Jessie Wrobel is a board-certified Family Nurse Practitioner. She earned a Bachelor of Science in Nursing from Southern Connecticut State University, concurrently graduating from their Honor’s College in 2009 and spent 9 years at the bedside focusing on heart failure and stroke populations. She then obtained a Master of Science in Nursing from Southern Connecticut State University and holds a certification with the American Academy of Nurse Practitioners (AANP) as a family nurse practitioner. She has since worked at Yale-New Haven’s Sleep Medicine Center where she follows patients for sleep disordered breathing, narcolepsy, parasomnias, restless leg syndrome and insomnia.

Jessie Wrobel is a board-certified Family Nurse Practitioner. She earned a Bachelor of Science in Nursing from Southern Connecticut State University, concurrently graduating from their Honor’s College in 2009 and spent 9 years at the bedside focusing on heart failure and stroke populations. She then obtained a Master of Science in Nursing from Southern Connecticut State University and holds a certification with the American Academy of Nurse Practitioners (AANP) as a family nurse practitioner. She has since worked at Yale-New Haven’s Sleep Medicine Center where she follows patients for sleep disordered breathing, narcolepsy, parasomnias, restless leg syndrome and insomnia.

Jessie Wrobel is a board-certified Family Nurse Practitioner. She earned a Bachelor of Science in Nursing from Southern Connecticut State University, concurrently graduating from their Honor’s College in 2009 and spent 9 years at the bedside focusing on heart failure and stroke populations. She then obtained a Master of Science in Nursing from Southern Connecticut State University and holds a certification with the American Academy of Nurse Practitioners (AANP) as a family nurse practitioner. She has since worked at Yale-New Haven’s Sleep Medicine Center where she follows patients for sleep disordered breathing, narcolepsy, parasomnias, restless leg syndrome and insomnia.

Pfizer asked the FDA on Thursday to expand emergency use authorization of its COVID-19 vaccine to children ages 5 to 11.

The request comes after the drugmaker submitted clinical trial data to the FDA on Sept. 28. Pfizer said the study of 2,268 children showed the vaccine was safe and produced a robust immune response.

Participants in the studies received a lower dose of the vaccine, 10 micrograms. Their response 2 weeks after a second dose was reportedly equal to the immune protection in a control group of 16- to 25-year-olds who received the fully approved 30-microgram doses.

Currently, the Pfizer EUA applies to 12- to 15-year-olds and people eligible for a Pfizer booster shot. The drugmaker received full FDA approval for the vaccine for Americans 16 years and older in August.

The filing for authorization in 5- to 11-year-olds comes as overall cases of COVID-19 in the United States continue to decline. The decrease includes a drop in new cases in children for the fourth consecutive week, according to analysis of data from the American Academy of Pediatrics and the Children’s Hospital Association.

The next step is an FDA decision on whether to expand the current emergency use authorization (EUA) for teenagers to the younger age group.

Timing of any official word from the agency is unknown. But possibly in anticipation of today’s filing, the FDA already scheduled a meeting of its Vaccines and Related Biological Products Advisory Committee for Oct. 25.

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

Pfizer asked the FDA on Thursday to expand emergency use authorization of its COVID-19 vaccine to children ages 5 to 11.

The request comes after the drugmaker submitted clinical trial data to the FDA on Sept. 28. Pfizer said the study of 2,268 children showed the vaccine was safe and produced a robust immune response.

Participants in the studies received a lower dose of the vaccine, 10 micrograms. Their response 2 weeks after a second dose was reportedly equal to the immune protection in a control group of 16- to 25-year-olds who received the fully approved 30-microgram doses.

Currently, the Pfizer EUA applies to 12- to 15-year-olds and people eligible for a Pfizer booster shot. The drugmaker received full FDA approval for the vaccine for Americans 16 years and older in August.

The filing for authorization in 5- to 11-year-olds comes as overall cases of COVID-19 in the United States continue to decline. The decrease includes a drop in new cases in children for the fourth consecutive week, according to analysis of data from the American Academy of Pediatrics and the Children’s Hospital Association.

The next step is an FDA decision on whether to expand the current emergency use authorization (EUA) for teenagers to the younger age group.

Timing of any official word from the agency is unknown. But possibly in anticipation of today’s filing, the FDA already scheduled a meeting of its Vaccines and Related Biological Products Advisory Committee for Oct. 25.

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

Pfizer asked the FDA on Thursday to expand emergency use authorization of its COVID-19 vaccine to children ages 5 to 11.

The request comes after the drugmaker submitted clinical trial data to the FDA on Sept. 28. Pfizer said the study of 2,268 children showed the vaccine was safe and produced a robust immune response.

Participants in the studies received a lower dose of the vaccine, 10 micrograms. Their response 2 weeks after a second dose was reportedly equal to the immune protection in a control group of 16- to 25-year-olds who received the fully approved 30-microgram doses.

Currently, the Pfizer EUA applies to 12- to 15-year-olds and people eligible for a Pfizer booster shot. The drugmaker received full FDA approval for the vaccine for Americans 16 years and older in August.

The filing for authorization in 5- to 11-year-olds comes as overall cases of COVID-19 in the United States continue to decline. The decrease includes a drop in new cases in children for the fourth consecutive week, according to analysis of data from the American Academy of Pediatrics and the Children’s Hospital Association.

The next step is an FDA decision on whether to expand the current emergency use authorization (EUA) for teenagers to the younger age group.

Timing of any official word from the agency is unknown. But possibly in anticipation of today’s filing, the FDA already scheduled a meeting of its Vaccines and Related Biological Products Advisory Committee for Oct. 25.

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

A drug approved to treat constipation appears to improve cognitive impairment and boost brain activity for patients with mental illness, new research suggests.

In a randomized controlled trial, 44 healthy individuals were assigned to receive the selective serotonin-4 (5-HT4) receptor agonist prucalopride (Motegrity) or placebo for 1 week.

After 6 days, the active-treatment group performed significantly better on memory tests than the participants who received placebo. In addition, the drug increased activity in brain areas related to cognition.

“What we’re hoping is...these agents may be able to help those with cognitive impairment as part of their mental illness,” lead author Angharad N. de Cates, a clinical DPhil student in the department of psychiatry, University of Oxford, Oxford, United Kingdom, told meeting attendees.

“Currently, we’re looking to see if we can translate our finding a step further and do a similar study in those with depression,” Ms. de Cates added.

The findings were presented at the 34th European College of Neuropsychopharmacology (ECNP) Congress and were simultaneously published in Translational Psychiatry.
 

“Exciting early evidence”

“Even when the low mood associated with depression is well-treated with conventional antidepressants, many patients continue to experience problems with their memory,” co-investigator Susannah Murphy, PhD, a senior research fellow at the University of Oxford, said in a release.

“Our study provides exciting early evidence in humans of a new approach that might be a helpful way to treat these residual cognitive symptoms,” Dr. Murphy added.

Preclinical and animal studies suggest that the 5-HT4 receptor is a promising treatment target for cognitive impairment in individuals with psychiatric disorders, although studies in humans have been limited by the adverse effects of early agents.

“We’ve had our eye on this receptor for a while,” explained de Cates, inasmuch as the animal data “have been so good.”

However, she said in an interview that “a lack of safe human agents made translation tricky.”

As previously reported, prucalopride, a selective high-affinity 5-HT4 partial agonist, was approved in 2018 by the U.S. Food and Drug Administration for the treatment of chronic idiopathic constipation.

The current researchers note that the drug has “good brain penetration,” which “allowed us to investigate 5-HT4-receptor agonism in humans.”

Having previously shown that a single dose of the drug has “pro-cognitive effects,” the investigators conducted the new trial in 44 healthy participants. All were randomly assigned in a 1:1 ratio to receive either prucalopride 1 mg for 7 days or placebo.

In accordance with enrollment criteria, patients were 18 to 36 years of age, right-handed, and were not pregnant or breastfeeding. Participants’ body mass index was 18 to 30 kg/m², and they had no contraindications to the study drug. The two treatment groups were well balanced; the participants who received placebo were significantly more likely to be nonnative English speakers (P = .02).

On day 6 of treatment administration, all participants underwent 3T MRI.

Before undergoing imaging, the participants were presented with eight emotionally neutral images of animals or landscapes and were asked to indicate whether or not the images were of animals. The task was then repeated with the eight familiar images and eight novel ones.

During the scan, participants were shown the same images or eight novel images and were again asked whether or not the images contained an animal. They were also instructed to try to remember the images for a subsequent memory task. In that task, the eight original images, 48 novel images, and 27 “distractor” images were presented.
 

Better memory

In the pre-scan assessment, results showed no significant differences in the ability of members of the prucalopride and placebo groups to identify images as being familiar or different.

However, taking prucalopride was associated with significantly improved memory performance in the post-scan recall task.

Compared to the placebo group, participants in the prucalopride group were more accurate in selecting images as familiar vs distractors (P = .029) and in distinguishing images as familiar, novel, or distractors (P = .035).

Functional MRI revealed increased activity in the left and right hippocampus in response to both novel and familiar images among the participants in the prucalopride group in comparison with those in the placebo group.

There was also increased activity in the right angular gyrus in the prucalopride group in comparison with the placebo group in response to familiar images (P < .005).

“Clinically, angular gyri lesions cause language dysfunction, low mood, and poor memory and can mimic dementia or pseudodementia,” the investigators write. They note that the right angular gyrus “shows significantly decreased activity” in mild cognitive impairment.

“Therefore, the increased activity seen in the right angular gyrus following prucalopride administration in our study is consistent with the pro-cognitive behavioural effects we observed,” they add.

Ms. De Cates noted that the dose used in their study was lower than the 2 mg given for constipation.

“At the low dose, there were no differences in side effects between groups and no withdrawals from the prucalopride group for side effects. We are going to try increasing the dose in our next study actually, as we don’t have PET data to tell us what the optimal dose for binding at the receptor should be,” said Ms. de Cates.

“In safety studies, the dose was trialled in healthy volunteers at 4 mg, which was found to be safe, although perhaps less well tolerated than 2 mg,” she said.
 

Generalizable findings?

Commenting on the research, Vibe G. Frøkjær, MD, adjunct professor, department of psychology, Copenhagen University, Denmark, said the study “highlights a very interesting and much needed potential for repurposing drugs to help cognitive dysfunction.”

He noted that cognitive dysfunction is often associated with psychiatric disorders -- even in states of remission.

“Importantly, as the authors also state, it will be vital to translate these findings from healthy populations into clinical populations,” said Dr. Frøkjær, who was not involved in the research.

“It will also be important to understand if prucalopride adds to the effects of existing antidepressant treatments or can be used as a stand-alone therapy,” he added.

The study was funded by the NIHR Oxford Health Biomedical Research Center and by the Wellcome Center for Integrative Neuroscience. Ms. De Cates has received a travel grant from the Royal College of Psychiatrists/Gatsby Foundation and support from Wellcome. The other authors have relationships with P1vital Ltd, Janssen Pharmaceuticals, Sage Therapeutics, Pfizer, Zogenix, Compass Pathways, and Lundbeck.

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

A drug approved to treat constipation appears to improve cognitive impairment and boost brain activity for patients with mental illness, new research suggests.

In a randomized controlled trial, 44 healthy individuals were assigned to receive the selective serotonin-4 (5-HT4) receptor agonist prucalopride (Motegrity) or placebo for 1 week.

After 6 days, the active-treatment group performed significantly better on memory tests than the participants who received placebo. In addition, the drug increased activity in brain areas related to cognition.

“What we’re hoping is...these agents may be able to help those with cognitive impairment as part of their mental illness,” lead author Angharad N. de Cates, a clinical DPhil student in the department of psychiatry, University of Oxford, Oxford, United Kingdom, told meeting attendees.

“Currently, we’re looking to see if we can translate our finding a step further and do a similar study in those with depression,” Ms. de Cates added.

The findings were presented at the 34th European College of Neuropsychopharmacology (ECNP) Congress and were simultaneously published in Translational Psychiatry.
 

“Exciting early evidence”

“Even when the low mood associated with depression is well-treated with conventional antidepressants, many patients continue to experience problems with their memory,” co-investigator Susannah Murphy, PhD, a senior research fellow at the University of Oxford, said in a release.

“Our study provides exciting early evidence in humans of a new approach that might be a helpful way to treat these residual cognitive symptoms,” Dr. Murphy added.

Preclinical and animal studies suggest that the 5-HT4 receptor is a promising treatment target for cognitive impairment in individuals with psychiatric disorders, although studies in humans have been limited by the adverse effects of early agents.

“We’ve had our eye on this receptor for a while,” explained de Cates, inasmuch as the animal data “have been so good.”

However, she said in an interview that “a lack of safe human agents made translation tricky.”

As previously reported, prucalopride, a selective high-affinity 5-HT4 partial agonist, was approved in 2018 by the U.S. Food and Drug Administration for the treatment of chronic idiopathic constipation.

The current researchers note that the drug has “good brain penetration,” which “allowed us to investigate 5-HT4-receptor agonism in humans.”

Having previously shown that a single dose of the drug has “pro-cognitive effects,” the investigators conducted the new trial in 44 healthy participants. All were randomly assigned in a 1:1 ratio to receive either prucalopride 1 mg for 7 days or placebo.

In accordance with enrollment criteria, patients were 18 to 36 years of age, right-handed, and were not pregnant or breastfeeding. Participants’ body mass index was 18 to 30 kg/m², and they had no contraindications to the study drug. The two treatment groups were well balanced; the participants who received placebo were significantly more likely to be nonnative English speakers (P = .02).

On day 6 of treatment administration, all participants underwent 3T MRI.

Before undergoing imaging, the participants were presented with eight emotionally neutral images of animals or landscapes and were asked to indicate whether or not the images were of animals. The task was then repeated with the eight familiar images and eight novel ones.

During the scan, participants were shown the same images or eight novel images and were again asked whether or not the images contained an animal. They were also instructed to try to remember the images for a subsequent memory task. In that task, the eight original images, 48 novel images, and 27 “distractor” images were presented.
 

Better memory

In the pre-scan assessment, results showed no significant differences in the ability of members of the prucalopride and placebo groups to identify images as being familiar or different.

However, taking prucalopride was associated with significantly improved memory performance in the post-scan recall task.

Compared to the placebo group, participants in the prucalopride group were more accurate in selecting images as familiar vs distractors (P = .029) and in distinguishing images as familiar, novel, or distractors (P = .035).

Functional MRI revealed increased activity in the left and right hippocampus in response to both novel and familiar images among the participants in the prucalopride group in comparison with those in the placebo group.

There was also increased activity in the right angular gyrus in the prucalopride group in comparison with the placebo group in response to familiar images (P < .005).

“Clinically, angular gyri lesions cause language dysfunction, low mood, and poor memory and can mimic dementia or pseudodementia,” the investigators write. They note that the right angular gyrus “shows significantly decreased activity” in mild cognitive impairment.

“Therefore, the increased activity seen in the right angular gyrus following prucalopride administration in our study is consistent with the pro-cognitive behavioural effects we observed,” they add.

Ms. De Cates noted that the dose used in their study was lower than the 2 mg given for constipation.

“At the low dose, there were no differences in side effects between groups and no withdrawals from the prucalopride group for side effects. We are going to try increasing the dose in our next study actually, as we don’t have PET data to tell us what the optimal dose for binding at the receptor should be,” said Ms. de Cates.

“In safety studies, the dose was trialled in healthy volunteers at 4 mg, which was found to be safe, although perhaps less well tolerated than 2 mg,” she said.
 

Generalizable findings?

Commenting on the research, Vibe G. Frøkjær, MD, adjunct professor, department of psychology, Copenhagen University, Denmark, said the study “highlights a very interesting and much needed potential for repurposing drugs to help cognitive dysfunction.”

He noted that cognitive dysfunction is often associated with psychiatric disorders -- even in states of remission.

“Importantly, as the authors also state, it will be vital to translate these findings from healthy populations into clinical populations,” said Dr. Frøkjær, who was not involved in the research.

“It will also be important to understand if prucalopride adds to the effects of existing antidepressant treatments or can be used as a stand-alone therapy,” he added.

The study was funded by the NIHR Oxford Health Biomedical Research Center and by the Wellcome Center for Integrative Neuroscience. Ms. De Cates has received a travel grant from the Royal College of Psychiatrists/Gatsby Foundation and support from Wellcome. The other authors have relationships with P1vital Ltd, Janssen Pharmaceuticals, Sage Therapeutics, Pfizer, Zogenix, Compass Pathways, and Lundbeck.

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

A drug approved to treat constipation appears to improve cognitive impairment and boost brain activity for patients with mental illness, new research suggests.

In a randomized controlled trial, 44 healthy individuals were assigned to receive the selective serotonin-4 (5-HT4) receptor agonist prucalopride (Motegrity) or placebo for 1 week.

After 6 days, the active-treatment group performed significantly better on memory tests than the participants who received placebo. In addition, the drug increased activity in brain areas related to cognition.

“What we’re hoping is...these agents may be able to help those with cognitive impairment as part of their mental illness,” lead author Angharad N. de Cates, a clinical DPhil student in the department of psychiatry, University of Oxford, Oxford, United Kingdom, told meeting attendees.

“Currently, we’re looking to see if we can translate our finding a step further and do a similar study in those with depression,” Ms. de Cates added.

The findings were presented at the 34th European College of Neuropsychopharmacology (ECNP) Congress and were simultaneously published in Translational Psychiatry.
 

“Exciting early evidence”

“Even when the low mood associated with depression is well-treated with conventional antidepressants, many patients continue to experience problems with their memory,” co-investigator Susannah Murphy, PhD, a senior research fellow at the University of Oxford, said in a release.

“Our study provides exciting early evidence in humans of a new approach that might be a helpful way to treat these residual cognitive symptoms,” Dr. Murphy added.

Preclinical and animal studies suggest that the 5-HT4 receptor is a promising treatment target for cognitive impairment in individuals with psychiatric disorders, although studies in humans have been limited by the adverse effects of early agents.

“We’ve had our eye on this receptor for a while,” explained de Cates, inasmuch as the animal data “have been so good.”

However, she said in an interview that “a lack of safe human agents made translation tricky.”

As previously reported, prucalopride, a selective high-affinity 5-HT4 partial agonist, was approved in 2018 by the U.S. Food and Drug Administration for the treatment of chronic idiopathic constipation.

The current researchers note that the drug has “good brain penetration,” which “allowed us to investigate 5-HT4-receptor agonism in humans.”

Having previously shown that a single dose of the drug has “pro-cognitive effects,” the investigators conducted the new trial in 44 healthy participants. All were randomly assigned in a 1:1 ratio to receive either prucalopride 1 mg for 7 days or placebo.

In accordance with enrollment criteria, patients were 18 to 36 years of age, right-handed, and were not pregnant or breastfeeding. Participants’ body mass index was 18 to 30 kg/m², and they had no contraindications to the study drug. The two treatment groups were well balanced; the participants who received placebo were significantly more likely to be nonnative English speakers (P = .02).

On day 6 of treatment administration, all participants underwent 3T MRI.

Before undergoing imaging, the participants were presented with eight emotionally neutral images of animals or landscapes and were asked to indicate whether or not the images were of animals. The task was then repeated with the eight familiar images and eight novel ones.

During the scan, participants were shown the same images or eight novel images and were again asked whether or not the images contained an animal. They were also instructed to try to remember the images for a subsequent memory task. In that task, the eight original images, 48 novel images, and 27 “distractor” images were presented.
 

Better memory

In the pre-scan assessment, results showed no significant differences in the ability of members of the prucalopride and placebo groups to identify images as being familiar or different.

However, taking prucalopride was associated with significantly improved memory performance in the post-scan recall task.

Compared to the placebo group, participants in the prucalopride group were more accurate in selecting images as familiar vs distractors (P = .029) and in distinguishing images as familiar, novel, or distractors (P = .035).

Functional MRI revealed increased activity in the left and right hippocampus in response to both novel and familiar images among the participants in the prucalopride group in comparison with those in the placebo group.

There was also increased activity in the right angular gyrus in the prucalopride group in comparison with the placebo group in response to familiar images (P < .005).

“Clinically, angular gyri lesions cause language dysfunction, low mood, and poor memory and can mimic dementia or pseudodementia,” the investigators write. They note that the right angular gyrus “shows significantly decreased activity” in mild cognitive impairment.

“Therefore, the increased activity seen in the right angular gyrus following prucalopride administration in our study is consistent with the pro-cognitive behavioural effects we observed,” they add.

Ms. De Cates noted that the dose used in their study was lower than the 2 mg given for constipation.

“At the low dose, there were no differences in side effects between groups and no withdrawals from the prucalopride group for side effects. We are going to try increasing the dose in our next study actually, as we don’t have PET data to tell us what the optimal dose for binding at the receptor should be,” said Ms. de Cates.

“In safety studies, the dose was trialled in healthy volunteers at 4 mg, which was found to be safe, although perhaps less well tolerated than 2 mg,” she said.
 

Generalizable findings?

Commenting on the research, Vibe G. Frøkjær, MD, adjunct professor, department of psychology, Copenhagen University, Denmark, said the study “highlights a very interesting and much needed potential for repurposing drugs to help cognitive dysfunction.”

He noted that cognitive dysfunction is often associated with psychiatric disorders -- even in states of remission.

“Importantly, as the authors also state, it will be vital to translate these findings from healthy populations into clinical populations,” said Dr. Frøkjær, who was not involved in the research.

“It will also be important to understand if prucalopride adds to the effects of existing antidepressant treatments or can be used as a stand-alone therapy,” he added.

The study was funded by the NIHR Oxford Health Biomedical Research Center and by the Wellcome Center for Integrative Neuroscience. Ms. De Cates has received a travel grant from the Royal College of Psychiatrists/Gatsby Foundation and support from Wellcome. The other authors have relationships with P1vital Ltd, Janssen Pharmaceuticals, Sage Therapeutics, Pfizer, Zogenix, Compass Pathways, and Lundbeck.

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

In patients with moderate to severe atopic dermatitis (AD), abrocitinib, an oral JAK inhibitor, relieved itch more quickly than the monoclonal antibody dupilumab (Dupixent), in a multicenter randomized trial presented as a late breaker at the annual meeting of the European Academy of Dermatology and Venereology.

The earlier onset of action with the JAK inhibitor was achieved even though most patients in both arms were on topical corticosteroids, a design element that “is clinically relevant” for a practical comparison of these two agents, according to Kristian Reich, MD, PhD, Center for Translational Research in Inflammatory Skin Diseases, University Medical Center, Hamburg-Eppendorf, Germany.    

The goal of this phase 3b trial, called JADE DARE, was to compare relative safety and efficacy of these strategies over the early course of treatment, he said.
 

Over 700 patients randomized

JADE DARE enrolled 727 patients over age 18 years who previously had an inadequate response to conventional topical therapies. All had moderate to severe AD defined by criteria such as body surface area greater than or equal to 10% and Eczema Area Severity Index (EASI) greater than or equal to 16. They were randomly assigned to 200 mg oral abrocitinib once daily or 300 mg subcutaneous dupilumab (after a loading dose of 600 mg) every 2 weeks. A double-dummy design preserved blinding.

The coprimary endpoints were at least a 4-point improvement in pruritus as measured with the Peak Pruritus Numerical Rating Scale (PP-NRS) score at week 2 and at least a 90% improvement in the EASI (EASI 90) at week 4.

The primary endpoint for pruritus at 2 weeks was reached by nearly twice as many patients randomly assigned to abrocitinib (46.2% vs. 25.5%; P < .001). The proportion of those meeting the EASI 90 endpoint at week 4 was also superior on abrocitinib (28.5% vs. 14.6%; P < .001)
 

Advantage for pruritus control dissipates

For the pruritus endpoint, the advantage of abrocitinib slowly diminished over time after the peak difference observed at 2 weeks. Although the advantage at week 4 (58.1% vs. 40.8%) and week 8 (65.8% vs. 52.7%) remained sizable, there were very small differences thereafter. However, Dr. Reich pointed out that the percentages continued to favor abrocitinib at least numerically through the 26 weeks of follow-up completed so far.

The pattern of response on EASI 90 was not the same. After demonstrating superiority at the 4-week timepoint, the advantage of abrocitinib persisted. When compared at week 16, which was a secondary endpoint of the JADE DARE trial, the advantage of abrocitinib remained significant (54.3% vs. 41.9%; P < .001). The advantage of abrocitinib narrowed but remained numerically superior at 26 weeks (54.6% vs. 47.6%).

Based on the data collected to date, “abrocitinib is clearly superior early on,” Dr. Reich said. Moreover, he reiterated that topical corticosteroids were allowed as background therapy in both arms.

“It is difficult to show an advantage for one active therapy over the other in patients on background corticosteroids,” Dr. Reich maintained.
 

Both drugs are well tolerated

The drugs were similarly well tolerated. Serious adverse events were uncommon in either arm. The rate of study dropouts due to an adverse event potentially related to treatment assignment was 3% in each group.

Nausea (19% vs. 2%), acne (13.5% vs. 2%), and headache (13% vs. 7.5%) were all more common in patients randomly assigned to abrocitinib. Conjunctivitis was more common in the group randomly assigned to dupilumab (10% vs. 2%).

The two deaths that occurred during this study were in the abrocitinib arm, but one was the result of COVID-19 infection and the other was a cardiovascular event in a patient with risk factors. Neither was considered to be treatment-related.

Abrocitinib’s relative selectivity for the JAK1 inhibitor is a potential differentiator from other currently available JAK inhibitors, although direct comparisons of these therapies for clinical activity in AD as well as most other diseases remains limited.

The relatively rapid relief of pruritus with the JAK inhibitor relative to the monoclonal antibody in the JADE DARE trial is likely to be perceived as clinically significant by patients with AD, according to Sonja Ständer, MD, professor of dermatology and neurodermatology at the University Hospital Münster, Germany.

“One of the highest needs of patients with atopic dermatitis is a rapid and profound relief of itch,” Dr. Ständer, who wrote a review article on AD earlier this year, said in an interview.

Although several current therapies are effective against pruritus, Dr. Ständer believes that the higher proportion of patients achieving itch control at 2 weeks on abrocitinib “will attract the attention of affected patients.”

However, she added that patients need to take both benefits and risks into account, indicating that clinical utility cannot be judged on a single outcome. In selecting one drug over the others, she advised “a balanced use of therapies.”

Abrocitinib was first approved in the United Kingdom in early September, followed by Japan last Thursday, for the treatment of moderate to severe AD in patients ages 12 and older. It is under review elsewhere, including in the United States and the European Union for AD.  

In September, the FDA approved the first JAK inhibitor for treating AD – a topical JAK inhibitor, ruxolitinib.

Dr. Reich reports financial relationships with 20 pharmaceutical companies, including Pfizer, which provided funding for the JADE DARE trial. Dr. Ständer reports financial relationships with Beiersdorf AG, Galderma, Kliniska, Lilly, Pfizer, and Sanofi.

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

In patients with moderate to severe atopic dermatitis (AD), abrocitinib, an oral JAK inhibitor, relieved itch more quickly than the monoclonal antibody dupilumab (Dupixent), in a multicenter randomized trial presented as a late breaker at the annual meeting of the European Academy of Dermatology and Venereology.

The earlier onset of action with the JAK inhibitor was achieved even though most patients in both arms were on topical corticosteroids, a design element that “is clinically relevant” for a practical comparison of these two agents, according to Kristian Reich, MD, PhD, Center for Translational Research in Inflammatory Skin Diseases, University Medical Center, Hamburg-Eppendorf, Germany.    

The goal of this phase 3b trial, called JADE DARE, was to compare relative safety and efficacy of these strategies over the early course of treatment, he said.
 

Over 700 patients randomized

JADE DARE enrolled 727 patients over age 18 years who previously had an inadequate response to conventional topical therapies. All had moderate to severe AD defined by criteria such as body surface area greater than or equal to 10% and Eczema Area Severity Index (EASI) greater than or equal to 16. They were randomly assigned to 200 mg oral abrocitinib once daily or 300 mg subcutaneous dupilumab (after a loading dose of 600 mg) every 2 weeks. A double-dummy design preserved blinding.

The coprimary endpoints were at least a 4-point improvement in pruritus as measured with the Peak Pruritus Numerical Rating Scale (PP-NRS) score at week 2 and at least a 90% improvement in the EASI (EASI 90) at week 4.

The primary endpoint for pruritus at 2 weeks was reached by nearly twice as many patients randomly assigned to abrocitinib (46.2% vs. 25.5%; P < .001). The proportion of those meeting the EASI 90 endpoint at week 4 was also superior on abrocitinib (28.5% vs. 14.6%; P < .001)
 

Advantage for pruritus control dissipates

For the pruritus endpoint, the advantage of abrocitinib slowly diminished over time after the peak difference observed at 2 weeks. Although the advantage at week 4 (58.1% vs. 40.8%) and week 8 (65.8% vs. 52.7%) remained sizable, there were very small differences thereafter. However, Dr. Reich pointed out that the percentages continued to favor abrocitinib at least numerically through the 26 weeks of follow-up completed so far.

The pattern of response on EASI 90 was not the same. After demonstrating superiority at the 4-week timepoint, the advantage of abrocitinib persisted. When compared at week 16, which was a secondary endpoint of the JADE DARE trial, the advantage of abrocitinib remained significant (54.3% vs. 41.9%; P < .001). The advantage of abrocitinib narrowed but remained numerically superior at 26 weeks (54.6% vs. 47.6%).

Based on the data collected to date, “abrocitinib is clearly superior early on,” Dr. Reich said. Moreover, he reiterated that topical corticosteroids were allowed as background therapy in both arms.

“It is difficult to show an advantage for one active therapy over the other in patients on background corticosteroids,” Dr. Reich maintained.
 

Both drugs are well tolerated

The drugs were similarly well tolerated. Serious adverse events were uncommon in either arm. The rate of study dropouts due to an adverse event potentially related to treatment assignment was 3% in each group.

Nausea (19% vs. 2%), acne (13.5% vs. 2%), and headache (13% vs. 7.5%) were all more common in patients randomly assigned to abrocitinib. Conjunctivitis was more common in the group randomly assigned to dupilumab (10% vs. 2%).

The two deaths that occurred during this study were in the abrocitinib arm, but one was the result of COVID-19 infection and the other was a cardiovascular event in a patient with risk factors. Neither was considered to be treatment-related.

Abrocitinib’s relative selectivity for the JAK1 inhibitor is a potential differentiator from other currently available JAK inhibitors, although direct comparisons of these therapies for clinical activity in AD as well as most other diseases remains limited.

The relatively rapid relief of pruritus with the JAK inhibitor relative to the monoclonal antibody in the JADE DARE trial is likely to be perceived as clinically significant by patients with AD, according to Sonja Ständer, MD, professor of dermatology and neurodermatology at the University Hospital Münster, Germany.

“One of the highest needs of patients with atopic dermatitis is a rapid and profound relief of itch,” Dr. Ständer, who wrote a review article on AD earlier this year, said in an interview.

Although several current therapies are effective against pruritus, Dr. Ständer believes that the higher proportion of patients achieving itch control at 2 weeks on abrocitinib “will attract the attention of affected patients.”

However, she added that patients need to take both benefits and risks into account, indicating that clinical utility cannot be judged on a single outcome. In selecting one drug over the others, she advised “a balanced use of therapies.”

Abrocitinib was first approved in the United Kingdom in early September, followed by Japan last Thursday, for the treatment of moderate to severe AD in patients ages 12 and older. It is under review elsewhere, including in the United States and the European Union for AD.  

In September, the FDA approved the first JAK inhibitor for treating AD – a topical JAK inhibitor, ruxolitinib.

Dr. Reich reports financial relationships with 20 pharmaceutical companies, including Pfizer, which provided funding for the JADE DARE trial. Dr. Ständer reports financial relationships with Beiersdorf AG, Galderma, Kliniska, Lilly, Pfizer, and Sanofi.

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

In patients with moderate to severe atopic dermatitis (AD), abrocitinib, an oral JAK inhibitor, relieved itch more quickly than the monoclonal antibody dupilumab (Dupixent), in a multicenter randomized trial presented as a late breaker at the annual meeting of the European Academy of Dermatology and Venereology.

The earlier onset of action with the JAK inhibitor was achieved even though most patients in both arms were on topical corticosteroids, a design element that “is clinically relevant” for a practical comparison of these two agents, according to Kristian Reich, MD, PhD, Center for Translational Research in Inflammatory Skin Diseases, University Medical Center, Hamburg-Eppendorf, Germany.    

The goal of this phase 3b trial, called JADE DARE, was to compare relative safety and efficacy of these strategies over the early course of treatment, he said.
 

Over 700 patients randomized

JADE DARE enrolled 727 patients over age 18 years who previously had an inadequate response to conventional topical therapies. All had moderate to severe AD defined by criteria such as body surface area greater than or equal to 10% and Eczema Area Severity Index (EASI) greater than or equal to 16. They were randomly assigned to 200 mg oral abrocitinib once daily or 300 mg subcutaneous dupilumab (after a loading dose of 600 mg) every 2 weeks. A double-dummy design preserved blinding.

The coprimary endpoints were at least a 4-point improvement in pruritus as measured with the Peak Pruritus Numerical Rating Scale (PP-NRS) score at week 2 and at least a 90% improvement in the EASI (EASI 90) at week 4.

The primary endpoint for pruritus at 2 weeks was reached by nearly twice as many patients randomly assigned to abrocitinib (46.2% vs. 25.5%; P < .001). The proportion of those meeting the EASI 90 endpoint at week 4 was also superior on abrocitinib (28.5% vs. 14.6%; P < .001)
 

Advantage for pruritus control dissipates

For the pruritus endpoint, the advantage of abrocitinib slowly diminished over time after the peak difference observed at 2 weeks. Although the advantage at week 4 (58.1% vs. 40.8%) and week 8 (65.8% vs. 52.7%) remained sizable, there were very small differences thereafter. However, Dr. Reich pointed out that the percentages continued to favor abrocitinib at least numerically through the 26 weeks of follow-up completed so far.

The pattern of response on EASI 90 was not the same. After demonstrating superiority at the 4-week timepoint, the advantage of abrocitinib persisted. When compared at week 16, which was a secondary endpoint of the JADE DARE trial, the advantage of abrocitinib remained significant (54.3% vs. 41.9%; P < .001). The advantage of abrocitinib narrowed but remained numerically superior at 26 weeks (54.6% vs. 47.6%).

Based on the data collected to date, “abrocitinib is clearly superior early on,” Dr. Reich said. Moreover, he reiterated that topical corticosteroids were allowed as background therapy in both arms.

“It is difficult to show an advantage for one active therapy over the other in patients on background corticosteroids,” Dr. Reich maintained.
 

Both drugs are well tolerated

The drugs were similarly well tolerated. Serious adverse events were uncommon in either arm. The rate of study dropouts due to an adverse event potentially related to treatment assignment was 3% in each group.

Nausea (19% vs. 2%), acne (13.5% vs. 2%), and headache (13% vs. 7.5%) were all more common in patients randomly assigned to abrocitinib. Conjunctivitis was more common in the group randomly assigned to dupilumab (10% vs. 2%).

The two deaths that occurred during this study were in the abrocitinib arm, but one was the result of COVID-19 infection and the other was a cardiovascular event in a patient with risk factors. Neither was considered to be treatment-related.

Abrocitinib’s relative selectivity for the JAK1 inhibitor is a potential differentiator from other currently available JAK inhibitors, although direct comparisons of these therapies for clinical activity in AD as well as most other diseases remains limited.

The relatively rapid relief of pruritus with the JAK inhibitor relative to the monoclonal antibody in the JADE DARE trial is likely to be perceived as clinically significant by patients with AD, according to Sonja Ständer, MD, professor of dermatology and neurodermatology at the University Hospital Münster, Germany.

“One of the highest needs of patients with atopic dermatitis is a rapid and profound relief of itch,” Dr. Ständer, who wrote a review article on AD earlier this year, said in an interview.

Although several current therapies are effective against pruritus, Dr. Ständer believes that the higher proportion of patients achieving itch control at 2 weeks on abrocitinib “will attract the attention of affected patients.”

However, she added that patients need to take both benefits and risks into account, indicating that clinical utility cannot be judged on a single outcome. In selecting one drug over the others, she advised “a balanced use of therapies.”

Abrocitinib was first approved in the United Kingdom in early September, followed by Japan last Thursday, for the treatment of moderate to severe AD in patients ages 12 and older. It is under review elsewhere, including in the United States and the European Union for AD.  

In September, the FDA approved the first JAK inhibitor for treating AD – a topical JAK inhibitor, ruxolitinib.

Dr. Reich reports financial relationships with 20 pharmaceutical companies, including Pfizer, which provided funding for the JADE DARE trial. Dr. Ständer reports financial relationships with Beiersdorf AG, Galderma, Kliniska, Lilly, Pfizer, and Sanofi.

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

An 8-year-old girl who was infected with SARS-CoV-2 died after developing an extremely rare condition known as acute fulminant cerebral edema (AFCE), according to pediatric neurologists who are urging colleagues to watch out for similar cases.

At least one other child in the United States has died after becoming infected with the virus and developing cerebral edema. “The rapid and devastating clinical course in both of these cases highlights the need for early recognition of a cerebral edema and AFCE as potential complications of COVID-19 in pediatric patients,” the neurologists wrote.

The case was highlighted in a poster presented at the annual meeting of the Child Neurology Society and in a report published earlier this year in Child Neurology Open.

According to pediatric neurologist Timothy Gershon, MD, PhD , of the University of North Carolina at Chapel Hill, the child appeared in clinic in July 2020. She had been healthy but was suffering from 1 day of fever, seizure-like activity (generalized convulsions and drooling), anorexia, and lethargy.

The girl, who was subsequently diagnosed with COVID-19, deteriorated in the hospital. “She received IV dexamethasone in attempts to reduce cerebral edema,” the neurologists wrote. “Regarding immunomodulatory therapy, she received intravenous immunoglobulin (2 g/kg), anakinra, and hydrocortisone; despite approval for remdesivir and COVID-19 convalescent plasma, these were ultimately withheld due to poor prognosis.”

Brain death examinations at 24 and 48 hours after cardiac arrest were consistent with brain death, they reported.

Neurologists believe the patient suffered from AFCE, “an often fatal pediatric clinical entity consisting of fever, encephalopathy, and new-onset seizures followed by rapid, diffuse, and medically-refractory cerebral edema.” They add that “AFCE occurs as a rare complication of a variety of common pediatric infections, and a CNS [central nervous system] pathogen is identified in only a minority of cases, suggesting a para-infectious mechanism of edema.”

Neurologists offered a case definition of the “recently recognized” AFCE earlier this year.

“This was an extremely rare rapid progression to cerebral edema. I think it was related to the patient’s COVID infection, but why this patient got it and others don’t is unknown,” Dr. Gershon said in an interview. “The full spectrum of neurological complications of COVID were not yet known [at the time]. We didn’t know, and still don’t know, what the causative links are between COVID and suddenly having seizures and brain swelling.”

He said he’d treat a similar patient differently now and give dexamethasone earlier in the clinical course, although “there is no data to tell us if any therapy could have reversed it.” Specifically, he said, “I’d give dexamethasone at the first sign of brain involvement, using the dosing recommended for cerebral edema, and try to get the MRI earlier in the course.”

Dr. Gershon and colleagues noted another case of fatal cerebral edema in a child, a 7-year-old boy who was treated in New York state. That case “shows that fatal cerebral edema may complicate pediatric multisystem inflammatory syndrome,” they wrote.

Pediatric critical care specialist Preetha Krishnan, MD, of Randall Children’s Hospital at Legacy Emanuel in Portland, Ore., helped develop the new definition of AFCE. In an interview, she said AFCE is difficult to diagnose because the signs/symptoms – such as fever, altered sensorium, and seizures – are found in other conditions such as febrile status epilepticus with a viral illness. 
“The key to recognition of AFCE is that unlike other disease processes, these children have rapid neurologic progression,” she said. “In addition, many of our AFCE patients also had vomiting and/or headache, which in retrospect was likely an indication of elevated ICP [intracranial pressure] rather than viral infection.”
She added that “if a child with fever, seizures, and encephalopathy has cerebral edema on imaging and/or has neurologic progression, AFCE should be considered. Most of our cases of AFCE had fulminant progression within the first 3 days of their head imaging noting cerebral edema. There are other neurologic diseases, such as acute necrotizing encephalopathy of childhood, that also have progressive signs/symptoms, but head imaging and lab work should help differentiate many of these etiologies.”
In regard to treatment, she said, “our unit would likely err on the side of providing as much neuroprotective measures as is reasonable, such as maintaining normothermia, consideration of hyperosmolar therapy, maintaining normocarbia and normoxemia, managing seizures, etc. I would recommend getting the entire neurocritical care team involved in the management discussion. This varies by center, but will likely include neurology, ID [infectious disease], possibly neurosurgery, and PICU.”
As for the new case report, Krishnan said COVID-19 has been linked to neurologic complications, “so it does not surprise me that AFCE is part of the neurologic spectrum of disease.”
No funding was reported, and the authors report no relevant disclosures. Dr. Krishnan has no disclosures.

An 8-year-old girl who was infected with SARS-CoV-2 died after developing an extremely rare condition known as acute fulminant cerebral edema (AFCE), according to pediatric neurologists who are urging colleagues to watch out for similar cases.

At least one other child in the United States has died after becoming infected with the virus and developing cerebral edema. “The rapid and devastating clinical course in both of these cases highlights the need for early recognition of a cerebral edema and AFCE as potential complications of COVID-19 in pediatric patients,” the neurologists wrote.

The case was highlighted in a poster presented at the annual meeting of the Child Neurology Society and in a report published earlier this year in Child Neurology Open.

According to pediatric neurologist Timothy Gershon, MD, PhD , of the University of North Carolina at Chapel Hill, the child appeared in clinic in July 2020. She had been healthy but was suffering from 1 day of fever, seizure-like activity (generalized convulsions and drooling), anorexia, and lethargy.

The girl, who was subsequently diagnosed with COVID-19, deteriorated in the hospital. “She received IV dexamethasone in attempts to reduce cerebral edema,” the neurologists wrote. “Regarding immunomodulatory therapy, she received intravenous immunoglobulin (2 g/kg), anakinra, and hydrocortisone; despite approval for remdesivir and COVID-19 convalescent plasma, these were ultimately withheld due to poor prognosis.”

Brain death examinations at 24 and 48 hours after cardiac arrest were consistent with brain death, they reported.

Neurologists believe the patient suffered from AFCE, “an often fatal pediatric clinical entity consisting of fever, encephalopathy, and new-onset seizures followed by rapid, diffuse, and medically-refractory cerebral edema.” They add that “AFCE occurs as a rare complication of a variety of common pediatric infections, and a CNS [central nervous system] pathogen is identified in only a minority of cases, suggesting a para-infectious mechanism of edema.”

Neurologists offered a case definition of the “recently recognized” AFCE earlier this year.

“This was an extremely rare rapid progression to cerebral edema. I think it was related to the patient’s COVID infection, but why this patient got it and others don’t is unknown,” Dr. Gershon said in an interview. “The full spectrum of neurological complications of COVID were not yet known [at the time]. We didn’t know, and still don’t know, what the causative links are between COVID and suddenly having seizures and brain swelling.”

He said he’d treat a similar patient differently now and give dexamethasone earlier in the clinical course, although “there is no data to tell us if any therapy could have reversed it.” Specifically, he said, “I’d give dexamethasone at the first sign of brain involvement, using the dosing recommended for cerebral edema, and try to get the MRI earlier in the course.”

Dr. Gershon and colleagues noted another case of fatal cerebral edema in a child, a 7-year-old boy who was treated in New York state. That case “shows that fatal cerebral edema may complicate pediatric multisystem inflammatory syndrome,” they wrote.

Pediatric critical care specialist Preetha Krishnan, MD, of Randall Children’s Hospital at Legacy Emanuel in Portland, Ore., helped develop the new definition of AFCE. In an interview, she said AFCE is difficult to diagnose because the signs/symptoms – such as fever, altered sensorium, and seizures – are found in other conditions such as febrile status epilepticus with a viral illness. 
“The key to recognition of AFCE is that unlike other disease processes, these children have rapid neurologic progression,” she said. “In addition, many of our AFCE patients also had vomiting and/or headache, which in retrospect was likely an indication of elevated ICP [intracranial pressure] rather than viral infection.”
She added that “if a child with fever, seizures, and encephalopathy has cerebral edema on imaging and/or has neurologic progression, AFCE should be considered. Most of our cases of AFCE had fulminant progression within the first 3 days of their head imaging noting cerebral edema. There are other neurologic diseases, such as acute necrotizing encephalopathy of childhood, that also have progressive signs/symptoms, but head imaging and lab work should help differentiate many of these etiologies.”
In regard to treatment, she said, “our unit would likely err on the side of providing as much neuroprotective measures as is reasonable, such as maintaining normothermia, consideration of hyperosmolar therapy, maintaining normocarbia and normoxemia, managing seizures, etc. I would recommend getting the entire neurocritical care team involved in the management discussion. This varies by center, but will likely include neurology, ID [infectious disease], possibly neurosurgery, and PICU.”
As for the new case report, Krishnan said COVID-19 has been linked to neurologic complications, “so it does not surprise me that AFCE is part of the neurologic spectrum of disease.”
No funding was reported, and the authors report no relevant disclosures. Dr. Krishnan has no disclosures.

An 8-year-old girl who was infected with SARS-CoV-2 died after developing an extremely rare condition known as acute fulminant cerebral edema (AFCE), according to pediatric neurologists who are urging colleagues to watch out for similar cases.

At least one other child in the United States has died after becoming infected with the virus and developing cerebral edema. “The rapid and devastating clinical course in both of these cases highlights the need for early recognition of a cerebral edema and AFCE as potential complications of COVID-19 in pediatric patients,” the neurologists wrote.

The case was highlighted in a poster presented at the annual meeting of the Child Neurology Society and in a report published earlier this year in Child Neurology Open.

According to pediatric neurologist Timothy Gershon, MD, PhD , of the University of North Carolina at Chapel Hill, the child appeared in clinic in July 2020. She had been healthy but was suffering from 1 day of fever, seizure-like activity (generalized convulsions and drooling), anorexia, and lethargy.

The girl, who was subsequently diagnosed with COVID-19, deteriorated in the hospital. “She received IV dexamethasone in attempts to reduce cerebral edema,” the neurologists wrote. “Regarding immunomodulatory therapy, she received intravenous immunoglobulin (2 g/kg), anakinra, and hydrocortisone; despite approval for remdesivir and COVID-19 convalescent plasma, these were ultimately withheld due to poor prognosis.”

Brain death examinations at 24 and 48 hours after cardiac arrest were consistent with brain death, they reported.

Neurologists believe the patient suffered from AFCE, “an often fatal pediatric clinical entity consisting of fever, encephalopathy, and new-onset seizures followed by rapid, diffuse, and medically-refractory cerebral edema.” They add that “AFCE occurs as a rare complication of a variety of common pediatric infections, and a CNS [central nervous system] pathogen is identified in only a minority of cases, suggesting a para-infectious mechanism of edema.”

Neurologists offered a case definition of the “recently recognized” AFCE earlier this year.

“This was an extremely rare rapid progression to cerebral edema. I think it was related to the patient’s COVID infection, but why this patient got it and others don’t is unknown,” Dr. Gershon said in an interview. “The full spectrum of neurological complications of COVID were not yet known [at the time]. We didn’t know, and still don’t know, what the causative links are between COVID and suddenly having seizures and brain swelling.”

He said he’d treat a similar patient differently now and give dexamethasone earlier in the clinical course, although “there is no data to tell us if any therapy could have reversed it.” Specifically, he said, “I’d give dexamethasone at the first sign of brain involvement, using the dosing recommended for cerebral edema, and try to get the MRI earlier in the course.”

Dr. Gershon and colleagues noted another case of fatal cerebral edema in a child, a 7-year-old boy who was treated in New York state. That case “shows that fatal cerebral edema may complicate pediatric multisystem inflammatory syndrome,” they wrote.

Pediatric critical care specialist Preetha Krishnan, MD, of Randall Children’s Hospital at Legacy Emanuel in Portland, Ore., helped develop the new definition of AFCE. In an interview, she said AFCE is difficult to diagnose because the signs/symptoms – such as fever, altered sensorium, and seizures – are found in other conditions such as febrile status epilepticus with a viral illness. 
“The key to recognition of AFCE is that unlike other disease processes, these children have rapid neurologic progression,” she said. “In addition, many of our AFCE patients also had vomiting and/or headache, which in retrospect was likely an indication of elevated ICP [intracranial pressure] rather than viral infection.”
She added that “if a child with fever, seizures, and encephalopathy has cerebral edema on imaging and/or has neurologic progression, AFCE should be considered. Most of our cases of AFCE had fulminant progression within the first 3 days of their head imaging noting cerebral edema. There are other neurologic diseases, such as acute necrotizing encephalopathy of childhood, that also have progressive signs/symptoms, but head imaging and lab work should help differentiate many of these etiologies.”
In regard to treatment, she said, “our unit would likely err on the side of providing as much neuroprotective measures as is reasonable, such as maintaining normothermia, consideration of hyperosmolar therapy, maintaining normocarbia and normoxemia, managing seizures, etc. I would recommend getting the entire neurocritical care team involved in the management discussion. This varies by center, but will likely include neurology, ID [infectious disease], possibly neurosurgery, and PICU.”
As for the new case report, Krishnan said COVID-19 has been linked to neurologic complications, “so it does not surprise me that AFCE is part of the neurologic spectrum of disease.”
No funding was reported, and the authors report no relevant disclosures. Dr. Krishnan has no disclosures.

Medical school clinical rotations are a rite of passage as students emerge from their basic science courses and first board exam to the clinical world where the patients vaguely resemble the question stem descriptions. Finally, intangible theory can be put into practice. Yet, it is becoming increasingly difficult for 3rd-year medical student clerkship directors to find enough clinical sites to support the growing number of medical students as enrollment numbers steadily increase and outpace the current clinical resources.

In a 2019 Association of American Medical Colleges report, 84% of medical school deans were concerned about the diminishing number of clerkship sites, and there was additional worry about lack of qualified specialty preceptors. This lack of clerkship availability is especially true for psychiatry sites.

Psychiatry clerkship directors are in need of more clinical sites to address the educational needs of medical students, and psychiatrists in the broader clinical community are positioned to help medical schools expand their clinical sites.

Inpatient psychiatric units and consult services continue to be popular sites for medical student rotations, but it has been hard to expand into other settings, where psychiatric treatment is seen as more private and intimate than other specialties. Reasons for falling site availability are varied and include 1) financial disincentive to take students – because they can be seen as a burden on supervisors who must meet revenue-generating patient quotas; 2) competition with other learners, including residents, PA students, NPs, and NP students; and 3) the general financial and operational obstacles to clinical practice inflicted by the pandemic. COVID-19 affected medical education – for better and worse (JAMA. 2020;324[11]:1033-4). Psychiatry clerkships particularly suffered from restricted patient access as inpatient units reduced their census to comply with COVID-19 safety protocols, and during the height of the pandemic inpatient units provided psychiatric care to COVID-19–positive patients, which precluded student involvement. On the other hand, many more students were introduced to telepsychiatry and witnessed creative forms of mental health intervention as clinicians adapted their practices to the pandemic.
 

When rotations began

Clinical rotations entered the American medical school curriculum in the 1890s when Sir William Osler brought the European standard of medical education with him as Physician in Chief at the newly opened Johns Hopkins University Hospital. He formalized the traditional apprenticeship model by standardizing 3rd- and 4th-year clerkships as rotations in which medical students worked in clinics and on the wards, learning from residents and attendings.

Clinical rotations, their location, the supervisors, and the patients and their ailments all go in to influence a student’s specialty choice. Some students enter medical school knowing they want to be a surgeon, a pediatrician, or a psychiatrist. And some are compelled by a specific rotation, when they realize that it’s not at all what they expected and maybe they could dedicate their professional life to this area of medicine.

High-quality clinical clerkship sites are essential to the future of psychiatry. At clerkship sites, undecided students interested in psychiatry may affirm their commitment to psychiatry. Other students will have their only dedicated exposure to psychiatrically ill patients. This represents students’ only opportunity to learn the skills to treat comorbid psychiatric and medical illness. Regardless of specialty, nearly every physician will have to treat patients with some psychiatric illnesses.

What constitutes a “high-quality clinical site” is difficult to measure and define. Some measures of quality include a safe learning environment, a reasonable ratio of students to supervisors (including residents, fellows, and attendings), and an adequate number and diversity of patients. Many medical schools may prefer an affiliated academic medical center or Veterans’ Affairs hospitals for their rotating students. Private psychiatric hospitals are proliferating, and if these are to be sites for medical students, the following standards are suggested: Private psychiatric hospitals must follow standard safety precautions with sufficient staff presence, ensure willing preceptors who can provide adequate student supervision, and adjust their expectations to students who can carry a few patients of diverse background, but are not to be treated merely as scribes.

Psychiatrists, whether they consider themselves “academic” or not, have a role to play in expanding access to clinical sites. Students are eager to learn in any setting. Inpatient settings have long been seen as the norm for clinical education in psychiatry. Yet inpatient settings perpetuate the idea that those with severe mental illness or individuals with psychosocial stressors or disabling, comorbid substance use disorders are the only people who seek help from a psychiatrist. This article is a call to action to our colleagues in community mental health centers, managed care settings, and other psychiatric treatment providers without an academic affiliation to explore the possibility of creating space for a medical student in their clinical practice.

We cannot deny the demands on psychiatrists’ time – every minute is counted by the patient and doctor, and every encounter is accounted for in some revenue stream. However, the academic world is running out of space for its students, and there’s a serious question as to whether an academic center is the only place for students. If you are a psychiatrist who still loves to learn and prides themselves on high-quality patient care, then you have an essential role in shaping the students who will one day be your peers in psychiatry, or the physicians treating your patients’ comorbid medical illnesses.

There are upfront challenges to teaching 3rd-year medical students, including teaching the psychiatric interview, note writing, persuading patients to allow students into their care, and setting time aside at the end of the workday to provide feedback on performance. Yet, after learning the ropes of psychiatric patient care, medical students can provide help in writing notes, calling collateral, contacting patients with their laboratory results, and even helping with the tedious but necessary administrative tasks like prior authorizations. In exchange for training students, some medical schools may offer perks, such as a volunteer faculty position that comes with access to usually expensive library resources, such as medical databases.

You can help expand clinical sites in psychiatry rotations by contacting your alma mater or the medical school closest to your community and asking about their need for clerkship sites. Many medical schools are branching out by sending students to stay near the clinical sites and immerse themselves in the community where their site director practices. Even one-half day a week in an outpatient setting provides patient and setting diversity to students and helps spread out students to different sites, easing the burden on inpatient supervisors while providing students more individualized supervision.

The practice of medicine is built on apprenticeship and teaching wisdom through patient care. Just because we leave residency doesn’t mean we leave academics. Taking students into your practice is an invaluable service to the medical education community and future physicians.
 

Dr. Posada is assistant clinical professor in the department of psychiatry and behavioral sciences at George Washington University in Washington, and staff physician at George Washington Medical Faculty Associates, also in Washington. She has no conflicts of interest. Dr. Ortiz is assistant professor and clerkship director in the department of psychiatry at Texas Tech University Health Sciences Center – El Paso. She has no conflicts of interest.

Medical school clinical rotations are a rite of passage as students emerge from their basic science courses and first board exam to the clinical world where the patients vaguely resemble the question stem descriptions. Finally, intangible theory can be put into practice. Yet, it is becoming increasingly difficult for 3rd-year medical student clerkship directors to find enough clinical sites to support the growing number of medical students as enrollment numbers steadily increase and outpace the current clinical resources.

In a 2019 Association of American Medical Colleges report, 84% of medical school deans were concerned about the diminishing number of clerkship sites, and there was additional worry about lack of qualified specialty preceptors. This lack of clerkship availability is especially true for psychiatry sites.

Psychiatry clerkship directors are in need of more clinical sites to address the educational needs of medical students, and psychiatrists in the broader clinical community are positioned to help medical schools expand their clinical sites.

Inpatient psychiatric units and consult services continue to be popular sites for medical student rotations, but it has been hard to expand into other settings, where psychiatric treatment is seen as more private and intimate than other specialties. Reasons for falling site availability are varied and include 1) financial disincentive to take students – because they can be seen as a burden on supervisors who must meet revenue-generating patient quotas; 2) competition with other learners, including residents, PA students, NPs, and NP students; and 3) the general financial and operational obstacles to clinical practice inflicted by the pandemic. COVID-19 affected medical education – for better and worse (JAMA. 2020;324[11]:1033-4). Psychiatry clerkships particularly suffered from restricted patient access as inpatient units reduced their census to comply with COVID-19 safety protocols, and during the height of the pandemic inpatient units provided psychiatric care to COVID-19–positive patients, which precluded student involvement. On the other hand, many more students were introduced to telepsychiatry and witnessed creative forms of mental health intervention as clinicians adapted their practices to the pandemic.
 

When rotations began

Clinical rotations entered the American medical school curriculum in the 1890s when Sir William Osler brought the European standard of medical education with him as Physician in Chief at the newly opened Johns Hopkins University Hospital. He formalized the traditional apprenticeship model by standardizing 3rd- and 4th-year clerkships as rotations in which medical students worked in clinics and on the wards, learning from residents and attendings.

Clinical rotations, their location, the supervisors, and the patients and their ailments all go in to influence a student’s specialty choice. Some students enter medical school knowing they want to be a surgeon, a pediatrician, or a psychiatrist. And some are compelled by a specific rotation, when they realize that it’s not at all what they expected and maybe they could dedicate their professional life to this area of medicine.

High-quality clinical clerkship sites are essential to the future of psychiatry. At clerkship sites, undecided students interested in psychiatry may affirm their commitment to psychiatry. Other students will have their only dedicated exposure to psychiatrically ill patients. This represents students’ only opportunity to learn the skills to treat comorbid psychiatric and medical illness. Regardless of specialty, nearly every physician will have to treat patients with some psychiatric illnesses.

What constitutes a “high-quality clinical site” is difficult to measure and define. Some measures of quality include a safe learning environment, a reasonable ratio of students to supervisors (including residents, fellows, and attendings), and an adequate number and diversity of patients. Many medical schools may prefer an affiliated academic medical center or Veterans’ Affairs hospitals for their rotating students. Private psychiatric hospitals are proliferating, and if these are to be sites for medical students, the following standards are suggested: Private psychiatric hospitals must follow standard safety precautions with sufficient staff presence, ensure willing preceptors who can provide adequate student supervision, and adjust their expectations to students who can carry a few patients of diverse background, but are not to be treated merely as scribes.

Psychiatrists, whether they consider themselves “academic” or not, have a role to play in expanding access to clinical sites. Students are eager to learn in any setting. Inpatient settings have long been seen as the norm for clinical education in psychiatry. Yet inpatient settings perpetuate the idea that those with severe mental illness or individuals with psychosocial stressors or disabling, comorbid substance use disorders are the only people who seek help from a psychiatrist. This article is a call to action to our colleagues in community mental health centers, managed care settings, and other psychiatric treatment providers without an academic affiliation to explore the possibility of creating space for a medical student in their clinical practice.

We cannot deny the demands on psychiatrists’ time – every minute is counted by the patient and doctor, and every encounter is accounted for in some revenue stream. However, the academic world is running out of space for its students, and there’s a serious question as to whether an academic center is the only place for students. If you are a psychiatrist who still loves to learn and prides themselves on high-quality patient care, then you have an essential role in shaping the students who will one day be your peers in psychiatry, or the physicians treating your patients’ comorbid medical illnesses.

There are upfront challenges to teaching 3rd-year medical students, including teaching the psychiatric interview, note writing, persuading patients to allow students into their care, and setting time aside at the end of the workday to provide feedback on performance. Yet, after learning the ropes of psychiatric patient care, medical students can provide help in writing notes, calling collateral, contacting patients with their laboratory results, and even helping with the tedious but necessary administrative tasks like prior authorizations. In exchange for training students, some medical schools may offer perks, such as a volunteer faculty position that comes with access to usually expensive library resources, such as medical databases.

You can help expand clinical sites in psychiatry rotations by contacting your alma mater or the medical school closest to your community and asking about their need for clerkship sites. Many medical schools are branching out by sending students to stay near the clinical sites and immerse themselves in the community where their site director practices. Even one-half day a week in an outpatient setting provides patient and setting diversity to students and helps spread out students to different sites, easing the burden on inpatient supervisors while providing students more individualized supervision.

The practice of medicine is built on apprenticeship and teaching wisdom through patient care. Just because we leave residency doesn’t mean we leave academics. Taking students into your practice is an invaluable service to the medical education community and future physicians.
 

Dr. Posada is assistant clinical professor in the department of psychiatry and behavioral sciences at George Washington University in Washington, and staff physician at George Washington Medical Faculty Associates, also in Washington. She has no conflicts of interest. Dr. Ortiz is assistant professor and clerkship director in the department of psychiatry at Texas Tech University Health Sciences Center – El Paso. She has no conflicts of interest.

Medical school clinical rotations are a rite of passage as students emerge from their basic science courses and first board exam to the clinical world where the patients vaguely resemble the question stem descriptions. Finally, intangible theory can be put into practice. Yet, it is becoming increasingly difficult for 3rd-year medical student clerkship directors to find enough clinical sites to support the growing number of medical students as enrollment numbers steadily increase and outpace the current clinical resources.

In a 2019 Association of American Medical Colleges report, 84% of medical school deans were concerned about the diminishing number of clerkship sites, and there was additional worry about lack of qualified specialty preceptors. This lack of clerkship availability is especially true for psychiatry sites.

Psychiatry clerkship directors are in need of more clinical sites to address the educational needs of medical students, and psychiatrists in the broader clinical community are positioned to help medical schools expand their clinical sites.

Inpatient psychiatric units and consult services continue to be popular sites for medical student rotations, but it has been hard to expand into other settings, where psychiatric treatment is seen as more private and intimate than other specialties. Reasons for falling site availability are varied and include 1) financial disincentive to take students – because they can be seen as a burden on supervisors who must meet revenue-generating patient quotas; 2) competition with other learners, including residents, PA students, NPs, and NP students; and 3) the general financial and operational obstacles to clinical practice inflicted by the pandemic. COVID-19 affected medical education – for better and worse (JAMA. 2020;324[11]:1033-4). Psychiatry clerkships particularly suffered from restricted patient access as inpatient units reduced their census to comply with COVID-19 safety protocols, and during the height of the pandemic inpatient units provided psychiatric care to COVID-19–positive patients, which precluded student involvement. On the other hand, many more students were introduced to telepsychiatry and witnessed creative forms of mental health intervention as clinicians adapted their practices to the pandemic.
 

When rotations began

Clinical rotations entered the American medical school curriculum in the 1890s when Sir William Osler brought the European standard of medical education with him as Physician in Chief at the newly opened Johns Hopkins University Hospital. He formalized the traditional apprenticeship model by standardizing 3rd- and 4th-year clerkships as rotations in which medical students worked in clinics and on the wards, learning from residents and attendings.

Clinical rotations, their location, the supervisors, and the patients and their ailments all go in to influence a student’s specialty choice. Some students enter medical school knowing they want to be a surgeon, a pediatrician, or a psychiatrist. And some are compelled by a specific rotation, when they realize that it’s not at all what they expected and maybe they could dedicate their professional life to this area of medicine.

High-quality clinical clerkship sites are essential to the future of psychiatry. At clerkship sites, undecided students interested in psychiatry may affirm their commitment to psychiatry. Other students will have their only dedicated exposure to psychiatrically ill patients. This represents students’ only opportunity to learn the skills to treat comorbid psychiatric and medical illness. Regardless of specialty, nearly every physician will have to treat patients with some psychiatric illnesses.

What constitutes a “high-quality clinical site” is difficult to measure and define. Some measures of quality include a safe learning environment, a reasonable ratio of students to supervisors (including residents, fellows, and attendings), and an adequate number and diversity of patients. Many medical schools may prefer an affiliated academic medical center or Veterans’ Affairs hospitals for their rotating students. Private psychiatric hospitals are proliferating, and if these are to be sites for medical students, the following standards are suggested: Private psychiatric hospitals must follow standard safety precautions with sufficient staff presence, ensure willing preceptors who can provide adequate student supervision, and adjust their expectations to students who can carry a few patients of diverse background, but are not to be treated merely as scribes.

Psychiatrists, whether they consider themselves “academic” or not, have a role to play in expanding access to clinical sites. Students are eager to learn in any setting. Inpatient settings have long been seen as the norm for clinical education in psychiatry. Yet inpatient settings perpetuate the idea that those with severe mental illness or individuals with psychosocial stressors or disabling, comorbid substance use disorders are the only people who seek help from a psychiatrist. This article is a call to action to our colleagues in community mental health centers, managed care settings, and other psychiatric treatment providers without an academic affiliation to explore the possibility of creating space for a medical student in their clinical practice.

We cannot deny the demands on psychiatrists’ time – every minute is counted by the patient and doctor, and every encounter is accounted for in some revenue stream. However, the academic world is running out of space for its students, and there’s a serious question as to whether an academic center is the only place for students. If you are a psychiatrist who still loves to learn and prides themselves on high-quality patient care, then you have an essential role in shaping the students who will one day be your peers in psychiatry, or the physicians treating your patients’ comorbid medical illnesses.

There are upfront challenges to teaching 3rd-year medical students, including teaching the psychiatric interview, note writing, persuading patients to allow students into their care, and setting time aside at the end of the workday to provide feedback on performance. Yet, after learning the ropes of psychiatric patient care, medical students can provide help in writing notes, calling collateral, contacting patients with their laboratory results, and even helping with the tedious but necessary administrative tasks like prior authorizations. In exchange for training students, some medical schools may offer perks, such as a volunteer faculty position that comes with access to usually expensive library resources, such as medical databases.

You can help expand clinical sites in psychiatry rotations by contacting your alma mater or the medical school closest to your community and asking about their need for clerkship sites. Many medical schools are branching out by sending students to stay near the clinical sites and immerse themselves in the community where their site director practices. Even one-half day a week in an outpatient setting provides patient and setting diversity to students and helps spread out students to different sites, easing the burden on inpatient supervisors while providing students more individualized supervision.

The practice of medicine is built on apprenticeship and teaching wisdom through patient care. Just because we leave residency doesn’t mean we leave academics. Taking students into your practice is an invaluable service to the medical education community and future physicians.
 

Dr. Posada is assistant clinical professor in the department of psychiatry and behavioral sciences at George Washington University in Washington, and staff physician at George Washington Medical Faculty Associates, also in Washington. She has no conflicts of interest. Dr. Ortiz is assistant professor and clerkship director in the department of psychiatry at Texas Tech University Health Sciences Center – El Paso. She has no conflicts of interest.

Newborns of pregnant women who were treated with selective serotonin reuptake inhibitors during the third trimester are almost three times as likely to develop neonatal encephalopathy (NE), although the overall risk remains extremely low, a new study finds.

The findings were presented in a poster at the 50th annual meeting of the Child Neurology Society.

“Our work showed that neonates exposed to SSRI in utero had higher risks of neonatal encephalopathy even when adjusting for confounders such as maternal mental health disorders and age. SSRIs could cause side effects such as encephalopathy in neonates, and these risks need to be balanced carefully with the potential benefits of treatment to the mother,” study lead author Marie Cornet, MD, a neonatology fellow with Benioff Children’s Hospital at the University of California, San Francisco, said in an interview.

According to Dr. Cornet, “we know that SSRI exposure in utero is associated with increased risks of respiratory distress at birth, need for positive-pressure ventilation, and an abnormal neurologic exam.” The researchers launched the new study to determine if the estimated 4%-8% of pregnant women who take SSRIs may be putting their newborns at greater risk of NE.

The researchers retrospectively tracked 305,426 infants who were born in the Kaiser Permanente Northern California health system (≥35 weeks) from 2011 to 2019. The mothers had an average age of 31 years, and approximately 34.7% were White, 34.7% of unknown race, 23.3% Asian, and 6.2% Black.

The researchers defined NE as a “5-minute APGAR score <7 and abnormal level of consciousness, activity, tone, or reflexes.”

A total of 8,024 infants (2.6%) had mothers who used SSRIs in the third trimester, and 510 (0.17%) were determined to have had NE.

After adjustment for maternal depression or anxiety, maternal age, race, and hospital, exposed neonates had 2.7 times higher odds of NE (odds ratio, 2.7).

Each 25 mg per day increase in the dose of SSRIs, as equalized to doses of sertraline (Zoloft), was linked to a significant 31% increase in the odds of developing NE (OR, 1.31).

The study doesn’t examine the benefits of SSRI treatment in pregnancy. Those taking SSRIs were much more likely to have depression during pregnancy (76.5% vs. 13.5%) and anxiety (56.7% vs. 6.9%), compared with those who did not take the drug.

The possible connection between SSRIs and NE is unclear. “SSRIs may contribute to NE by a withdrawal mechanism or by a toxicity mechanism. It is also possible that SSRIs themselves are not responsible for encephalopathy, or that the severity of maternal mental health is itself responsible for increased neonatal encephalopathy,” Dr. Cornet said. “However, we believe we adjusted our results thoroughly for that. Furthermore, in this cohort, neonates born from mothers with untreated depression were not at higher risk of encephalopathy than neonates born to mothers without depression.”

She added: “When infants have acidosis or require prolonged resuscitation after birth, they get treated with therapeutic hypothermia. This invasive treatment was shown to decrease mortality and morbidity in neonates with hypoxic-ischemic encephalopathy. However, therapeutic hypothermia may not be helpful in infants with encephalopathy due to other causes than acute hypoxia-ischemia, such as infection, inflammation, genetic conditions, or exposure to toxins. In the case of SSRIs, our results show that, while neonates often have encephalopathy, this encephalopathy is often mild and self-resolved. We did not see a statistically significant increase in acidosis or treatment with therapeutic hypothermia.”

In the future neurologists should consider SSRI use as a potential cause in cases of NE, Dr. Cornet said. “If there are no signs of hypoxic-ischemic encephalopathy – no evidence of acidosis, acute perinatal event – treatment with therapeutic hypothermia may not be indicated.”

Dr. Cornet said more research is in the works. “Studying the long-term side effect of SSRIs on neonatal brain development and injury is essential,” she said. “We plan to compare brain injury in neonates exposed and unexposed to SSRIs and examine long-term outcomes to assess if the effect of SSRI exposure is transient or has a lasting impact.”

This study was funded by the Thrasher Early Career Research Grant and by the Newborn Brain Research Innovation Award at UCSF. The authors have no relevant disclosures.
 

Newborns of pregnant women who were treated with selective serotonin reuptake inhibitors during the third trimester are almost three times as likely to develop neonatal encephalopathy (NE), although the overall risk remains extremely low, a new study finds.

The findings were presented in a poster at the 50th annual meeting of the Child Neurology Society.

“Our work showed that neonates exposed to SSRI in utero had higher risks of neonatal encephalopathy even when adjusting for confounders such as maternal mental health disorders and age. SSRIs could cause side effects such as encephalopathy in neonates, and these risks need to be balanced carefully with the potential benefits of treatment to the mother,” study lead author Marie Cornet, MD, a neonatology fellow with Benioff Children’s Hospital at the University of California, San Francisco, said in an interview.

According to Dr. Cornet, “we know that SSRI exposure in utero is associated with increased risks of respiratory distress at birth, need for positive-pressure ventilation, and an abnormal neurologic exam.” The researchers launched the new study to determine if the estimated 4%-8% of pregnant women who take SSRIs may be putting their newborns at greater risk of NE.

The researchers retrospectively tracked 305,426 infants who were born in the Kaiser Permanente Northern California health system (≥35 weeks) from 2011 to 2019. The mothers had an average age of 31 years, and approximately 34.7% were White, 34.7% of unknown race, 23.3% Asian, and 6.2% Black.

The researchers defined NE as a “5-minute APGAR score <7 and abnormal level of consciousness, activity, tone, or reflexes.”

A total of 8,024 infants (2.6%) had mothers who used SSRIs in the third trimester, and 510 (0.17%) were determined to have had NE.

After adjustment for maternal depression or anxiety, maternal age, race, and hospital, exposed neonates had 2.7 times higher odds of NE (odds ratio, 2.7).

Each 25 mg per day increase in the dose of SSRIs, as equalized to doses of sertraline (Zoloft), was linked to a significant 31% increase in the odds of developing NE (OR, 1.31).

The study doesn’t examine the benefits of SSRI treatment in pregnancy. Those taking SSRIs were much more likely to have depression during pregnancy (76.5% vs. 13.5%) and anxiety (56.7% vs. 6.9%), compared with those who did not take the drug.

The possible connection between SSRIs and NE is unclear. “SSRIs may contribute to NE by a withdrawal mechanism or by a toxicity mechanism. It is also possible that SSRIs themselves are not responsible for encephalopathy, or that the severity of maternal mental health is itself responsible for increased neonatal encephalopathy,” Dr. Cornet said. “However, we believe we adjusted our results thoroughly for that. Furthermore, in this cohort, neonates born from mothers with untreated depression were not at higher risk of encephalopathy than neonates born to mothers without depression.”

She added: “When infants have acidosis or require prolonged resuscitation after birth, they get treated with therapeutic hypothermia. This invasive treatment was shown to decrease mortality and morbidity in neonates with hypoxic-ischemic encephalopathy. However, therapeutic hypothermia may not be helpful in infants with encephalopathy due to other causes than acute hypoxia-ischemia, such as infection, inflammation, genetic conditions, or exposure to toxins. In the case of SSRIs, our results show that, while neonates often have encephalopathy, this encephalopathy is often mild and self-resolved. We did not see a statistically significant increase in acidosis or treatment with therapeutic hypothermia.”

In the future neurologists should consider SSRI use as a potential cause in cases of NE, Dr. Cornet said. “If there are no signs of hypoxic-ischemic encephalopathy – no evidence of acidosis, acute perinatal event – treatment with therapeutic hypothermia may not be indicated.”

Dr. Cornet said more research is in the works. “Studying the long-term side effect of SSRIs on neonatal brain development and injury is essential,” she said. “We plan to compare brain injury in neonates exposed and unexposed to SSRIs and examine long-term outcomes to assess if the effect of SSRI exposure is transient or has a lasting impact.”

This study was funded by the Thrasher Early Career Research Grant and by the Newborn Brain Research Innovation Award at UCSF. The authors have no relevant disclosures.
 

Newborns of pregnant women who were treated with selective serotonin reuptake inhibitors during the third trimester are almost three times as likely to develop neonatal encephalopathy (NE), although the overall risk remains extremely low, a new study finds.

The findings were presented in a poster at the 50th annual meeting of the Child Neurology Society.

“Our work showed that neonates exposed to SSRI in utero had higher risks of neonatal encephalopathy even when adjusting for confounders such as maternal mental health disorders and age. SSRIs could cause side effects such as encephalopathy in neonates, and these risks need to be balanced carefully with the potential benefits of treatment to the mother,” study lead author Marie Cornet, MD, a neonatology fellow with Benioff Children’s Hospital at the University of California, San Francisco, said in an interview.

According to Dr. Cornet, “we know that SSRI exposure in utero is associated with increased risks of respiratory distress at birth, need for positive-pressure ventilation, and an abnormal neurologic exam.” The researchers launched the new study to determine if the estimated 4%-8% of pregnant women who take SSRIs may be putting their newborns at greater risk of NE.

The researchers retrospectively tracked 305,426 infants who were born in the Kaiser Permanente Northern California health system (≥35 weeks) from 2011 to 2019. The mothers had an average age of 31 years, and approximately 34.7% were White, 34.7% of unknown race, 23.3% Asian, and 6.2% Black.

The researchers defined NE as a “5-minute APGAR score <7 and abnormal level of consciousness, activity, tone, or reflexes.”

A total of 8,024 infants (2.6%) had mothers who used SSRIs in the third trimester, and 510 (0.17%) were determined to have had NE.

After adjustment for maternal depression or anxiety, maternal age, race, and hospital, exposed neonates had 2.7 times higher odds of NE (odds ratio, 2.7).

Each 25 mg per day increase in the dose of SSRIs, as equalized to doses of sertraline (Zoloft), was linked to a significant 31% increase in the odds of developing NE (OR, 1.31).

The study doesn’t examine the benefits of SSRI treatment in pregnancy. Those taking SSRIs were much more likely to have depression during pregnancy (76.5% vs. 13.5%) and anxiety (56.7% vs. 6.9%), compared with those who did not take the drug.

The possible connection between SSRIs and NE is unclear. “SSRIs may contribute to NE by a withdrawal mechanism or by a toxicity mechanism. It is also possible that SSRIs themselves are not responsible for encephalopathy, or that the severity of maternal mental health is itself responsible for increased neonatal encephalopathy,” Dr. Cornet said. “However, we believe we adjusted our results thoroughly for that. Furthermore, in this cohort, neonates born from mothers with untreated depression were not at higher risk of encephalopathy than neonates born to mothers without depression.”

She added: “When infants have acidosis or require prolonged resuscitation after birth, they get treated with therapeutic hypothermia. This invasive treatment was shown to decrease mortality and morbidity in neonates with hypoxic-ischemic encephalopathy. However, therapeutic hypothermia may not be helpful in infants with encephalopathy due to other causes than acute hypoxia-ischemia, such as infection, inflammation, genetic conditions, or exposure to toxins. In the case of SSRIs, our results show that, while neonates often have encephalopathy, this encephalopathy is often mild and self-resolved. We did not see a statistically significant increase in acidosis or treatment with therapeutic hypothermia.”

In the future neurologists should consider SSRI use as a potential cause in cases of NE, Dr. Cornet said. “If there are no signs of hypoxic-ischemic encephalopathy – no evidence of acidosis, acute perinatal event – treatment with therapeutic hypothermia may not be indicated.”

Dr. Cornet said more research is in the works. “Studying the long-term side effect of SSRIs on neonatal brain development and injury is essential,” she said. “We plan to compare brain injury in neonates exposed and unexposed to SSRIs and examine long-term outcomes to assess if the effect of SSRI exposure is transient or has a lasting impact.”

This study was funded by the Thrasher Early Career Research Grant and by the Newborn Brain Research Innovation Award at UCSF. The authors have no relevant disclosures.
 

About half of patients with rheumatoid arthritis who taper or stop disease-modifying antirheumatic drugs (DMARDs) retain stable remission after 12 months, and a majority of those who do relapse regain remission when back on their original treatments, according to data from the open-label, randomized Rheumatoid Arthritis in Ongoing Remission (RETRO) study.

“Currently, 40%-50% of patients with rheumatoid arthritis reach stable remission,” as a result of factors including earlier diagnosis and a wider range of treatments, Koray Tascilar, MD, of Friedrich Alexander University Erlangen-Nuremberg (Germany) and colleagues wrote in their publication of the RETRO trial results in Lancet Rheumatology.

Previous studies have suggested that patients with RA in sustained remission may be able to taper or withdraw treatment, but data from randomized trials are limited, the researchers said.

In the RETRO trial, researchers compared three strategies for RA patients in remission, which was defined as <2.6 on the 28-joint Disease Activity Score with erythrocyte sedimentation rate (DAS28-ESR). They randomized 100 adults to continue DMARDs and glucocorticoids, 102 to taper DMARDs and glucocorticoids to half their prior doses, and 101 to reduce the doses to half for 6 months and then stop DMARDs. Patients were enrolled between May 26, 2010, and May 29, 2018, from 14 treatment centers in Germany. The final analysis included 282 patients; 92 in the continuation group, 93 in the taper group, and 96 in the stop group. The mean age of the patients was 56.5 years, and 59% were women. The mean duration of RA was 7.4 years, and the mean duration of remission was 20 months.

Overall, at 12 months, 61% of the patients remained in remission without relapse; 81.2% of the continuation group, 58.6% of the taper group, and 43.3% of the stop group. Relapses occurred in 17%, 43%, and 55% of patients in the continuation, taper, and stop groups, respectively. The median times to relapse in the three groups were 30.6 weeks, 24.3 weeks, and 26.1 weeks, respectively.

Most of the relapses occurred between weeks 24 and 36 after stopping treatment, the researchers wrote. Corresponding hazard ratios for relapse were 3.02 for the taper group and 4.34 for the stop group, compared with the continuation group. In comparison to continuing treatment, the number needed to treat for one more relapse to occur during the 12-month observation period was four for tapering and three for stopping, they noted.

The study protocol called for a return to baseline treatment for any patients who relapsed in the taper and stop groups, and most patients who relapsed regained remission after restarting their baseline treatments. Among patients who had a follow-up visit after a relapse, 10 (63%) of 16 patients in the continuation group reachieved remission before the end of the study, as did 21 (62%) of 34 in the taper group and 35 (76%) of 46 in the stop group.

The most common treatments at baseline were methotrexate (76%) and tumor necrosis factor (TNF) inhibitors (32%).

The researchers also identified several baseline characteristics associated with relapse. Overall, relapse occurred more often in biologic DMARD users than in participants treated with other drugs, more often in women than men, and more often in those with a longer disease duration, higher baseline DAS28-ESR and Health Assessment Questionnaire scores, and in those who were positive for rheumatoid factor or anti–citrullinated protein antibodies.

A total of 38 serious adverse events occurred in 29 participants during the study period, but none were deemed treatment related, and none led to study withdrawal.

The study findings were limited by several factors including the lack of masking of patients and assessors and potential underestimation of disease activity, the researchers noted. Also, the study did not include radiographic data that might have been used to confirm progression; however, such data could have produced a null result and were not feasible in the study population, they wrote.

“If RETRO had been a trial to test the superiority of 100% dose continuation, compared with tapering plus rescue treatment or stopping plus rescue treatment, we would not be able to show that continuation is superior to tapering or stopping,” the researchers noted.

The study results support “an increasingly dynamic management approach in patients with rheumatoid arthritis in stable remission,” given the changing nature of RA management, that may help reduce overtreatment in many RA patients, the researchers concluded. “Furthermore, the observation that most of the patients regained remission after reintroduction of antirheumatic treatments is helpful with regard to the benefit-risk aspect of treatment reduction.”

Real-world setting serves as starting point

The RETRO study is unique in that it tried to reflect a real-life setting by enrolling patients on baseline treatment with combinations of conventional synthetic DMARDs and biologic DMARDs seen in clinical practice rather than only patients taking biologic DMARDs – primarily TNF inhibitors – as done in previous studies of tapering and stopping DMARDs, wrote Catherine L. Hill, MD, of the University of Adelaide (Australia), in an accompanying editorial. It is also “used a simple, pragmatic one-size-fits-all treatment-tapering strategy,” she wrote.

However, she emphasized that answers are needed to questions about what relapse rates are acceptable, what duration of treatment-free time is ideal, and whether benefits to the patient outweigh risks.

Dr. Hill also highlighted the issue of identifying patients who are appropriate candidates for tapering or withdrawal. Stricter remission criteria may not be feasible in routine practice, and so “the development of algorithms to guide patient selection is likely to be the most practical way forward for clinicians and patients,” she wrote.

“Contemplation of treatment tapering or discontinuation in some patients with rheumatoid arthritis is remarkable and a measure of how far treatments have advanced,” Dr. Hill wrote. “However, further work to address outstanding questions on who should taper and how best to do it is still required,” she concluded.

The study received no outside funding. Lead author Dr. Tascilar disclosed lecture fees from Gilead and Union Chimique Belge; several coauthors disclosed relationships with multiple companies outside the current study. Dr. Hill had no financial conflicts to disclose.

About half of patients with rheumatoid arthritis who taper or stop disease-modifying antirheumatic drugs (DMARDs) retain stable remission after 12 months, and a majority of those who do relapse regain remission when back on their original treatments, according to data from the open-label, randomized Rheumatoid Arthritis in Ongoing Remission (RETRO) study.

“Currently, 40%-50% of patients with rheumatoid arthritis reach stable remission,” as a result of factors including earlier diagnosis and a wider range of treatments, Koray Tascilar, MD, of Friedrich Alexander University Erlangen-Nuremberg (Germany) and colleagues wrote in their publication of the RETRO trial results in Lancet Rheumatology.

Previous studies have suggested that patients with RA in sustained remission may be able to taper or withdraw treatment, but data from randomized trials are limited, the researchers said.

In the RETRO trial, researchers compared three strategies for RA patients in remission, which was defined as <2.6 on the 28-joint Disease Activity Score with erythrocyte sedimentation rate (DAS28-ESR). They randomized 100 adults to continue DMARDs and glucocorticoids, 102 to taper DMARDs and glucocorticoids to half their prior doses, and 101 to reduce the doses to half for 6 months and then stop DMARDs. Patients were enrolled between May 26, 2010, and May 29, 2018, from 14 treatment centers in Germany. The final analysis included 282 patients; 92 in the continuation group, 93 in the taper group, and 96 in the stop group. The mean age of the patients was 56.5 years, and 59% were women. The mean duration of RA was 7.4 years, and the mean duration of remission was 20 months.

Overall, at 12 months, 61% of the patients remained in remission without relapse; 81.2% of the continuation group, 58.6% of the taper group, and 43.3% of the stop group. Relapses occurred in 17%, 43%, and 55% of patients in the continuation, taper, and stop groups, respectively. The median times to relapse in the three groups were 30.6 weeks, 24.3 weeks, and 26.1 weeks, respectively.

Most of the relapses occurred between weeks 24 and 36 after stopping treatment, the researchers wrote. Corresponding hazard ratios for relapse were 3.02 for the taper group and 4.34 for the stop group, compared with the continuation group. In comparison to continuing treatment, the number needed to treat for one more relapse to occur during the 12-month observation period was four for tapering and three for stopping, they noted.

The study protocol called for a return to baseline treatment for any patients who relapsed in the taper and stop groups, and most patients who relapsed regained remission after restarting their baseline treatments. Among patients who had a follow-up visit after a relapse, 10 (63%) of 16 patients in the continuation group reachieved remission before the end of the study, as did 21 (62%) of 34 in the taper group and 35 (76%) of 46 in the stop group.

The most common treatments at baseline were methotrexate (76%) and tumor necrosis factor (TNF) inhibitors (32%).

The researchers also identified several baseline characteristics associated with relapse. Overall, relapse occurred more often in biologic DMARD users than in participants treated with other drugs, more often in women than men, and more often in those with a longer disease duration, higher baseline DAS28-ESR and Health Assessment Questionnaire scores, and in those who were positive for rheumatoid factor or anti–citrullinated protein antibodies.

A total of 38 serious adverse events occurred in 29 participants during the study period, but none were deemed treatment related, and none led to study withdrawal.

The study findings were limited by several factors including the lack of masking of patients and assessors and potential underestimation of disease activity, the researchers noted. Also, the study did not include radiographic data that might have been used to confirm progression; however, such data could have produced a null result and were not feasible in the study population, they wrote.

“If RETRO had been a trial to test the superiority of 100% dose continuation, compared with tapering plus rescue treatment or stopping plus rescue treatment, we would not be able to show that continuation is superior to tapering or stopping,” the researchers noted.

The study results support “an increasingly dynamic management approach in patients with rheumatoid arthritis in stable remission,” given the changing nature of RA management, that may help reduce overtreatment in many RA patients, the researchers concluded. “Furthermore, the observation that most of the patients regained remission after reintroduction of antirheumatic treatments is helpful with regard to the benefit-risk aspect of treatment reduction.”

Real-world setting serves as starting point

The RETRO study is unique in that it tried to reflect a real-life setting by enrolling patients on baseline treatment with combinations of conventional synthetic DMARDs and biologic DMARDs seen in clinical practice rather than only patients taking biologic DMARDs – primarily TNF inhibitors – as done in previous studies of tapering and stopping DMARDs, wrote Catherine L. Hill, MD, of the University of Adelaide (Australia), in an accompanying editorial. It is also “used a simple, pragmatic one-size-fits-all treatment-tapering strategy,” she wrote.

However, she emphasized that answers are needed to questions about what relapse rates are acceptable, what duration of treatment-free time is ideal, and whether benefits to the patient outweigh risks.

Dr. Hill also highlighted the issue of identifying patients who are appropriate candidates for tapering or withdrawal. Stricter remission criteria may not be feasible in routine practice, and so “the development of algorithms to guide patient selection is likely to be the most practical way forward for clinicians and patients,” she wrote.

“Contemplation of treatment tapering or discontinuation in some patients with rheumatoid arthritis is remarkable and a measure of how far treatments have advanced,” Dr. Hill wrote. “However, further work to address outstanding questions on who should taper and how best to do it is still required,” she concluded.

The study received no outside funding. Lead author Dr. Tascilar disclosed lecture fees from Gilead and Union Chimique Belge; several coauthors disclosed relationships with multiple companies outside the current study. Dr. Hill had no financial conflicts to disclose.

About half of patients with rheumatoid arthritis who taper or stop disease-modifying antirheumatic drugs (DMARDs) retain stable remission after 12 months, and a majority of those who do relapse regain remission when back on their original treatments, according to data from the open-label, randomized Rheumatoid Arthritis in Ongoing Remission (RETRO) study.

“Currently, 40%-50% of patients with rheumatoid arthritis reach stable remission,” as a result of factors including earlier diagnosis and a wider range of treatments, Koray Tascilar, MD, of Friedrich Alexander University Erlangen-Nuremberg (Germany) and colleagues wrote in their publication of the RETRO trial results in Lancet Rheumatology.

Previous studies have suggested that patients with RA in sustained remission may be able to taper or withdraw treatment, but data from randomized trials are limited, the researchers said.

In the RETRO trial, researchers compared three strategies for RA patients in remission, which was defined as <2.6 on the 28-joint Disease Activity Score with erythrocyte sedimentation rate (DAS28-ESR). They randomized 100 adults to continue DMARDs and glucocorticoids, 102 to taper DMARDs and glucocorticoids to half their prior doses, and 101 to reduce the doses to half for 6 months and then stop DMARDs. Patients were enrolled between May 26, 2010, and May 29, 2018, from 14 treatment centers in Germany. The final analysis included 282 patients; 92 in the continuation group, 93 in the taper group, and 96 in the stop group. The mean age of the patients was 56.5 years, and 59% were women. The mean duration of RA was 7.4 years, and the mean duration of remission was 20 months.

Overall, at 12 months, 61% of the patients remained in remission without relapse; 81.2% of the continuation group, 58.6% of the taper group, and 43.3% of the stop group. Relapses occurred in 17%, 43%, and 55% of patients in the continuation, taper, and stop groups, respectively. The median times to relapse in the three groups were 30.6 weeks, 24.3 weeks, and 26.1 weeks, respectively.

Most of the relapses occurred between weeks 24 and 36 after stopping treatment, the researchers wrote. Corresponding hazard ratios for relapse were 3.02 for the taper group and 4.34 for the stop group, compared with the continuation group. In comparison to continuing treatment, the number needed to treat for one more relapse to occur during the 12-month observation period was four for tapering and three for stopping, they noted.

The study protocol called for a return to baseline treatment for any patients who relapsed in the taper and stop groups, and most patients who relapsed regained remission after restarting their baseline treatments. Among patients who had a follow-up visit after a relapse, 10 (63%) of 16 patients in the continuation group reachieved remission before the end of the study, as did 21 (62%) of 34 in the taper group and 35 (76%) of 46 in the stop group.

The most common treatments at baseline were methotrexate (76%) and tumor necrosis factor (TNF) inhibitors (32%).

The researchers also identified several baseline characteristics associated with relapse. Overall, relapse occurred more often in biologic DMARD users than in participants treated with other drugs, more often in women than men, and more often in those with a longer disease duration, higher baseline DAS28-ESR and Health Assessment Questionnaire scores, and in those who were positive for rheumatoid factor or anti–citrullinated protein antibodies.

A total of 38 serious adverse events occurred in 29 participants during the study period, but none were deemed treatment related, and none led to study withdrawal.

The study findings were limited by several factors including the lack of masking of patients and assessors and potential underestimation of disease activity, the researchers noted. Also, the study did not include radiographic data that might have been used to confirm progression; however, such data could have produced a null result and were not feasible in the study population, they wrote.

“If RETRO had been a trial to test the superiority of 100% dose continuation, compared with tapering plus rescue treatment or stopping plus rescue treatment, we would not be able to show that continuation is superior to tapering or stopping,” the researchers noted.

The study results support “an increasingly dynamic management approach in patients with rheumatoid arthritis in stable remission,” given the changing nature of RA management, that may help reduce overtreatment in many RA patients, the researchers concluded. “Furthermore, the observation that most of the patients regained remission after reintroduction of antirheumatic treatments is helpful with regard to the benefit-risk aspect of treatment reduction.”

Real-world setting serves as starting point

The RETRO study is unique in that it tried to reflect a real-life setting by enrolling patients on baseline treatment with combinations of conventional synthetic DMARDs and biologic DMARDs seen in clinical practice rather than only patients taking biologic DMARDs – primarily TNF inhibitors – as done in previous studies of tapering and stopping DMARDs, wrote Catherine L. Hill, MD, of the University of Adelaide (Australia), in an accompanying editorial. It is also “used a simple, pragmatic one-size-fits-all treatment-tapering strategy,” she wrote.

However, she emphasized that answers are needed to questions about what relapse rates are acceptable, what duration of treatment-free time is ideal, and whether benefits to the patient outweigh risks.

Dr. Hill also highlighted the issue of identifying patients who are appropriate candidates for tapering or withdrawal. Stricter remission criteria may not be feasible in routine practice, and so “the development of algorithms to guide patient selection is likely to be the most practical way forward for clinicians and patients,” she wrote.

“Contemplation of treatment tapering or discontinuation in some patients with rheumatoid arthritis is remarkable and a measure of how far treatments have advanced,” Dr. Hill wrote. “However, further work to address outstanding questions on who should taper and how best to do it is still required,” she concluded.

The study received no outside funding. Lead author Dr. Tascilar disclosed lecture fees from Gilead and Union Chimique Belge; several coauthors disclosed relationships with multiple companies outside the current study. Dr. Hill had no financial conflicts to disclose.

To the Editor:

Pityriasis rubra pilaris (PRP) is a rare inflammatory dermatosis of unknown etiology characterized by erythematosquamous salmon-colored plaques with well-demarcated islands of unaffected skin and hyperkeratotic follicles.¹ In the United States, an incidence of 1 in 3500to 5000 patients presenting to dermatology clinics has been reported.² Pityriasis rubra pilaris has several subtypes and variability in presentation that can make accurate and timely diagnosis challenging.^3-5 Herein, we present a case of PRP with complex diagnostic and therapeutic challenges.

A 22-year-old woman presented with symmetrical, well-demarcated, hyperkeratotic, erythematous plaques with a carnauba wax–like appearance on the palms (Figure 1), soles, elbows, and trunk covering approximately 5% of the body surface area. Two weeks prior to presentation, she experienced an upper respiratory tract infection without any treatment and subsequently developed redness on the palms, which became very hard and scaly. The redness then spread to the elbows, soles, and trunk. She reported itching as well as pain in areas of fissuring. Hand mobility became restricted due to thick scale.

The patient’s medical history was notable for suspected psoriasis 9 years prior, but there were no records or biopsy reports that could be obtained to confirm the diagnosis. She also reported a similar skin condition in her father, which also was diagnosed as psoriasis, but this diagnosis could not be verified.

Although the morphology of the lesions was most consistent with localized PRP, atypical psoriasis, palmoplantar keratoderma (PPK), and erythroderma progressive symmetrica (EPS) also were considered given the personal and family history of suspected psoriasis. A biopsy could not be obtained due to an insurance issue. She was started on clobetasol cream 0.05% and ointment. At 2-week follow-up, her condition remained unchanged. Empiric systemic treatment was discussed, which would potentially work for diagnoses of both PRP and psoriasis. Due to the history of psoriasis and level of discomfort, cyclosporine 300 mg once daily was started to gain rapid control of the disease. Methotrexate also was considered due to its efficacy and economic considerations but was not selected due to patient concerns about the medication.

After 10 weeks of cyclosporine treatment, our patient showed some improvement of the skin with decreased scale and flattening of plaques but not complete resolution. At this point, a biopsy was able to be obtained with prior authorization. A 4-mm punch biopsy of the right flank demonstrated a psoriasiform and papillated epidermis with multifocally capped, compact parakeratosis and minimal lymphocytic infiltrate consistent with PRP. Although EPS also was on the histologic differential, clinical history was more consistent with a diagnosis of PRP. There was some minimal improvement with cyclosporine, but with the diagnosis of PRP confirmed, a systemic retinoid became the treatment of choice. Although acitretin is the preferred treatment for PRP, given that pregnancy would be contraindicated during and for 3 years following acitretin therapy, a trial of isotretinoin 40 mg once daily was started due to its shorter half-life compared to acitretin and was continued for 3 months (Figure 2).^6,7

The diagnosis of PRP often can be challenging given the variety of clinical presentations. This case was an atypical presentation of PRP with several learning points, as our patient’s condition did not fit perfectly into any of the 6 types of PRP. The age of onset was atypical at 22 years old. Pityriasis rubra pilaris typically presents with a bimodal age distribution, appearing either in the first decade or the fifth to sixth decades of life.^3,8 Her clinical presentation was atypical for adult-onset types I and II, which typically present with cephalocaudal progression or ichthyosiform dermatitis, respectively. Her presentation also was atypical for juvenile onset in types III, IV, and V, which tend to present in younger children and with different physical examination findings.^3,8

The morphology of our patient’s lesions also was atypical for PRP, PPK, EPS, and psoriasis. The clinical presentation had features of these entities with erythema, fissuring, xerosis, carnauba wax–like appearance, symmetric scale, and well-demarcated plaques. Although these findings are not mutually exclusive, their combined presentation is atypical. Coupled with the ambiguous family history of similar skin disease in the patient’s father, the discussion of genodermatoses, particularly PPK, further confounded the diagnosis.^4,9 When evaluating for PRP, especially with any family history of skin conditions, genodermatoses should be considered. Furthermore, our patient’s remote and unverifiable history of psoriasis serves as a cautionary reminder that prior diagnoses and medical history always should be reasonably scrutinized. Additionally, a drug-induced PRP eruption also should be considered. Although our patient received no medical treatment for the upper respiratory tract infection prior to the onset of PRP, there have been several reports of drug-induced PRP.^10-12

The therapeutic challenge in this case is one that often is encountered in clinical practice. The health care system often may pose a barrier to diagnosis by inhibiting particular services required for adequate patient care. For our patient, diagnosis was delayed by several weeks due to difficulties obtaining a diagnostic skin biopsy. When faced with challenges from health care infrastructure, creativity with treatment options, such as finding an empiric treatment option (cyclosporine in this case), must be considered.

Systemic retinoids have been found to be efficacious treatment options for PRP, but when dealing with a woman of reproductive age, reproductive preferences must be discussed before identifying an appropriate treatment regimen.^1,13-15 The half-life of acitretin compared to isotretinoin is 2 days vs 22 hours.^6,16 With alcohol consumption, acitretin can be metabolized to etretinate, which has a half-life of 120 days.¹⁷ In our patient, isotretinoin was a more manageable option to allow for greater reproductive freedom upon treatment completion.

To the Editor:

Pityriasis rubra pilaris (PRP) is a rare inflammatory dermatosis of unknown etiology characterized by erythematosquamous salmon-colored plaques with well-demarcated islands of unaffected skin and hyperkeratotic follicles.¹ In the United States, an incidence of 1 in 3500to 5000 patients presenting to dermatology clinics has been reported.² Pityriasis rubra pilaris has several subtypes and variability in presentation that can make accurate and timely diagnosis challenging.^3-5 Herein, we present a case of PRP with complex diagnostic and therapeutic challenges.

A 22-year-old woman presented with symmetrical, well-demarcated, hyperkeratotic, erythematous plaques with a carnauba wax–like appearance on the palms (Figure 1), soles, elbows, and trunk covering approximately 5% of the body surface area. Two weeks prior to presentation, she experienced an upper respiratory tract infection without any treatment and subsequently developed redness on the palms, which became very hard and scaly. The redness then spread to the elbows, soles, and trunk. She reported itching as well as pain in areas of fissuring. Hand mobility became restricted due to thick scale.

The patient’s medical history was notable for suspected psoriasis 9 years prior, but there were no records or biopsy reports that could be obtained to confirm the diagnosis. She also reported a similar skin condition in her father, which also was diagnosed as psoriasis, but this diagnosis could not be verified.

Although the morphology of the lesions was most consistent with localized PRP, atypical psoriasis, palmoplantar keratoderma (PPK), and erythroderma progressive symmetrica (EPS) also were considered given the personal and family history of suspected psoriasis. A biopsy could not be obtained due to an insurance issue. She was started on clobetasol cream 0.05% and ointment. At 2-week follow-up, her condition remained unchanged. Empiric systemic treatment was discussed, which would potentially work for diagnoses of both PRP and psoriasis. Due to the history of psoriasis and level of discomfort, cyclosporine 300 mg once daily was started to gain rapid control of the disease. Methotrexate also was considered due to its efficacy and economic considerations but was not selected due to patient concerns about the medication.

After 10 weeks of cyclosporine treatment, our patient showed some improvement of the skin with decreased scale and flattening of plaques but not complete resolution. At this point, a biopsy was able to be obtained with prior authorization. A 4-mm punch biopsy of the right flank demonstrated a psoriasiform and papillated epidermis with multifocally capped, compact parakeratosis and minimal lymphocytic infiltrate consistent with PRP. Although EPS also was on the histologic differential, clinical history was more consistent with a diagnosis of PRP. There was some minimal improvement with cyclosporine, but with the diagnosis of PRP confirmed, a systemic retinoid became the treatment of choice. Although acitretin is the preferred treatment for PRP, given that pregnancy would be contraindicated during and for 3 years following acitretin therapy, a trial of isotretinoin 40 mg once daily was started due to its shorter half-life compared to acitretin and was continued for 3 months (Figure 2).^6,7

The diagnosis of PRP often can be challenging given the variety of clinical presentations. This case was an atypical presentation of PRP with several learning points, as our patient’s condition did not fit perfectly into any of the 6 types of PRP. The age of onset was atypical at 22 years old. Pityriasis rubra pilaris typically presents with a bimodal age distribution, appearing either in the first decade or the fifth to sixth decades of life.^3,8 Her clinical presentation was atypical for adult-onset types I and II, which typically present with cephalocaudal progression or ichthyosiform dermatitis, respectively. Her presentation also was atypical for juvenile onset in types III, IV, and V, which tend to present in younger children and with different physical examination findings.^3,8

The morphology of our patient’s lesions also was atypical for PRP, PPK, EPS, and psoriasis. The clinical presentation had features of these entities with erythema, fissuring, xerosis, carnauba wax–like appearance, symmetric scale, and well-demarcated plaques. Although these findings are not mutually exclusive, their combined presentation is atypical. Coupled with the ambiguous family history of similar skin disease in the patient’s father, the discussion of genodermatoses, particularly PPK, further confounded the diagnosis.^4,9 When evaluating for PRP, especially with any family history of skin conditions, genodermatoses should be considered. Furthermore, our patient’s remote and unverifiable history of psoriasis serves as a cautionary reminder that prior diagnoses and medical history always should be reasonably scrutinized. Additionally, a drug-induced PRP eruption also should be considered. Although our patient received no medical treatment for the upper respiratory tract infection prior to the onset of PRP, there have been several reports of drug-induced PRP.^10-12

The therapeutic challenge in this case is one that often is encountered in clinical practice. The health care system often may pose a barrier to diagnosis by inhibiting particular services required for adequate patient care. For our patient, diagnosis was delayed by several weeks due to difficulties obtaining a diagnostic skin biopsy. When faced with challenges from health care infrastructure, creativity with treatment options, such as finding an empiric treatment option (cyclosporine in this case), must be considered.

Systemic retinoids have been found to be efficacious treatment options for PRP, but when dealing with a woman of reproductive age, reproductive preferences must be discussed before identifying an appropriate treatment regimen.^1,13-15 The half-life of acitretin compared to isotretinoin is 2 days vs 22 hours.^6,16 With alcohol consumption, acitretin can be metabolized to etretinate, which has a half-life of 120 days.¹⁷ In our patient, isotretinoin was a more manageable option to allow for greater reproductive freedom upon treatment completion.

To the Editor:

Pityriasis rubra pilaris (PRP) is a rare inflammatory dermatosis of unknown etiology characterized by erythematosquamous salmon-colored plaques with well-demarcated islands of unaffected skin and hyperkeratotic follicles.¹ In the United States, an incidence of 1 in 3500to 5000 patients presenting to dermatology clinics has been reported.² Pityriasis rubra pilaris has several subtypes and variability in presentation that can make accurate and timely diagnosis challenging.^3-5 Herein, we present a case of PRP with complex diagnostic and therapeutic challenges.

A 22-year-old woman presented with symmetrical, well-demarcated, hyperkeratotic, erythematous plaques with a carnauba wax–like appearance on the palms (Figure 1), soles, elbows, and trunk covering approximately 5% of the body surface area. Two weeks prior to presentation, she experienced an upper respiratory tract infection without any treatment and subsequently developed redness on the palms, which became very hard and scaly. The redness then spread to the elbows, soles, and trunk. She reported itching as well as pain in areas of fissuring. Hand mobility became restricted due to thick scale.

The patient’s medical history was notable for suspected psoriasis 9 years prior, but there were no records or biopsy reports that could be obtained to confirm the diagnosis. She also reported a similar skin condition in her father, which also was diagnosed as psoriasis, but this diagnosis could not be verified.

Although the morphology of the lesions was most consistent with localized PRP, atypical psoriasis, palmoplantar keratoderma (PPK), and erythroderma progressive symmetrica (EPS) also were considered given the personal and family history of suspected psoriasis. A biopsy could not be obtained due to an insurance issue. She was started on clobetasol cream 0.05% and ointment. At 2-week follow-up, her condition remained unchanged. Empiric systemic treatment was discussed, which would potentially work for diagnoses of both PRP and psoriasis. Due to the history of psoriasis and level of discomfort, cyclosporine 300 mg once daily was started to gain rapid control of the disease. Methotrexate also was considered due to its efficacy and economic considerations but was not selected due to patient concerns about the medication.

After 10 weeks of cyclosporine treatment, our patient showed some improvement of the skin with decreased scale and flattening of plaques but not complete resolution. At this point, a biopsy was able to be obtained with prior authorization. A 4-mm punch biopsy of the right flank demonstrated a psoriasiform and papillated epidermis with multifocally capped, compact parakeratosis and minimal lymphocytic infiltrate consistent with PRP. Although EPS also was on the histologic differential, clinical history was more consistent with a diagnosis of PRP. There was some minimal improvement with cyclosporine, but with the diagnosis of PRP confirmed, a systemic retinoid became the treatment of choice. Although acitretin is the preferred treatment for PRP, given that pregnancy would be contraindicated during and for 3 years following acitretin therapy, a trial of isotretinoin 40 mg once daily was started due to its shorter half-life compared to acitretin and was continued for 3 months (Figure 2).^6,7

The diagnosis of PRP often can be challenging given the variety of clinical presentations. This case was an atypical presentation of PRP with several learning points, as our patient’s condition did not fit perfectly into any of the 6 types of PRP. The age of onset was atypical at 22 years old. Pityriasis rubra pilaris typically presents with a bimodal age distribution, appearing either in the first decade or the fifth to sixth decades of life.^3,8 Her clinical presentation was atypical for adult-onset types I and II, which typically present with cephalocaudal progression or ichthyosiform dermatitis, respectively. Her presentation also was atypical for juvenile onset in types III, IV, and V, which tend to present in younger children and with different physical examination findings.^3,8

The morphology of our patient’s lesions also was atypical for PRP, PPK, EPS, and psoriasis. The clinical presentation had features of these entities with erythema, fissuring, xerosis, carnauba wax–like appearance, symmetric scale, and well-demarcated plaques. Although these findings are not mutually exclusive, their combined presentation is atypical. Coupled with the ambiguous family history of similar skin disease in the patient’s father, the discussion of genodermatoses, particularly PPK, further confounded the diagnosis.^4,9 When evaluating for PRP, especially with any family history of skin conditions, genodermatoses should be considered. Furthermore, our patient’s remote and unverifiable history of psoriasis serves as a cautionary reminder that prior diagnoses and medical history always should be reasonably scrutinized. Additionally, a drug-induced PRP eruption also should be considered. Although our patient received no medical treatment for the upper respiratory tract infection prior to the onset of PRP, there have been several reports of drug-induced PRP.^10-12

The therapeutic challenge in this case is one that often is encountered in clinical practice. The health care system often may pose a barrier to diagnosis by inhibiting particular services required for adequate patient care. For our patient, diagnosis was delayed by several weeks due to difficulties obtaining a diagnostic skin biopsy. When faced with challenges from health care infrastructure, creativity with treatment options, such as finding an empiric treatment option (cyclosporine in this case), must be considered.

Systemic retinoids have been found to be efficacious treatment options for PRP, but when dealing with a woman of reproductive age, reproductive preferences must be discussed before identifying an appropriate treatment regimen.^1,13-15 The half-life of acitretin compared to isotretinoin is 2 days vs 22 hours.^6,16 With alcohol consumption, acitretin can be metabolized to etretinate, which has a half-life of 120 days.¹⁷ In our patient, isotretinoin was a more manageable option to allow for greater reproductive freedom upon treatment completion.

Exhaustion. Defeat. Hopelessness. Physicians, nurses, physician assistants, and nurse practitioners are overwhelmed with burnout.

The recent round of COVID-19 is more frustrating than the first, with scientific evidence supporting ways we can prevent disease and disease progression. The health care team is no longer viewed as heroes but as the enemy, fraudulently proposing a vaccine and painting a fictional story of death, though it’s all true. The daily educational battle with patients and family members creates a challenging environment that cultivates hopelessness.

Clinicians are physically exhausted from the numerous COVID cases. Gone are the medical patients we trained for, who either remain home and risk their health or lack access to medical providers because of excessive wait times. Empathy for COVID patients is being tested even more with this new surge, and without the two-way bond of trust, clinicians are running out of fuel. Anger and distrust regarding vaccination guidance dominate the interaction when patients present demanding urgent intervention, while clinicians know that more than 95% of hospitalized patients are unvaccinated.

The struggle to find the commitment to medicine and serving patients is made worse by the pandemic fog and loss of trust from patients. Every day, health care teams risk their personal well-being to provide medical care and intervention. Not by choice do we gown up, mask up, and glove up. Each time we enter a COVID patient’s room, we expose ourselves and risk our own lives and the lives of our families for the patients who have elected to ignore medical guidance.

This national wave of resistance to vaccination is spurring an exodus from health care. Physicians are retiring early and physician assistants and nurse practitioners are seeking non–patient-facing positions to improve their own wellness and balance. A national nursing shortage is impacting patients seeking care in every medical discipline. The underlying wave of exhaustion and frustration has not completely destroyed their empathy but has depleted their drive.

How can we regain this drive amid exhausting work hours and angry patients?

As much as we have heard it, we need to protect our time to recharge. The demand to pick up extra shifts and support our colleagues has affected our personal health. Setting boundaries and building time for exercise, meditation, and connecting with family is essential for survival. Mental health is key to retaining empathy and finding hope. Education is one path to reigniting the fires of critical thinking and commitment to patient care – consider precepting students to support the growth of health care teams. Memories of patient care before this pandemic give us the hope that there is light at the end of this tunnel.

Dr. Gadalla is a hospitalist at Treasure Coast Hospitalists in Port St. Lucie, Fla. She is a member of the Hospitalist’s editorial advisory board and also serves as a physician assistant program director at South University in West Palm Beach, Fla. She disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.

Exhaustion. Defeat. Hopelessness. Physicians, nurses, physician assistants, and nurse practitioners are overwhelmed with burnout.

The recent round of COVID-19 is more frustrating than the first, with scientific evidence supporting ways we can prevent disease and disease progression. The health care team is no longer viewed as heroes but as the enemy, fraudulently proposing a vaccine and painting a fictional story of death, though it’s all true. The daily educational battle with patients and family members creates a challenging environment that cultivates hopelessness.

Clinicians are physically exhausted from the numerous COVID cases. Gone are the medical patients we trained for, who either remain home and risk their health or lack access to medical providers because of excessive wait times. Empathy for COVID patients is being tested even more with this new surge, and without the two-way bond of trust, clinicians are running out of fuel. Anger and distrust regarding vaccination guidance dominate the interaction when patients present demanding urgent intervention, while clinicians know that more than 95% of hospitalized patients are unvaccinated.

The struggle to find the commitment to medicine and serving patients is made worse by the pandemic fog and loss of trust from patients. Every day, health care teams risk their personal well-being to provide medical care and intervention. Not by choice do we gown up, mask up, and glove up. Each time we enter a COVID patient’s room, we expose ourselves and risk our own lives and the lives of our families for the patients who have elected to ignore medical guidance.

This national wave of resistance to vaccination is spurring an exodus from health care. Physicians are retiring early and physician assistants and nurse practitioners are seeking non–patient-facing positions to improve their own wellness and balance. A national nursing shortage is impacting patients seeking care in every medical discipline. The underlying wave of exhaustion and frustration has not completely destroyed their empathy but has depleted their drive.

How can we regain this drive amid exhausting work hours and angry patients?

As much as we have heard it, we need to protect our time to recharge. The demand to pick up extra shifts and support our colleagues has affected our personal health. Setting boundaries and building time for exercise, meditation, and connecting with family is essential for survival. Mental health is key to retaining empathy and finding hope. Education is one path to reigniting the fires of critical thinking and commitment to patient care – consider precepting students to support the growth of health care teams. Memories of patient care before this pandemic give us the hope that there is light at the end of this tunnel.

Dr. Gadalla is a hospitalist at Treasure Coast Hospitalists in Port St. Lucie, Fla. She is a member of the Hospitalist’s editorial advisory board and also serves as a physician assistant program director at South University in West Palm Beach, Fla. She disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.

Exhaustion. Defeat. Hopelessness. Physicians, nurses, physician assistants, and nurse practitioners are overwhelmed with burnout.

The recent round of COVID-19 is more frustrating than the first, with scientific evidence supporting ways we can prevent disease and disease progression. The health care team is no longer viewed as heroes but as the enemy, fraudulently proposing a vaccine and painting a fictional story of death, though it’s all true. The daily educational battle with patients and family members creates a challenging environment that cultivates hopelessness.

Clinicians are physically exhausted from the numerous COVID cases. Gone are the medical patients we trained for, who either remain home and risk their health or lack access to medical providers because of excessive wait times. Empathy for COVID patients is being tested even more with this new surge, and without the two-way bond of trust, clinicians are running out of fuel. Anger and distrust regarding vaccination guidance dominate the interaction when patients present demanding urgent intervention, while clinicians know that more than 95% of hospitalized patients are unvaccinated.

The struggle to find the commitment to medicine and serving patients is made worse by the pandemic fog and loss of trust from patients. Every day, health care teams risk their personal well-being to provide medical care and intervention. Not by choice do we gown up, mask up, and glove up. Each time we enter a COVID patient’s room, we expose ourselves and risk our own lives and the lives of our families for the patients who have elected to ignore medical guidance.

This national wave of resistance to vaccination is spurring an exodus from health care. Physicians are retiring early and physician assistants and nurse practitioners are seeking non–patient-facing positions to improve their own wellness and balance. A national nursing shortage is impacting patients seeking care in every medical discipline. The underlying wave of exhaustion and frustration has not completely destroyed their empathy but has depleted their drive.

How can we regain this drive amid exhausting work hours and angry patients?

As much as we have heard it, we need to protect our time to recharge. The demand to pick up extra shifts and support our colleagues has affected our personal health. Setting boundaries and building time for exercise, meditation, and connecting with family is essential for survival. Mental health is key to retaining empathy and finding hope. Education is one path to reigniting the fires of critical thinking and commitment to patient care – consider precepting students to support the growth of health care teams. Memories of patient care before this pandemic give us the hope that there is light at the end of this tunnel.

Dr. Gadalla is a hospitalist at Treasure Coast Hospitalists in Port St. Lucie, Fla. She is a member of the Hospitalist’s editorial advisory board and also serves as a physician assistant program director at South University in West Palm Beach, Fla. She disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.