas, as well as for palmoplantar, nail, and scalp psoriasis. Up to 10 mg/mL of triamcinolone acetonide used every 3 to 4 weeks is an effective regimen.¹⁰Pregnancy/Breastfeeding—Women of childbearing potential have additional safety precautions that should be considered during medication selection. Emollients have been shown to be safe during pregnancy and lactation. Currently, there is little known about CNI use during pregnancy. During lactation, CNIs can be used by breastfeeding mothers in most areas, excluding the breasts. Evaluation of the safety of anthralin and vitamin D analogues during pregnancy and lactation have not been studied. For these agents, dermatologists need to use their clinical judgment to weigh the risks and benefits of medication, particularly in patients requiring occlusion, higher medication doses, or treatment over a large surface area. Salicylic acid should be used with caution in pregnant and breastfeeding mothers because it is a pregnancy category C drug. Lower-potency corticosteroids may be used with caution during pregnancy and breastfeeding. More potent corticosteroids and coal tar, however, should be avoided. Similarly, tazarotene use is contraindicated in pregnancy. According to the US Food and Drug Administration labels for all forms of topical tazarotene, a pregnancy test must be obtained 2 weeks prior to tazarotene treatment initiation in women of childbearing potential because of the risk for serious fetal malformations and toxicity.

Recommendations, Risks, and Benefits of Topical Therapy for the Management of Psoriasis

Topical Corticosteroids—Topical corticosteroids (TCs) are widely used for inflammatory skin conditions and are available in a variety of strengths (Table 2). They are thought to exert their action by regulating the gene transcription of proinflammatory mediators. For psoriasis, steroids are recommended for 2 to 4 weeks, depending on disease severity. Although potent and superpotent steroids are more effective than mild- to moderate-strength TCs, use of lower-potency TCs may be warranted depending on disease distribution and localization.¹¹ For treatment of psoriasis with no involvement of the intertriginous areas, use of class 1 to 5 TCs for up to 4 weeks is recommended.

For moderate to severe psoriasis with 20% or less body surface area (BSA) affected, combination therapy consisting of mometasone and salicylic acid has been shown to be more effective than mometasone alone.^12,13 There currently is a level A recommendation for the use of combination therapy with class 1 TCs and etanercept for 12 weeks in patients with moderate to severe psoriasis who require both systemic and topical therapies for disease control. Similarly, combination therapy with infliximab and high-potency TCs has a level B recommendation to enhance efficacy for the treatment of moderate to severe psoriasis.¹⁴ High-quality studies on the use of TCs with anti–IL-12/IL-23, anti–IL-23, and anti–IL-17 currently are unavailable, but the combination is not expected to be unsafe.^14,15 Combination therapy of betamethasone dipropionate ointment and low-dose cyclosporine is an alternative regimen with a level B recommendation.

The most common adverse effects with use of TCs are skin thinning and atrophy, telangiectasia, and striae (Table 1). With clinical improvement of disease, it is recommended that clinicians taper TCs to prevent rebound effect. To decrease TC-related adverse effects, clinicians should use combination therapy with steroid-sparing agents for disease maintenance, transition to lower-potency corticosteroids, or use intermittent steroid therapy. Systemic effects of TC use include hypothalamic-pituitary-adrenal axis suppression, Cushing syndrome, and osteonecrosis of the femoral head.^16-18 These systemic effects with TC use are rare unless treatment is for disease involving greater than 20% BSA or occlusion for more than 4 weeks.

Calcineurin Inhibitors—Calcineurin inhibitors inhibit calcineurin phosphorylation and T-cell activation, subsequently decreasing the expression of proinflammatory cytokines. Currently, they are not approved by the US Food and Drug Administration to treat psoriasis but have demonstrated efficacy in randomized control trials (RCTs) for facial and intertriginous psoriasis. In RCTs, 71% of patients using pimecrolimus cream 0.1% twice daily for 8 weeks achieved an investigator global assessment score of clear (0) or almost clear (1) compared with 21% of placebo-treated patients (N=57).¹⁹ Other trials have shown that 65% of patients receiving tacrolimus ointment 0.1% for 8 weeks achieved an investigator global assessment score of 0 or 1 compared with 31% of placebo-treated patients (N=167).²⁰ Because of their efficacy in RCTs, CNIs commonly are used off label to treat psoriasis.

The most common adverse effects with CNI use are burning, pruritus, and flushing with alcohol ingestion (Table 1). Additionally, CNIs have a black box warning that use may increase the risk for malignancy, but this risk has not been demonstrated with topical use in humans.²¹Vitamin D Analogues—The class of vitamin D analogues—calcipotriol/calcipotriene and calcitriol—frequently are used to treat psoriasis. Vitamin D analogues exert their beneficial effects by inhibiting keratinocyte proliferation and enhancing keratinocyte differentiation. They also are ideal for long-term use (up to 52 weeks) in mild to moderate psoriasis and can be used in combination with class 2 and 3 TCs. There is a level A recommendation that supports the use of combination therapy with calcipotriol and TCs for the treatment of mild to moderate psoriasis.

For severe psoriasis, many studies have investigated the efficacy of combination therapy with vitamin D analogues and systemic treatments. Combination therapy with calcipotriol and methotrexate or calcipotriol and acitretin are effective treatment regimens with level A recommendations. Calcipotriol–betamethasone dipropionate ointment in combination with low-dose cyclosporine is an alternative option with a level B recommendation. Because vitamin D analogues are inactivated by UVA and UVB radiation, clinicians should advise their patients to use vitamin D analogues after receiving UVB phototherapy.²²

Common adverse effects of vitamin D analogues include burning, pruritus, erythema, and dryness (Table 1). Hypercalcemia and parathyroid hormone suppression are extremely rare unless treatment occurs over a large surface area (>30% BSA) or the patient has concurrent renal disease or impairments in calcium metabolism.

Tazarotene—Tazarotene is a topical retinoid that acts by decreasing keratinocyte proliferation, facilitating keratinocyte differentiation, and inhibiting inflammation. Patients with mild to moderate psoriasis are recommended to receive tazarotene treatment for 8 to 12 weeks. In several RCTs, tazarotene gel 0.1% and tazarotene cream 0.1% and 0.05% achieved treatment success in treating plaque psoriasis.^23,24

For increased efficacy, clinicians can recommend combination therapy with tazarotene and a TC. Combination therapy with tazarotene and a mid- or high-potency TC for 8 to 16 weeks has been shown to be more effective than treatment with tazarotene alone.²⁵ Thus, there is a level A recommendation for use of this combination to treat mild to moderate psoriasis. Agents used in combination therapy work synergistically to decrease the length of treatment and increase the duration of remission. The frequency of adverse effects, such as irritation from tazarotene and skin atrophy from TCs, also are reduced.²⁶ Combination therapy with tazarotene and narrowband UVB (NB-UVB) is another effective option that requires less UV radiation than NB-UVB alone because of the synergistic effects of both treatment modalities.²⁷ Clinicians should counsel patients on the adverse effects of tazarotene, which include local irritation, burning, pruritus, and erythema (Table 1).

Emollients—Emollients are nonmedicated moisturizers that decrease the amount of transepidermal water loss. There is a level B recommendation for use of emollients and TCs in combination for 4 to 8 weeks to treat psoriasis. In fact, combination therapy with mometasone and emollients has demonstrated greater improvement in symptoms of palmoplantar psoriasis (ie, erythema, desquamation, infiltration, BSA involvement) than mometasone alone.²⁸ Emollients are safe options that can be used on all areas of the body and during pregnancy and lactation. Although adverse effects of emollients are rare, clinicians should counsel patients on the risk for contact dermatitis if specific allergies to ingredients/fragrances exist (Table 1).

Salicylic Acid—Salicylic acid is a topical keratolytic that can be used to treat psoriatic plaques. Use of salicylic acid for 8 to 16 weeks has been shown to be effective for mild to moderate psoriasis. Combination therapy of salicylic acid and TCs in patients with 20% or less BSA affected is a safe and effective option with a level B recommendation. Combination therapy with salicylic acid and calcipotriene, however, should be avoided because calcipotriene is inactivated by salicylic acid. It also is recommended that salicylic acid application follow phototherapy when both treatment modalities are used in combination.^29,30 Clinicians should be cautious about using salicylic acid in patients with renal or hepatic disease because of the increased risk for salicylate toxicity (Table 1).

Anthralin—Anthralin is a synthetic hydrocarbon derivative that has been shown to reduce inflammation and normalize keratinocyte proliferation through an unknown mechanism. It is recommended that patients with mild to moderate psoriasis receive anthralin treatment for 8 to 12 weeks, with a maximum application time of 2 hours per day. Combination therapy of excimer laser and anthralin has been shown to be more effective in treating psoriasis than anthralin alone.³¹ Therefore, clinicians have the option of including excimer laser therapy for additional disease control. Anthralin should be avoided on the face, flexural regions, and highly visible areas because of potential skin staining (Table 1). Other adverse effects include application-site burning and erythema.

Coal Tar—Coal tar is a heterogenous mixture of aromatic hydrocarbons that is an effective treatment of psoriasis because of its inherent anti-inflammatory and keratoplastic properties. There is high-quality evidence supporting a level A recommendation for coal tar use in mild to moderate psoriasis. Combination therapy with NB-UVB and coal tar (also known as Goeckerman therapy) is a recommended treatment option with a quicker onset of action and improved outcomes compared with NB-UVB therapy alone.^32,33 Adverse events of coal tar include application-site irritation, folliculitis, contact dermatitis, phototoxicity, and skin pigmentation (Table 1).

Conclusion

Topical medications are versatile treatment options that can be utilized as monotherapy or adjunct therapy for mild to severe psoriasis. Benefits of topical agents include minimal required monitoring, few contraindications, and direct localized effect on plaques. Therefore, side effects with topical agent use rarely are systemic. Medication interactions are less of a concern with topical therapies; thus, they have better safety profiles compared with systemic therapies. This clinical review summarizes the recently published evidence-based guidelines from the AAD and NPF on the use of topical agents in psoriasis and may be a useful guiding framework for clinicians in their everyday practice.

Psoriasis is a chronic inflammatory skin disease characterized by erythematous scaly plaques that can invoke substantial pain, pruritus, and quality-of-life disturbance in patients. Topical therapies are the most commonly used medications for treating psoriasis, with one study (N = 128,308) showing that more than 85% of patients with psoriasis were managed solely with topical medications. ¹ For patients with mild to moderate psoriasis, topical agents alone may be able to control disease completely. For those with more severe disease, topical agents are used adjunctively with systemic or biologic agents to optimize disease control in localized areas.

The American Academy of Dermatology (AAD) and National Psoriasis Foundation (NPF) published guidelines in 2020 for managing psoriasis with topical agents in adults.² This review presents the most up-to-date clinical recommendations for topical agent use in adult patients with psoriasis and elaborates on each drug’s pharmacologic and safety profile. Specifically, evidence-based treatment recommendations for topical steroids, calcineurin inhibitors (CNIs), vitamin D analogues, retinoids (tazarotene), emollients, keratolytics (salicylic acid), anthracenes (anthralin), and keratoplastics (coal tar) will be addressed (Table 1). Recommendations for combination therapy with other treatment modalities including UVB light therapy, biologics, and systemic nonbiologic agents also will be discussed.

Selecting a Topical Agent Based on Disease Localization

When treating patients with psoriasis with topical therapies, clinicians should take into consideration drug potency, as it determines how effective a treatment will be in penetrating the skin barrier. Plaque characteristics, such as distribution (localized vs widespread), anatomical localization (flexural, scalp, palms/soles/nails), size (large vs small), and thickness (thick vs thin), not only influence treatment effectiveness but also the incidence of drug-related adverse events. Furthermore, preferred topical therapies are tailored to each patient based on disease characteristics and activity. Coal tar and anthralin have been used less frequently than other topical therapies for psoriasis because of their undesirable side-effect profiles (Table 1).³

Face and Intertriginous Regions—The face and intertriginous areas are sensitive because skin tends to be thin in these regions. Emollients are recommended for disease in these locations given their safety and flexibility in use for most areas. Conversely, anthralin should be avoided on the face, intertriginous areas, and even highly visible locations because of the potential for skin staining. Low-potency corticosteroids also have utility in psoriasis distributed on the face and intertriginous regions. Additionally, application of steroids around the eyes should be cautioned because topical steroids can induce ocular complications such as glaucoma and cataracts in rare circumstances.⁴

Off-label use of CNIs for psoriasis on the face and intertriginous areas also is effective. Currently, there is a level B recommendation for off-label use of 0.1% tacrolimus for up to 8 weeks for inverse psoriasis or psoriasis on the face. Off-label use of pimecrolimus for 4 to 8 weeks also can be considered for inverse psoriasis. Combination therapy consisting of hydrocortisone with calcipotriol ointment is another effective regimen.⁵ One study also suggested that use of crisaborole for 4 to 8 weeks in intertriginous psoriasis can be effective and well tolerated.⁶

Scalp—The vehicle of medication administration is especially important in hair-bearing areas such as the scalp, as these areas are challenging for medication application and patient adherence. Thus, patient preferences for the vehicle must be considered. Several studies have been conducted to assess preference for various vehicles in scalp psoriasis. A foam or solution may be preferable to ointments, gels, or creams.⁷ Gels may be preferred over ointments.⁸ There is a level A recommendation supporting the use of class 1 to 7 topical steroids for a minimum of 4 weeks as initial and maintenance treatment of scalp psoriasis. The highest level of evidence (level A) also supports the use of calcipotriol foam or combination therapy of calcipotriol–betamethasone dipropionate gel for 4 to 12 weeks as treatment of mild to moderate scalp psoriasis.

Nails—Several options for topical medications have been recommended for the treatment of nail psoriasis. Currently, there is a level B recommendation for the use of tazarotene for the treatment of nail psoriasis. Another effective regimen is combination therapy with vitamin D analogues and betamethasone dipropionate.⁹ Topical steroid use for nail psoriasis should be limited to 12 weeks because of the risk for bone atrophy with chronic steroid use.

Palmoplantar—The palms and soles have a thicker epidermal layer than other areas of the body. As a result, class 1 corticosteroids can be used for palmoplantar psoriasis for more than 4 weeks with vigilant monitoring for adverse effects such as skin atrophy, tachyphylaxis, or tinea infection. Tazarotene also has been shown to be helpful in treating palmoplantar psoriasis.

Resistant Disease—Intralesional steroids are beneficial treatment options for recalcitrant psoriasis in glabrous areas, as well as for palmoplantar, nail, and scalp psoriasis. Up to 10 mg/mL of triamcinolone acetonide used every 3 to 4 weeks is an effective regimen.¹⁰Pregnancy/Breastfeeding—Women of childbearing potential have additional safety precautions that should be considered during medication selection. Emollients have been shown to be safe during pregnancy and lactation. Currently, there is little known about CNI use during pregnancy. During lactation, CNIs can be used by breastfeeding mothers in most areas, excluding the breasts. Evaluation of the safety of anthralin and vitamin D analogues during pregnancy and lactation have not been studied. For these agents, dermatologists need to use their clinical judgment to weigh the risks and benefits of medication, particularly in patients requiring occlusion, higher medication doses, or treatment over a large surface area. Salicylic acid should be used with caution in pregnant and breastfeeding mothers because it is a pregnancy category C drug. Lower-potency corticosteroids may be used with caution during pregnancy and breastfeeding. More potent corticosteroids and coal tar, however, should be avoided. Similarly, tazarotene use is contraindicated in pregnancy. According to the US Food and Drug Administration labels for all forms of topical tazarotene, a pregnancy test must be obtained 2 weeks prior to tazarotene treatment initiation in women of childbearing potential because of the risk for serious fetal malformations and toxicity.

Recommendations, Risks, and Benefits of Topical Therapy for the Management of Psoriasis

Topical Corticosteroids—Topical corticosteroids (TCs) are widely used for inflammatory skin conditions and are available in a variety of strengths (Table 2). They are thought to exert their action by regulating the gene transcription of proinflammatory mediators. For psoriasis, steroids are recommended for 2 to 4 weeks, depending on disease severity. Although potent and superpotent steroids are more effective than mild- to moderate-strength TCs, use of lower-potency TCs may be warranted depending on disease distribution and localization.¹¹ For treatment of psoriasis with no involvement of the intertriginous areas, use of class 1 to 5 TCs for up to 4 weeks is recommended.

For moderate to severe psoriasis with 20% or less body surface area (BSA) affected, combination therapy consisting of mometasone and salicylic acid has been shown to be more effective than mometasone alone.^12,13 There currently is a level A recommendation for the use of combination therapy with class 1 TCs and etanercept for 12 weeks in patients with moderate to severe psoriasis who require both systemic and topical therapies for disease control. Similarly, combination therapy with infliximab and high-potency TCs has a level B recommendation to enhance efficacy for the treatment of moderate to severe psoriasis.¹⁴ High-quality studies on the use of TCs with anti–IL-12/IL-23, anti–IL-23, and anti–IL-17 currently are unavailable, but the combination is not expected to be unsafe.^14,15 Combination therapy of betamethasone dipropionate ointment and low-dose cyclosporine is an alternative regimen with a level B recommendation.

The most common adverse effects with use of TCs are skin thinning and atrophy, telangiectasia, and striae (Table 1). With clinical improvement of disease, it is recommended that clinicians taper TCs to prevent rebound effect. To decrease TC-related adverse effects, clinicians should use combination therapy with steroid-sparing agents for disease maintenance, transition to lower-potency corticosteroids, or use intermittent steroid therapy. Systemic effects of TC use include hypothalamic-pituitary-adrenal axis suppression, Cushing syndrome, and osteonecrosis of the femoral head.^16-18 These systemic effects with TC use are rare unless treatment is for disease involving greater than 20% BSA or occlusion for more than 4 weeks.

Calcineurin Inhibitors—Calcineurin inhibitors inhibit calcineurin phosphorylation and T-cell activation, subsequently decreasing the expression of proinflammatory cytokines. Currently, they are not approved by the US Food and Drug Administration to treat psoriasis but have demonstrated efficacy in randomized control trials (RCTs) for facial and intertriginous psoriasis. In RCTs, 71% of patients using pimecrolimus cream 0.1% twice daily for 8 weeks achieved an investigator global assessment score of clear (0) or almost clear (1) compared with 21% of placebo-treated patients (N=57).¹⁹ Other trials have shown that 65% of patients receiving tacrolimus ointment 0.1% for 8 weeks achieved an investigator global assessment score of 0 or 1 compared with 31% of placebo-treated patients (N=167).²⁰ Because of their efficacy in RCTs, CNIs commonly are used off label to treat psoriasis.

The most common adverse effects with CNI use are burning, pruritus, and flushing with alcohol ingestion (Table 1). Additionally, CNIs have a black box warning that use may increase the risk for malignancy, but this risk has not been demonstrated with topical use in humans.²¹Vitamin D Analogues—The class of vitamin D analogues—calcipotriol/calcipotriene and calcitriol—frequently are used to treat psoriasis. Vitamin D analogues exert their beneficial effects by inhibiting keratinocyte proliferation and enhancing keratinocyte differentiation. They also are ideal for long-term use (up to 52 weeks) in mild to moderate psoriasis and can be used in combination with class 2 and 3 TCs. There is a level A recommendation that supports the use of combination therapy with calcipotriol and TCs for the treatment of mild to moderate psoriasis.

For severe psoriasis, many studies have investigated the efficacy of combination therapy with vitamin D analogues and systemic treatments. Combination therapy with calcipotriol and methotrexate or calcipotriol and acitretin are effective treatment regimens with level A recommendations. Calcipotriol–betamethasone dipropionate ointment in combination with low-dose cyclosporine is an alternative option with a level B recommendation. Because vitamin D analogues are inactivated by UVA and UVB radiation, clinicians should advise their patients to use vitamin D analogues after receiving UVB phototherapy.²²

Common adverse effects of vitamin D analogues include burning, pruritus, erythema, and dryness (Table 1). Hypercalcemia and parathyroid hormone suppression are extremely rare unless treatment occurs over a large surface area (>30% BSA) or the patient has concurrent renal disease or impairments in calcium metabolism.

Tazarotene—Tazarotene is a topical retinoid that acts by decreasing keratinocyte proliferation, facilitating keratinocyte differentiation, and inhibiting inflammation. Patients with mild to moderate psoriasis are recommended to receive tazarotene treatment for 8 to 12 weeks. In several RCTs, tazarotene gel 0.1% and tazarotene cream 0.1% and 0.05% achieved treatment success in treating plaque psoriasis.^23,24

For increased efficacy, clinicians can recommend combination therapy with tazarotene and a TC. Combination therapy with tazarotene and a mid- or high-potency TC for 8 to 16 weeks has been shown to be more effective than treatment with tazarotene alone.²⁵ Thus, there is a level A recommendation for use of this combination to treat mild to moderate psoriasis. Agents used in combination therapy work synergistically to decrease the length of treatment and increase the duration of remission. The frequency of adverse effects, such as irritation from tazarotene and skin atrophy from TCs, also are reduced.²⁶ Combination therapy with tazarotene and narrowband UVB (NB-UVB) is another effective option that requires less UV radiation than NB-UVB alone because of the synergistic effects of both treatment modalities.²⁷ Clinicians should counsel patients on the adverse effects of tazarotene, which include local irritation, burning, pruritus, and erythema (Table 1).

Emollients—Emollients are nonmedicated moisturizers that decrease the amount of transepidermal water loss. There is a level B recommendation for use of emollients and TCs in combination for 4 to 8 weeks to treat psoriasis. In fact, combination therapy with mometasone and emollients has demonstrated greater improvement in symptoms of palmoplantar psoriasis (ie, erythema, desquamation, infiltration, BSA involvement) than mometasone alone.²⁸ Emollients are safe options that can be used on all areas of the body and during pregnancy and lactation. Although adverse effects of emollients are rare, clinicians should counsel patients on the risk for contact dermatitis if specific allergies to ingredients/fragrances exist (Table 1).

Salicylic Acid—Salicylic acid is a topical keratolytic that can be used to treat psoriatic plaques. Use of salicylic acid for 8 to 16 weeks has been shown to be effective for mild to moderate psoriasis. Combination therapy of salicylic acid and TCs in patients with 20% or less BSA affected is a safe and effective option with a level B recommendation. Combination therapy with salicylic acid and calcipotriene, however, should be avoided because calcipotriene is inactivated by salicylic acid. It also is recommended that salicylic acid application follow phototherapy when both treatment modalities are used in combination.^29,30 Clinicians should be cautious about using salicylic acid in patients with renal or hepatic disease because of the increased risk for salicylate toxicity (Table 1).

Anthralin—Anthralin is a synthetic hydrocarbon derivative that has been shown to reduce inflammation and normalize keratinocyte proliferation through an unknown mechanism. It is recommended that patients with mild to moderate psoriasis receive anthralin treatment for 8 to 12 weeks, with a maximum application time of 2 hours per day. Combination therapy of excimer laser and anthralin has been shown to be more effective in treating psoriasis than anthralin alone.³¹ Therefore, clinicians have the option of including excimer laser therapy for additional disease control. Anthralin should be avoided on the face, flexural regions, and highly visible areas because of potential skin staining (Table 1). Other adverse effects include application-site burning and erythema.

Coal Tar—Coal tar is a heterogenous mixture of aromatic hydrocarbons that is an effective treatment of psoriasis because of its inherent anti-inflammatory and keratoplastic properties. There is high-quality evidence supporting a level A recommendation for coal tar use in mild to moderate psoriasis. Combination therapy with NB-UVB and coal tar (also known as Goeckerman therapy) is a recommended treatment option with a quicker onset of action and improved outcomes compared with NB-UVB therapy alone.^32,33 Adverse events of coal tar include application-site irritation, folliculitis, contact dermatitis, phototoxicity, and skin pigmentation (Table 1).

Conclusion

Topical medications are versatile treatment options that can be utilized as monotherapy or adjunct therapy for mild to severe psoriasis. Benefits of topical agents include minimal required monitoring, few contraindications, and direct localized effect on plaques. Therefore, side effects with topical agent use rarely are systemic. Medication interactions are less of a concern with topical therapies; thus, they have better safety profiles compared with systemic therapies. This clinical review summarizes the recently published evidence-based guidelines from the AAD and NPF on the use of topical agents in psoriasis and may be a useful guiding framework for clinicians in their everyday practice.

When COVID-19 emerged in March 2020, physicians were forced to evaluate the potential impacts of the pandemic on our patients and the conditions that we treat. For dermatologists, psoriasis came into particular focus, as many patients were being treated with biologic therapies. The initial concern was that these biologics might render our patients more susceptible to both COVID-19 infection and/or a more severe disease course.

In early 2020, the National Psoriasis Foundation (NPF) presented its own recommendations for treating patients with psoriatic disease during the pandemic.¹ Some highlights included the following¹:

• At the time, it was stipulated that patients with COVID-19 infection should stop taking a biologic.

• Psoriasis patients in high-risk groups (eg, concomitant systemic disease) should discuss with their dermatologist if their therapeutic regimen should be continued or altered.

• Patients taking oral immunosuppressive therapy may be at greater risk for COVID-19 infection, though there is no strong COVID-19–related evidence to provide specific guidelines or risk level.

In May 2020, the NPF COVID-19 Task Force was formed. This group—chaired by dermatologist Joel M. Gelfand, MD, MSCE (Philadelphia, Pennsylvania), and rheumatologist Christopher T. Ritchlin, MD, MPH (Rochester, New York)—was comprised of members from both the NPF Medical Board and Scientific Advisory Committee in dermatology, rheumatology, infectious disease, and critical care. The NPF COVID-19 Task Force has been critical in keeping the dermatology community apprised of the latest scientific thinking related to COVID-19 and publishing guidance statements that are updated and amended on a regular basis as new data becomes available.² Key recommendations most relevant to the daily care of patients with psoriatic disease included the following²:

• Patients with psoriasis and/or psoriatic arthritis have similar rates of SARS-CoV-2 infection and COVID-19 outcomes as the general population based on existing data, with some exceptions.

• Therapies for psoriasis and/or psoriatic arthritis do not meaningfully alter the risk for acquiring SARS-CoV-2 infection or having worse COVID-19 outcomes.

• Patients should continue their biologic or oral therapies for psoriasis and/or psoriatic arthritis in most cases, unless they become infected with SARS-CoV-2.

• Chronic systemic steroid use for psoriatic disease in the setting of acute infection with COVID-19 may be associated with worse outcomes; however, steroids may improve outcomes for COVID-19 when initiated in hospitalized patients who require oxygen therapy.

• When local restrictions or pandemic conditions limit the ability for in-person visits, offer telemedicine to manage patients.

• Patients with psoriatic disease who do not have contraindications to vaccination should receive a messenger RNA (mRNA)–based COVID-19 vaccine and boosters, based on federal, state, and local guidance. Systemic medications for psoriasis or psoriatic arthritis are not a contraindication to the mRNA-based COVID-19 vaccine. 

• Patients who are to receive an mRNA-based COVID-19 vaccine should continue their biologic or oral therapies for psoriasis and/or psoriatic arthritis in most cases.

• The use of hydroxychloroquine, chloroquine, and ivermectin is not suggested for the prevention or treatment of COVID-19 disease.

These guidelines have been critical in addressing some of the most pressing issues in psoriasis patient care, particularly the susceptibility to COVID-19, the role of psoriasis therapies in initial infection and health outcomes, and issues related to the administration of vaccines in those on systemic therapies. Based on these recommendations, we have been given a solid foundation that our current standard of care can (for the most part) continue with the continued presence of COVID-19 in our society. I encourage all providers to familiarize themselves with the NPF COVID-19 Task Force guidelines and keep abreast of updates as they become available (https://www.psoriasis.org/covid-19-task-force-guidance-statements/).

When COVID-19 emerged in March 2020, physicians were forced to evaluate the potential impacts of the pandemic on our patients and the conditions that we treat. For dermatologists, psoriasis came into particular focus, as many patients were being treated with biologic therapies. The initial concern was that these biologics might render our patients more susceptible to both COVID-19 infection and/or a more severe disease course.

In early 2020, the National Psoriasis Foundation (NPF) presented its own recommendations for treating patients with psoriatic disease during the pandemic.¹ Some highlights included the following¹:

• At the time, it was stipulated that patients with COVID-19 infection should stop taking a biologic.

• Psoriasis patients in high-risk groups (eg, concomitant systemic disease) should discuss with their dermatologist if their therapeutic regimen should be continued or altered.

• Patients taking oral immunosuppressive therapy may be at greater risk for COVID-19 infection, though there is no strong COVID-19–related evidence to provide specific guidelines or risk level.

In May 2020, the NPF COVID-19 Task Force was formed. This group—chaired by dermatologist Joel M. Gelfand, MD, MSCE (Philadelphia, Pennsylvania), and rheumatologist Christopher T. Ritchlin, MD, MPH (Rochester, New York)—was comprised of members from both the NPF Medical Board and Scientific Advisory Committee in dermatology, rheumatology, infectious disease, and critical care. The NPF COVID-19 Task Force has been critical in keeping the dermatology community apprised of the latest scientific thinking related to COVID-19 and publishing guidance statements that are updated and amended on a regular basis as new data becomes available.² Key recommendations most relevant to the daily care of patients with psoriatic disease included the following²:

• Patients with psoriasis and/or psoriatic arthritis have similar rates of SARS-CoV-2 infection and COVID-19 outcomes as the general population based on existing data, with some exceptions.

• Therapies for psoriasis and/or psoriatic arthritis do not meaningfully alter the risk for acquiring SARS-CoV-2 infection or having worse COVID-19 outcomes.

• Patients should continue their biologic or oral therapies for psoriasis and/or psoriatic arthritis in most cases, unless they become infected with SARS-CoV-2.

• Chronic systemic steroid use for psoriatic disease in the setting of acute infection with COVID-19 may be associated with worse outcomes; however, steroids may improve outcomes for COVID-19 when initiated in hospitalized patients who require oxygen therapy.

• When local restrictions or pandemic conditions limit the ability for in-person visits, offer telemedicine to manage patients.

• Patients with psoriatic disease who do not have contraindications to vaccination should receive a messenger RNA (mRNA)–based COVID-19 vaccine and boosters, based on federal, state, and local guidance. Systemic medications for psoriasis or psoriatic arthritis are not a contraindication to the mRNA-based COVID-19 vaccine. 

• Patients who are to receive an mRNA-based COVID-19 vaccine should continue their biologic or oral therapies for psoriasis and/or psoriatic arthritis in most cases.

• The use of hydroxychloroquine, chloroquine, and ivermectin is not suggested for the prevention or treatment of COVID-19 disease.

These guidelines have been critical in addressing some of the most pressing issues in psoriasis patient care, particularly the susceptibility to COVID-19, the role of psoriasis therapies in initial infection and health outcomes, and issues related to the administration of vaccines in those on systemic therapies. Based on these recommendations, we have been given a solid foundation that our current standard of care can (for the most part) continue with the continued presence of COVID-19 in our society. I encourage all providers to familiarize themselves with the NPF COVID-19 Task Force guidelines and keep abreast of updates as they become available (https://www.psoriasis.org/covid-19-task-force-guidance-statements/).

When COVID-19 emerged in March 2020, physicians were forced to evaluate the potential impacts of the pandemic on our patients and the conditions that we treat. For dermatologists, psoriasis came into particular focus, as many patients were being treated with biologic therapies. The initial concern was that these biologics might render our patients more susceptible to both COVID-19 infection and/or a more severe disease course.

In early 2020, the National Psoriasis Foundation (NPF) presented its own recommendations for treating patients with psoriatic disease during the pandemic.¹ Some highlights included the following¹:

• At the time, it was stipulated that patients with COVID-19 infection should stop taking a biologic.

• Psoriasis patients in high-risk groups (eg, concomitant systemic disease) should discuss with their dermatologist if their therapeutic regimen should be continued or altered.

• Patients taking oral immunosuppressive therapy may be at greater risk for COVID-19 infection, though there is no strong COVID-19–related evidence to provide specific guidelines or risk level.

In May 2020, the NPF COVID-19 Task Force was formed. This group—chaired by dermatologist Joel M. Gelfand, MD, MSCE (Philadelphia, Pennsylvania), and rheumatologist Christopher T. Ritchlin, MD, MPH (Rochester, New York)—was comprised of members from both the NPF Medical Board and Scientific Advisory Committee in dermatology, rheumatology, infectious disease, and critical care. The NPF COVID-19 Task Force has been critical in keeping the dermatology community apprised of the latest scientific thinking related to COVID-19 and publishing guidance statements that are updated and amended on a regular basis as new data becomes available.² Key recommendations most relevant to the daily care of patients with psoriatic disease included the following²:

• Patients with psoriasis and/or psoriatic arthritis have similar rates of SARS-CoV-2 infection and COVID-19 outcomes as the general population based on existing data, with some exceptions.

• Therapies for psoriasis and/or psoriatic arthritis do not meaningfully alter the risk for acquiring SARS-CoV-2 infection or having worse COVID-19 outcomes.

• Patients should continue their biologic or oral therapies for psoriasis and/or psoriatic arthritis in most cases, unless they become infected with SARS-CoV-2.

• Chronic systemic steroid use for psoriatic disease in the setting of acute infection with COVID-19 may be associated with worse outcomes; however, steroids may improve outcomes for COVID-19 when initiated in hospitalized patients who require oxygen therapy.

• When local restrictions or pandemic conditions limit the ability for in-person visits, offer telemedicine to manage patients.

• Patients with psoriatic disease who do not have contraindications to vaccination should receive a messenger RNA (mRNA)–based COVID-19 vaccine and boosters, based on federal, state, and local guidance. Systemic medications for psoriasis or psoriatic arthritis are not a contraindication to the mRNA-based COVID-19 vaccine. 

• Patients who are to receive an mRNA-based COVID-19 vaccine should continue their biologic or oral therapies for psoriasis and/or psoriatic arthritis in most cases.

• The use of hydroxychloroquine, chloroquine, and ivermectin is not suggested for the prevention or treatment of COVID-19 disease.

These guidelines have been critical in addressing some of the most pressing issues in psoriasis patient care, particularly the susceptibility to COVID-19, the role of psoriasis therapies in initial infection and health outcomes, and issues related to the administration of vaccines in those on systemic therapies. Based on these recommendations, we have been given a solid foundation that our current standard of care can (for the most part) continue with the continued presence of COVID-19 in our society. I encourage all providers to familiarize themselves with the NPF COVID-19 Task Force guidelines and keep abreast of updates as they become available (https://www.psoriasis.org/covid-19-task-force-guidance-statements/).

The incidence of lice and scabies decreased significantly among children and adults in North Carolina during the confinement period of the COVID-19 pandemic, between March 2020 and February 2021, according to a report in Pediatric Dermatology.

When COVID-19 was declared a public health emergency by the World Health Organization in March 2020, many countries including the United States enacted lockdown and isolation measures to help contain the spread of the disease. Since scabies and lice are both spread by direct contact, “we hypothesized that the nationwide lockdown would influence the transmission of these two conditions among individuals,” wrote Marianne Bonanno, MD, of the University of North Carolina, Chapel Hill, and colleagues.

“The pandemic created a unique opportunity for real-life observations following physical distancing measures being put in place,” coauthor Christopher Sayed, MD, associate professor of dermatology at UNC, said in an interview. “It makes intuitive sense that since lice and scabies spread by cost physical contact that rates would decrease with school closures and other physical distancing measures. Reports from other countries in which extended families more often live together and were forced to spend more time in close quarters saw increased rates so it was interesting to see this contrast,” he noted.

In the study, the researchers reviewed data from 1,858 cases of adult scabies, 893 cases of pediatric scabies, and 804 cases of pediatric lice reported in North Carolina between March 2017 and February 2021. They compared monthly cases of scabies and lice, and prescriptions during the period before the pandemic (March 2017 to February 2020), and during the pandemic (March 2020 to February 2021).

Pediatric lice cases decreased by 60.6% over the study period (P < .001). Significant decreases also occurred in adult scabies (31.1%, P < .001) and pediatric scabies (39%, P < .01).

The number of prescriptions for lice and scabies also decreased significantly (P < .01) during the study period, although these numbers differed from the actual cases. Prescriptions decreased by 41.4%, 29.9%, and 69.3% for pediatric scabies, adult scabies, and pediatric lice, respectively.

Both pediatric scabies and pediatric lice showed a greater drop in prescriptions than in cases, while the drop in prescriptions for adult scabies was slightly less than the drop in cases.

The difference in the decreased numbers between cases and prescriptions may stem from the decrease in close contacts during the pandemic, which decreased the need for multiple prescriptions, but other potential explanations could be examined in future studies, the researchers wrote in their discussion.

The study findings were limited by several factors including the cross-sectional design and potential underdiagnosis and underreporting, as well as the focus only on a population in a single state, which may limit generalizability, the researchers noted.

However, the results offer preliminary insights on the impact of COVID-19 restrictions on scabies and lice, and suggest the potential value of physical distancing to reduce transmission of both conditions, especially in settings such as schools and prisons, to help contain future outbreaks, they concluded.

The study findings reinforce physical contact as the likely route of disease transmission, for lice and scabies, Dr. Sayed said in the interview. “It’s possible distancing measures on a small scale could be considered for outbreaks in institutional settings, though the risks of these infestations are much lower than with COVID-19,” he said. “It will be interesting to observe trends as physical distancing measures end to see if cases rebound in the next few years,” he added.

Drop in cases likely temporary

“Examining the epidemiology of different infectious diseases over time is an interesting and important area of study,” said Sheilagh Maguiness, MD, associate professor of dermatology and pediatrics at the University of Minnesota, Minneapolis, who was asked to comment on the results.

“The pandemic dramatically altered the daily lives of adults and children across the globe, and we can learn a lot from studying how social distancing and prolonged masking has made an impact on the incidence and prevalence of different infectious illnesses in the country and across the world,” she said in an interview.

Dr. Maguiness said she was not surprised by the study findings. “In fact, other countries have published similar studies documenting a reduction in both head lice and scabies infestations during the time of the pandemic,” she said. “In France, it was noted that during March to December 2020, there was a reduction in sales for topical head lice and scabies treatments of 44% and 14%, respectively. Similarly, a study from Argentina documented a decline in head lice infestations by about 25% among children,” she said.

“I personally noted a marked decrease in both of these diagnoses among children in my own clinic,” she added.

“Since both of these conditions are spread through close physical contact with others, it makes sense that there would be a steep decline in ectoparasitic infections during times of social distancing. However, anecdotally we are now diagnosing and treating these infestations again more regularly in our clinic,” said Dr. Maguiness. “As social distancing relaxes, I would expect that the incidence of both head lice and scabies will again increase.” 

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

The incidence of lice and scabies decreased significantly among children and adults in North Carolina during the confinement period of the COVID-19 pandemic, between March 2020 and February 2021, according to a report in Pediatric Dermatology.

When COVID-19 was declared a public health emergency by the World Health Organization in March 2020, many countries including the United States enacted lockdown and isolation measures to help contain the spread of the disease. Since scabies and lice are both spread by direct contact, “we hypothesized that the nationwide lockdown would influence the transmission of these two conditions among individuals,” wrote Marianne Bonanno, MD, of the University of North Carolina, Chapel Hill, and colleagues.

“The pandemic created a unique opportunity for real-life observations following physical distancing measures being put in place,” coauthor Christopher Sayed, MD, associate professor of dermatology at UNC, said in an interview. “It makes intuitive sense that since lice and scabies spread by cost physical contact that rates would decrease with school closures and other physical distancing measures. Reports from other countries in which extended families more often live together and were forced to spend more time in close quarters saw increased rates so it was interesting to see this contrast,” he noted.

In the study, the researchers reviewed data from 1,858 cases of adult scabies, 893 cases of pediatric scabies, and 804 cases of pediatric lice reported in North Carolina between March 2017 and February 2021. They compared monthly cases of scabies and lice, and prescriptions during the period before the pandemic (March 2017 to February 2020), and during the pandemic (March 2020 to February 2021).

Pediatric lice cases decreased by 60.6% over the study period (P < .001). Significant decreases also occurred in adult scabies (31.1%, P < .001) and pediatric scabies (39%, P < .01).

The number of prescriptions for lice and scabies also decreased significantly (P < .01) during the study period, although these numbers differed from the actual cases. Prescriptions decreased by 41.4%, 29.9%, and 69.3% for pediatric scabies, adult scabies, and pediatric lice, respectively.

Both pediatric scabies and pediatric lice showed a greater drop in prescriptions than in cases, while the drop in prescriptions for adult scabies was slightly less than the drop in cases.

The difference in the decreased numbers between cases and prescriptions may stem from the decrease in close contacts during the pandemic, which decreased the need for multiple prescriptions, but other potential explanations could be examined in future studies, the researchers wrote in their discussion.

The study findings were limited by several factors including the cross-sectional design and potential underdiagnosis and underreporting, as well as the focus only on a population in a single state, which may limit generalizability, the researchers noted.

However, the results offer preliminary insights on the impact of COVID-19 restrictions on scabies and lice, and suggest the potential value of physical distancing to reduce transmission of both conditions, especially in settings such as schools and prisons, to help contain future outbreaks, they concluded.

The study findings reinforce physical contact as the likely route of disease transmission, for lice and scabies, Dr. Sayed said in the interview. “It’s possible distancing measures on a small scale could be considered for outbreaks in institutional settings, though the risks of these infestations are much lower than with COVID-19,” he said. “It will be interesting to observe trends as physical distancing measures end to see if cases rebound in the next few years,” he added.

Drop in cases likely temporary

“Examining the epidemiology of different infectious diseases over time is an interesting and important area of study,” said Sheilagh Maguiness, MD, associate professor of dermatology and pediatrics at the University of Minnesota, Minneapolis, who was asked to comment on the results.

“The pandemic dramatically altered the daily lives of adults and children across the globe, and we can learn a lot from studying how social distancing and prolonged masking has made an impact on the incidence and prevalence of different infectious illnesses in the country and across the world,” she said in an interview.

Dr. Maguiness said she was not surprised by the study findings. “In fact, other countries have published similar studies documenting a reduction in both head lice and scabies infestations during the time of the pandemic,” she said. “In France, it was noted that during March to December 2020, there was a reduction in sales for topical head lice and scabies treatments of 44% and 14%, respectively. Similarly, a study from Argentina documented a decline in head lice infestations by about 25% among children,” she said.

“I personally noted a marked decrease in both of these diagnoses among children in my own clinic,” she added.

“Since both of these conditions are spread through close physical contact with others, it makes sense that there would be a steep decline in ectoparasitic infections during times of social distancing. However, anecdotally we are now diagnosing and treating these infestations again more regularly in our clinic,” said Dr. Maguiness. “As social distancing relaxes, I would expect that the incidence of both head lice and scabies will again increase.” 

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

The incidence of lice and scabies decreased significantly among children and adults in North Carolina during the confinement period of the COVID-19 pandemic, between March 2020 and February 2021, according to a report in Pediatric Dermatology.

When COVID-19 was declared a public health emergency by the World Health Organization in March 2020, many countries including the United States enacted lockdown and isolation measures to help contain the spread of the disease. Since scabies and lice are both spread by direct contact, “we hypothesized that the nationwide lockdown would influence the transmission of these two conditions among individuals,” wrote Marianne Bonanno, MD, of the University of North Carolina, Chapel Hill, and colleagues.

“The pandemic created a unique opportunity for real-life observations following physical distancing measures being put in place,” coauthor Christopher Sayed, MD, associate professor of dermatology at UNC, said in an interview. “It makes intuitive sense that since lice and scabies spread by cost physical contact that rates would decrease with school closures and other physical distancing measures. Reports from other countries in which extended families more often live together and were forced to spend more time in close quarters saw increased rates so it was interesting to see this contrast,” he noted.

In the study, the researchers reviewed data from 1,858 cases of adult scabies, 893 cases of pediatric scabies, and 804 cases of pediatric lice reported in North Carolina between March 2017 and February 2021. They compared monthly cases of scabies and lice, and prescriptions during the period before the pandemic (March 2017 to February 2020), and during the pandemic (March 2020 to February 2021).

Pediatric lice cases decreased by 60.6% over the study period (P < .001). Significant decreases also occurred in adult scabies (31.1%, P < .001) and pediatric scabies (39%, P < .01).

The number of prescriptions for lice and scabies also decreased significantly (P < .01) during the study period, although these numbers differed from the actual cases. Prescriptions decreased by 41.4%, 29.9%, and 69.3% for pediatric scabies, adult scabies, and pediatric lice, respectively.

Both pediatric scabies and pediatric lice showed a greater drop in prescriptions than in cases, while the drop in prescriptions for adult scabies was slightly less than the drop in cases.

The difference in the decreased numbers between cases and prescriptions may stem from the decrease in close contacts during the pandemic, which decreased the need for multiple prescriptions, but other potential explanations could be examined in future studies, the researchers wrote in their discussion.

The study findings were limited by several factors including the cross-sectional design and potential underdiagnosis and underreporting, as well as the focus only on a population in a single state, which may limit generalizability, the researchers noted.

However, the results offer preliminary insights on the impact of COVID-19 restrictions on scabies and lice, and suggest the potential value of physical distancing to reduce transmission of both conditions, especially in settings such as schools and prisons, to help contain future outbreaks, they concluded.

The study findings reinforce physical contact as the likely route of disease transmission, for lice and scabies, Dr. Sayed said in the interview. “It’s possible distancing measures on a small scale could be considered for outbreaks in institutional settings, though the risks of these infestations are much lower than with COVID-19,” he said. “It will be interesting to observe trends as physical distancing measures end to see if cases rebound in the next few years,” he added.

Drop in cases likely temporary

“Examining the epidemiology of different infectious diseases over time is an interesting and important area of study,” said Sheilagh Maguiness, MD, associate professor of dermatology and pediatrics at the University of Minnesota, Minneapolis, who was asked to comment on the results.

“The pandemic dramatically altered the daily lives of adults and children across the globe, and we can learn a lot from studying how social distancing and prolonged masking has made an impact on the incidence and prevalence of different infectious illnesses in the country and across the world,” she said in an interview.

Dr. Maguiness said she was not surprised by the study findings. “In fact, other countries have published similar studies documenting a reduction in both head lice and scabies infestations during the time of the pandemic,” she said. “In France, it was noted that during March to December 2020, there was a reduction in sales for topical head lice and scabies treatments of 44% and 14%, respectively. Similarly, a study from Argentina documented a decline in head lice infestations by about 25% among children,” she said.

“I personally noted a marked decrease in both of these diagnoses among children in my own clinic,” she added.

“Since both of these conditions are spread through close physical contact with others, it makes sense that there would be a steep decline in ectoparasitic infections during times of social distancing. However, anecdotally we are now diagnosing and treating these infestations again more regularly in our clinic,” said Dr. Maguiness. “As social distancing relaxes, I would expect that the incidence of both head lice and scabies will again increase.” 

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

An extensive new study shows that climate change can aggravate over half of known human pathogenic diseases. This comprehensive systematic review of the literature narrowed down 3,213 cases, linking 286 infectious diseases to specific climate change hazards. Of these, 58% were worsened, and only 9 conditions showed any benefit associated with environmental change.

The study was published online in Nature Climate Change. The complete list of cases, transmission pathways, and associated papers can be explored in detail – a remarkable, interactive data visualization.

To compile the data, investigators searched 10 keywords on the Global Infectious Disease and Epidemiology Network (GIDEON) and Center for Disease Control and Prevention databases. They then filled gaps by examining alternative names of the diseases, pathogens, and hazards.

Coauthor Tristan McKenzie, PhD, a postdoctoral researcher at the University of Gothenburg, Sweden, told this news organization: “If someone is interested in a certain pathway, it’s a beautiful starting point.” Or if someone wants to “do a modeling study and they want to focus on a specific area, the specific examples in the literature are already there” in the extensive database.

An early key finding is that warming and increased precipitation broadened the range of many pathogens through expansion of their habitat. This shift brings many pathogens closer to people. We have already seen vectors such as mosquitoes, ticks, fleas, birds, and several mammals spreading infections over a broader range. Examples are viruses (dengue, Chikungunya), bacteria (Lyme), protozoans (trypanosomes), and more. Warming has affected aquatic systems (for example, Vibrio) and higher altitudes and latitudes (malaria, dengue).

Pathogenic hazards are not just moving closer to people. People are also moving closer to the pathogenic hazards, with heat waves causing people to seek refuge with water activities, for example. This increases their exposure to pathogens, such as Vibrio, hepatitis, and water-borne gastroenteritis.

Some hazards, such as warming, can even make pathogens more virulent. Heat can upregulate Vibrio’s gene expression of proteins affecting transmission, adhesion, penetration, and host injury.

Heat and rainfall can increase stagnant water, enhancing mosquitoes’ breeding and growing grounds and enabling them to transmit many more infections.

People’s capacity to respond to climate hazards can also be impaired. For example, there is a reduced concentration of nutrients in crops under high CO2 levels, which can result in malnutrition. Lower crop yields can further fuel outbreaks of measles, cholera, or Cryptosporidium. Drought also likely forces people to drink contaminated water.

Among all this bad news, the authors found a small number of cases where climate hazards reduced the risk of infection. For example, droughts reduced the breeding grounds of mosquitoes, reducing the prevalence of malaria and chikungunya. But in other cases, the density of mosquitoes increased in some pools, causing an increased local risk of infection.

Naomi Hauser, MD, MPH, assistant clinical professor at UC Davis, Sacramento, told this news organization she was particularly impressed with the data visualization. “It really emphasizes the magnitude of what we’re dealing with. It makes you feel the weight of what they’re trying to represent,” she said.

On the other hand, Dr. Hauser said she would have liked “more emphasis on how the climate hazards interact with each other. It sort of made it sound like each of these climate hazards is in a vacuum – like when there’s floods, and that’s the problem. But there are a lot of other things ... like when we have warming and surface water temperature changes, it can also change the pH of the water and the salinity of the water, and those can also impact what we see with pathogens in the water.”

Dr. McKenzie explained one limitation: The study looked only at 10 keywords. So an example of a dust storm in Africa causing an increase in Vibrio in the United States could not be identified by this approach. “This also goes back to the scale of the problem, because we have something going on in the Sahara that’s impacting the East Coast of the United States,” he said. “And finding that link is not necessarily obvious – or at least not as obvious as [if] there [were] a hurricane and a bunch of people got sick from waterborne disease. So I think that really highlights the scale of this problem.”

Instead of looking at only one individual or group of pathogens, the study provided a much broader review of infections caused by an array of climate hazards. As Dr. McKenzie said, “no one’s actually done the work previously to really just try and get a comprehensive picture of what we might be dealing with. And so that was the goal for us.” The 58% estimate of diseases worsened by climate change is conservative, and, he says, “arguably, this is an even bigger problem than what we present.”

Dr. McKenzie concluded: “If we’re looking at the spread of some more serious or rare diseases in areas, to me then the answer is ... we need to be aggressively mitigating greenhouse gas emissions. Let’s start with the source.”

Dr. McKenzie and Dr. Hauser report no relevant financial relationships.

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

An extensive new study shows that climate change can aggravate over half of known human pathogenic diseases. This comprehensive systematic review of the literature narrowed down 3,213 cases, linking 286 infectious diseases to specific climate change hazards. Of these, 58% were worsened, and only 9 conditions showed any benefit associated with environmental change.

The study was published online in Nature Climate Change. The complete list of cases, transmission pathways, and associated papers can be explored in detail – a remarkable, interactive data visualization.

To compile the data, investigators searched 10 keywords on the Global Infectious Disease and Epidemiology Network (GIDEON) and Center for Disease Control and Prevention databases. They then filled gaps by examining alternative names of the diseases, pathogens, and hazards.

Coauthor Tristan McKenzie, PhD, a postdoctoral researcher at the University of Gothenburg, Sweden, told this news organization: “If someone is interested in a certain pathway, it’s a beautiful starting point.” Or if someone wants to “do a modeling study and they want to focus on a specific area, the specific examples in the literature are already there” in the extensive database.

An early key finding is that warming and increased precipitation broadened the range of many pathogens through expansion of their habitat. This shift brings many pathogens closer to people. We have already seen vectors such as mosquitoes, ticks, fleas, birds, and several mammals spreading infections over a broader range. Examples are viruses (dengue, Chikungunya), bacteria (Lyme), protozoans (trypanosomes), and more. Warming has affected aquatic systems (for example, Vibrio) and higher altitudes and latitudes (malaria, dengue).

Pathogenic hazards are not just moving closer to people. People are also moving closer to the pathogenic hazards, with heat waves causing people to seek refuge with water activities, for example. This increases their exposure to pathogens, such as Vibrio, hepatitis, and water-borne gastroenteritis.

Some hazards, such as warming, can even make pathogens more virulent. Heat can upregulate Vibrio’s gene expression of proteins affecting transmission, adhesion, penetration, and host injury.

Heat and rainfall can increase stagnant water, enhancing mosquitoes’ breeding and growing grounds and enabling them to transmit many more infections.

People’s capacity to respond to climate hazards can also be impaired. For example, there is a reduced concentration of nutrients in crops under high CO2 levels, which can result in malnutrition. Lower crop yields can further fuel outbreaks of measles, cholera, or Cryptosporidium. Drought also likely forces people to drink contaminated water.

Among all this bad news, the authors found a small number of cases where climate hazards reduced the risk of infection. For example, droughts reduced the breeding grounds of mosquitoes, reducing the prevalence of malaria and chikungunya. But in other cases, the density of mosquitoes increased in some pools, causing an increased local risk of infection.

Naomi Hauser, MD, MPH, assistant clinical professor at UC Davis, Sacramento, told this news organization she was particularly impressed with the data visualization. “It really emphasizes the magnitude of what we’re dealing with. It makes you feel the weight of what they’re trying to represent,” she said.

On the other hand, Dr. Hauser said she would have liked “more emphasis on how the climate hazards interact with each other. It sort of made it sound like each of these climate hazards is in a vacuum – like when there’s floods, and that’s the problem. But there are a lot of other things ... like when we have warming and surface water temperature changes, it can also change the pH of the water and the salinity of the water, and those can also impact what we see with pathogens in the water.”

Dr. McKenzie explained one limitation: The study looked only at 10 keywords. So an example of a dust storm in Africa causing an increase in Vibrio in the United States could not be identified by this approach. “This also goes back to the scale of the problem, because we have something going on in the Sahara that’s impacting the East Coast of the United States,” he said. “And finding that link is not necessarily obvious – or at least not as obvious as [if] there [were] a hurricane and a bunch of people got sick from waterborne disease. So I think that really highlights the scale of this problem.”

Instead of looking at only one individual or group of pathogens, the study provided a much broader review of infections caused by an array of climate hazards. As Dr. McKenzie said, “no one’s actually done the work previously to really just try and get a comprehensive picture of what we might be dealing with. And so that was the goal for us.” The 58% estimate of diseases worsened by climate change is conservative, and, he says, “arguably, this is an even bigger problem than what we present.”

Dr. McKenzie concluded: “If we’re looking at the spread of some more serious or rare diseases in areas, to me then the answer is ... we need to be aggressively mitigating greenhouse gas emissions. Let’s start with the source.”

Dr. McKenzie and Dr. Hauser report no relevant financial relationships.

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

An extensive new study shows that climate change can aggravate over half of known human pathogenic diseases. This comprehensive systematic review of the literature narrowed down 3,213 cases, linking 286 infectious diseases to specific climate change hazards. Of these, 58% were worsened, and only 9 conditions showed any benefit associated with environmental change.

The study was published online in Nature Climate Change. The complete list of cases, transmission pathways, and associated papers can be explored in detail – a remarkable, interactive data visualization.

To compile the data, investigators searched 10 keywords on the Global Infectious Disease and Epidemiology Network (GIDEON) and Center for Disease Control and Prevention databases. They then filled gaps by examining alternative names of the diseases, pathogens, and hazards.

Coauthor Tristan McKenzie, PhD, a postdoctoral researcher at the University of Gothenburg, Sweden, told this news organization: “If someone is interested in a certain pathway, it’s a beautiful starting point.” Or if someone wants to “do a modeling study and they want to focus on a specific area, the specific examples in the literature are already there” in the extensive database.

An early key finding is that warming and increased precipitation broadened the range of many pathogens through expansion of their habitat. This shift brings many pathogens closer to people. We have already seen vectors such as mosquitoes, ticks, fleas, birds, and several mammals spreading infections over a broader range. Examples are viruses (dengue, Chikungunya), bacteria (Lyme), protozoans (trypanosomes), and more. Warming has affected aquatic systems (for example, Vibrio) and higher altitudes and latitudes (malaria, dengue).

Pathogenic hazards are not just moving closer to people. People are also moving closer to the pathogenic hazards, with heat waves causing people to seek refuge with water activities, for example. This increases their exposure to pathogens, such as Vibrio, hepatitis, and water-borne gastroenteritis.

Some hazards, such as warming, can even make pathogens more virulent. Heat can upregulate Vibrio’s gene expression of proteins affecting transmission, adhesion, penetration, and host injury.

Heat and rainfall can increase stagnant water, enhancing mosquitoes’ breeding and growing grounds and enabling them to transmit many more infections.

People’s capacity to respond to climate hazards can also be impaired. For example, there is a reduced concentration of nutrients in crops under high CO2 levels, which can result in malnutrition. Lower crop yields can further fuel outbreaks of measles, cholera, or Cryptosporidium. Drought also likely forces people to drink contaminated water.

Among all this bad news, the authors found a small number of cases where climate hazards reduced the risk of infection. For example, droughts reduced the breeding grounds of mosquitoes, reducing the prevalence of malaria and chikungunya. But in other cases, the density of mosquitoes increased in some pools, causing an increased local risk of infection.

Naomi Hauser, MD, MPH, assistant clinical professor at UC Davis, Sacramento, told this news organization she was particularly impressed with the data visualization. “It really emphasizes the magnitude of what we’re dealing with. It makes you feel the weight of what they’re trying to represent,” she said.

On the other hand, Dr. Hauser said she would have liked “more emphasis on how the climate hazards interact with each other. It sort of made it sound like each of these climate hazards is in a vacuum – like when there’s floods, and that’s the problem. But there are a lot of other things ... like when we have warming and surface water temperature changes, it can also change the pH of the water and the salinity of the water, and those can also impact what we see with pathogens in the water.”

Dr. McKenzie explained one limitation: The study looked only at 10 keywords. So an example of a dust storm in Africa causing an increase in Vibrio in the United States could not be identified by this approach. “This also goes back to the scale of the problem, because we have something going on in the Sahara that’s impacting the East Coast of the United States,” he said. “And finding that link is not necessarily obvious – or at least not as obvious as [if] there [were] a hurricane and a bunch of people got sick from waterborne disease. So I think that really highlights the scale of this problem.”

Instead of looking at only one individual or group of pathogens, the study provided a much broader review of infections caused by an array of climate hazards. As Dr. McKenzie said, “no one’s actually done the work previously to really just try and get a comprehensive picture of what we might be dealing with. And so that was the goal for us.” The 58% estimate of diseases worsened by climate change is conservative, and, he says, “arguably, this is an even bigger problem than what we present.”

Dr. McKenzie concluded: “If we’re looking at the spread of some more serious or rare diseases in areas, to me then the answer is ... we need to be aggressively mitigating greenhouse gas emissions. Let’s start with the source.”

Dr. McKenzie and Dr. Hauser report no relevant financial relationships.

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

Individuals of nonwhite race/ethnicity are underrepresented in cosmetic clinical trials. Individuals of nonwhite race/ethnicity are not underrepresented in cosmetic clinical trials, according to a recent literature review. The explanation for those contradictory conclusions comes down to money, or, more specifically, the source of the money.

Among the cosmetic studies funded by industry, non-Whites represented about 25% of the patient populations. That proportion, however, rose to 62% for studies that were funded by universities/governments or had no funding source reported, Lisa Akintilo, MD, and associates said in their review.

“Lack of inclusion of diverse patient populations is both a medical and moral issue as conclusions of such homogeneous studies may not be generalizable. In the realm of cosmetic dermatology, diverse research cohorts are needed to identify potential disparities in therapies for cosmetic concerns and fully investigate effective treatments for all,” wrote Dr. Akintilo of New York University and coauthors.

Data from the U.S. Census show that non-Hispanic Whites made up 60% of the population in 2019, with that proportion falling to about 50% by 2045, the investigators noted. A report from the American Society of Plastic Surgeons showed that about 34% of cosmetic patients identified as skin of color in 2020.

The availability of data was an issue in the review of the literature from 1990 to 2020, as 55% of the 318 randomized controlled trials that were reviewed did not include any information on racial/ethnic diversity and the other 143 studies offered only enough to determine White/non-White status, they explained.

That limitation meant that those 143 studies had to form the basis of the funding analysis, which also indicated that the studies with funding outside of industry were significantly more likely (odds ratio, 7.8) to have more than 50% non-White participants, compared with the industry-funded trials. The projects with industry backing, however, had a larger mean sample size than did those without: 139 vs. 81, Dr. Akintilo and associates said.

“The protocols of cosmetic trials should be questioned, as many target Caucasian‐centric treatment goals that may not be in alignment with the goals of skin of color patients,” they wrote. “It is important for cosmetic providers to recognize the well-established anatomical variations between different races and ethnicities and how they can inform desired cosmetic procedures.”

The investigators said that they had no conflicts of interest.

[email protected]

Individuals of nonwhite race/ethnicity are underrepresented in cosmetic clinical trials. Individuals of nonwhite race/ethnicity are not underrepresented in cosmetic clinical trials, according to a recent literature review. The explanation for those contradictory conclusions comes down to money, or, more specifically, the source of the money.

Among the cosmetic studies funded by industry, non-Whites represented about 25% of the patient populations. That proportion, however, rose to 62% for studies that were funded by universities/governments or had no funding source reported, Lisa Akintilo, MD, and associates said in their review.

“Lack of inclusion of diverse patient populations is both a medical and moral issue as conclusions of such homogeneous studies may not be generalizable. In the realm of cosmetic dermatology, diverse research cohorts are needed to identify potential disparities in therapies for cosmetic concerns and fully investigate effective treatments for all,” wrote Dr. Akintilo of New York University and coauthors.

Data from the U.S. Census show that non-Hispanic Whites made up 60% of the population in 2019, with that proportion falling to about 50% by 2045, the investigators noted. A report from the American Society of Plastic Surgeons showed that about 34% of cosmetic patients identified as skin of color in 2020.

The availability of data was an issue in the review of the literature from 1990 to 2020, as 55% of the 318 randomized controlled trials that were reviewed did not include any information on racial/ethnic diversity and the other 143 studies offered only enough to determine White/non-White status, they explained.

That limitation meant that those 143 studies had to form the basis of the funding analysis, which also indicated that the studies with funding outside of industry were significantly more likely (odds ratio, 7.8) to have more than 50% non-White participants, compared with the industry-funded trials. The projects with industry backing, however, had a larger mean sample size than did those without: 139 vs. 81, Dr. Akintilo and associates said.

“The protocols of cosmetic trials should be questioned, as many target Caucasian‐centric treatment goals that may not be in alignment with the goals of skin of color patients,” they wrote. “It is important for cosmetic providers to recognize the well-established anatomical variations between different races and ethnicities and how they can inform desired cosmetic procedures.”

The investigators said that they had no conflicts of interest.

[email protected]

Individuals of nonwhite race/ethnicity are underrepresented in cosmetic clinical trials. Individuals of nonwhite race/ethnicity are not underrepresented in cosmetic clinical trials, according to a recent literature review. The explanation for those contradictory conclusions comes down to money, or, more specifically, the source of the money.

Among the cosmetic studies funded by industry, non-Whites represented about 25% of the patient populations. That proportion, however, rose to 62% for studies that were funded by universities/governments or had no funding source reported, Lisa Akintilo, MD, and associates said in their review.

“Lack of inclusion of diverse patient populations is both a medical and moral issue as conclusions of such homogeneous studies may not be generalizable. In the realm of cosmetic dermatology, diverse research cohorts are needed to identify potential disparities in therapies for cosmetic concerns and fully investigate effective treatments for all,” wrote Dr. Akintilo of New York University and coauthors.

Data from the U.S. Census show that non-Hispanic Whites made up 60% of the population in 2019, with that proportion falling to about 50% by 2045, the investigators noted. A report from the American Society of Plastic Surgeons showed that about 34% of cosmetic patients identified as skin of color in 2020.

The availability of data was an issue in the review of the literature from 1990 to 2020, as 55% of the 318 randomized controlled trials that were reviewed did not include any information on racial/ethnic diversity and the other 143 studies offered only enough to determine White/non-White status, they explained.

That limitation meant that those 143 studies had to form the basis of the funding analysis, which also indicated that the studies with funding outside of industry were significantly more likely (odds ratio, 7.8) to have more than 50% non-White participants, compared with the industry-funded trials. The projects with industry backing, however, had a larger mean sample size than did those without: 139 vs. 81, Dr. Akintilo and associates said.

“The protocols of cosmetic trials should be questioned, as many target Caucasian‐centric treatment goals that may not be in alignment with the goals of skin of color patients,” they wrote. “It is important for cosmetic providers to recognize the well-established anatomical variations between different races and ethnicities and how they can inform desired cosmetic procedures.”

The investigators said that they had no conflicts of interest.

[email protected]

The Diagnosis: Leiomyosarcoma

Cutaneous leiomyosarcomas are relatively rare neoplasms that favor the head, neck, and extremities of older adults.¹ Dermal leiomyosarcomas originate from arrector pili and are locally aggressive, whereas subcutaneous leiomyosarcomas arise from vascular smooth muscle and metastasize in 30% to 60% of cases.² Clinically, leiomyosarcomas present as solitary, firm, well-circumscribed nodules with possible ulceration and crusting.³ Histopathology of leiomyosarcoma shows fascicles of atypical spindle cells with blunt-ended nuclei and perinuclear glycogen vacuoles, variable atypia, and mitotic figures (quiz images). Definitive diagnosis is based on positive immunohistochemical staining for desmin and smooth muscle actin.⁴ Treatment entails complete removal via wide local excision or Mohs micrographic surgery.⁵

Atypical fibroxanthoma (AFX) is a malignant fibrohistiocytic neoplasm that arises in the dermis and preferentially affects the head and neck in older individuals.³ Atypical fibroxanthoma presents as a nonspecific, pinkred, sometimes ulcerated papule on sun-damaged skin that may clinically resemble a squamous cell carcinoma (SCC) or basal cell carcinoma.6 Histopathology shows pleomorphic spindle cells with hyperchromatic nuclei and abundant cytoplasm mixed with multinucleated giant cells and scattered mitotic figures (Figure 1). Immunohistochemistry is essential for distinguishing AFX from other spindle cell neoplasms. Atypical fibroxanthoma stains positively for vimentin, procollagen-1, CD10, and CD68 but is negative for S-100, human melanoma black 45, Melan-A, desmin, cytokeratin, p40, and p63.⁶ Treatment includes wide local excision or Mohs micrographic surgery.

Melanoma is an aggressive cancer with the propensity to metastasize. Both desmoplastic and spindle cell variants demonstrate atypical spindled melanocytes on histology, and desmoplasia is seen in the desmoplastic variant (Figure 2). In some cases, evaluation of the epidermis for melanoma in situ may aid in diagnosis.⁷ Clinical and prognostic features differ between the 2 variants. Desmoplastic melanomas usually present on the head and neck as scarlike nodules with a low rate of nodal involvement, while spindle cell melanomas can occur anywhere on the body, often are amelanotic, and are associated with widespread metastatic disease at the time of presentation.⁸ SOX10 (SRY-box transcription factor 10) and S-100 may be the only markers that are positive in desmoplastic melanoma.^9,10 Treatment depends on the thickness of the lesion.¹¹

Spindle cell SCC is a histologic variant of SCC characterized by spindled epithelial cells. Spindle cell SCC typically presents as an ulcerated or exophytic mass in sun-exposed areas or areas exposed to ionizing radiation, or in immunocompromised individuals. Histopathology shows spindled pleomorphic keratinocytes with elongated nuclei infiltrating the dermis and minimal keratinization (Figure 3).¹² Immunohistochemistry is necessary to distinguish spindle cell SCC from other spindle cell tumors such as spindle cell melanoma, AFX, and leiomyosarcoma. Spindle cell SCC is positive for high-molecular-weight cytokeratin, p40, and p63. Mohs micrographic surgery provides the highest cure rate, and radiation therapy may be considered when clear surgical margins cannot be obtained.⁶

Undifferentiated pleomorphic sarcoma (UPS) (formerly known as malignant fibrous histiocytoma) describes tumors that resemble AFX but are more invasive. They commonly involve the soft tissue with a higher risk for both recurrence and metastasis than AFX.¹³ Histopathology shows marked cytologic pleomorphism, bizarre cellular forms, atypical mitoses, and ulceration (Figure 4).¹⁴ Diagnosis of UPS is by exclusion and is dependent on immunohistochemical studies. In contrast to AFX, UPS is more likely to be positive for LN-2 (CD74).⁶ Undifferentiated pleomorphic sarcoma has been treated with surgical excision in combination with chemical and radiation therapy, but due to limited data, optimal management is less clear compared to AFX.¹⁵ There is a substantial risk for local recurrence and metastasis, and the lungs are the most common sites of distant metastasis.¹³ In a study of 23 individuals with high-grade UPS, 5-year metastasis-free survival and local recurrence-free survival were 26% and 16%, respectively.¹⁰

The Diagnosis: Leiomyosarcoma

Cutaneous leiomyosarcomas are relatively rare neoplasms that favor the head, neck, and extremities of older adults.¹ Dermal leiomyosarcomas originate from arrector pili and are locally aggressive, whereas subcutaneous leiomyosarcomas arise from vascular smooth muscle and metastasize in 30% to 60% of cases.² Clinically, leiomyosarcomas present as solitary, firm, well-circumscribed nodules with possible ulceration and crusting.³ Histopathology of leiomyosarcoma shows fascicles of atypical spindle cells with blunt-ended nuclei and perinuclear glycogen vacuoles, variable atypia, and mitotic figures (quiz images). Definitive diagnosis is based on positive immunohistochemical staining for desmin and smooth muscle actin.⁴ Treatment entails complete removal via wide local excision or Mohs micrographic surgery.⁵

Atypical fibroxanthoma (AFX) is a malignant fibrohistiocytic neoplasm that arises in the dermis and preferentially affects the head and neck in older individuals.³ Atypical fibroxanthoma presents as a nonspecific, pinkred, sometimes ulcerated papule on sun-damaged skin that may clinically resemble a squamous cell carcinoma (SCC) or basal cell carcinoma.6 Histopathology shows pleomorphic spindle cells with hyperchromatic nuclei and abundant cytoplasm mixed with multinucleated giant cells and scattered mitotic figures (Figure 1). Immunohistochemistry is essential for distinguishing AFX from other spindle cell neoplasms. Atypical fibroxanthoma stains positively for vimentin, procollagen-1, CD10, and CD68 but is negative for S-100, human melanoma black 45, Melan-A, desmin, cytokeratin, p40, and p63.⁶ Treatment includes wide local excision or Mohs micrographic surgery.

Melanoma is an aggressive cancer with the propensity to metastasize. Both desmoplastic and spindle cell variants demonstrate atypical spindled melanocytes on histology, and desmoplasia is seen in the desmoplastic variant (Figure 2). In some cases, evaluation of the epidermis for melanoma in situ may aid in diagnosis.⁷ Clinical and prognostic features differ between the 2 variants. Desmoplastic melanomas usually present on the head and neck as scarlike nodules with a low rate of nodal involvement, while spindle cell melanomas can occur anywhere on the body, often are amelanotic, and are associated with widespread metastatic disease at the time of presentation.⁸ SOX10 (SRY-box transcription factor 10) and S-100 may be the only markers that are positive in desmoplastic melanoma.^9,10 Treatment depends on the thickness of the lesion.¹¹

Spindle cell SCC is a histologic variant of SCC characterized by spindled epithelial cells. Spindle cell SCC typically presents as an ulcerated or exophytic mass in sun-exposed areas or areas exposed to ionizing radiation, or in immunocompromised individuals. Histopathology shows spindled pleomorphic keratinocytes with elongated nuclei infiltrating the dermis and minimal keratinization (Figure 3).¹² Immunohistochemistry is necessary to distinguish spindle cell SCC from other spindle cell tumors such as spindle cell melanoma, AFX, and leiomyosarcoma. Spindle cell SCC is positive for high-molecular-weight cytokeratin, p40, and p63. Mohs micrographic surgery provides the highest cure rate, and radiation therapy may be considered when clear surgical margins cannot be obtained.⁶

Undifferentiated pleomorphic sarcoma (UPS) (formerly known as malignant fibrous histiocytoma) describes tumors that resemble AFX but are more invasive. They commonly involve the soft tissue with a higher risk for both recurrence and metastasis than AFX.¹³ Histopathology shows marked cytologic pleomorphism, bizarre cellular forms, atypical mitoses, and ulceration (Figure 4).¹⁴ Diagnosis of UPS is by exclusion and is dependent on immunohistochemical studies. In contrast to AFX, UPS is more likely to be positive for LN-2 (CD74).⁶ Undifferentiated pleomorphic sarcoma has been treated with surgical excision in combination with chemical and radiation therapy, but due to limited data, optimal management is less clear compared to AFX.¹⁵ There is a substantial risk for local recurrence and metastasis, and the lungs are the most common sites of distant metastasis.¹³ In a study of 23 individuals with high-grade UPS, 5-year metastasis-free survival and local recurrence-free survival were 26% and 16%, respectively.¹⁰

The Diagnosis: Leiomyosarcoma

Cutaneous leiomyosarcomas are relatively rare neoplasms that favor the head, neck, and extremities of older adults.¹ Dermal leiomyosarcomas originate from arrector pili and are locally aggressive, whereas subcutaneous leiomyosarcomas arise from vascular smooth muscle and metastasize in 30% to 60% of cases.² Clinically, leiomyosarcomas present as solitary, firm, well-circumscribed nodules with possible ulceration and crusting.³ Histopathology of leiomyosarcoma shows fascicles of atypical spindle cells with blunt-ended nuclei and perinuclear glycogen vacuoles, variable atypia, and mitotic figures (quiz images). Definitive diagnosis is based on positive immunohistochemical staining for desmin and smooth muscle actin.⁴ Treatment entails complete removal via wide local excision or Mohs micrographic surgery.⁵

Atypical fibroxanthoma (AFX) is a malignant fibrohistiocytic neoplasm that arises in the dermis and preferentially affects the head and neck in older individuals.³ Atypical fibroxanthoma presents as a nonspecific, pinkred, sometimes ulcerated papule on sun-damaged skin that may clinically resemble a squamous cell carcinoma (SCC) or basal cell carcinoma.6 Histopathology shows pleomorphic spindle cells with hyperchromatic nuclei and abundant cytoplasm mixed with multinucleated giant cells and scattered mitotic figures (Figure 1). Immunohistochemistry is essential for distinguishing AFX from other spindle cell neoplasms. Atypical fibroxanthoma stains positively for vimentin, procollagen-1, CD10, and CD68 but is negative for S-100, human melanoma black 45, Melan-A, desmin, cytokeratin, p40, and p63.⁶ Treatment includes wide local excision or Mohs micrographic surgery.

Melanoma is an aggressive cancer with the propensity to metastasize. Both desmoplastic and spindle cell variants demonstrate atypical spindled melanocytes on histology, and desmoplasia is seen in the desmoplastic variant (Figure 2). In some cases, evaluation of the epidermis for melanoma in situ may aid in diagnosis.⁷ Clinical and prognostic features differ between the 2 variants. Desmoplastic melanomas usually present on the head and neck as scarlike nodules with a low rate of nodal involvement, while spindle cell melanomas can occur anywhere on the body, often are amelanotic, and are associated with widespread metastatic disease at the time of presentation.⁸ SOX10 (SRY-box transcription factor 10) and S-100 may be the only markers that are positive in desmoplastic melanoma.^9,10 Treatment depends on the thickness of the lesion.¹¹

Spindle cell SCC is a histologic variant of SCC characterized by spindled epithelial cells. Spindle cell SCC typically presents as an ulcerated or exophytic mass in sun-exposed areas or areas exposed to ionizing radiation, or in immunocompromised individuals. Histopathology shows spindled pleomorphic keratinocytes with elongated nuclei infiltrating the dermis and minimal keratinization (Figure 3).¹² Immunohistochemistry is necessary to distinguish spindle cell SCC from other spindle cell tumors such as spindle cell melanoma, AFX, and leiomyosarcoma. Spindle cell SCC is positive for high-molecular-weight cytokeratin, p40, and p63. Mohs micrographic surgery provides the highest cure rate, and radiation therapy may be considered when clear surgical margins cannot be obtained.⁶

Undifferentiated pleomorphic sarcoma (UPS) (formerly known as malignant fibrous histiocytoma) describes tumors that resemble AFX but are more invasive. They commonly involve the soft tissue with a higher risk for both recurrence and metastasis than AFX.¹³ Histopathology shows marked cytologic pleomorphism, bizarre cellular forms, atypical mitoses, and ulceration (Figure 4).¹⁴ Diagnosis of UPS is by exclusion and is dependent on immunohistochemical studies. In contrast to AFX, UPS is more likely to be positive for LN-2 (CD74).⁶ Undifferentiated pleomorphic sarcoma has been treated with surgical excision in combination with chemical and radiation therapy, but due to limited data, optimal management is less clear compared to AFX.¹⁵ There is a substantial risk for local recurrence and metastasis, and the lungs are the most common sites of distant metastasis.¹³ In a study of 23 individuals with high-grade UPS, 5-year metastasis-free survival and local recurrence-free survival were 26% and 16%, respectively.¹⁰