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Phase 3 trial supports topical JAK inhibitor for AD in young children
BERLIN – as previously shown in adolescents and adults for whom it already has an approved indication.
In this study – TRUE-AD3 – systemic exposure to ruxolitinib, which is selective for JAK1 and 2, was followed closely, and the low mean plasma concentrations “suggest systemic JAK inhibition is highly unlikely,” Lawrence F. Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, said at the annual congress of the European Academy of Dermatology and Venereology.
For example, at a plasma concentration no greater than 27 nM in both younger and older patients at 4 weeks and again at 8 weeks, the systemic exposure was about a tenth of that (281 nM) previously associated with myelosuppression, he reported.
Given the boxed warning for oral JAK inhibitors, which was based largely on a 2022 study in adults with rheumatoid arthritis that associated tofacitinib, a nonspecific JAK inhibitor, with an increased risk of thrombotic events in adults already at risk for these events, safety was a focus of this phase 3 trial. The boxed warning is also in the labeling for topical ruxolitinib, 1.5% (Opzelura), approved for treating to mild to moderate atopic dermatitis in patients 12 years of age and older.
Dr. Eichenfield said there were no significant safety signals in the younger pediatric population. “There were no treatment-emergent adverse events suggestive of systemic JAK inhibition,” he said. This not only included the absence of serious infections, cardiac events, thromboses, or malignancies, but there was no signal of hematologic abnormalities, such as change in hemoglobin or neutrophil count.
Application site reactions
Rather, in the study of children ages 2-11, the only adverse events associated with topical ruxolitinib not observed in the control arm, which received the vehicle alone, were application site reactions, such as pain, erythema, and irritation. None of these occurred in more than 3% of those randomized to ruxolitinib regardless of dose.
Overall, in the trial, which randomized 329 patients ages from 2 to under 12 years with mild to moderate AD to ruxolitinib 1.5% cream, ruxolitinib 0.75% cream, or vehicle in a 2:2:1 fashion, there were just two (0.8%) discontinuations in the ruxolitinib groups (one in each dosing arm). There were none in the vehicle arm.
The safety supports an expansion of the AD indication for topical ruxolitinib in young children, because the rates of response were very similar to that seen in adolescents and adults in the previously published TRUE AD-1 and TRUE AD-2 trials, he said.
For the primary endpoint of Investigator’s Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) with at least a 2 grade improvement in IGA score from baseline, the response rates were 56.5%, 36.6%, and 10.8% for ruxolitinib 1.5%, ruxolitinib 0.75%, and vehicle respectively, at 8 weeks (P < .0001 for both doses relative to vehicle).
For the secondary efficacy endpoint of 75% or greater clearance on the Eczema Area and Severity Index, the rates were 67.2%, 51.5%, and 15.4%, for ruxolitinib 1.5%, ruxolitinib 0.75%, and vehicle respectively. Again, the advantage of both doses of ruxolitinib relative to vehicle was highly statistically significant (P < .0001).
Control of itch, evaluated with the Numerical Rating Scale was only evaluated in children 6-2 because of concern of the reliability of reporting in younger children. Control was defined as at least a 4-point improvement from baseline. It was achieved by 43.4%, 37.5%, and 29.7% by week 8 in the arms receiving the higher dose of ruxolitinib, the lower dose, and vehicle, respectively. The median time to achieving itch control was 11 days, 13 days, and 23 days, respectively. For all of these endpoints, the separation of the curves was readily apparent within the first 2 weeks.
The efficacy and tolerability of ruxolitinib appeared to be similar in younger children (ages 2-6) relative to older children.
Extension study in children near completion
Most of the patients who participated in TRUE AD-3 have been rolled over to the open-label extension trial, which is nearing completion. Those originally randomized to vehicle have been rerandomized to the lower or higher dose of ruxolitinib.
While this trial was focused on ruxolitinib as monotherapy, Thrasyvoulos Tzellos, MD, head of the department of dermatology, Nordland Hospital Trust, Bødo, Norway, questioned whether this is will be how it will be used in clinical practice. With the increasing array of therapies for AD, the “concept of combination therapy becomes more and more relevant,” he said after Dr. Eichenfield’s presentation.
Questioning whether an effective nonsteroidal anti-inflammatory agent like ruxolitinib should be considered a first-line treatment in mild disease or an adjunctive treatment for AD of any severity, he suggested that it might be best considered within a combination.
Dr. Eichenfield agreed. “Once we get the drug approved in a controlled trial, I think we then figure out how to use it in clinical practice.” Based on his own use of ruxolitinib in adults, he noted that he has not seen this drug replace other therapies so much as provide another option for control.
“We have an increasing armamentarium of drugs to use for involvement in different areas of the body in order to get more long-term control of disease,” he said. As an effective topical nonsteroidal drug, he believes its addition to clinical care in younger children, if approved, will be meaningful.
Dr. Eichenfield disclosed financial relationships with more multiple pharmaceutical companies, including Incyte, the manufacturer of ruxolitinib cream that provided funding for the True-AD trials. Dr. Tzellos reported financial relationships with AbbVie and UCB.
BERLIN – as previously shown in adolescents and adults for whom it already has an approved indication.
In this study – TRUE-AD3 – systemic exposure to ruxolitinib, which is selective for JAK1 and 2, was followed closely, and the low mean plasma concentrations “suggest systemic JAK inhibition is highly unlikely,” Lawrence F. Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, said at the annual congress of the European Academy of Dermatology and Venereology.
For example, at a plasma concentration no greater than 27 nM in both younger and older patients at 4 weeks and again at 8 weeks, the systemic exposure was about a tenth of that (281 nM) previously associated with myelosuppression, he reported.
Given the boxed warning for oral JAK inhibitors, which was based largely on a 2022 study in adults with rheumatoid arthritis that associated tofacitinib, a nonspecific JAK inhibitor, with an increased risk of thrombotic events in adults already at risk for these events, safety was a focus of this phase 3 trial. The boxed warning is also in the labeling for topical ruxolitinib, 1.5% (Opzelura), approved for treating to mild to moderate atopic dermatitis in patients 12 years of age and older.
Dr. Eichenfield said there were no significant safety signals in the younger pediatric population. “There were no treatment-emergent adverse events suggestive of systemic JAK inhibition,” he said. This not only included the absence of serious infections, cardiac events, thromboses, or malignancies, but there was no signal of hematologic abnormalities, such as change in hemoglobin or neutrophil count.
Application site reactions
Rather, in the study of children ages 2-11, the only adverse events associated with topical ruxolitinib not observed in the control arm, which received the vehicle alone, were application site reactions, such as pain, erythema, and irritation. None of these occurred in more than 3% of those randomized to ruxolitinib regardless of dose.
Overall, in the trial, which randomized 329 patients ages from 2 to under 12 years with mild to moderate AD to ruxolitinib 1.5% cream, ruxolitinib 0.75% cream, or vehicle in a 2:2:1 fashion, there were just two (0.8%) discontinuations in the ruxolitinib groups (one in each dosing arm). There were none in the vehicle arm.
The safety supports an expansion of the AD indication for topical ruxolitinib in young children, because the rates of response were very similar to that seen in adolescents and adults in the previously published TRUE AD-1 and TRUE AD-2 trials, he said.
For the primary endpoint of Investigator’s Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) with at least a 2 grade improvement in IGA score from baseline, the response rates were 56.5%, 36.6%, and 10.8% for ruxolitinib 1.5%, ruxolitinib 0.75%, and vehicle respectively, at 8 weeks (P < .0001 for both doses relative to vehicle).
For the secondary efficacy endpoint of 75% or greater clearance on the Eczema Area and Severity Index, the rates were 67.2%, 51.5%, and 15.4%, for ruxolitinib 1.5%, ruxolitinib 0.75%, and vehicle respectively. Again, the advantage of both doses of ruxolitinib relative to vehicle was highly statistically significant (P < .0001).
Control of itch, evaluated with the Numerical Rating Scale was only evaluated in children 6-2 because of concern of the reliability of reporting in younger children. Control was defined as at least a 4-point improvement from baseline. It was achieved by 43.4%, 37.5%, and 29.7% by week 8 in the arms receiving the higher dose of ruxolitinib, the lower dose, and vehicle, respectively. The median time to achieving itch control was 11 days, 13 days, and 23 days, respectively. For all of these endpoints, the separation of the curves was readily apparent within the first 2 weeks.
The efficacy and tolerability of ruxolitinib appeared to be similar in younger children (ages 2-6) relative to older children.
Extension study in children near completion
Most of the patients who participated in TRUE AD-3 have been rolled over to the open-label extension trial, which is nearing completion. Those originally randomized to vehicle have been rerandomized to the lower or higher dose of ruxolitinib.
While this trial was focused on ruxolitinib as monotherapy, Thrasyvoulos Tzellos, MD, head of the department of dermatology, Nordland Hospital Trust, Bødo, Norway, questioned whether this is will be how it will be used in clinical practice. With the increasing array of therapies for AD, the “concept of combination therapy becomes more and more relevant,” he said after Dr. Eichenfield’s presentation.
Questioning whether an effective nonsteroidal anti-inflammatory agent like ruxolitinib should be considered a first-line treatment in mild disease or an adjunctive treatment for AD of any severity, he suggested that it might be best considered within a combination.
Dr. Eichenfield agreed. “Once we get the drug approved in a controlled trial, I think we then figure out how to use it in clinical practice.” Based on his own use of ruxolitinib in adults, he noted that he has not seen this drug replace other therapies so much as provide another option for control.
“We have an increasing armamentarium of drugs to use for involvement in different areas of the body in order to get more long-term control of disease,” he said. As an effective topical nonsteroidal drug, he believes its addition to clinical care in younger children, if approved, will be meaningful.
Dr. Eichenfield disclosed financial relationships with more multiple pharmaceutical companies, including Incyte, the manufacturer of ruxolitinib cream that provided funding for the True-AD trials. Dr. Tzellos reported financial relationships with AbbVie and UCB.
BERLIN – as previously shown in adolescents and adults for whom it already has an approved indication.
In this study – TRUE-AD3 – systemic exposure to ruxolitinib, which is selective for JAK1 and 2, was followed closely, and the low mean plasma concentrations “suggest systemic JAK inhibition is highly unlikely,” Lawrence F. Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, said at the annual congress of the European Academy of Dermatology and Venereology.
For example, at a plasma concentration no greater than 27 nM in both younger and older patients at 4 weeks and again at 8 weeks, the systemic exposure was about a tenth of that (281 nM) previously associated with myelosuppression, he reported.
Given the boxed warning for oral JAK inhibitors, which was based largely on a 2022 study in adults with rheumatoid arthritis that associated tofacitinib, a nonspecific JAK inhibitor, with an increased risk of thrombotic events in adults already at risk for these events, safety was a focus of this phase 3 trial. The boxed warning is also in the labeling for topical ruxolitinib, 1.5% (Opzelura), approved for treating to mild to moderate atopic dermatitis in patients 12 years of age and older.
Dr. Eichenfield said there were no significant safety signals in the younger pediatric population. “There were no treatment-emergent adverse events suggestive of systemic JAK inhibition,” he said. This not only included the absence of serious infections, cardiac events, thromboses, or malignancies, but there was no signal of hematologic abnormalities, such as change in hemoglobin or neutrophil count.
Application site reactions
Rather, in the study of children ages 2-11, the only adverse events associated with topical ruxolitinib not observed in the control arm, which received the vehicle alone, were application site reactions, such as pain, erythema, and irritation. None of these occurred in more than 3% of those randomized to ruxolitinib regardless of dose.
Overall, in the trial, which randomized 329 patients ages from 2 to under 12 years with mild to moderate AD to ruxolitinib 1.5% cream, ruxolitinib 0.75% cream, or vehicle in a 2:2:1 fashion, there were just two (0.8%) discontinuations in the ruxolitinib groups (one in each dosing arm). There were none in the vehicle arm.
The safety supports an expansion of the AD indication for topical ruxolitinib in young children, because the rates of response were very similar to that seen in adolescents and adults in the previously published TRUE AD-1 and TRUE AD-2 trials, he said.
For the primary endpoint of Investigator’s Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) with at least a 2 grade improvement in IGA score from baseline, the response rates were 56.5%, 36.6%, and 10.8% for ruxolitinib 1.5%, ruxolitinib 0.75%, and vehicle respectively, at 8 weeks (P < .0001 for both doses relative to vehicle).
For the secondary efficacy endpoint of 75% or greater clearance on the Eczema Area and Severity Index, the rates were 67.2%, 51.5%, and 15.4%, for ruxolitinib 1.5%, ruxolitinib 0.75%, and vehicle respectively. Again, the advantage of both doses of ruxolitinib relative to vehicle was highly statistically significant (P < .0001).
Control of itch, evaluated with the Numerical Rating Scale was only evaluated in children 6-2 because of concern of the reliability of reporting in younger children. Control was defined as at least a 4-point improvement from baseline. It was achieved by 43.4%, 37.5%, and 29.7% by week 8 in the arms receiving the higher dose of ruxolitinib, the lower dose, and vehicle, respectively. The median time to achieving itch control was 11 days, 13 days, and 23 days, respectively. For all of these endpoints, the separation of the curves was readily apparent within the first 2 weeks.
The efficacy and tolerability of ruxolitinib appeared to be similar in younger children (ages 2-6) relative to older children.
Extension study in children near completion
Most of the patients who participated in TRUE AD-3 have been rolled over to the open-label extension trial, which is nearing completion. Those originally randomized to vehicle have been rerandomized to the lower or higher dose of ruxolitinib.
While this trial was focused on ruxolitinib as monotherapy, Thrasyvoulos Tzellos, MD, head of the department of dermatology, Nordland Hospital Trust, Bødo, Norway, questioned whether this is will be how it will be used in clinical practice. With the increasing array of therapies for AD, the “concept of combination therapy becomes more and more relevant,” he said after Dr. Eichenfield’s presentation.
Questioning whether an effective nonsteroidal anti-inflammatory agent like ruxolitinib should be considered a first-line treatment in mild disease or an adjunctive treatment for AD of any severity, he suggested that it might be best considered within a combination.
Dr. Eichenfield agreed. “Once we get the drug approved in a controlled trial, I think we then figure out how to use it in clinical practice.” Based on his own use of ruxolitinib in adults, he noted that he has not seen this drug replace other therapies so much as provide another option for control.
“We have an increasing armamentarium of drugs to use for involvement in different areas of the body in order to get more long-term control of disease,” he said. As an effective topical nonsteroidal drug, he believes its addition to clinical care in younger children, if approved, will be meaningful.
Dr. Eichenfield disclosed financial relationships with more multiple pharmaceutical companies, including Incyte, the manufacturer of ruxolitinib cream that provided funding for the True-AD trials. Dr. Tzellos reported financial relationships with AbbVie and UCB.
AT THE EADV CONGRESS
Teens streaming on Twitch vulnerable to predators
WASHINGTON – Half of youth broadcasting live streams on the online platform Twitch revealed their real-world location, and nearly half provided their name to viewers, according to research presented at the annual meeting of the American Academy of Pediatrics. It took researchers less than 5 minutes – and sometimes as little as 12 seconds – to find minors in different video game categories, suggesting the environment offers opportunities to predators to gain sensitive information about minors, reported Fiona Dubrosa, BS, BA, a visiting scholar at Cohen Children’s Medical Center, New York, and colleagues.
A ‘clandestine, threatening digital environment’
the authors concluded. “The nature of live streaming makes it particularly dangerous, as there is no way to take back information that has been revealed or regulate content or viewers. Parents and pediatricians should be aware of the dangers presented by Twitch and other live-streaming platforms and counsel children on best practices for Internet safety.”
Twitch is an online streaming platform where people can watch creator’s live content, such as music performances or narrating real-time video game playing. The platform requires live streamers to be 13 years old with a valid email address or phone number to create an account, but no age restrictions or identification requirements exist for viewers, “potentially putting minors in danger of being watched, followed, and groomed by predators,” the researchers noted. They added that people following different streamers receive notifications when those streamers are live. Further, “viewers can donate money to streamers, which can make it easier for predators to manipulate, track, and encourage risky behaviors from minors.”
To better understand the risks the platform might pose to minors, the researchers searched for and analyzed popular video game live streams that appeared to be streamed by minors who had their cameras on and their faces visible. Then the researchers noted the name of the video game, the topics discussed by the streamers, the time it took to find minors under each game, and each streamer’s age, name, follower count, location, streaming schedule, and social media links for money donations.
The researchers analyzed 100 Twitch streamers who were minors, who had a combined 1,755,452 million followers. Nearly half the streamers (47%) provided their presumably real names, and half (50%) gave out their location. Nearly two-thirds (64%) linked other social media accounts they had and encouraged viewers to follow them. Detailed schedules of when they would be live were available for 38% of the streamers, and 37% of the minor streamers were accepting money donations.
Only 11% of the discussion on the streams revealed personal details, most often related to trying on different outfits for viewers and talking about real-world locations they liked to visit. The researchers needed anywhere from 12 seconds to 5 minutes to find a minor in each game category.
”Young users clearly feel a false sense of safety on the platform; a significant proportion were willing to reveal personal information despite having no knowledge of who might be listening,” the researchers said. “The donation system provides a menacing avenue for manipulation and continued exploitation of minors. Our findings reveal the need for stricter age limitations for streamers and more stringent identity verification of audience members on Twitch.”
Open-minded parental guidance is warranted
Jenny Radesky, MD, a developmental behavioral pediatrician and media researcher at University of Michigan Medicine, Ann Arbor, was not surprised that many teens live stream on Twitch since it’s a popular platform for video gaming, but she was surprised at how many revealed their locations and other personal details.
“I suspect that they do this to build closeness with their viewers, by seeming more authentic,” said Dr. Radesky, who was not involved in the study. “It is this type of parasocial relationship with influencers and gamers that keeps an audience engaged, and encourages future viewing and purchases.”
Their willingness to share personal details suggests it’s important to conduct qualitative research to find out how teen live streamers think about privacy risks, what privacy settings they can use and choose to use, and how they handle inappropriate contact from adults, Dr. Radesky said.
Meanwhile, parents should talk with their kids in an open-minded way about what platforms they use and what they like and dislike about them. She recommended parents read the Common Sense Media guide about different social platforms ”to understand what attracts kids to content on specific sites, what their pitfalls are, and what types of privacy and safety settings are available.”
“A child or teen is much more likely to be honest about negative experiences online if they think their parent will hear them out – not judge them or take away their tech. No teen wants to talk with a panicky parent,” Dr. Radesky said.
David Hill, MD, a hospitalist pediatrician for Goldsboro Pediatrics in Wayne County, North Carolina, who also specializes in media communication, said that Twitch is just one example of a social media platform where children can encounter a variety of dangers, including sometimes adult predators.
“This just highlights the importance of parents having an ongoing conversation with their children about how they use their social media platforms and ensuring, just as we do with learning to ride a bicycle or learning to drive a car, that they apply some basic rules of safety,” Dr. Hill said. Then it’s important to keep coming back to that conversation “again and again as they grow and change and as those platforms change to ensure that those kids are continuing to apply those rules consistently.
“The best way for parents to keep up is ask your kids,” he said. “They love to share. They love to teach. They love to be in a position to show you something, especially if it’s something that interests them.”
An example of a rule would be setting personal accounts to private, not public, by default, Dr. Radesky said. “When interviewed, teens often say that they feel intruded upon by older people ‘stalking’ them or trying to connect with them on social platforms,” so making an account private can reduce those opportunities.
For teens who specifically want to create content on social platforms, parent oversight is needed, she said, but she acknowledged it can be a lot of work. “This might take the form of talking about what a teen plans to post before they do, expectations for positive behaviors or language, plans for privacy settings (such as public vs. private accounts), and what to do with trolls or hateful comment,” she said. “Parents may want to follow their child’s account to check in on it.”
Useful advice
Dr. Radesky also provided a handful of talking points that pediatricians can use in talking with patients who use these platforms:
- Keep your account private to just your friends and people you want to interact with. There are a lot of people on the Internet that you don’t want intruding upon your social life.
- Maintain your feed and the accounts you follow to keep it positive, entertaining, and not a source of stress or self-doubt. Content creators are always trying to grab your attention in new ways, some of which are rude or dehumanizing, so don’t waste your time on things that bring you down.
- Talk about why you want to post or live stream. Is it to get reactions or feel validated? If so, can you find other ways to feel validated that don’t require performing for other people? Is it to share a special skill? If so, how do you keep your posts creative and community building rather than attention grabbing? And how can you keep your parents involved so that they can help you navigate challenges?”
Ms. Dubrosa and Dr. Hill had no disclosures. Dr. Radesky is a consultant for Melissa & Doug. No information on external funding was provided.
WASHINGTON – Half of youth broadcasting live streams on the online platform Twitch revealed their real-world location, and nearly half provided their name to viewers, according to research presented at the annual meeting of the American Academy of Pediatrics. It took researchers less than 5 minutes – and sometimes as little as 12 seconds – to find minors in different video game categories, suggesting the environment offers opportunities to predators to gain sensitive information about minors, reported Fiona Dubrosa, BS, BA, a visiting scholar at Cohen Children’s Medical Center, New York, and colleagues.
A ‘clandestine, threatening digital environment’
the authors concluded. “The nature of live streaming makes it particularly dangerous, as there is no way to take back information that has been revealed or regulate content or viewers. Parents and pediatricians should be aware of the dangers presented by Twitch and other live-streaming platforms and counsel children on best practices for Internet safety.”
Twitch is an online streaming platform where people can watch creator’s live content, such as music performances or narrating real-time video game playing. The platform requires live streamers to be 13 years old with a valid email address or phone number to create an account, but no age restrictions or identification requirements exist for viewers, “potentially putting minors in danger of being watched, followed, and groomed by predators,” the researchers noted. They added that people following different streamers receive notifications when those streamers are live. Further, “viewers can donate money to streamers, which can make it easier for predators to manipulate, track, and encourage risky behaviors from minors.”
To better understand the risks the platform might pose to minors, the researchers searched for and analyzed popular video game live streams that appeared to be streamed by minors who had their cameras on and their faces visible. Then the researchers noted the name of the video game, the topics discussed by the streamers, the time it took to find minors under each game, and each streamer’s age, name, follower count, location, streaming schedule, and social media links for money donations.
The researchers analyzed 100 Twitch streamers who were minors, who had a combined 1,755,452 million followers. Nearly half the streamers (47%) provided their presumably real names, and half (50%) gave out their location. Nearly two-thirds (64%) linked other social media accounts they had and encouraged viewers to follow them. Detailed schedules of when they would be live were available for 38% of the streamers, and 37% of the minor streamers were accepting money donations.
Only 11% of the discussion on the streams revealed personal details, most often related to trying on different outfits for viewers and talking about real-world locations they liked to visit. The researchers needed anywhere from 12 seconds to 5 minutes to find a minor in each game category.
”Young users clearly feel a false sense of safety on the platform; a significant proportion were willing to reveal personal information despite having no knowledge of who might be listening,” the researchers said. “The donation system provides a menacing avenue for manipulation and continued exploitation of minors. Our findings reveal the need for stricter age limitations for streamers and more stringent identity verification of audience members on Twitch.”
Open-minded parental guidance is warranted
Jenny Radesky, MD, a developmental behavioral pediatrician and media researcher at University of Michigan Medicine, Ann Arbor, was not surprised that many teens live stream on Twitch since it’s a popular platform for video gaming, but she was surprised at how many revealed their locations and other personal details.
“I suspect that they do this to build closeness with their viewers, by seeming more authentic,” said Dr. Radesky, who was not involved in the study. “It is this type of parasocial relationship with influencers and gamers that keeps an audience engaged, and encourages future viewing and purchases.”
Their willingness to share personal details suggests it’s important to conduct qualitative research to find out how teen live streamers think about privacy risks, what privacy settings they can use and choose to use, and how they handle inappropriate contact from adults, Dr. Radesky said.
Meanwhile, parents should talk with their kids in an open-minded way about what platforms they use and what they like and dislike about them. She recommended parents read the Common Sense Media guide about different social platforms ”to understand what attracts kids to content on specific sites, what their pitfalls are, and what types of privacy and safety settings are available.”
“A child or teen is much more likely to be honest about negative experiences online if they think their parent will hear them out – not judge them or take away their tech. No teen wants to talk with a panicky parent,” Dr. Radesky said.
David Hill, MD, a hospitalist pediatrician for Goldsboro Pediatrics in Wayne County, North Carolina, who also specializes in media communication, said that Twitch is just one example of a social media platform where children can encounter a variety of dangers, including sometimes adult predators.
“This just highlights the importance of parents having an ongoing conversation with their children about how they use their social media platforms and ensuring, just as we do with learning to ride a bicycle or learning to drive a car, that they apply some basic rules of safety,” Dr. Hill said. Then it’s important to keep coming back to that conversation “again and again as they grow and change and as those platforms change to ensure that those kids are continuing to apply those rules consistently.
“The best way for parents to keep up is ask your kids,” he said. “They love to share. They love to teach. They love to be in a position to show you something, especially if it’s something that interests them.”
An example of a rule would be setting personal accounts to private, not public, by default, Dr. Radesky said. “When interviewed, teens often say that they feel intruded upon by older people ‘stalking’ them or trying to connect with them on social platforms,” so making an account private can reduce those opportunities.
For teens who specifically want to create content on social platforms, parent oversight is needed, she said, but she acknowledged it can be a lot of work. “This might take the form of talking about what a teen plans to post before they do, expectations for positive behaviors or language, plans for privacy settings (such as public vs. private accounts), and what to do with trolls or hateful comment,” she said. “Parents may want to follow their child’s account to check in on it.”
Useful advice
Dr. Radesky also provided a handful of talking points that pediatricians can use in talking with patients who use these platforms:
- Keep your account private to just your friends and people you want to interact with. There are a lot of people on the Internet that you don’t want intruding upon your social life.
- Maintain your feed and the accounts you follow to keep it positive, entertaining, and not a source of stress or self-doubt. Content creators are always trying to grab your attention in new ways, some of which are rude or dehumanizing, so don’t waste your time on things that bring you down.
- Talk about why you want to post or live stream. Is it to get reactions or feel validated? If so, can you find other ways to feel validated that don’t require performing for other people? Is it to share a special skill? If so, how do you keep your posts creative and community building rather than attention grabbing? And how can you keep your parents involved so that they can help you navigate challenges?”
Ms. Dubrosa and Dr. Hill had no disclosures. Dr. Radesky is a consultant for Melissa & Doug. No information on external funding was provided.
WASHINGTON – Half of youth broadcasting live streams on the online platform Twitch revealed their real-world location, and nearly half provided their name to viewers, according to research presented at the annual meeting of the American Academy of Pediatrics. It took researchers less than 5 minutes – and sometimes as little as 12 seconds – to find minors in different video game categories, suggesting the environment offers opportunities to predators to gain sensitive information about minors, reported Fiona Dubrosa, BS, BA, a visiting scholar at Cohen Children’s Medical Center, New York, and colleagues.
A ‘clandestine, threatening digital environment’
the authors concluded. “The nature of live streaming makes it particularly dangerous, as there is no way to take back information that has been revealed or regulate content or viewers. Parents and pediatricians should be aware of the dangers presented by Twitch and other live-streaming platforms and counsel children on best practices for Internet safety.”
Twitch is an online streaming platform where people can watch creator’s live content, such as music performances or narrating real-time video game playing. The platform requires live streamers to be 13 years old with a valid email address or phone number to create an account, but no age restrictions or identification requirements exist for viewers, “potentially putting minors in danger of being watched, followed, and groomed by predators,” the researchers noted. They added that people following different streamers receive notifications when those streamers are live. Further, “viewers can donate money to streamers, which can make it easier for predators to manipulate, track, and encourage risky behaviors from minors.”
To better understand the risks the platform might pose to minors, the researchers searched for and analyzed popular video game live streams that appeared to be streamed by minors who had their cameras on and their faces visible. Then the researchers noted the name of the video game, the topics discussed by the streamers, the time it took to find minors under each game, and each streamer’s age, name, follower count, location, streaming schedule, and social media links for money donations.
The researchers analyzed 100 Twitch streamers who were minors, who had a combined 1,755,452 million followers. Nearly half the streamers (47%) provided their presumably real names, and half (50%) gave out their location. Nearly two-thirds (64%) linked other social media accounts they had and encouraged viewers to follow them. Detailed schedules of when they would be live were available for 38% of the streamers, and 37% of the minor streamers were accepting money donations.
Only 11% of the discussion on the streams revealed personal details, most often related to trying on different outfits for viewers and talking about real-world locations they liked to visit. The researchers needed anywhere from 12 seconds to 5 minutes to find a minor in each game category.
”Young users clearly feel a false sense of safety on the platform; a significant proportion were willing to reveal personal information despite having no knowledge of who might be listening,” the researchers said. “The donation system provides a menacing avenue for manipulation and continued exploitation of minors. Our findings reveal the need for stricter age limitations for streamers and more stringent identity verification of audience members on Twitch.”
Open-minded parental guidance is warranted
Jenny Radesky, MD, a developmental behavioral pediatrician and media researcher at University of Michigan Medicine, Ann Arbor, was not surprised that many teens live stream on Twitch since it’s a popular platform for video gaming, but she was surprised at how many revealed their locations and other personal details.
“I suspect that they do this to build closeness with their viewers, by seeming more authentic,” said Dr. Radesky, who was not involved in the study. “It is this type of parasocial relationship with influencers and gamers that keeps an audience engaged, and encourages future viewing and purchases.”
Their willingness to share personal details suggests it’s important to conduct qualitative research to find out how teen live streamers think about privacy risks, what privacy settings they can use and choose to use, and how they handle inappropriate contact from adults, Dr. Radesky said.
Meanwhile, parents should talk with their kids in an open-minded way about what platforms they use and what they like and dislike about them. She recommended parents read the Common Sense Media guide about different social platforms ”to understand what attracts kids to content on specific sites, what their pitfalls are, and what types of privacy and safety settings are available.”
“A child or teen is much more likely to be honest about negative experiences online if they think their parent will hear them out – not judge them or take away their tech. No teen wants to talk with a panicky parent,” Dr. Radesky said.
David Hill, MD, a hospitalist pediatrician for Goldsboro Pediatrics in Wayne County, North Carolina, who also specializes in media communication, said that Twitch is just one example of a social media platform where children can encounter a variety of dangers, including sometimes adult predators.
“This just highlights the importance of parents having an ongoing conversation with their children about how they use their social media platforms and ensuring, just as we do with learning to ride a bicycle or learning to drive a car, that they apply some basic rules of safety,” Dr. Hill said. Then it’s important to keep coming back to that conversation “again and again as they grow and change and as those platforms change to ensure that those kids are continuing to apply those rules consistently.
“The best way for parents to keep up is ask your kids,” he said. “They love to share. They love to teach. They love to be in a position to show you something, especially if it’s something that interests them.”
An example of a rule would be setting personal accounts to private, not public, by default, Dr. Radesky said. “When interviewed, teens often say that they feel intruded upon by older people ‘stalking’ them or trying to connect with them on social platforms,” so making an account private can reduce those opportunities.
For teens who specifically want to create content on social platforms, parent oversight is needed, she said, but she acknowledged it can be a lot of work. “This might take the form of talking about what a teen plans to post before they do, expectations for positive behaviors or language, plans for privacy settings (such as public vs. private accounts), and what to do with trolls or hateful comment,” she said. “Parents may want to follow their child’s account to check in on it.”
Useful advice
Dr. Radesky also provided a handful of talking points that pediatricians can use in talking with patients who use these platforms:
- Keep your account private to just your friends and people you want to interact with. There are a lot of people on the Internet that you don’t want intruding upon your social life.
- Maintain your feed and the accounts you follow to keep it positive, entertaining, and not a source of stress or self-doubt. Content creators are always trying to grab your attention in new ways, some of which are rude or dehumanizing, so don’t waste your time on things that bring you down.
- Talk about why you want to post or live stream. Is it to get reactions or feel validated? If so, can you find other ways to feel validated that don’t require performing for other people? Is it to share a special skill? If so, how do you keep your posts creative and community building rather than attention grabbing? And how can you keep your parents involved so that they can help you navigate challenges?”
Ms. Dubrosa and Dr. Hill had no disclosures. Dr. Radesky is a consultant for Melissa & Doug. No information on external funding was provided.
AT AAP 2023
Breastfeeding and colorectal cancer
I, like every pediatrician I know, believe that breast milk is the best nutrition for human newborns. Its balance of nutritive elements and its role in preventing of a wide range of illnesses are so great that we are still learning the extent of their magnitude. It just makes sense that a mother’s milk is most well suited for her baby.
I am a bit less unambiguous about breastfeeding. By that I mean the process of providing breast milk to an infant directly from its mother’s breast. Before you yank my AAP membership card, let me make it clear that I think every woman should consider breastfeeding her infant. But we must accept that in a few situations, even with help from caring and enlightened health care providers and family members, breastfeeding doesn’t work as well as we would have hoped. Fortunately, there are alternatives.
My reservations about the process are few, and until recently I have had an unwaveringly positive attitude toward the safety of breast milk. The cause of my little bit of uncertainty arrived in a recent study by two researchers at the Dana Farber Institute in Boston, in which the A younger cohort within that larger group had a dramatic 40% increased risk of developing high-risk cancer before reaching age 55.
The population the investigators studied came from the large Nurses’ Health Study II, a well-known repository of longitudinal health data. The researchers reported that they included biometric data and a large collection of lifestyle factors including smoking, alcohol intake, and diet in their calculations. However, breastfeeding continued to register the highest association. Interestingly, the investigators found that women who were breastfed for 9 months or longer had twice the risk of colorectal cancer as those who breastfed for from 4 to 8 months.
The study population was all women and predominantly white. However, in the general population it is the non-Hispanic white population that is experiencing the greatest increase in incidence. Of course, the study could not answer whether this association with breastfeeding also existed in minority populations.
The researchers suspect that what they are seeing is a reflection of the Westernization of the American lifestyle. One of the researchers is interested in the gut biome of infants and plans to further the investigation in that direction. Could some substance from the environment be concentrating in breast milk? Or is something missing in breast milk? She points out that, while formulas are generally fortified with vitamin D, breast milk is not.
As concerning as the results of this study may sound, the authors are very careful to urge mothers to continue to breastfeed and choose it as their first choice for feeding their babies. I have been pleasantly surprised that this study has not gotten widespread media attention because bad news travels fast. I have chosen to share it with you because at some point you may begin getting questions from concerned parents.
While apparently well done, this study is just the beginning. Like any good research, it poses more questions than it answers. For us as pediatricians it means we should continue to recommend breast milk as the first food. But, we must stay alert as further research looks deeper into this association.
We should also take advantage of our special access to young parents, a demographic that less frequently sees a physician for preventive care. For whatever reason colorectal cancer is occurring at younger ages. When we have the opportunity we should be reminding 40-year-olds not to wait until age 50 to screen for colorectal cancer, particularly if they have a family history of the disease.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].
I, like every pediatrician I know, believe that breast milk is the best nutrition for human newborns. Its balance of nutritive elements and its role in preventing of a wide range of illnesses are so great that we are still learning the extent of their magnitude. It just makes sense that a mother’s milk is most well suited for her baby.
I am a bit less unambiguous about breastfeeding. By that I mean the process of providing breast milk to an infant directly from its mother’s breast. Before you yank my AAP membership card, let me make it clear that I think every woman should consider breastfeeding her infant. But we must accept that in a few situations, even with help from caring and enlightened health care providers and family members, breastfeeding doesn’t work as well as we would have hoped. Fortunately, there are alternatives.
My reservations about the process are few, and until recently I have had an unwaveringly positive attitude toward the safety of breast milk. The cause of my little bit of uncertainty arrived in a recent study by two researchers at the Dana Farber Institute in Boston, in which the A younger cohort within that larger group had a dramatic 40% increased risk of developing high-risk cancer before reaching age 55.
The population the investigators studied came from the large Nurses’ Health Study II, a well-known repository of longitudinal health data. The researchers reported that they included biometric data and a large collection of lifestyle factors including smoking, alcohol intake, and diet in their calculations. However, breastfeeding continued to register the highest association. Interestingly, the investigators found that women who were breastfed for 9 months or longer had twice the risk of colorectal cancer as those who breastfed for from 4 to 8 months.
The study population was all women and predominantly white. However, in the general population it is the non-Hispanic white population that is experiencing the greatest increase in incidence. Of course, the study could not answer whether this association with breastfeeding also existed in minority populations.
The researchers suspect that what they are seeing is a reflection of the Westernization of the American lifestyle. One of the researchers is interested in the gut biome of infants and plans to further the investigation in that direction. Could some substance from the environment be concentrating in breast milk? Or is something missing in breast milk? She points out that, while formulas are generally fortified with vitamin D, breast milk is not.
As concerning as the results of this study may sound, the authors are very careful to urge mothers to continue to breastfeed and choose it as their first choice for feeding their babies. I have been pleasantly surprised that this study has not gotten widespread media attention because bad news travels fast. I have chosen to share it with you because at some point you may begin getting questions from concerned parents.
While apparently well done, this study is just the beginning. Like any good research, it poses more questions than it answers. For us as pediatricians it means we should continue to recommend breast milk as the first food. But, we must stay alert as further research looks deeper into this association.
We should also take advantage of our special access to young parents, a demographic that less frequently sees a physician for preventive care. For whatever reason colorectal cancer is occurring at younger ages. When we have the opportunity we should be reminding 40-year-olds not to wait until age 50 to screen for colorectal cancer, particularly if they have a family history of the disease.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].
I, like every pediatrician I know, believe that breast milk is the best nutrition for human newborns. Its balance of nutritive elements and its role in preventing of a wide range of illnesses are so great that we are still learning the extent of their magnitude. It just makes sense that a mother’s milk is most well suited for her baby.
I am a bit less unambiguous about breastfeeding. By that I mean the process of providing breast milk to an infant directly from its mother’s breast. Before you yank my AAP membership card, let me make it clear that I think every woman should consider breastfeeding her infant. But we must accept that in a few situations, even with help from caring and enlightened health care providers and family members, breastfeeding doesn’t work as well as we would have hoped. Fortunately, there are alternatives.
My reservations about the process are few, and until recently I have had an unwaveringly positive attitude toward the safety of breast milk. The cause of my little bit of uncertainty arrived in a recent study by two researchers at the Dana Farber Institute in Boston, in which the A younger cohort within that larger group had a dramatic 40% increased risk of developing high-risk cancer before reaching age 55.
The population the investigators studied came from the large Nurses’ Health Study II, a well-known repository of longitudinal health data. The researchers reported that they included biometric data and a large collection of lifestyle factors including smoking, alcohol intake, and diet in their calculations. However, breastfeeding continued to register the highest association. Interestingly, the investigators found that women who were breastfed for 9 months or longer had twice the risk of colorectal cancer as those who breastfed for from 4 to 8 months.
The study population was all women and predominantly white. However, in the general population it is the non-Hispanic white population that is experiencing the greatest increase in incidence. Of course, the study could not answer whether this association with breastfeeding also existed in minority populations.
The researchers suspect that what they are seeing is a reflection of the Westernization of the American lifestyle. One of the researchers is interested in the gut biome of infants and plans to further the investigation in that direction. Could some substance from the environment be concentrating in breast milk? Or is something missing in breast milk? She points out that, while formulas are generally fortified with vitamin D, breast milk is not.
As concerning as the results of this study may sound, the authors are very careful to urge mothers to continue to breastfeed and choose it as their first choice for feeding their babies. I have been pleasantly surprised that this study has not gotten widespread media attention because bad news travels fast. I have chosen to share it with you because at some point you may begin getting questions from concerned parents.
While apparently well done, this study is just the beginning. Like any good research, it poses more questions than it answers. For us as pediatricians it means we should continue to recommend breast milk as the first food. But, we must stay alert as further research looks deeper into this association.
We should also take advantage of our special access to young parents, a demographic that less frequently sees a physician for preventive care. For whatever reason colorectal cancer is occurring at younger ages. When we have the opportunity we should be reminding 40-year-olds not to wait until age 50 to screen for colorectal cancer, particularly if they have a family history of the disease.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].
Teens have easy online access to Delta-8 cannabinoid products
WASHINGTON – , researchers reported at the 2023 annual meeting of the American Academy of Pediatrics. Most of the products identified came in bright, colorful, kid-friendly packaging and cost less than $10, the researchers found, and only 2 out of 45 sites had a third-party age verification requirement for purchases.
Delta-8 THC, also called D8, is a synthetically produced cannabinoid whose chemical structure and effects are nearly identical to traditional THC, the authors explained, and past research has found that D8 products, such as e-cigarettes, can contain toxic byproducts and contaminants.
”Since D8 is not traditional THC, minors may underestimate its strength and potential danger,” wrote lead author Abhijeet Grewal, BS, a research assistant at Cohen Children’s Medical Center, New York, and senior author Ruth Milanaik, DO, director of the Neonatal Neurodevelopmental Program at Cohen Children’s and a developmental/behavioral pediatrician at Northwell Health, also in New York. “Although traditional THC is a federally banned substance, D8 is legal on a federal level and less restricted on a state by state basis, making it easier for individuals to acquire D8.”
Easily accessible
During the first seven moments of 2021, 77% of reports of accidental exposure occurred in people under age 18, including some children who required ICU admission. The U.S. Food and Drug Administration also received 104 reports of adverse events from products containing D8 between December 2020-February 2022, and more than half of those required medical intervention.
To better understand how easy it is to access D8, the authors collected data on 45 websites they identified that sold D8. The researchers looked for age verification questions for accessing the site, third-party age certification, what kinds of products (edibles, smoke products, or tinctures) were sold, the price and dosage of the cheapest product, and examples of packaging, flavors, marketing claims, and warning statements at each site.
More than a third of the sites (36%) did not ask for customers’ age and almost none of the sites asked for proof: 96% of the sites lacked formal third-party age verification procedures. All but one of the sites sold D8 edibles, and most (82%) sold D8 vaping or smoking products. Only 42% sold tinctures, a mix of concentrated D8 with oil that’s orally consumed.
The cheapest product was priced under $5 on one-third of the sites and under $10 on another third of the sites. The cheapest product was between $10-20 on 16% of the sites while the remaining nine sites’ cheapest product was more than $20. In assessing only the cheapest D8 products on each site, nearly half (47%) contained 51 mg or more of D8, and 20% of the products didn’t report the dosage. Another 22% contained 41-50 mg of D8, and the remaining five products contained 20-40 mg.
Kid-friendly D8
More than half of the D8 products were sold in kid-friendly packaging – packages with bright, colorful designs and fonts that resemble candy or snack food, sometimes cartoon characters or fun items like dice on the packaging. Further, 24% of the websites did not include any warnings or other health information about D8.
“The low prices, high dosages available, and eye-popping packaging make these products extremely attractive to teens who are looking for a high,” the researchers concluded. They advised clinicians to talk with teen patients about the dangers of D8 and advocated for policymakers to more strictly regulate online distributors of D8 products, particularly in requiring age verification procedures and prohibiting kid-friendly packaging.
Megan Moreno, MD, MSEd, MPH, an adolescent medicine physician and researcher at the University of Wisconsin, Madison, School of Medicine and Public Health and UWHealthKids, was particularly struck by how eye-catching the packaging was. “The bright colors and font choices are really designed to attract adolescents,” commented Dr. Moreno, who was not involved in the study. But she was not surprised overall by the findings.
“Other studies have found that the cannabis industry leverages online tools and social media, alongside youth-friendly packaging, to attract youth to their products,” she said. “What is disappointing is that these companies do not use industry standard approaches, such as the alcohol industry, to age-gate their websites.”
It’s important for providers who care for adolescents to ask about substance use but to especially include questions about substances that teens might not think of as “drugs,” such as Delta 8, Dr. Moreno said.
“Prior research on other types of substance such as these has found that teens can think these are less dangerous versions of cannabis, so providing accurate information and asking about these products can prevent harm to kids,” Dr. Moreno said. Although this study focused on websites that sell D8 products, she said that “another important area of influence to consider is social media messaging around these products, which may drive traffic to the purchasing site.” It’s clear this industry is not going to self-regulate without policy changes, Dr. Moreno added, so she noted the importance of advocating for policy that regulates these sites.
Mr. Grewal, Dr. Milanaik and Dr. Moreno had no disclosures. No external funding sources were noted.
WASHINGTON – , researchers reported at the 2023 annual meeting of the American Academy of Pediatrics. Most of the products identified came in bright, colorful, kid-friendly packaging and cost less than $10, the researchers found, and only 2 out of 45 sites had a third-party age verification requirement for purchases.
Delta-8 THC, also called D8, is a synthetically produced cannabinoid whose chemical structure and effects are nearly identical to traditional THC, the authors explained, and past research has found that D8 products, such as e-cigarettes, can contain toxic byproducts and contaminants.
”Since D8 is not traditional THC, minors may underestimate its strength and potential danger,” wrote lead author Abhijeet Grewal, BS, a research assistant at Cohen Children’s Medical Center, New York, and senior author Ruth Milanaik, DO, director of the Neonatal Neurodevelopmental Program at Cohen Children’s and a developmental/behavioral pediatrician at Northwell Health, also in New York. “Although traditional THC is a federally banned substance, D8 is legal on a federal level and less restricted on a state by state basis, making it easier for individuals to acquire D8.”
Easily accessible
During the first seven moments of 2021, 77% of reports of accidental exposure occurred in people under age 18, including some children who required ICU admission. The U.S. Food and Drug Administration also received 104 reports of adverse events from products containing D8 between December 2020-February 2022, and more than half of those required medical intervention.
To better understand how easy it is to access D8, the authors collected data on 45 websites they identified that sold D8. The researchers looked for age verification questions for accessing the site, third-party age certification, what kinds of products (edibles, smoke products, or tinctures) were sold, the price and dosage of the cheapest product, and examples of packaging, flavors, marketing claims, and warning statements at each site.
More than a third of the sites (36%) did not ask for customers’ age and almost none of the sites asked for proof: 96% of the sites lacked formal third-party age verification procedures. All but one of the sites sold D8 edibles, and most (82%) sold D8 vaping or smoking products. Only 42% sold tinctures, a mix of concentrated D8 with oil that’s orally consumed.
The cheapest product was priced under $5 on one-third of the sites and under $10 on another third of the sites. The cheapest product was between $10-20 on 16% of the sites while the remaining nine sites’ cheapest product was more than $20. In assessing only the cheapest D8 products on each site, nearly half (47%) contained 51 mg or more of D8, and 20% of the products didn’t report the dosage. Another 22% contained 41-50 mg of D8, and the remaining five products contained 20-40 mg.
Kid-friendly D8
More than half of the D8 products were sold in kid-friendly packaging – packages with bright, colorful designs and fonts that resemble candy or snack food, sometimes cartoon characters or fun items like dice on the packaging. Further, 24% of the websites did not include any warnings or other health information about D8.
“The low prices, high dosages available, and eye-popping packaging make these products extremely attractive to teens who are looking for a high,” the researchers concluded. They advised clinicians to talk with teen patients about the dangers of D8 and advocated for policymakers to more strictly regulate online distributors of D8 products, particularly in requiring age verification procedures and prohibiting kid-friendly packaging.
Megan Moreno, MD, MSEd, MPH, an adolescent medicine physician and researcher at the University of Wisconsin, Madison, School of Medicine and Public Health and UWHealthKids, was particularly struck by how eye-catching the packaging was. “The bright colors and font choices are really designed to attract adolescents,” commented Dr. Moreno, who was not involved in the study. But she was not surprised overall by the findings.
“Other studies have found that the cannabis industry leverages online tools and social media, alongside youth-friendly packaging, to attract youth to their products,” she said. “What is disappointing is that these companies do not use industry standard approaches, such as the alcohol industry, to age-gate their websites.”
It’s important for providers who care for adolescents to ask about substance use but to especially include questions about substances that teens might not think of as “drugs,” such as Delta 8, Dr. Moreno said.
“Prior research on other types of substance such as these has found that teens can think these are less dangerous versions of cannabis, so providing accurate information and asking about these products can prevent harm to kids,” Dr. Moreno said. Although this study focused on websites that sell D8 products, she said that “another important area of influence to consider is social media messaging around these products, which may drive traffic to the purchasing site.” It’s clear this industry is not going to self-regulate without policy changes, Dr. Moreno added, so she noted the importance of advocating for policy that regulates these sites.
Mr. Grewal, Dr. Milanaik and Dr. Moreno had no disclosures. No external funding sources were noted.
WASHINGTON – , researchers reported at the 2023 annual meeting of the American Academy of Pediatrics. Most of the products identified came in bright, colorful, kid-friendly packaging and cost less than $10, the researchers found, and only 2 out of 45 sites had a third-party age verification requirement for purchases.
Delta-8 THC, also called D8, is a synthetically produced cannabinoid whose chemical structure and effects are nearly identical to traditional THC, the authors explained, and past research has found that D8 products, such as e-cigarettes, can contain toxic byproducts and contaminants.
”Since D8 is not traditional THC, minors may underestimate its strength and potential danger,” wrote lead author Abhijeet Grewal, BS, a research assistant at Cohen Children’s Medical Center, New York, and senior author Ruth Milanaik, DO, director of the Neonatal Neurodevelopmental Program at Cohen Children’s and a developmental/behavioral pediatrician at Northwell Health, also in New York. “Although traditional THC is a federally banned substance, D8 is legal on a federal level and less restricted on a state by state basis, making it easier for individuals to acquire D8.”
Easily accessible
During the first seven moments of 2021, 77% of reports of accidental exposure occurred in people under age 18, including some children who required ICU admission. The U.S. Food and Drug Administration also received 104 reports of adverse events from products containing D8 between December 2020-February 2022, and more than half of those required medical intervention.
To better understand how easy it is to access D8, the authors collected data on 45 websites they identified that sold D8. The researchers looked for age verification questions for accessing the site, third-party age certification, what kinds of products (edibles, smoke products, or tinctures) were sold, the price and dosage of the cheapest product, and examples of packaging, flavors, marketing claims, and warning statements at each site.
More than a third of the sites (36%) did not ask for customers’ age and almost none of the sites asked for proof: 96% of the sites lacked formal third-party age verification procedures. All but one of the sites sold D8 edibles, and most (82%) sold D8 vaping or smoking products. Only 42% sold tinctures, a mix of concentrated D8 with oil that’s orally consumed.
The cheapest product was priced under $5 on one-third of the sites and under $10 on another third of the sites. The cheapest product was between $10-20 on 16% of the sites while the remaining nine sites’ cheapest product was more than $20. In assessing only the cheapest D8 products on each site, nearly half (47%) contained 51 mg or more of D8, and 20% of the products didn’t report the dosage. Another 22% contained 41-50 mg of D8, and the remaining five products contained 20-40 mg.
Kid-friendly D8
More than half of the D8 products were sold in kid-friendly packaging – packages with bright, colorful designs and fonts that resemble candy or snack food, sometimes cartoon characters or fun items like dice on the packaging. Further, 24% of the websites did not include any warnings or other health information about D8.
“The low prices, high dosages available, and eye-popping packaging make these products extremely attractive to teens who are looking for a high,” the researchers concluded. They advised clinicians to talk with teen patients about the dangers of D8 and advocated for policymakers to more strictly regulate online distributors of D8 products, particularly in requiring age verification procedures and prohibiting kid-friendly packaging.
Megan Moreno, MD, MSEd, MPH, an adolescent medicine physician and researcher at the University of Wisconsin, Madison, School of Medicine and Public Health and UWHealthKids, was particularly struck by how eye-catching the packaging was. “The bright colors and font choices are really designed to attract adolescents,” commented Dr. Moreno, who was not involved in the study. But she was not surprised overall by the findings.
“Other studies have found that the cannabis industry leverages online tools and social media, alongside youth-friendly packaging, to attract youth to their products,” she said. “What is disappointing is that these companies do not use industry standard approaches, such as the alcohol industry, to age-gate their websites.”
It’s important for providers who care for adolescents to ask about substance use but to especially include questions about substances that teens might not think of as “drugs,” such as Delta 8, Dr. Moreno said.
“Prior research on other types of substance such as these has found that teens can think these are less dangerous versions of cannabis, so providing accurate information and asking about these products can prevent harm to kids,” Dr. Moreno said. Although this study focused on websites that sell D8 products, she said that “another important area of influence to consider is social media messaging around these products, which may drive traffic to the purchasing site.” It’s clear this industry is not going to self-regulate without policy changes, Dr. Moreno added, so she noted the importance of advocating for policy that regulates these sites.
Mr. Grewal, Dr. Milanaik and Dr. Moreno had no disclosures. No external funding sources were noted.
At AAP 2023
FDA okays drug for Duchenne muscular dystrophy
Duchenne muscular dystrophy (DMD) in patients as young as age 2 years, the company has announced Vamorolone is a structurally unique steroidal anti-inflammatory drug that potently inhibits proinflammatory NFkB pathways via high-affinity binding to the glucocorticoid receptor.
“Corticosteroids have been a first line treatment for DMD for many years, but their utility has always been limited by the side effect profile, which includes weight gain, short stature, and decreased bone density, among others,” Sharon Hesterlee, PhD, chief research officer for the Muscular Dystrophy Association, said in a statement.
The approval of vamorolone “provides people living with Duchenne, and their families, a powerful tool to treat the disease, while limiting some negative side effects associated with corticosteroids,” Dr. Hesterlee added.
The approval was based on data from the phase 2b VISION-DMD study, supplemented with safety information collected from three open-label studies.
Vamorolone was administered at doses ranging from 2-6 mg/kg/d for a period of up to 48 months.
Vamorolone demonstrated efficacy similar to that of traditional corticosteroids, with data suggesting a reduction in adverse events – notably related to bone health, growth trajectory, and behavior.
Vamorolone had received orphan drug status for DMD, as well as fast track and rare pediatric disease designations. It will be made available in the United States by Catalyst Pharmaceuticals.
A version of this article first appeared on Medscape.com .
Duchenne muscular dystrophy (DMD) in patients as young as age 2 years, the company has announced Vamorolone is a structurally unique steroidal anti-inflammatory drug that potently inhibits proinflammatory NFkB pathways via high-affinity binding to the glucocorticoid receptor.
“Corticosteroids have been a first line treatment for DMD for many years, but their utility has always been limited by the side effect profile, which includes weight gain, short stature, and decreased bone density, among others,” Sharon Hesterlee, PhD, chief research officer for the Muscular Dystrophy Association, said in a statement.
The approval of vamorolone “provides people living with Duchenne, and their families, a powerful tool to treat the disease, while limiting some negative side effects associated with corticosteroids,” Dr. Hesterlee added.
The approval was based on data from the phase 2b VISION-DMD study, supplemented with safety information collected from three open-label studies.
Vamorolone was administered at doses ranging from 2-6 mg/kg/d for a period of up to 48 months.
Vamorolone demonstrated efficacy similar to that of traditional corticosteroids, with data suggesting a reduction in adverse events – notably related to bone health, growth trajectory, and behavior.
Vamorolone had received orphan drug status for DMD, as well as fast track and rare pediatric disease designations. It will be made available in the United States by Catalyst Pharmaceuticals.
A version of this article first appeared on Medscape.com .
Duchenne muscular dystrophy (DMD) in patients as young as age 2 years, the company has announced Vamorolone is a structurally unique steroidal anti-inflammatory drug that potently inhibits proinflammatory NFkB pathways via high-affinity binding to the glucocorticoid receptor.
“Corticosteroids have been a first line treatment for DMD for many years, but their utility has always been limited by the side effect profile, which includes weight gain, short stature, and decreased bone density, among others,” Sharon Hesterlee, PhD, chief research officer for the Muscular Dystrophy Association, said in a statement.
The approval of vamorolone “provides people living with Duchenne, and their families, a powerful tool to treat the disease, while limiting some negative side effects associated with corticosteroids,” Dr. Hesterlee added.
The approval was based on data from the phase 2b VISION-DMD study, supplemented with safety information collected from three open-label studies.
Vamorolone was administered at doses ranging from 2-6 mg/kg/d for a period of up to 48 months.
Vamorolone demonstrated efficacy similar to that of traditional corticosteroids, with data suggesting a reduction in adverse events – notably related to bone health, growth trajectory, and behavior.
Vamorolone had received orphan drug status for DMD, as well as fast track and rare pediatric disease designations. It will be made available in the United States by Catalyst Pharmaceuticals.
A version of this article first appeared on Medscape.com .
Online nicotine toothpick vendors ignore age restrictions
WASHINGTON – according to a study of 77 stores and 16 online sites.
Online nicotine toothpick sales are “the Wild West” in terms of regulation, said Abhijeet Grewal, a research assistant at Cohen Children’s Medical Center, in New Hyde Park, N.Y., who presented the findings at the annual meeting of the American Academy of Pediatrics.
Nicotine toothpicks have become popular among teenagers as a relatively inconspicuous way to access the drug, Mr. Grewal said. The nicotine content of the toothpicks varies, but many contain as much as 2-3 mg per pick compared with the 1.1-1.8–mg amount inhaled per the average cigarette, he said. The cheap price and teen-friendly flavors like cherry and mocha add to the appeal of the picks. However, data on the marketplace and accessibility of these products are lacking, Mr. Grewal said.
To find out how easily youth can buy nicotine toothpicks through in-person and online channels, Mr. Grewal and colleagues identified and called 404 brick-and-mortar retailers across the United States by phone and asked whether they required ID for purchase of nicotine toothpicks; of the 77 locations that responded, only 1 said that they would sell nicotine toothpicks without asking for proof of age.
The researchers also collected data on 16 vendor websites that sold nicotine toothpicks with shipment to the United States (identified from pixotine.com).
Overall, 11 sites (69%) prompted users to confirm that they were aged 21 years or older to either view the site or place orders, but 12 sites (75%) required no formal method of verification.
Warnings or disclaimers, such as “nicotine is an addictive chemical,” appeared on 69% of sites. Marketing statements including terms such as “discreet” and “cost-effective” to describe the toothpicks, Mr. Grewal said, and online reviews endorsed the products as “convenient” and “rich in flavor.”
The sites in the study offered a total of 32 different flavors, Mr. Grewal said, and 44% of the sites offered some type of discount on prices, which land in the range of approximately $5 for a tube of 20 toothpicks.
Nicotine toothpicks and flavored toothpicks without nicotine were originally marketed as smoking cessation aids, said Mr. Grewal, but their low price point and ability to be consumed discreetly makes them appealing to teens for nicotine use in many environments.
More research is needed to characterize youth use of nicotine toothpick products, as well as purchasing patterns, he said. However, the results highlight the need for regulation of nicotine toothpick vendors to protect youth from accessing nicotine in this form, he said.
Ask adolescents about toothpicks
“While nicotine replacement therapy [NRT] products may be an effective way for people to quit smoking, these products have the potential to introduce minors to nicotine in a seemingly innocent way resulting in dependence,” senior author Ruth Milanaik, DO, also of Cohen Children’s Medical Center, said in an interview. “Many children are intrigued by these fun flavored products, and our team was interested in examining the availability of these products to minors.”
Overall, “our team was quite pleased with brick-and-mortar stores’ spoken requirements of age verification for purchase, and quite worried about the availability of nic picks through online vendors,” she continued.
Clinicians, educators, and parents should be aware of the existence of nicotine toothpicks and the ease with which minors can attain them through online vendors, Dr. Milanaik said. “While NRT is a part of smoking cessation programs, nicotine toothpicks should not be used by minors without clinical reasons,” she said. “The innocuous and innocent nature of these toothpicks may entice minors to try and regularly use these without regard to future dependence.”
The study received no outside funding. The researchers had no financial conflicts to disclose.
A version of this article first appeared on Medscape.com.
WASHINGTON – according to a study of 77 stores and 16 online sites.
Online nicotine toothpick sales are “the Wild West” in terms of regulation, said Abhijeet Grewal, a research assistant at Cohen Children’s Medical Center, in New Hyde Park, N.Y., who presented the findings at the annual meeting of the American Academy of Pediatrics.
Nicotine toothpicks have become popular among teenagers as a relatively inconspicuous way to access the drug, Mr. Grewal said. The nicotine content of the toothpicks varies, but many contain as much as 2-3 mg per pick compared with the 1.1-1.8–mg amount inhaled per the average cigarette, he said. The cheap price and teen-friendly flavors like cherry and mocha add to the appeal of the picks. However, data on the marketplace and accessibility of these products are lacking, Mr. Grewal said.
To find out how easily youth can buy nicotine toothpicks through in-person and online channels, Mr. Grewal and colleagues identified and called 404 brick-and-mortar retailers across the United States by phone and asked whether they required ID for purchase of nicotine toothpicks; of the 77 locations that responded, only 1 said that they would sell nicotine toothpicks without asking for proof of age.
The researchers also collected data on 16 vendor websites that sold nicotine toothpicks with shipment to the United States (identified from pixotine.com).
Overall, 11 sites (69%) prompted users to confirm that they were aged 21 years or older to either view the site or place orders, but 12 sites (75%) required no formal method of verification.
Warnings or disclaimers, such as “nicotine is an addictive chemical,” appeared on 69% of sites. Marketing statements including terms such as “discreet” and “cost-effective” to describe the toothpicks, Mr. Grewal said, and online reviews endorsed the products as “convenient” and “rich in flavor.”
The sites in the study offered a total of 32 different flavors, Mr. Grewal said, and 44% of the sites offered some type of discount on prices, which land in the range of approximately $5 for a tube of 20 toothpicks.
Nicotine toothpicks and flavored toothpicks without nicotine were originally marketed as smoking cessation aids, said Mr. Grewal, but their low price point and ability to be consumed discreetly makes them appealing to teens for nicotine use in many environments.
More research is needed to characterize youth use of nicotine toothpick products, as well as purchasing patterns, he said. However, the results highlight the need for regulation of nicotine toothpick vendors to protect youth from accessing nicotine in this form, he said.
Ask adolescents about toothpicks
“While nicotine replacement therapy [NRT] products may be an effective way for people to quit smoking, these products have the potential to introduce minors to nicotine in a seemingly innocent way resulting in dependence,” senior author Ruth Milanaik, DO, also of Cohen Children’s Medical Center, said in an interview. “Many children are intrigued by these fun flavored products, and our team was interested in examining the availability of these products to minors.”
Overall, “our team was quite pleased with brick-and-mortar stores’ spoken requirements of age verification for purchase, and quite worried about the availability of nic picks through online vendors,” she continued.
Clinicians, educators, and parents should be aware of the existence of nicotine toothpicks and the ease with which minors can attain them through online vendors, Dr. Milanaik said. “While NRT is a part of smoking cessation programs, nicotine toothpicks should not be used by minors without clinical reasons,” she said. “The innocuous and innocent nature of these toothpicks may entice minors to try and regularly use these without regard to future dependence.”
The study received no outside funding. The researchers had no financial conflicts to disclose.
A version of this article first appeared on Medscape.com.
WASHINGTON – according to a study of 77 stores and 16 online sites.
Online nicotine toothpick sales are “the Wild West” in terms of regulation, said Abhijeet Grewal, a research assistant at Cohen Children’s Medical Center, in New Hyde Park, N.Y., who presented the findings at the annual meeting of the American Academy of Pediatrics.
Nicotine toothpicks have become popular among teenagers as a relatively inconspicuous way to access the drug, Mr. Grewal said. The nicotine content of the toothpicks varies, but many contain as much as 2-3 mg per pick compared with the 1.1-1.8–mg amount inhaled per the average cigarette, he said. The cheap price and teen-friendly flavors like cherry and mocha add to the appeal of the picks. However, data on the marketplace and accessibility of these products are lacking, Mr. Grewal said.
To find out how easily youth can buy nicotine toothpicks through in-person and online channels, Mr. Grewal and colleagues identified and called 404 brick-and-mortar retailers across the United States by phone and asked whether they required ID for purchase of nicotine toothpicks; of the 77 locations that responded, only 1 said that they would sell nicotine toothpicks without asking for proof of age.
The researchers also collected data on 16 vendor websites that sold nicotine toothpicks with shipment to the United States (identified from pixotine.com).
Overall, 11 sites (69%) prompted users to confirm that they were aged 21 years or older to either view the site or place orders, but 12 sites (75%) required no formal method of verification.
Warnings or disclaimers, such as “nicotine is an addictive chemical,” appeared on 69% of sites. Marketing statements including terms such as “discreet” and “cost-effective” to describe the toothpicks, Mr. Grewal said, and online reviews endorsed the products as “convenient” and “rich in flavor.”
The sites in the study offered a total of 32 different flavors, Mr. Grewal said, and 44% of the sites offered some type of discount on prices, which land in the range of approximately $5 for a tube of 20 toothpicks.
Nicotine toothpicks and flavored toothpicks without nicotine were originally marketed as smoking cessation aids, said Mr. Grewal, but their low price point and ability to be consumed discreetly makes them appealing to teens for nicotine use in many environments.
More research is needed to characterize youth use of nicotine toothpick products, as well as purchasing patterns, he said. However, the results highlight the need for regulation of nicotine toothpick vendors to protect youth from accessing nicotine in this form, he said.
Ask adolescents about toothpicks
“While nicotine replacement therapy [NRT] products may be an effective way for people to quit smoking, these products have the potential to introduce minors to nicotine in a seemingly innocent way resulting in dependence,” senior author Ruth Milanaik, DO, also of Cohen Children’s Medical Center, said in an interview. “Many children are intrigued by these fun flavored products, and our team was interested in examining the availability of these products to minors.”
Overall, “our team was quite pleased with brick-and-mortar stores’ spoken requirements of age verification for purchase, and quite worried about the availability of nic picks through online vendors,” she continued.
Clinicians, educators, and parents should be aware of the existence of nicotine toothpicks and the ease with which minors can attain them through online vendors, Dr. Milanaik said. “While NRT is a part of smoking cessation programs, nicotine toothpicks should not be used by minors without clinical reasons,” she said. “The innocuous and innocent nature of these toothpicks may entice minors to try and regularly use these without regard to future dependence.”
The study received no outside funding. The researchers had no financial conflicts to disclose.
A version of this article first appeared on Medscape.com.
AT AAP 2023
Potential Uses of Nonthermal Atmospheric Pressure Technology for Dermatologic Conditions in Children
Nonthermal atmospheric plasma (NTAP)(or cold atmospheric plasma [CAP]) is a rapidly developing treatment modality for a wide range of dermatologic conditions. Plasma (or ionized gas) refers to a state of matter composed of electrons, protons, and neutral atoms that generate reactive oxygen and nitrogen species.1 Plasma previously was created using thermal energy, but recent advances have allowed the creation of plasma using atmospheric pressure and room temperature; thus, NTAP can be used without causing damage to living tissue through heat.1 Plasma technology varies greatly, but it generally can be classified as either direct or indirect therapy; direct therapy uses the human body as an electrode, whereas indirect therapy creates plasma through the interaction between 2 electrode devices.1,2 When used on the skin, important dose-dependent relationships have been observed, with CAP application longer than 2 minutes being associated with increased keratinocyte and fibroblast apoptosis.2 Thus, CAP can cause diverse changes to the skin depending on application time and methodology. At adequate yet low concentrations, plasma can promote fibroblast proliferation and upregulate genes involved in collagen and transforming growth factor synthesis.1 Additionally, the reactive oxygen and nitrogen species created by NTAP have been shown to inactivate microorganisms through the destruction of biofilms, lead to diminished immune cell infiltration and cytokine release in autoimmune dermatologic conditions, and exert antitumor properties through cellular DNA damage.1-3 In dermatology, these properties can be harvested to promote wound healing at low doses and the treatment of proliferative skin conditions at high doses.1
Because of its novelty, the safety profile of NTAP is still under investigation, but preliminary studies are promising and show no damage to the skin barrier when excessive plasma exposure is avoided.4 However, dose- and time-dependent damage to cells has been shown. As a result, the exact dose of plasma considered safe is highly variable depending on the vessel, technique, and user, and future clinical research is needed to guide this methodology.4 Additionally, CAP has been shown to cause little pain at the skin surface and may lead to decreased levels of pain in healing wound sites.5 Given this promising safety profile and minimal discomfort to patients, NTAP technology remains promising for use in pediatric dermatology, but there are limited data to characterize its potential use in this population. In this systematic review, we aimed to elucidate reported applications of NTAP for skin conditions in children and discuss the trajectory of this technology in the future of pediatric dermatology.
Methodology
A comprehensive literature review was conducted to identify studies evaluating NTAP technology in pediatric populations using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines. A search of PubMed, Embase, and Web of Science articles was conducted in April 2023 using the terms nonthermal atmospheric plasma or cold atmospheric plasma. All English-language articles that described the use of NTAP as a treatment in pediatric populations or articles that described NTAP use in the treatment of common conditions in this patient group were included based on a review of the article titles and abstracts by 2 independent reviewers, followed by full-text review of relevant articles (M.G., C.L.). Any discrepancies in eligible articles were settled by a third independent researcher (M.V.). One hundred twenty studies were identified, and 95 were screened for inclusion; 9 studies met inclusion criteria and were summarized in this review.
Results
A total of 9 studies were included in this review: 3 describing the success of NTAP in pediatric populations6-8 and 6 describing the potential success of NTAP for dermatologic conditions commonly seen in children (Table).9-14
Studies Describing Success of NTAP—Three clinical reports described the efficacy of NTAP in pediatric dermatology. A case series from 2020 showed full clearance of warts in 100% of patients (n=5) with a 0% recurrence rate when NTAP treatment was applied for 2 minutes to each lesion during each treatment session with the electrode held 1 mm from the lesional surface.6 Each patient was followed up at 3 to 4 weeks, and treatment was repeated if lesions persisted. Patients reported no pain during the procedure, and no adverse effects were noted over the course of treatment.6 Second, a case report described full clearance of diaper dermatitis with no recurrence after 6 months following 6 treatments with NTAP in a 14-month-old girl.7 After treatment with econazole nitrate cream, oral antibiotics, and prednisone failed, CAP treatment was initiated. Each treatment lasted 15 minutes with 3-day time intervals between each of the 6 treatments. There were no adverse events or recurrence of rash at 6-month follow-up.7 A final case report described full clearance of molluscum contagiosum (MC), with no recurrence after 2 months following 4 treatments with NTAP in a 12-year-old boy.8 The patient had untreated MC on the face, neck, shoulder, and thighs. Lesions of the face were treated with CAP, while the other sites were treated with cantharidin using a 0.7% collodion-based solution. Four CAP treatments were performed at 1-month intervals, with CAP applied 1 mm from the lesional surfaces in a circular pattern for 2 minutes. At follow-up 2 months after the final treatment, the patient had no adverse effects and showed no pigmentary changes or scarring.8
Studies Describing the Potential Success of NTAP—Beyond these studies, limited research has been done on NTAP in pediatric populations. The Table summarizes 6 additional studies completed with promising treatment results for dermatologic conditions commonly seen in children: striae distensae, keloids, atopic dermatitis, psoriasis, inverse psoriasis, and acne vulgaris. Across all reports and studies, patients showed significant improvement in their dermatologic conditions following the use of NTAP technology with limited adverse effects reported (P<.05). Suwanchinda and Nararatwanchai9 studied the use of CAP for the treatment of striae distensae. They recruited 23 patients and treated half the body with CAP biweekly for 5 sessions; the other half was left untreated. At follow-up 30 days after the final treatment, striae distensae had improved for both patient and observer assessment scores.9 Another study performed by Suwanchinda and Nararatwanchai10 looked at the efficacy of CAP in treating keloids. They recruited 18 patients, and keloid scars were treated in halves—one half treated with CAP biweekly for 5 sessions and the other left untreated. At follow-up 30 days after the final treatment, keloids significantly improved in color, melanin, texture, and hemoglobin based on assessment by the Antera 3D imaging system (Miravex Limited)(P<.05).10
Kim et al11 studied the efficacy of CAP for the treatment of atopic dermatitis in 22 patients. Each patient had mild to moderate atopic dermatitis that had not been treated with topical agents or antibiotics for at least 2 weeks prior to beginning the study. Additionally, only patients with symmetric lesions—meaning only patients with lesions on both sides of the anatomical extremities—were included. Each patient then received CAP on 1 symmetric lesion and placebo on the other. Cold atmospheric plasma treatment was done 5 mm away from the lesion, and each treatment lasted for 5 minutes. Treatments were done at weeks 0, 1, and 2, with follow-up 4 weeks after the final treatment. The clinical severity of disease was assessed at weeks 0, 1, 2, and 4. Results showed that at week 4, the mean (SD) modified Atopic Dermatitis Antecubital Severity score decreased from 33.73 (21.21) at week 0 to 13.12 (15.92). Additionally, the pruritic visual analog scale showed significant improvement with treatment vs baseline (P≤.0001).11
Two studies examined how NTAP can be used in the treatment of psoriasis. First, Gareri et al12 used CAP to treat a psoriatic plaque in a 20-year-old woman. These plaques on the left hand previously had been unresponsive to topical psoriasis treatments. The patient received 2 treatments with CAP on days 0 and 3; at 14 days, the plaque completely resolved with an itch score of 0.12 Next, Zheng et al13 treated 2 patients with NTAP for inverse psoriasis. The first patient was a 26-year-old woman with plaques in the axilla and buttocks as well as inframammary lesions that failed to respond to treatment with topicals and vitamin D analogues. She received CAP treatments 2 to 3 times weekly for 5 total treatments with application to each region occurring 1 mm from the skin surface. The lesions completely resolved with no recurrence at 6 weeks. The second patient was a 38-year-old woman with inverse psoriasis in the axilla and groin; she received treatment every 3 days for 8 total treatments, which led to complete remission, with no recurrence noted at 1 month.13
Arisi et al14 used NTAP to treat acne vulgaris in 2 patients. The first patient was a 24-year-old man with moderate acne on the face that did not improve with topicals or oral antibiotics. The patient received 5 CAP treatments with no adverse events noted. The patient discontinued treatment on his own, but the number of lesions decreased after the fifth treatment. The second patient was a 21-year-old woman with moderate facial acne that failed to respond to treatment with topicals and oral tetracycline. The patient received 8 CAP treatments and experienced a reduction in the number of lesions during treatment. There were no adverse events, and improvement was maintained at 3-month follow-up.14
Comment
Although the use of NTAP in pediatric dermatology is scarcely described in the literature, the technology will certainly have applications in the future treatment of a wide variety of pediatric disorders. In addition to the clinical success shown in several studies,6-14 this technology has been shown to cause minimal damage to skin when application time is minimized. One study conducted on ex vivo skin showed that NTAP technology can safely be used for up to 2 minutes without major DNA damage.15 Through its diverse mechanisms of action, NTAP can induce modification of proteins and cell membranes in a noninvasive manner.2 In conditions with impaired barrier function, such as atopic and diaper dermatitis, studies in mouse models have shown improvement in lesions via upregulation of mesencephalic astrocyte-derived neurotrophic factor that contributes to decreased inflammation and cell apoptosis.16 Additionally, the generation of reactive oxygen and nitrogen species has been shown to decrease Staphylococcus aureus colonization to improve atopic dermatitis lesions in patients.11
Many other proposed benefits of NTAP in dermatologic disease also have been proposed. Nonthermal atmospheric plasma has been shown to increase messenger RNA expression of proinflammatory cytokines (IL-1, IL-6) and upregulate type III collagen production in early stages of wound healing.17 Furthermore, NTAP has been shown to stimulate nuclear factor erythroid 2–related pathways involved in antioxidant production in keratinocytes, further promoting wound healing.18 Additionally, CAP has been shown to increase expression of caspases and induce mitochondrial dysfunction that promotes cell death in different cancer cell lines.19 It is clear that the exact breadth of NTAP’s biochemical effects are unknown, but the current literature shows promise for its use in cutaneous healing and cancer treatment.
Beyond its diverse applications, treatment with NTAP yields a unique advantage to pharmacologic therapies in that there is no risk for medication interactions or risk for pharmacologic adverse effects. Cantharidin is not approved by the US Food and Drug Administration but commonly is used to treat MC. It is a blister beetle extract that causes a blister to form when applied to the skin. When orally ingested, the drug is toxic to the gastrointestinal tract and kidneys because of its phosphodiesterase inhibition, a feared complication in pediatric patients who may inadvertently ingest it during treatment.20 This utility extends beyond MC, such as the beneficial outcomes described by Suwanchinda and Nararatwanchai10 in using NTAP for keloid scars. Treatment with NTAP may replace triamcinolone injections, which are commonly associated with skin atrophy and ulceration. In addition, NTAP application to the skin has been reported to be relatively painless.5 Thus, NTAP maintains a distinct advantage over other commonly used nonpharmacologic treatment options, including curettage and cryosurgery. Curettage has widely been noted to be traumatic for the patient, may be more likely to leave a mark, and is prone to user error.20 Cryosurgery is a common form of treatment for MC because it is cost-effective and has good cosmetic results; however, it is more painful than cantharidin or anesthetized curettage.21 Treatment with NTAP is an emerging therapeutic tool with an expanding role in the treatment of dermatologic patients because it provides advantages over many standard therapies due to its minimal side-effect profile involving pain and nonpharmacologic nature.
Limitations of this report include exclusion of non–English-language articles and lack of control or comparison groups to standard therapies across studies. Additionally, reports of NTAP success occurred in many conditions that are self-limited and may have resolved on their own. Regardless, we aimed to summarize how NTAP currently is being used in pediatric populations and highlight its potential uses moving forward. Given its promising safety profile and painless nature, future clinical trials should prioritize the investigation of NTAP use in common pediatric dermatologic conditions to determine if they are equal or superior to current standards of care.
- Gan L, Zhang S, Poorun D, et al. Medical applications of nonthermal atmospheric pressure plasma in dermatology. J Dtsch Dermatol Ges. 2018;16:7-13. doi:https://doi.org/10.1111/ddg.13373
- Gay-Mimbrera J, García MC, Isla-Tejera B, et al. Clinical and biological principles of cold atmospheric plasma application in skin cancer. Adv Ther. 2016;33:894-909. doi:10.1007/s12325-016-0338-1. Published correction appears in Adv Ther. 2017;34:280. doi:10.1007/s12325-016-0437-z
- Zhai SY, Kong MG, Xia YM. Cold atmospheric plasma ameliorates skin diseases involving reactive oxygen/nitrogen species-mediated functions. Front Immunol. 2022;13:868386. doi:10.3389/fimmu.2022.868386
- Tan F, Wang Y, Zhang S, et al. Plasma dermatology: skin therapy using cold atmospheric plasma. Front Oncol. 2022;12:918484. doi:10.3389/fonc.2022.918484
- van Welzen A, Hoch M, Wahl P, et al. The response and tolerability of a novel cold atmospheric plasma wound dressing for the healing of split skin graft donor sites: a controlled pilot study. Skin Pharmacol Physiol. 2021;34:328-336. doi:10.1159/000517524
- Friedman PC, Fridman G, Fridman A. Using cold plasma to treat warts in children: a case series. Pediatr Dermatol. 2020;37:706-709. doi:10.1111/pde.14180
- Zhang C, Zhao J, Gao Y, et al. Cold atmospheric plasma treatment for diaper dermatitis: a case report [published online January 27, 2021]. Dermatol Ther. 2021;34:E14739. doi:10.1111/dth.14739
- Friedman PC, Fridman G, Fridman A. Cold atmospheric pressure plasma clears molluscum contagiosum. Exp Dermatol. 2023;32:562-563. doi:10.1111/exd.14695
- Suwanchinda A, Nararatwanchai T. The efficacy and safety of the innovative cold atmospheric-pressure plasma technology in the treatment of striae distensae: a randomized controlled trial. J Cosmet Dermatol. 2022;21:6805-6814. doi:10.1111/jocd.15458
- Suwanchinda A, Nararatwanchai T. Efficacy and safety of the innovative cold atmospheric-pressure plasma technology in the treatment of keloid: a randomized controlled trial. J Cosmet Dermatol. 2022;21:6788-6797. doi:10.1111/jocd.15397
- Kim YJ, Lim DJ, Lee MY, et al. Prospective, comparative clinical pilot study of cold atmospheric plasma device in the treatment of atopic dermatitis. Sci Rep. 2021;11:14461. doi:10.1038/s41598-021-93941-y
- Gareri C, Bennardo L, De Masi G. Use of a new cold plasma tool for psoriasis treatment: a case report. SAGE Open Med Case Rep. 2020;8:2050313X20922709. doi:10.1177/2050313X20922709
- Zheng L, Gao J, Cao Y, et al. Two case reports of inverse psoriasis treated with cold atmospheric plasma. Dermatol Ther. 2020;33:E14257. doi:10.1111/dth.14257
- Arisi M, Venturuzzo A, Gelmetti A, et al. Cold atmospheric plasma (CAP) as a promising therapeutic option for mild to moderate acne vulgaris: clinical and non-invasive evaluation of two cases. Clin Plasma Med. 2020;19-20:100110.
- Isbary G, Köritzer J, Mitra A, et al. Ex vivo human skin experiments for the evaluation of safety of new cold atmospheric plasma devices. Clin Plasma Med. 2013;1:36-44.
- Sun T, Zhang X, Hou C, et al. Cold plasma irradiation attenuates atopic dermatitis via enhancing HIF-1α-induced MANF transcription expression. Front Immunol. 2022;13:941219. doi:10.3389/fimmu.2022.941219
- Eggers B, Marciniak J, Memmert S, et al. The beneficial effect of cold atmospheric plasma on parameters of molecules and cell function involved in wound healing in human osteoblast-like cells in vitro. Odontology. 2020;108:607-616. doi:10.1007/s10266-020-00487-y
- Conway GE, He Z, Hutanu AL, et al. Cold atmospheric plasma induces accumulation of lysosomes and caspase-independent cell death in U373MG glioblastoma multiforme cells. Sci Rep. 2019;9:12891. doi:10.1038/s41598-019-49013-3
- Schmidt A, Dietrich S, Steuer A, et al. Non-thermal plasma activates human keratinocytes by stimulation of antioxidant and phase II pathways. J Biol Chem. 2015;290:6731-6750. doi:10.1074/jbc.M114.603555
- Silverberg NB. Pediatric molluscum contagiosum. Pediatr Drugs. 2003;5:505-511. doi:10.2165/00148581-200305080-00001
- Cotton DW, Cooper C, Barrett DF, et al. Severe atypical molluscum contagiosum infection in an immunocompromised host. Br J Dermatol. 1987;116:871-876. doi:10.1111/j.1365-2133.1987.tb04908.x
Nonthermal atmospheric plasma (NTAP)(or cold atmospheric plasma [CAP]) is a rapidly developing treatment modality for a wide range of dermatologic conditions. Plasma (or ionized gas) refers to a state of matter composed of electrons, protons, and neutral atoms that generate reactive oxygen and nitrogen species.1 Plasma previously was created using thermal energy, but recent advances have allowed the creation of plasma using atmospheric pressure and room temperature; thus, NTAP can be used without causing damage to living tissue through heat.1 Plasma technology varies greatly, but it generally can be classified as either direct or indirect therapy; direct therapy uses the human body as an electrode, whereas indirect therapy creates plasma through the interaction between 2 electrode devices.1,2 When used on the skin, important dose-dependent relationships have been observed, with CAP application longer than 2 minutes being associated with increased keratinocyte and fibroblast apoptosis.2 Thus, CAP can cause diverse changes to the skin depending on application time and methodology. At adequate yet low concentrations, plasma can promote fibroblast proliferation and upregulate genes involved in collagen and transforming growth factor synthesis.1 Additionally, the reactive oxygen and nitrogen species created by NTAP have been shown to inactivate microorganisms through the destruction of biofilms, lead to diminished immune cell infiltration and cytokine release in autoimmune dermatologic conditions, and exert antitumor properties through cellular DNA damage.1-3 In dermatology, these properties can be harvested to promote wound healing at low doses and the treatment of proliferative skin conditions at high doses.1
Because of its novelty, the safety profile of NTAP is still under investigation, but preliminary studies are promising and show no damage to the skin barrier when excessive plasma exposure is avoided.4 However, dose- and time-dependent damage to cells has been shown. As a result, the exact dose of plasma considered safe is highly variable depending on the vessel, technique, and user, and future clinical research is needed to guide this methodology.4 Additionally, CAP has been shown to cause little pain at the skin surface and may lead to decreased levels of pain in healing wound sites.5 Given this promising safety profile and minimal discomfort to patients, NTAP technology remains promising for use in pediatric dermatology, but there are limited data to characterize its potential use in this population. In this systematic review, we aimed to elucidate reported applications of NTAP for skin conditions in children and discuss the trajectory of this technology in the future of pediatric dermatology.
Methodology
A comprehensive literature review was conducted to identify studies evaluating NTAP technology in pediatric populations using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines. A search of PubMed, Embase, and Web of Science articles was conducted in April 2023 using the terms nonthermal atmospheric plasma or cold atmospheric plasma. All English-language articles that described the use of NTAP as a treatment in pediatric populations or articles that described NTAP use in the treatment of common conditions in this patient group were included based on a review of the article titles and abstracts by 2 independent reviewers, followed by full-text review of relevant articles (M.G., C.L.). Any discrepancies in eligible articles were settled by a third independent researcher (M.V.). One hundred twenty studies were identified, and 95 were screened for inclusion; 9 studies met inclusion criteria and were summarized in this review.
Results
A total of 9 studies were included in this review: 3 describing the success of NTAP in pediatric populations6-8 and 6 describing the potential success of NTAP for dermatologic conditions commonly seen in children (Table).9-14
Studies Describing Success of NTAP—Three clinical reports described the efficacy of NTAP in pediatric dermatology. A case series from 2020 showed full clearance of warts in 100% of patients (n=5) with a 0% recurrence rate when NTAP treatment was applied for 2 minutes to each lesion during each treatment session with the electrode held 1 mm from the lesional surface.6 Each patient was followed up at 3 to 4 weeks, and treatment was repeated if lesions persisted. Patients reported no pain during the procedure, and no adverse effects were noted over the course of treatment.6 Second, a case report described full clearance of diaper dermatitis with no recurrence after 6 months following 6 treatments with NTAP in a 14-month-old girl.7 After treatment with econazole nitrate cream, oral antibiotics, and prednisone failed, CAP treatment was initiated. Each treatment lasted 15 minutes with 3-day time intervals between each of the 6 treatments. There were no adverse events or recurrence of rash at 6-month follow-up.7 A final case report described full clearance of molluscum contagiosum (MC), with no recurrence after 2 months following 4 treatments with NTAP in a 12-year-old boy.8 The patient had untreated MC on the face, neck, shoulder, and thighs. Lesions of the face were treated with CAP, while the other sites were treated with cantharidin using a 0.7% collodion-based solution. Four CAP treatments were performed at 1-month intervals, with CAP applied 1 mm from the lesional surfaces in a circular pattern for 2 minutes. At follow-up 2 months after the final treatment, the patient had no adverse effects and showed no pigmentary changes or scarring.8
Studies Describing the Potential Success of NTAP—Beyond these studies, limited research has been done on NTAP in pediatric populations. The Table summarizes 6 additional studies completed with promising treatment results for dermatologic conditions commonly seen in children: striae distensae, keloids, atopic dermatitis, psoriasis, inverse psoriasis, and acne vulgaris. Across all reports and studies, patients showed significant improvement in their dermatologic conditions following the use of NTAP technology with limited adverse effects reported (P<.05). Suwanchinda and Nararatwanchai9 studied the use of CAP for the treatment of striae distensae. They recruited 23 patients and treated half the body with CAP biweekly for 5 sessions; the other half was left untreated. At follow-up 30 days after the final treatment, striae distensae had improved for both patient and observer assessment scores.9 Another study performed by Suwanchinda and Nararatwanchai10 looked at the efficacy of CAP in treating keloids. They recruited 18 patients, and keloid scars were treated in halves—one half treated with CAP biweekly for 5 sessions and the other left untreated. At follow-up 30 days after the final treatment, keloids significantly improved in color, melanin, texture, and hemoglobin based on assessment by the Antera 3D imaging system (Miravex Limited)(P<.05).10
Kim et al11 studied the efficacy of CAP for the treatment of atopic dermatitis in 22 patients. Each patient had mild to moderate atopic dermatitis that had not been treated with topical agents or antibiotics for at least 2 weeks prior to beginning the study. Additionally, only patients with symmetric lesions—meaning only patients with lesions on both sides of the anatomical extremities—were included. Each patient then received CAP on 1 symmetric lesion and placebo on the other. Cold atmospheric plasma treatment was done 5 mm away from the lesion, and each treatment lasted for 5 minutes. Treatments were done at weeks 0, 1, and 2, with follow-up 4 weeks after the final treatment. The clinical severity of disease was assessed at weeks 0, 1, 2, and 4. Results showed that at week 4, the mean (SD) modified Atopic Dermatitis Antecubital Severity score decreased from 33.73 (21.21) at week 0 to 13.12 (15.92). Additionally, the pruritic visual analog scale showed significant improvement with treatment vs baseline (P≤.0001).11
Two studies examined how NTAP can be used in the treatment of psoriasis. First, Gareri et al12 used CAP to treat a psoriatic plaque in a 20-year-old woman. These plaques on the left hand previously had been unresponsive to topical psoriasis treatments. The patient received 2 treatments with CAP on days 0 and 3; at 14 days, the plaque completely resolved with an itch score of 0.12 Next, Zheng et al13 treated 2 patients with NTAP for inverse psoriasis. The first patient was a 26-year-old woman with plaques in the axilla and buttocks as well as inframammary lesions that failed to respond to treatment with topicals and vitamin D analogues. She received CAP treatments 2 to 3 times weekly for 5 total treatments with application to each region occurring 1 mm from the skin surface. The lesions completely resolved with no recurrence at 6 weeks. The second patient was a 38-year-old woman with inverse psoriasis in the axilla and groin; she received treatment every 3 days for 8 total treatments, which led to complete remission, with no recurrence noted at 1 month.13
Arisi et al14 used NTAP to treat acne vulgaris in 2 patients. The first patient was a 24-year-old man with moderate acne on the face that did not improve with topicals or oral antibiotics. The patient received 5 CAP treatments with no adverse events noted. The patient discontinued treatment on his own, but the number of lesions decreased after the fifth treatment. The second patient was a 21-year-old woman with moderate facial acne that failed to respond to treatment with topicals and oral tetracycline. The patient received 8 CAP treatments and experienced a reduction in the number of lesions during treatment. There were no adverse events, and improvement was maintained at 3-month follow-up.14
Comment
Although the use of NTAP in pediatric dermatology is scarcely described in the literature, the technology will certainly have applications in the future treatment of a wide variety of pediatric disorders. In addition to the clinical success shown in several studies,6-14 this technology has been shown to cause minimal damage to skin when application time is minimized. One study conducted on ex vivo skin showed that NTAP technology can safely be used for up to 2 minutes without major DNA damage.15 Through its diverse mechanisms of action, NTAP can induce modification of proteins and cell membranes in a noninvasive manner.2 In conditions with impaired barrier function, such as atopic and diaper dermatitis, studies in mouse models have shown improvement in lesions via upregulation of mesencephalic astrocyte-derived neurotrophic factor that contributes to decreased inflammation and cell apoptosis.16 Additionally, the generation of reactive oxygen and nitrogen species has been shown to decrease Staphylococcus aureus colonization to improve atopic dermatitis lesions in patients.11
Many other proposed benefits of NTAP in dermatologic disease also have been proposed. Nonthermal atmospheric plasma has been shown to increase messenger RNA expression of proinflammatory cytokines (IL-1, IL-6) and upregulate type III collagen production in early stages of wound healing.17 Furthermore, NTAP has been shown to stimulate nuclear factor erythroid 2–related pathways involved in antioxidant production in keratinocytes, further promoting wound healing.18 Additionally, CAP has been shown to increase expression of caspases and induce mitochondrial dysfunction that promotes cell death in different cancer cell lines.19 It is clear that the exact breadth of NTAP’s biochemical effects are unknown, but the current literature shows promise for its use in cutaneous healing and cancer treatment.
Beyond its diverse applications, treatment with NTAP yields a unique advantage to pharmacologic therapies in that there is no risk for medication interactions or risk for pharmacologic adverse effects. Cantharidin is not approved by the US Food and Drug Administration but commonly is used to treat MC. It is a blister beetle extract that causes a blister to form when applied to the skin. When orally ingested, the drug is toxic to the gastrointestinal tract and kidneys because of its phosphodiesterase inhibition, a feared complication in pediatric patients who may inadvertently ingest it during treatment.20 This utility extends beyond MC, such as the beneficial outcomes described by Suwanchinda and Nararatwanchai10 in using NTAP for keloid scars. Treatment with NTAP may replace triamcinolone injections, which are commonly associated with skin atrophy and ulceration. In addition, NTAP application to the skin has been reported to be relatively painless.5 Thus, NTAP maintains a distinct advantage over other commonly used nonpharmacologic treatment options, including curettage and cryosurgery. Curettage has widely been noted to be traumatic for the patient, may be more likely to leave a mark, and is prone to user error.20 Cryosurgery is a common form of treatment for MC because it is cost-effective and has good cosmetic results; however, it is more painful than cantharidin or anesthetized curettage.21 Treatment with NTAP is an emerging therapeutic tool with an expanding role in the treatment of dermatologic patients because it provides advantages over many standard therapies due to its minimal side-effect profile involving pain and nonpharmacologic nature.
Limitations of this report include exclusion of non–English-language articles and lack of control or comparison groups to standard therapies across studies. Additionally, reports of NTAP success occurred in many conditions that are self-limited and may have resolved on their own. Regardless, we aimed to summarize how NTAP currently is being used in pediatric populations and highlight its potential uses moving forward. Given its promising safety profile and painless nature, future clinical trials should prioritize the investigation of NTAP use in common pediatric dermatologic conditions to determine if they are equal or superior to current standards of care.
Nonthermal atmospheric plasma (NTAP)(or cold atmospheric plasma [CAP]) is a rapidly developing treatment modality for a wide range of dermatologic conditions. Plasma (or ionized gas) refers to a state of matter composed of electrons, protons, and neutral atoms that generate reactive oxygen and nitrogen species.1 Plasma previously was created using thermal energy, but recent advances have allowed the creation of plasma using atmospheric pressure and room temperature; thus, NTAP can be used without causing damage to living tissue through heat.1 Plasma technology varies greatly, but it generally can be classified as either direct or indirect therapy; direct therapy uses the human body as an electrode, whereas indirect therapy creates plasma through the interaction between 2 electrode devices.1,2 When used on the skin, important dose-dependent relationships have been observed, with CAP application longer than 2 minutes being associated with increased keratinocyte and fibroblast apoptosis.2 Thus, CAP can cause diverse changes to the skin depending on application time and methodology. At adequate yet low concentrations, plasma can promote fibroblast proliferation and upregulate genes involved in collagen and transforming growth factor synthesis.1 Additionally, the reactive oxygen and nitrogen species created by NTAP have been shown to inactivate microorganisms through the destruction of biofilms, lead to diminished immune cell infiltration and cytokine release in autoimmune dermatologic conditions, and exert antitumor properties through cellular DNA damage.1-3 In dermatology, these properties can be harvested to promote wound healing at low doses and the treatment of proliferative skin conditions at high doses.1
Because of its novelty, the safety profile of NTAP is still under investigation, but preliminary studies are promising and show no damage to the skin barrier when excessive plasma exposure is avoided.4 However, dose- and time-dependent damage to cells has been shown. As a result, the exact dose of plasma considered safe is highly variable depending on the vessel, technique, and user, and future clinical research is needed to guide this methodology.4 Additionally, CAP has been shown to cause little pain at the skin surface and may lead to decreased levels of pain in healing wound sites.5 Given this promising safety profile and minimal discomfort to patients, NTAP technology remains promising for use in pediatric dermatology, but there are limited data to characterize its potential use in this population. In this systematic review, we aimed to elucidate reported applications of NTAP for skin conditions in children and discuss the trajectory of this technology in the future of pediatric dermatology.
Methodology
A comprehensive literature review was conducted to identify studies evaluating NTAP technology in pediatric populations using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines. A search of PubMed, Embase, and Web of Science articles was conducted in April 2023 using the terms nonthermal atmospheric plasma or cold atmospheric plasma. All English-language articles that described the use of NTAP as a treatment in pediatric populations or articles that described NTAP use in the treatment of common conditions in this patient group were included based on a review of the article titles and abstracts by 2 independent reviewers, followed by full-text review of relevant articles (M.G., C.L.). Any discrepancies in eligible articles were settled by a third independent researcher (M.V.). One hundred twenty studies were identified, and 95 were screened for inclusion; 9 studies met inclusion criteria and were summarized in this review.
Results
A total of 9 studies were included in this review: 3 describing the success of NTAP in pediatric populations6-8 and 6 describing the potential success of NTAP for dermatologic conditions commonly seen in children (Table).9-14
Studies Describing Success of NTAP—Three clinical reports described the efficacy of NTAP in pediatric dermatology. A case series from 2020 showed full clearance of warts in 100% of patients (n=5) with a 0% recurrence rate when NTAP treatment was applied for 2 minutes to each lesion during each treatment session with the electrode held 1 mm from the lesional surface.6 Each patient was followed up at 3 to 4 weeks, and treatment was repeated if lesions persisted. Patients reported no pain during the procedure, and no adverse effects were noted over the course of treatment.6 Second, a case report described full clearance of diaper dermatitis with no recurrence after 6 months following 6 treatments with NTAP in a 14-month-old girl.7 After treatment with econazole nitrate cream, oral antibiotics, and prednisone failed, CAP treatment was initiated. Each treatment lasted 15 minutes with 3-day time intervals between each of the 6 treatments. There were no adverse events or recurrence of rash at 6-month follow-up.7 A final case report described full clearance of molluscum contagiosum (MC), with no recurrence after 2 months following 4 treatments with NTAP in a 12-year-old boy.8 The patient had untreated MC on the face, neck, shoulder, and thighs. Lesions of the face were treated with CAP, while the other sites were treated with cantharidin using a 0.7% collodion-based solution. Four CAP treatments were performed at 1-month intervals, with CAP applied 1 mm from the lesional surfaces in a circular pattern for 2 minutes. At follow-up 2 months after the final treatment, the patient had no adverse effects and showed no pigmentary changes or scarring.8
Studies Describing the Potential Success of NTAP—Beyond these studies, limited research has been done on NTAP in pediatric populations. The Table summarizes 6 additional studies completed with promising treatment results for dermatologic conditions commonly seen in children: striae distensae, keloids, atopic dermatitis, psoriasis, inverse psoriasis, and acne vulgaris. Across all reports and studies, patients showed significant improvement in their dermatologic conditions following the use of NTAP technology with limited adverse effects reported (P<.05). Suwanchinda and Nararatwanchai9 studied the use of CAP for the treatment of striae distensae. They recruited 23 patients and treated half the body with CAP biweekly for 5 sessions; the other half was left untreated. At follow-up 30 days after the final treatment, striae distensae had improved for both patient and observer assessment scores.9 Another study performed by Suwanchinda and Nararatwanchai10 looked at the efficacy of CAP in treating keloids. They recruited 18 patients, and keloid scars were treated in halves—one half treated with CAP biweekly for 5 sessions and the other left untreated. At follow-up 30 days after the final treatment, keloids significantly improved in color, melanin, texture, and hemoglobin based on assessment by the Antera 3D imaging system (Miravex Limited)(P<.05).10
Kim et al11 studied the efficacy of CAP for the treatment of atopic dermatitis in 22 patients. Each patient had mild to moderate atopic dermatitis that had not been treated with topical agents or antibiotics for at least 2 weeks prior to beginning the study. Additionally, only patients with symmetric lesions—meaning only patients with lesions on both sides of the anatomical extremities—were included. Each patient then received CAP on 1 symmetric lesion and placebo on the other. Cold atmospheric plasma treatment was done 5 mm away from the lesion, and each treatment lasted for 5 minutes. Treatments were done at weeks 0, 1, and 2, with follow-up 4 weeks after the final treatment. The clinical severity of disease was assessed at weeks 0, 1, 2, and 4. Results showed that at week 4, the mean (SD) modified Atopic Dermatitis Antecubital Severity score decreased from 33.73 (21.21) at week 0 to 13.12 (15.92). Additionally, the pruritic visual analog scale showed significant improvement with treatment vs baseline (P≤.0001).11
Two studies examined how NTAP can be used in the treatment of psoriasis. First, Gareri et al12 used CAP to treat a psoriatic plaque in a 20-year-old woman. These plaques on the left hand previously had been unresponsive to topical psoriasis treatments. The patient received 2 treatments with CAP on days 0 and 3; at 14 days, the plaque completely resolved with an itch score of 0.12 Next, Zheng et al13 treated 2 patients with NTAP for inverse psoriasis. The first patient was a 26-year-old woman with plaques in the axilla and buttocks as well as inframammary lesions that failed to respond to treatment with topicals and vitamin D analogues. She received CAP treatments 2 to 3 times weekly for 5 total treatments with application to each region occurring 1 mm from the skin surface. The lesions completely resolved with no recurrence at 6 weeks. The second patient was a 38-year-old woman with inverse psoriasis in the axilla and groin; she received treatment every 3 days for 8 total treatments, which led to complete remission, with no recurrence noted at 1 month.13
Arisi et al14 used NTAP to treat acne vulgaris in 2 patients. The first patient was a 24-year-old man with moderate acne on the face that did not improve with topicals or oral antibiotics. The patient received 5 CAP treatments with no adverse events noted. The patient discontinued treatment on his own, but the number of lesions decreased after the fifth treatment. The second patient was a 21-year-old woman with moderate facial acne that failed to respond to treatment with topicals and oral tetracycline. The patient received 8 CAP treatments and experienced a reduction in the number of lesions during treatment. There were no adverse events, and improvement was maintained at 3-month follow-up.14
Comment
Although the use of NTAP in pediatric dermatology is scarcely described in the literature, the technology will certainly have applications in the future treatment of a wide variety of pediatric disorders. In addition to the clinical success shown in several studies,6-14 this technology has been shown to cause minimal damage to skin when application time is minimized. One study conducted on ex vivo skin showed that NTAP technology can safely be used for up to 2 minutes without major DNA damage.15 Through its diverse mechanisms of action, NTAP can induce modification of proteins and cell membranes in a noninvasive manner.2 In conditions with impaired barrier function, such as atopic and diaper dermatitis, studies in mouse models have shown improvement in lesions via upregulation of mesencephalic astrocyte-derived neurotrophic factor that contributes to decreased inflammation and cell apoptosis.16 Additionally, the generation of reactive oxygen and nitrogen species has been shown to decrease Staphylococcus aureus colonization to improve atopic dermatitis lesions in patients.11
Many other proposed benefits of NTAP in dermatologic disease also have been proposed. Nonthermal atmospheric plasma has been shown to increase messenger RNA expression of proinflammatory cytokines (IL-1, IL-6) and upregulate type III collagen production in early stages of wound healing.17 Furthermore, NTAP has been shown to stimulate nuclear factor erythroid 2–related pathways involved in antioxidant production in keratinocytes, further promoting wound healing.18 Additionally, CAP has been shown to increase expression of caspases and induce mitochondrial dysfunction that promotes cell death in different cancer cell lines.19 It is clear that the exact breadth of NTAP’s biochemical effects are unknown, but the current literature shows promise for its use in cutaneous healing and cancer treatment.
Beyond its diverse applications, treatment with NTAP yields a unique advantage to pharmacologic therapies in that there is no risk for medication interactions or risk for pharmacologic adverse effects. Cantharidin is not approved by the US Food and Drug Administration but commonly is used to treat MC. It is a blister beetle extract that causes a blister to form when applied to the skin. When orally ingested, the drug is toxic to the gastrointestinal tract and kidneys because of its phosphodiesterase inhibition, a feared complication in pediatric patients who may inadvertently ingest it during treatment.20 This utility extends beyond MC, such as the beneficial outcomes described by Suwanchinda and Nararatwanchai10 in using NTAP for keloid scars. Treatment with NTAP may replace triamcinolone injections, which are commonly associated with skin atrophy and ulceration. In addition, NTAP application to the skin has been reported to be relatively painless.5 Thus, NTAP maintains a distinct advantage over other commonly used nonpharmacologic treatment options, including curettage and cryosurgery. Curettage has widely been noted to be traumatic for the patient, may be more likely to leave a mark, and is prone to user error.20 Cryosurgery is a common form of treatment for MC because it is cost-effective and has good cosmetic results; however, it is more painful than cantharidin or anesthetized curettage.21 Treatment with NTAP is an emerging therapeutic tool with an expanding role in the treatment of dermatologic patients because it provides advantages over many standard therapies due to its minimal side-effect profile involving pain and nonpharmacologic nature.
Limitations of this report include exclusion of non–English-language articles and lack of control or comparison groups to standard therapies across studies. Additionally, reports of NTAP success occurred in many conditions that are self-limited and may have resolved on their own. Regardless, we aimed to summarize how NTAP currently is being used in pediatric populations and highlight its potential uses moving forward. Given its promising safety profile and painless nature, future clinical trials should prioritize the investigation of NTAP use in common pediatric dermatologic conditions to determine if they are equal or superior to current standards of care.
- Gan L, Zhang S, Poorun D, et al. Medical applications of nonthermal atmospheric pressure plasma in dermatology. J Dtsch Dermatol Ges. 2018;16:7-13. doi:https://doi.org/10.1111/ddg.13373
- Gay-Mimbrera J, García MC, Isla-Tejera B, et al. Clinical and biological principles of cold atmospheric plasma application in skin cancer. Adv Ther. 2016;33:894-909. doi:10.1007/s12325-016-0338-1. Published correction appears in Adv Ther. 2017;34:280. doi:10.1007/s12325-016-0437-z
- Zhai SY, Kong MG, Xia YM. Cold atmospheric plasma ameliorates skin diseases involving reactive oxygen/nitrogen species-mediated functions. Front Immunol. 2022;13:868386. doi:10.3389/fimmu.2022.868386
- Tan F, Wang Y, Zhang S, et al. Plasma dermatology: skin therapy using cold atmospheric plasma. Front Oncol. 2022;12:918484. doi:10.3389/fonc.2022.918484
- van Welzen A, Hoch M, Wahl P, et al. The response and tolerability of a novel cold atmospheric plasma wound dressing for the healing of split skin graft donor sites: a controlled pilot study. Skin Pharmacol Physiol. 2021;34:328-336. doi:10.1159/000517524
- Friedman PC, Fridman G, Fridman A. Using cold plasma to treat warts in children: a case series. Pediatr Dermatol. 2020;37:706-709. doi:10.1111/pde.14180
- Zhang C, Zhao J, Gao Y, et al. Cold atmospheric plasma treatment for diaper dermatitis: a case report [published online January 27, 2021]. Dermatol Ther. 2021;34:E14739. doi:10.1111/dth.14739
- Friedman PC, Fridman G, Fridman A. Cold atmospheric pressure plasma clears molluscum contagiosum. Exp Dermatol. 2023;32:562-563. doi:10.1111/exd.14695
- Suwanchinda A, Nararatwanchai T. The efficacy and safety of the innovative cold atmospheric-pressure plasma technology in the treatment of striae distensae: a randomized controlled trial. J Cosmet Dermatol. 2022;21:6805-6814. doi:10.1111/jocd.15458
- Suwanchinda A, Nararatwanchai T. Efficacy and safety of the innovative cold atmospheric-pressure plasma technology in the treatment of keloid: a randomized controlled trial. J Cosmet Dermatol. 2022;21:6788-6797. doi:10.1111/jocd.15397
- Kim YJ, Lim DJ, Lee MY, et al. Prospective, comparative clinical pilot study of cold atmospheric plasma device in the treatment of atopic dermatitis. Sci Rep. 2021;11:14461. doi:10.1038/s41598-021-93941-y
- Gareri C, Bennardo L, De Masi G. Use of a new cold plasma tool for psoriasis treatment: a case report. SAGE Open Med Case Rep. 2020;8:2050313X20922709. doi:10.1177/2050313X20922709
- Zheng L, Gao J, Cao Y, et al. Two case reports of inverse psoriasis treated with cold atmospheric plasma. Dermatol Ther. 2020;33:E14257. doi:10.1111/dth.14257
- Arisi M, Venturuzzo A, Gelmetti A, et al. Cold atmospheric plasma (CAP) as a promising therapeutic option for mild to moderate acne vulgaris: clinical and non-invasive evaluation of two cases. Clin Plasma Med. 2020;19-20:100110.
- Isbary G, Köritzer J, Mitra A, et al. Ex vivo human skin experiments for the evaluation of safety of new cold atmospheric plasma devices. Clin Plasma Med. 2013;1:36-44.
- Sun T, Zhang X, Hou C, et al. Cold plasma irradiation attenuates atopic dermatitis via enhancing HIF-1α-induced MANF transcription expression. Front Immunol. 2022;13:941219. doi:10.3389/fimmu.2022.941219
- Eggers B, Marciniak J, Memmert S, et al. The beneficial effect of cold atmospheric plasma on parameters of molecules and cell function involved in wound healing in human osteoblast-like cells in vitro. Odontology. 2020;108:607-616. doi:10.1007/s10266-020-00487-y
- Conway GE, He Z, Hutanu AL, et al. Cold atmospheric plasma induces accumulation of lysosomes and caspase-independent cell death in U373MG glioblastoma multiforme cells. Sci Rep. 2019;9:12891. doi:10.1038/s41598-019-49013-3
- Schmidt A, Dietrich S, Steuer A, et al. Non-thermal plasma activates human keratinocytes by stimulation of antioxidant and phase II pathways. J Biol Chem. 2015;290:6731-6750. doi:10.1074/jbc.M114.603555
- Silverberg NB. Pediatric molluscum contagiosum. Pediatr Drugs. 2003;5:505-511. doi:10.2165/00148581-200305080-00001
- Cotton DW, Cooper C, Barrett DF, et al. Severe atypical molluscum contagiosum infection in an immunocompromised host. Br J Dermatol. 1987;116:871-876. doi:10.1111/j.1365-2133.1987.tb04908.x
- Gan L, Zhang S, Poorun D, et al. Medical applications of nonthermal atmospheric pressure plasma in dermatology. J Dtsch Dermatol Ges. 2018;16:7-13. doi:https://doi.org/10.1111/ddg.13373
- Gay-Mimbrera J, García MC, Isla-Tejera B, et al. Clinical and biological principles of cold atmospheric plasma application in skin cancer. Adv Ther. 2016;33:894-909. doi:10.1007/s12325-016-0338-1. Published correction appears in Adv Ther. 2017;34:280. doi:10.1007/s12325-016-0437-z
- Zhai SY, Kong MG, Xia YM. Cold atmospheric plasma ameliorates skin diseases involving reactive oxygen/nitrogen species-mediated functions. Front Immunol. 2022;13:868386. doi:10.3389/fimmu.2022.868386
- Tan F, Wang Y, Zhang S, et al. Plasma dermatology: skin therapy using cold atmospheric plasma. Front Oncol. 2022;12:918484. doi:10.3389/fonc.2022.918484
- van Welzen A, Hoch M, Wahl P, et al. The response and tolerability of a novel cold atmospheric plasma wound dressing for the healing of split skin graft donor sites: a controlled pilot study. Skin Pharmacol Physiol. 2021;34:328-336. doi:10.1159/000517524
- Friedman PC, Fridman G, Fridman A. Using cold plasma to treat warts in children: a case series. Pediatr Dermatol. 2020;37:706-709. doi:10.1111/pde.14180
- Zhang C, Zhao J, Gao Y, et al. Cold atmospheric plasma treatment for diaper dermatitis: a case report [published online January 27, 2021]. Dermatol Ther. 2021;34:E14739. doi:10.1111/dth.14739
- Friedman PC, Fridman G, Fridman A. Cold atmospheric pressure plasma clears molluscum contagiosum. Exp Dermatol. 2023;32:562-563. doi:10.1111/exd.14695
- Suwanchinda A, Nararatwanchai T. The efficacy and safety of the innovative cold atmospheric-pressure plasma technology in the treatment of striae distensae: a randomized controlled trial. J Cosmet Dermatol. 2022;21:6805-6814. doi:10.1111/jocd.15458
- Suwanchinda A, Nararatwanchai T. Efficacy and safety of the innovative cold atmospheric-pressure plasma technology in the treatment of keloid: a randomized controlled trial. J Cosmet Dermatol. 2022;21:6788-6797. doi:10.1111/jocd.15397
- Kim YJ, Lim DJ, Lee MY, et al. Prospective, comparative clinical pilot study of cold atmospheric plasma device in the treatment of atopic dermatitis. Sci Rep. 2021;11:14461. doi:10.1038/s41598-021-93941-y
- Gareri C, Bennardo L, De Masi G. Use of a new cold plasma tool for psoriasis treatment: a case report. SAGE Open Med Case Rep. 2020;8:2050313X20922709. doi:10.1177/2050313X20922709
- Zheng L, Gao J, Cao Y, et al. Two case reports of inverse psoriasis treated with cold atmospheric plasma. Dermatol Ther. 2020;33:E14257. doi:10.1111/dth.14257
- Arisi M, Venturuzzo A, Gelmetti A, et al. Cold atmospheric plasma (CAP) as a promising therapeutic option for mild to moderate acne vulgaris: clinical and non-invasive evaluation of two cases. Clin Plasma Med. 2020;19-20:100110.
- Isbary G, Köritzer J, Mitra A, et al. Ex vivo human skin experiments for the evaluation of safety of new cold atmospheric plasma devices. Clin Plasma Med. 2013;1:36-44.
- Sun T, Zhang X, Hou C, et al. Cold plasma irradiation attenuates atopic dermatitis via enhancing HIF-1α-induced MANF transcription expression. Front Immunol. 2022;13:941219. doi:10.3389/fimmu.2022.941219
- Eggers B, Marciniak J, Memmert S, et al. The beneficial effect of cold atmospheric plasma on parameters of molecules and cell function involved in wound healing in human osteoblast-like cells in vitro. Odontology. 2020;108:607-616. doi:10.1007/s10266-020-00487-y
- Conway GE, He Z, Hutanu AL, et al. Cold atmospheric plasma induces accumulation of lysosomes and caspase-independent cell death in U373MG glioblastoma multiforme cells. Sci Rep. 2019;9:12891. doi:10.1038/s41598-019-49013-3
- Schmidt A, Dietrich S, Steuer A, et al. Non-thermal plasma activates human keratinocytes by stimulation of antioxidant and phase II pathways. J Biol Chem. 2015;290:6731-6750. doi:10.1074/jbc.M114.603555
- Silverberg NB. Pediatric molluscum contagiosum. Pediatr Drugs. 2003;5:505-511. doi:10.2165/00148581-200305080-00001
- Cotton DW, Cooper C, Barrett DF, et al. Severe atypical molluscum contagiosum infection in an immunocompromised host. Br J Dermatol. 1987;116:871-876. doi:10.1111/j.1365-2133.1987.tb04908.x
Practice Points
- Nonthermal atmospheric plasma (NTAP)(also known as cold atmospheric plasma) has been shown to cause minimal damage to skin when application time is minimized.
- Beyond its diverse applications, treatment with NTAP yields a unique advantage to pharmacologic therapies in that there is no risk for medication interactions or pharmacologic adverse effects.
- Although the use of NTAP in pediatric dermatology is scarcely described in the literature, the technology will certainly have applications in the future treatment of a wide variety of pediatric disorders.
Dupilumab promising for children aged 1-11 with EoE
VANCOUVER –
High exposure to dupilumab was associated with significantly improved histologic, endoscopic, and transcriptomic improvements, compared with placebo at week 16. Sustained response or improvements continued to week 52 with continued treatment in the high-exposure dupilumab group. Children in the high-exposure dupilumab group also gained more weight during the study than those initially assigned to placebo.
“Eosinophilic esophagitis is a chronic, aggressive, type 2 inflammatory disease that has a substantial impact on quality of life,” said Mirna Chehade, MD, MPH, of the Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai in New York. And the incidence and prevalence of the disease is increasing.
Dupilumab is already indicated for treating EoE in adolescents aged 12 or older as well as adults, but “there are no approved treatments for EoE in children under 12,” said Dr. Chehade, who presented the results of the late-breaking abstract at the ACG: American College of Gastroenterology 2023 annual scientific meeting.
She and her colleagues randomly assigned 102 children aged 1-11 years with active EoE to three groups for the first 16 weeks of the study: 37 to high-exposure dupilumab; 31 to low-exposure dupilumab; and 34 others to placebo, followed by either high- or low-dose dupilumab. Baseline demographics and disease characteristics were comparable between groups.
During an active 36-week extension period, the 37 participants who were initially assigned to receive high-exposure dupilumab continued the same treatment up to week 52. A total of 29 participants initially assigned to receive low-exposure dupilumab continues their regimen as well. Those initially assigned to receive placebo switched to a preassigned active treatment group; 18 children started to take high-exposure dupilumab, and 14 began to take low-exposure dupilumab.
The children in the study had a high burden of disease, as reflected by the duration of EoE as well as histologic, endoscopic, and clinical scores. The mean age was 7.2 years in the placebo group and 6.8 years in the dupilumab group. They were mostly White boys, Dr. Chehade said.
Key outcomes
At week 16, the high-exposure dupilumab group met the primary study endpoint with a peak esophageal intraepithelial eosinophil count ≤ 6 on high-power field assessment. This was significantly different from the placebo group (least squares mean difference, 64.5; 95% confidence interval, 48.19-80.85; P < .0001).
At week 52, 63% of children who remained on high-exposure dupilumab and 53% of those who switched from placebo to high-exposure dupilumab achieved a peak eosinophil count ≤ 6.
The study included multiple secondary outcomes. For example, at week 16, the following measures improved from baseline with high-exposure dupilumab, compared with placebo:
- EoE-Histologic Scoring System grade and stage scores (–0.88 and –0.84 vs. +0.02 and +0.05; both P < .0001).
- EoE-Endoscopic Reference Score (–3.5 vs. +0.3; P < .0001).
- Change in body weight for age percentile (+3.09 vs. +0.29).
- Numeric improvement in caregiver-reported proportion of days experiencing one or more EoE sign (–0.28 vs. –0.17).
At week 52, these outcomes were sustained or improved with continued high-exposure dupilumab. The researchers also saw improvements among the placebo recipients who switched to high-exposure dupilumab.
The reason the children were randomly assigned to high-exposure or low-exposure groups instead of high-dose and low-dose cohorts is because the children grew during the study, Dr. Chehade explained. “As you can see, there was a nice change in weight, and at specific time periods the doses were adjusted to match.”
‘Good safety profile’
Dupilumab was well tolerated. “The safety profile is very similar to what has been so far described and published for dupilumab in adults,” said Dr. Chehade. At week 16, adverse events that were more frequent with dupilumab vs. placebo included COVID-19, rash, headache, and injection-site erythema, for example. Similar safety results were seen up to week 52.
“I think it’s promising as we wait for the actual study to be published,” said Asmeen Bhatt, MD, PhD, co-moderator of the session and assistant professor of medicine at University of Texas Health Science Center, Houston. “The drug was recently approved for adult EOE use, just last year, and it has been shown to be effective.”
“There are a lot of adult drugs that are now being tested in the pediatric population, and this is one of them,” Dr. Bhatt added. “It has a very good safety profile. I’m not a pediatric gastroenterologist but I expect that it will have a lot of utility.”
The study was funded by Regeneron and Sanofi. Dr. Chehade is a consultant for Sanofi and Regeneron and receives research funding from Regeneron. Dr. Bhatt had no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
VANCOUVER –
High exposure to dupilumab was associated with significantly improved histologic, endoscopic, and transcriptomic improvements, compared with placebo at week 16. Sustained response or improvements continued to week 52 with continued treatment in the high-exposure dupilumab group. Children in the high-exposure dupilumab group also gained more weight during the study than those initially assigned to placebo.
“Eosinophilic esophagitis is a chronic, aggressive, type 2 inflammatory disease that has a substantial impact on quality of life,” said Mirna Chehade, MD, MPH, of the Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai in New York. And the incidence and prevalence of the disease is increasing.
Dupilumab is already indicated for treating EoE in adolescents aged 12 or older as well as adults, but “there are no approved treatments for EoE in children under 12,” said Dr. Chehade, who presented the results of the late-breaking abstract at the ACG: American College of Gastroenterology 2023 annual scientific meeting.
She and her colleagues randomly assigned 102 children aged 1-11 years with active EoE to three groups for the first 16 weeks of the study: 37 to high-exposure dupilumab; 31 to low-exposure dupilumab; and 34 others to placebo, followed by either high- or low-dose dupilumab. Baseline demographics and disease characteristics were comparable between groups.
During an active 36-week extension period, the 37 participants who were initially assigned to receive high-exposure dupilumab continued the same treatment up to week 52. A total of 29 participants initially assigned to receive low-exposure dupilumab continues their regimen as well. Those initially assigned to receive placebo switched to a preassigned active treatment group; 18 children started to take high-exposure dupilumab, and 14 began to take low-exposure dupilumab.
The children in the study had a high burden of disease, as reflected by the duration of EoE as well as histologic, endoscopic, and clinical scores. The mean age was 7.2 years in the placebo group and 6.8 years in the dupilumab group. They were mostly White boys, Dr. Chehade said.
Key outcomes
At week 16, the high-exposure dupilumab group met the primary study endpoint with a peak esophageal intraepithelial eosinophil count ≤ 6 on high-power field assessment. This was significantly different from the placebo group (least squares mean difference, 64.5; 95% confidence interval, 48.19-80.85; P < .0001).
At week 52, 63% of children who remained on high-exposure dupilumab and 53% of those who switched from placebo to high-exposure dupilumab achieved a peak eosinophil count ≤ 6.
The study included multiple secondary outcomes. For example, at week 16, the following measures improved from baseline with high-exposure dupilumab, compared with placebo:
- EoE-Histologic Scoring System grade and stage scores (–0.88 and –0.84 vs. +0.02 and +0.05; both P < .0001).
- EoE-Endoscopic Reference Score (–3.5 vs. +0.3; P < .0001).
- Change in body weight for age percentile (+3.09 vs. +0.29).
- Numeric improvement in caregiver-reported proportion of days experiencing one or more EoE sign (–0.28 vs. –0.17).
At week 52, these outcomes were sustained or improved with continued high-exposure dupilumab. The researchers also saw improvements among the placebo recipients who switched to high-exposure dupilumab.
The reason the children were randomly assigned to high-exposure or low-exposure groups instead of high-dose and low-dose cohorts is because the children grew during the study, Dr. Chehade explained. “As you can see, there was a nice change in weight, and at specific time periods the doses were adjusted to match.”
‘Good safety profile’
Dupilumab was well tolerated. “The safety profile is very similar to what has been so far described and published for dupilumab in adults,” said Dr. Chehade. At week 16, adverse events that were more frequent with dupilumab vs. placebo included COVID-19, rash, headache, and injection-site erythema, for example. Similar safety results were seen up to week 52.
“I think it’s promising as we wait for the actual study to be published,” said Asmeen Bhatt, MD, PhD, co-moderator of the session and assistant professor of medicine at University of Texas Health Science Center, Houston. “The drug was recently approved for adult EOE use, just last year, and it has been shown to be effective.”
“There are a lot of adult drugs that are now being tested in the pediatric population, and this is one of them,” Dr. Bhatt added. “It has a very good safety profile. I’m not a pediatric gastroenterologist but I expect that it will have a lot of utility.”
The study was funded by Regeneron and Sanofi. Dr. Chehade is a consultant for Sanofi and Regeneron and receives research funding from Regeneron. Dr. Bhatt had no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
VANCOUVER –
High exposure to dupilumab was associated with significantly improved histologic, endoscopic, and transcriptomic improvements, compared with placebo at week 16. Sustained response or improvements continued to week 52 with continued treatment in the high-exposure dupilumab group. Children in the high-exposure dupilumab group also gained more weight during the study than those initially assigned to placebo.
“Eosinophilic esophagitis is a chronic, aggressive, type 2 inflammatory disease that has a substantial impact on quality of life,” said Mirna Chehade, MD, MPH, of the Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai in New York. And the incidence and prevalence of the disease is increasing.
Dupilumab is already indicated for treating EoE in adolescents aged 12 or older as well as adults, but “there are no approved treatments for EoE in children under 12,” said Dr. Chehade, who presented the results of the late-breaking abstract at the ACG: American College of Gastroenterology 2023 annual scientific meeting.
She and her colleagues randomly assigned 102 children aged 1-11 years with active EoE to three groups for the first 16 weeks of the study: 37 to high-exposure dupilumab; 31 to low-exposure dupilumab; and 34 others to placebo, followed by either high- or low-dose dupilumab. Baseline demographics and disease characteristics were comparable between groups.
During an active 36-week extension period, the 37 participants who were initially assigned to receive high-exposure dupilumab continued the same treatment up to week 52. A total of 29 participants initially assigned to receive low-exposure dupilumab continues their regimen as well. Those initially assigned to receive placebo switched to a preassigned active treatment group; 18 children started to take high-exposure dupilumab, and 14 began to take low-exposure dupilumab.
The children in the study had a high burden of disease, as reflected by the duration of EoE as well as histologic, endoscopic, and clinical scores. The mean age was 7.2 years in the placebo group and 6.8 years in the dupilumab group. They were mostly White boys, Dr. Chehade said.
Key outcomes
At week 16, the high-exposure dupilumab group met the primary study endpoint with a peak esophageal intraepithelial eosinophil count ≤ 6 on high-power field assessment. This was significantly different from the placebo group (least squares mean difference, 64.5; 95% confidence interval, 48.19-80.85; P < .0001).
At week 52, 63% of children who remained on high-exposure dupilumab and 53% of those who switched from placebo to high-exposure dupilumab achieved a peak eosinophil count ≤ 6.
The study included multiple secondary outcomes. For example, at week 16, the following measures improved from baseline with high-exposure dupilumab, compared with placebo:
- EoE-Histologic Scoring System grade and stage scores (–0.88 and –0.84 vs. +0.02 and +0.05; both P < .0001).
- EoE-Endoscopic Reference Score (–3.5 vs. +0.3; P < .0001).
- Change in body weight for age percentile (+3.09 vs. +0.29).
- Numeric improvement in caregiver-reported proportion of days experiencing one or more EoE sign (–0.28 vs. –0.17).
At week 52, these outcomes were sustained or improved with continued high-exposure dupilumab. The researchers also saw improvements among the placebo recipients who switched to high-exposure dupilumab.
The reason the children were randomly assigned to high-exposure or low-exposure groups instead of high-dose and low-dose cohorts is because the children grew during the study, Dr. Chehade explained. “As you can see, there was a nice change in weight, and at specific time periods the doses were adjusted to match.”
‘Good safety profile’
Dupilumab was well tolerated. “The safety profile is very similar to what has been so far described and published for dupilumab in adults,” said Dr. Chehade. At week 16, adverse events that were more frequent with dupilumab vs. placebo included COVID-19, rash, headache, and injection-site erythema, for example. Similar safety results were seen up to week 52.
“I think it’s promising as we wait for the actual study to be published,” said Asmeen Bhatt, MD, PhD, co-moderator of the session and assistant professor of medicine at University of Texas Health Science Center, Houston. “The drug was recently approved for adult EOE use, just last year, and it has been shown to be effective.”
“There are a lot of adult drugs that are now being tested in the pediatric population, and this is one of them,” Dr. Bhatt added. “It has a very good safety profile. I’m not a pediatric gastroenterologist but I expect that it will have a lot of utility.”
The study was funded by Regeneron and Sanofi. Dr. Chehade is a consultant for Sanofi and Regeneron and receives research funding from Regeneron. Dr. Bhatt had no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
AT ACG 2023
Clustered Vesicles on the Neck
The Diagnosis: Microcystic Lymphatic Malformation
A punch biopsy demonstrated anastomosing fluidfilled spaces within the papillary and reticular dermal layers (Figure), confirming the diagnosis of microcystic lymphatic malformation (LM)(formerly known as lymphangioma circumscriptum), a congenital vascular malformation composed of slow-flow lymphatic channels.1 The patient underwent serial excisions with improvement of the LM, though the treatment course was complicated by hypertrophic scar formation.
The classic clinical presentation of microcystic LM includes a crop of vesicles containing clear or hemorrhagic fluid with associated oozing or bleeding.2 When cutaneous lesions resembling microcystic LM develop in response to lymphatic damage and resulting stasis, such as from prior radiotherapy or surgery, the term lymphangiectasia is used to distinguish this entity from congenital microcystic LM.3
Microcystic LMs are histologically indistinguishable from macrocystic LMs; however, macrocystic LMs typically are clinically evident at birth as ill-defined subcutaneous masses.2,4-6 Dermatitis herpetiformis, a dermatologic manifestation of gluten sensitivity, causes intensely pruritic vesicles in a symmetric distribution on the elbows, knees, and buttocks. Histopathology shows neutrophilic microabscesses in the dermal papillae with subepidermal blistering. Direct immunofluorescence demonstrates the deposition of IgA along the basement membrane with dermal papillae aggregates.6 The underlying dermis also may contain a lymphohistiocytic infiltrate rich in neutrophils. The vesicles of herpes zoster virus are painful and present in a dermatomal distribution. A viral cytopathic effect often is observed in keratinocytes, specifically with multinucleation, molding, and margination of chromatin material. The lesions are accompanied by variable lymphocytic inflammation and epithelial necrosis resulting in intraepidermal blistering.7 Extragenital lichen sclerosus presents as polygonal white papules merging to form plaques and may include hemorrhagic blisters in some instances. Histopathology shows hyperkeratosis, epidermal atrophy with flattened rete ridges, vacuolar interface changes, loss of elastic fibers, and hyalinization of the lamina propria with lymphocytic infiltrate.8
Endothelial cells in LM exhibit activating mutations in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha gene, PIK3CA, which may lead to proliferation and overgrowth of the lymphatic vasculature, as well as increased production of cyclic guanosine monophosphate.9,10 Phosphodiesterase 5 (PDE5) is expressed in the perivascular smooth muscle adjacent to lymphatic spaces in LMs but not in the their vasculature. 10 This pattern of PDE5 expression may cause perilesional vasculature to constrict, preventing lymphatic fluid from draining into the veins.11 It is theorized that the PDE5 inhibitor sildenafil leads to relaxation of the vasculature adjacent to LMs, allowing the outflow of the accumulated lymphatic fluid and thus decompression.11-13
Management of LM should not only take into account the depth and location of involvement but also any associated symptoms or complications, such as pruritus, pain, bleeding, or secondary infections. Magnetic resonance imaging (MRI) typically has been considered the gold standard for determining the size and depth of involvement of the malformation.1,3,4 However, ultrasonography with Doppler flow may be considered an initial diagnostic and screening test, as it can distinguish between macrocystic and microcystic components and provide superior images of microcystic lesions, which are below the resolution capacity of MRI.4 Notably, our patient’s LM was undetectable on ultrasonography and was found to be largely superficial in nature on MRI.
Serial excision of the microcystic LM was conducted in our patient, but there currently is no consensus on optimal treatment of LM, and many treatment options are complicated by high recurrence rates or complications.5 Procedural approaches may include excision, cryotherapy, radiotherapy, sclerotherapy, or laser therapy, while pharmacologic approaches may include sildenafil for its inhibition of PDE5 or sirolimus (oral or topical) for its inhibition of mammalian target of rapamycin.5,12-14 Because recurrence is highly likely, patients may require repeat treatments or a combination approach to therapy.1,5 The development of targeted therapies may lead to a shift in management of LMs in the future, as successful use of the PIK3CA inhibitor alpelisib recently has been reported to lead to clinical improvement of PIK3CA-related LMs, including in patients with PIK3CA-related overgrowth syndromes.15
- Garzon MC, Huang JT, Enjolras O, et al. Vascular malformations: part I. J Am Acad Dermatol. 2007;56:353-374. doi:10.1016/j.jaad.2006.05.069
- Alrashdan MS, Hammad HM, Alzumaili BAI, et al. Lymphangioma circumscriptum of the tongue: a case with marked hemorrhagic component. J Cutan Pathol. 2018;45:278-281. doi:10.1111/cup.13101
- Osborne GE, Chinn RJ, Francis ND, et al. Magnetic resonance imaging in the investigation of penile lymphangioma circumscriptum. Br J Dermatol. 2000;143:467-468. doi:10.1046/j.1365-2133.2000.03695.x
- Davies D, Rogers M, Lam A, et al. Localized microcystic lymphatic malformations—ultrasound diagnosis. Pediatr Dermatol. 1999;16: 423-429. doi:10.1046/j.1525-1470.1999.00110.x
- García-Montero P, Del Boz J, Baselga-Torres E, et al. Use of topical rapamycin in the treatment of superficial lymphatic malformations. J Am Acad Dermatol. 2019;80:508-515. doi:10.1016/j.jaad.2018.09.050
- Clarindo MV, Possebon AT, Soligo EM, et al. Dermatitis herpetiformis: pathophysiology, clinical presentation, diagnosis and treatment. An Bras Dermatol. 2014;89:865-875; quiz 876-877. doi:10.1590/abd1806-4841.20142966
- Leinweber B, Kerl H, Cerroni L. Histopathologic features of cutaneous herpes virus infections (herpes simplex, herpes varicella/zoster): a broad spectrum of presentations with common pseudolymphomatous aspects. Am J Surg Pathol. 2006;30:50-58.
- Shiver M, Papasakelariou C, Brown JA, et al. Extragenital bullous lichen sclerosus in a pediatric patient: a case report and literature review. Pediatr Dermatol. 2014;31:383-385. doi:10.1111 /pde.12025
- Blesinger H, Kaulfuß S, Aung T, et al. PIK3CA mutations are specifically localized to lymphatic endothelial cells of lymphatic malformations [published online July 9, 2018]. PLoS One. 2018;13:E0200343. doi:10.1371/journal.pone.0200343
- Green JS, Prok L, Bruckner AL. Expression of phosphodiesterase-5 in lymphatic malformation tissue. JAMA Dermatol. 2014;150:455-456. doi:10.1001/jamadermatol.2013.7002
- Swetman GL, Berk DR, Vasanawala SS, et al. Sildenafil for severe lymphatic malformations. N Engl J Med. 2012;366:384-386. doi:10.1056 /NEJMc1112482
- Tu JH, Tafoya E, Jeng M, et al. Long-term follow-up of lymphatic malformations in children treated with sildenafil. Pediatr Dermatol. 2017;34:559-565. doi:10.1111/pde.13237
- Maruani A, Tavernier E, Boccara O, et al. Sirolimus (rapamycin) for slow-flow malformations in children: the Observational-Phase Randomized Clinical PERFORMUS Trial. JAMA Dermatol. 2021;157:1289-1298. doi:10.1001/jamadermatol.2021.3459
- Delestre F, Venot Q, Bayard C, et al. Alpelisib administration reduced lymphatic malformations in a mouse model and in patients. Sci Transl Med. 2021;13:eabg0809. doi:10.1126/scitranslmed .abg0809
- Garreta Fontelles G, Pardo Pastor J, Grande Moreillo C. Alpelisib to treat CLOVES syndrome, a member of the PIK3CA-related overgrowth syndrome spectrum [published online February 21, 2022]. Br J Clin Pharmacol. 2022;88:3891-3895. doi:10.1111/bcp.15270
The Diagnosis: Microcystic Lymphatic Malformation
A punch biopsy demonstrated anastomosing fluidfilled spaces within the papillary and reticular dermal layers (Figure), confirming the diagnosis of microcystic lymphatic malformation (LM)(formerly known as lymphangioma circumscriptum), a congenital vascular malformation composed of slow-flow lymphatic channels.1 The patient underwent serial excisions with improvement of the LM, though the treatment course was complicated by hypertrophic scar formation.
The classic clinical presentation of microcystic LM includes a crop of vesicles containing clear or hemorrhagic fluid with associated oozing or bleeding.2 When cutaneous lesions resembling microcystic LM develop in response to lymphatic damage and resulting stasis, such as from prior radiotherapy or surgery, the term lymphangiectasia is used to distinguish this entity from congenital microcystic LM.3
Microcystic LMs are histologically indistinguishable from macrocystic LMs; however, macrocystic LMs typically are clinically evident at birth as ill-defined subcutaneous masses.2,4-6 Dermatitis herpetiformis, a dermatologic manifestation of gluten sensitivity, causes intensely pruritic vesicles in a symmetric distribution on the elbows, knees, and buttocks. Histopathology shows neutrophilic microabscesses in the dermal papillae with subepidermal blistering. Direct immunofluorescence demonstrates the deposition of IgA along the basement membrane with dermal papillae aggregates.6 The underlying dermis also may contain a lymphohistiocytic infiltrate rich in neutrophils. The vesicles of herpes zoster virus are painful and present in a dermatomal distribution. A viral cytopathic effect often is observed in keratinocytes, specifically with multinucleation, molding, and margination of chromatin material. The lesions are accompanied by variable lymphocytic inflammation and epithelial necrosis resulting in intraepidermal blistering.7 Extragenital lichen sclerosus presents as polygonal white papules merging to form plaques and may include hemorrhagic blisters in some instances. Histopathology shows hyperkeratosis, epidermal atrophy with flattened rete ridges, vacuolar interface changes, loss of elastic fibers, and hyalinization of the lamina propria with lymphocytic infiltrate.8
Endothelial cells in LM exhibit activating mutations in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha gene, PIK3CA, which may lead to proliferation and overgrowth of the lymphatic vasculature, as well as increased production of cyclic guanosine monophosphate.9,10 Phosphodiesterase 5 (PDE5) is expressed in the perivascular smooth muscle adjacent to lymphatic spaces in LMs but not in the their vasculature. 10 This pattern of PDE5 expression may cause perilesional vasculature to constrict, preventing lymphatic fluid from draining into the veins.11 It is theorized that the PDE5 inhibitor sildenafil leads to relaxation of the vasculature adjacent to LMs, allowing the outflow of the accumulated lymphatic fluid and thus decompression.11-13
Management of LM should not only take into account the depth and location of involvement but also any associated symptoms or complications, such as pruritus, pain, bleeding, or secondary infections. Magnetic resonance imaging (MRI) typically has been considered the gold standard for determining the size and depth of involvement of the malformation.1,3,4 However, ultrasonography with Doppler flow may be considered an initial diagnostic and screening test, as it can distinguish between macrocystic and microcystic components and provide superior images of microcystic lesions, which are below the resolution capacity of MRI.4 Notably, our patient’s LM was undetectable on ultrasonography and was found to be largely superficial in nature on MRI.
Serial excision of the microcystic LM was conducted in our patient, but there currently is no consensus on optimal treatment of LM, and many treatment options are complicated by high recurrence rates or complications.5 Procedural approaches may include excision, cryotherapy, radiotherapy, sclerotherapy, or laser therapy, while pharmacologic approaches may include sildenafil for its inhibition of PDE5 or sirolimus (oral or topical) for its inhibition of mammalian target of rapamycin.5,12-14 Because recurrence is highly likely, patients may require repeat treatments or a combination approach to therapy.1,5 The development of targeted therapies may lead to a shift in management of LMs in the future, as successful use of the PIK3CA inhibitor alpelisib recently has been reported to lead to clinical improvement of PIK3CA-related LMs, including in patients with PIK3CA-related overgrowth syndromes.15
The Diagnosis: Microcystic Lymphatic Malformation
A punch biopsy demonstrated anastomosing fluidfilled spaces within the papillary and reticular dermal layers (Figure), confirming the diagnosis of microcystic lymphatic malformation (LM)(formerly known as lymphangioma circumscriptum), a congenital vascular malformation composed of slow-flow lymphatic channels.1 The patient underwent serial excisions with improvement of the LM, though the treatment course was complicated by hypertrophic scar formation.
The classic clinical presentation of microcystic LM includes a crop of vesicles containing clear or hemorrhagic fluid with associated oozing or bleeding.2 When cutaneous lesions resembling microcystic LM develop in response to lymphatic damage and resulting stasis, such as from prior radiotherapy or surgery, the term lymphangiectasia is used to distinguish this entity from congenital microcystic LM.3
Microcystic LMs are histologically indistinguishable from macrocystic LMs; however, macrocystic LMs typically are clinically evident at birth as ill-defined subcutaneous masses.2,4-6 Dermatitis herpetiformis, a dermatologic manifestation of gluten sensitivity, causes intensely pruritic vesicles in a symmetric distribution on the elbows, knees, and buttocks. Histopathology shows neutrophilic microabscesses in the dermal papillae with subepidermal blistering. Direct immunofluorescence demonstrates the deposition of IgA along the basement membrane with dermal papillae aggregates.6 The underlying dermis also may contain a lymphohistiocytic infiltrate rich in neutrophils. The vesicles of herpes zoster virus are painful and present in a dermatomal distribution. A viral cytopathic effect often is observed in keratinocytes, specifically with multinucleation, molding, and margination of chromatin material. The lesions are accompanied by variable lymphocytic inflammation and epithelial necrosis resulting in intraepidermal blistering.7 Extragenital lichen sclerosus presents as polygonal white papules merging to form plaques and may include hemorrhagic blisters in some instances. Histopathology shows hyperkeratosis, epidermal atrophy with flattened rete ridges, vacuolar interface changes, loss of elastic fibers, and hyalinization of the lamina propria with lymphocytic infiltrate.8
Endothelial cells in LM exhibit activating mutations in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha gene, PIK3CA, which may lead to proliferation and overgrowth of the lymphatic vasculature, as well as increased production of cyclic guanosine monophosphate.9,10 Phosphodiesterase 5 (PDE5) is expressed in the perivascular smooth muscle adjacent to lymphatic spaces in LMs but not in the their vasculature. 10 This pattern of PDE5 expression may cause perilesional vasculature to constrict, preventing lymphatic fluid from draining into the veins.11 It is theorized that the PDE5 inhibitor sildenafil leads to relaxation of the vasculature adjacent to LMs, allowing the outflow of the accumulated lymphatic fluid and thus decompression.11-13
Management of LM should not only take into account the depth and location of involvement but also any associated symptoms or complications, such as pruritus, pain, bleeding, or secondary infections. Magnetic resonance imaging (MRI) typically has been considered the gold standard for determining the size and depth of involvement of the malformation.1,3,4 However, ultrasonography with Doppler flow may be considered an initial diagnostic and screening test, as it can distinguish between macrocystic and microcystic components and provide superior images of microcystic lesions, which are below the resolution capacity of MRI.4 Notably, our patient’s LM was undetectable on ultrasonography and was found to be largely superficial in nature on MRI.
Serial excision of the microcystic LM was conducted in our patient, but there currently is no consensus on optimal treatment of LM, and many treatment options are complicated by high recurrence rates or complications.5 Procedural approaches may include excision, cryotherapy, radiotherapy, sclerotherapy, or laser therapy, while pharmacologic approaches may include sildenafil for its inhibition of PDE5 or sirolimus (oral or topical) for its inhibition of mammalian target of rapamycin.5,12-14 Because recurrence is highly likely, patients may require repeat treatments or a combination approach to therapy.1,5 The development of targeted therapies may lead to a shift in management of LMs in the future, as successful use of the PIK3CA inhibitor alpelisib recently has been reported to lead to clinical improvement of PIK3CA-related LMs, including in patients with PIK3CA-related overgrowth syndromes.15
- Garzon MC, Huang JT, Enjolras O, et al. Vascular malformations: part I. J Am Acad Dermatol. 2007;56:353-374. doi:10.1016/j.jaad.2006.05.069
- Alrashdan MS, Hammad HM, Alzumaili BAI, et al. Lymphangioma circumscriptum of the tongue: a case with marked hemorrhagic component. J Cutan Pathol. 2018;45:278-281. doi:10.1111/cup.13101
- Osborne GE, Chinn RJ, Francis ND, et al. Magnetic resonance imaging in the investigation of penile lymphangioma circumscriptum. Br J Dermatol. 2000;143:467-468. doi:10.1046/j.1365-2133.2000.03695.x
- Davies D, Rogers M, Lam A, et al. Localized microcystic lymphatic malformations—ultrasound diagnosis. Pediatr Dermatol. 1999;16: 423-429. doi:10.1046/j.1525-1470.1999.00110.x
- García-Montero P, Del Boz J, Baselga-Torres E, et al. Use of topical rapamycin in the treatment of superficial lymphatic malformations. J Am Acad Dermatol. 2019;80:508-515. doi:10.1016/j.jaad.2018.09.050
- Clarindo MV, Possebon AT, Soligo EM, et al. Dermatitis herpetiformis: pathophysiology, clinical presentation, diagnosis and treatment. An Bras Dermatol. 2014;89:865-875; quiz 876-877. doi:10.1590/abd1806-4841.20142966
- Leinweber B, Kerl H, Cerroni L. Histopathologic features of cutaneous herpes virus infections (herpes simplex, herpes varicella/zoster): a broad spectrum of presentations with common pseudolymphomatous aspects. Am J Surg Pathol. 2006;30:50-58.
- Shiver M, Papasakelariou C, Brown JA, et al. Extragenital bullous lichen sclerosus in a pediatric patient: a case report and literature review. Pediatr Dermatol. 2014;31:383-385. doi:10.1111 /pde.12025
- Blesinger H, Kaulfuß S, Aung T, et al. PIK3CA mutations are specifically localized to lymphatic endothelial cells of lymphatic malformations [published online July 9, 2018]. PLoS One. 2018;13:E0200343. doi:10.1371/journal.pone.0200343
- Green JS, Prok L, Bruckner AL. Expression of phosphodiesterase-5 in lymphatic malformation tissue. JAMA Dermatol. 2014;150:455-456. doi:10.1001/jamadermatol.2013.7002
- Swetman GL, Berk DR, Vasanawala SS, et al. Sildenafil for severe lymphatic malformations. N Engl J Med. 2012;366:384-386. doi:10.1056 /NEJMc1112482
- Tu JH, Tafoya E, Jeng M, et al. Long-term follow-up of lymphatic malformations in children treated with sildenafil. Pediatr Dermatol. 2017;34:559-565. doi:10.1111/pde.13237
- Maruani A, Tavernier E, Boccara O, et al. Sirolimus (rapamycin) for slow-flow malformations in children: the Observational-Phase Randomized Clinical PERFORMUS Trial. JAMA Dermatol. 2021;157:1289-1298. doi:10.1001/jamadermatol.2021.3459
- Delestre F, Venot Q, Bayard C, et al. Alpelisib administration reduced lymphatic malformations in a mouse model and in patients. Sci Transl Med. 2021;13:eabg0809. doi:10.1126/scitranslmed .abg0809
- Garreta Fontelles G, Pardo Pastor J, Grande Moreillo C. Alpelisib to treat CLOVES syndrome, a member of the PIK3CA-related overgrowth syndrome spectrum [published online February 21, 2022]. Br J Clin Pharmacol. 2022;88:3891-3895. doi:10.1111/bcp.15270
- Garzon MC, Huang JT, Enjolras O, et al. Vascular malformations: part I. J Am Acad Dermatol. 2007;56:353-374. doi:10.1016/j.jaad.2006.05.069
- Alrashdan MS, Hammad HM, Alzumaili BAI, et al. Lymphangioma circumscriptum of the tongue: a case with marked hemorrhagic component. J Cutan Pathol. 2018;45:278-281. doi:10.1111/cup.13101
- Osborne GE, Chinn RJ, Francis ND, et al. Magnetic resonance imaging in the investigation of penile lymphangioma circumscriptum. Br J Dermatol. 2000;143:467-468. doi:10.1046/j.1365-2133.2000.03695.x
- Davies D, Rogers M, Lam A, et al. Localized microcystic lymphatic malformations—ultrasound diagnosis. Pediatr Dermatol. 1999;16: 423-429. doi:10.1046/j.1525-1470.1999.00110.x
- García-Montero P, Del Boz J, Baselga-Torres E, et al. Use of topical rapamycin in the treatment of superficial lymphatic malformations. J Am Acad Dermatol. 2019;80:508-515. doi:10.1016/j.jaad.2018.09.050
- Clarindo MV, Possebon AT, Soligo EM, et al. Dermatitis herpetiformis: pathophysiology, clinical presentation, diagnosis and treatment. An Bras Dermatol. 2014;89:865-875; quiz 876-877. doi:10.1590/abd1806-4841.20142966
- Leinweber B, Kerl H, Cerroni L. Histopathologic features of cutaneous herpes virus infections (herpes simplex, herpes varicella/zoster): a broad spectrum of presentations with common pseudolymphomatous aspects. Am J Surg Pathol. 2006;30:50-58.
- Shiver M, Papasakelariou C, Brown JA, et al. Extragenital bullous lichen sclerosus in a pediatric patient: a case report and literature review. Pediatr Dermatol. 2014;31:383-385. doi:10.1111 /pde.12025
- Blesinger H, Kaulfuß S, Aung T, et al. PIK3CA mutations are specifically localized to lymphatic endothelial cells of lymphatic malformations [published online July 9, 2018]. PLoS One. 2018;13:E0200343. doi:10.1371/journal.pone.0200343
- Green JS, Prok L, Bruckner AL. Expression of phosphodiesterase-5 in lymphatic malformation tissue. JAMA Dermatol. 2014;150:455-456. doi:10.1001/jamadermatol.2013.7002
- Swetman GL, Berk DR, Vasanawala SS, et al. Sildenafil for severe lymphatic malformations. N Engl J Med. 2012;366:384-386. doi:10.1056 /NEJMc1112482
- Tu JH, Tafoya E, Jeng M, et al. Long-term follow-up of lymphatic malformations in children treated with sildenafil. Pediatr Dermatol. 2017;34:559-565. doi:10.1111/pde.13237
- Maruani A, Tavernier E, Boccara O, et al. Sirolimus (rapamycin) for slow-flow malformations in children: the Observational-Phase Randomized Clinical PERFORMUS Trial. JAMA Dermatol. 2021;157:1289-1298. doi:10.1001/jamadermatol.2021.3459
- Delestre F, Venot Q, Bayard C, et al. Alpelisib administration reduced lymphatic malformations in a mouse model and in patients. Sci Transl Med. 2021;13:eabg0809. doi:10.1126/scitranslmed .abg0809
- Garreta Fontelles G, Pardo Pastor J, Grande Moreillo C. Alpelisib to treat CLOVES syndrome, a member of the PIK3CA-related overgrowth syndrome spectrum [published online February 21, 2022]. Br J Clin Pharmacol. 2022;88:3891-3895. doi:10.1111/bcp.15270
A 6-year-old girl presented to the dermatology clinic with a rash on the right side of the neck that was noted at birth as a small raised lesion but slowly increased over time in size and number of lesions. She reported pruritus and irritation, particularly when rubbed or scratched. There was no family history of similar skin abnormalities. Her medical history was notable for a left-sided cholesteatoma on tympanomastoidectomy. Physical examination revealed clustered vesicles on the right side of the neck with underlying erythema. The vesicles contained mostly clear fluid with a few focal areas of hemorrhagic fluid. Ultrasonography was unremarkable, and magnetic resonance imaging revealed superficial T2 hyperintense nonenhancing cutaneous and subcutaneous lesions overlying the right lateral neck with minimal extension into the superficial right supraclavicular soft tissues.
Neurologic nuggets of wisdom for pediatric practice
WASHINGTON – Get the back story before rushing to diagnose a seizure disorder in a child, Michael Strunc, MD, said in a presentation at the annual meeting of the American Academy of Pediatrics.
Clinicians should ask parents or caregivers about the child’s behavior before the suspected seizure, whether there were any triggers, and if so, what might they have been, according to Dr. Strunc, a child neurologist and sleep medicine specialist at Children’s Hospital of the King’s Daughters, Norfolk, Va.
“Most seizures don’t have triggers,” he said. Rather, patients often become stiff, experience a motor event that builds in intensity then slows and stops, and finally, the patient is sleepy and tired. Clinicians should also find out whether the event had a beginning, middle, and end.
Approximately 0.6% of children younger than 17 years in the United States have active epilepsy, according to the Centers for Disease Control and Prevention.
Dr. Strunc offered a few more tips for diagnosing a child:
- Ask whether the patient’s eyes were open during the event. If the eyes were closed or squished closed, “it is almost never a seizure,” he said.
- Find out whether the patient was awake or asleep, and how, if at all, caregivers attempted to stop the event.
- Ask if the child’s experiences were repeating and predictable, and inquire about a family history of seizures or other events.
- Inquire about any developmental changes and other changes in the child, such as irritability, regression, or ataxia.
The differential diagnosis for a seizure includes nonepileptic events that occur with and without changes in consciousness or sleep. These events range from breath-holding and hyperventilation to night terrors, narcolepsy, migraine, and attention-deficit/hyperactivity disorder, he said.
Is it epilepsy?
Dr. Strunc shared several cases of neurologic “events” ranging from simple to severe.
In one case, a 10-month-old infant girl with a potential tonic/staring seizure presented with a history of events that involved getting stuck in a stiff position, usually while sitting in a car seat or highchair, with adducting of legs, redness of face, and “zoned-out” expression. The infant was healthy, smart, and precocious, with no illness, fever, or trauma, but the mother was very concerned, Dr. Strunc said.
The diagnosis: Self-gratification, which is benign and usually outgrown, although it can become extreme, he said.
By contrast, “absence,” also known as idiopathic generalized epilepsy, presents as brief events of 4-10 seconds that may occur up to hundreds of times a day. This type of epilepsy is associated with the sudden onset of impaired consciousness and unresponsiveness. These events end abruptly, and the child may be unaware. Absence is more common in girls. It usually occurs after age 4 and usually remits by about age 12, Dr. Strunc said.
However, the onset of absence in patients younger than age 3 is associated with increased odds of neurodevelopmental abnormalities “and probably represents another epilepsy syndrome,” he said.
Absence symptoms may mirror those of children who are simply daydreamers, Dr. Strunc noted. One way to confirm absence is by provoking hyperventilation, which will bring on an episode of absence if present, he said. EEGs provide evidence as well.
Acute ataxia in children has a wide differential that sends kids and families to the pediatrician or emergency department, Dr. Strunc said. Acute cerebellar ataxia is characterized by abrupt and symmetric symptoms, with no mental status changes, no fever, no meningitis, and no headache. A wide, unstable gait is a distinguishing feature, Dr. Strunc said.
However, other causes of acute ataxia should be ruled out, including toxic ingestion, tick paralysis, central nervous system infections, vascular conditions, and genetic conditions.
Don’t miss those ticks
Especially during periods when kids are outdoors, clinicians should consider a tick bite as a source of ataxia and neurologic symptoms in children, Dr. Strunc emphasized. Tick paralysis notably resembles many symptoms of Guillain-Barré syndrome (acute inflammatory demyelinating polyneuropathy).
Dr. Strunc described a case involving a 5-year-old girl who developed sudden problems with gait. The problems worsened quickly and prompted an emergency department visit.
The girl had an unremarkable history, she had not experienced mental status changes, her strength was normal, and she had just returned from a Girl Scouts trip. The patient was presumed to have Guillain-Barré. IVIG was initiated when an emergency nurse found a tick on her scalp. The tick was removed, and the patient left the hospital within 24 hours.
Children with tick paralysis are usually symptomatic after 5-7 days with the tick attached, Dr. Strunc said. They recover within a day after tick removal.
Overall, actual seizures are less common than other neurologic events in children, according to Dr. Strunc. Details on history, lack or presence of neurologic feature, and normal child development can help guide evaluation.
Take advantage of videos, he emphasized, as many parents and caregivers record a child’s neurologic events.
“Ataxia is scary, but exam and associated findings will help you with etiology,” he said.
Dr. Strunc has received research support from Jazz and Harmony and has served on the speakers’ bureau for Jazz Pharmaceuticals, Harmony Biosciences, and Avadel, unrelated to his presentation.
A version of this article first appeared on Medscape.com.
WASHINGTON – Get the back story before rushing to diagnose a seizure disorder in a child, Michael Strunc, MD, said in a presentation at the annual meeting of the American Academy of Pediatrics.
Clinicians should ask parents or caregivers about the child’s behavior before the suspected seizure, whether there were any triggers, and if so, what might they have been, according to Dr. Strunc, a child neurologist and sleep medicine specialist at Children’s Hospital of the King’s Daughters, Norfolk, Va.
“Most seizures don’t have triggers,” he said. Rather, patients often become stiff, experience a motor event that builds in intensity then slows and stops, and finally, the patient is sleepy and tired. Clinicians should also find out whether the event had a beginning, middle, and end.
Approximately 0.6% of children younger than 17 years in the United States have active epilepsy, according to the Centers for Disease Control and Prevention.
Dr. Strunc offered a few more tips for diagnosing a child:
- Ask whether the patient’s eyes were open during the event. If the eyes were closed or squished closed, “it is almost never a seizure,” he said.
- Find out whether the patient was awake or asleep, and how, if at all, caregivers attempted to stop the event.
- Ask if the child’s experiences were repeating and predictable, and inquire about a family history of seizures or other events.
- Inquire about any developmental changes and other changes in the child, such as irritability, regression, or ataxia.
The differential diagnosis for a seizure includes nonepileptic events that occur with and without changes in consciousness or sleep. These events range from breath-holding and hyperventilation to night terrors, narcolepsy, migraine, and attention-deficit/hyperactivity disorder, he said.
Is it epilepsy?
Dr. Strunc shared several cases of neurologic “events” ranging from simple to severe.
In one case, a 10-month-old infant girl with a potential tonic/staring seizure presented with a history of events that involved getting stuck in a stiff position, usually while sitting in a car seat or highchair, with adducting of legs, redness of face, and “zoned-out” expression. The infant was healthy, smart, and precocious, with no illness, fever, or trauma, but the mother was very concerned, Dr. Strunc said.
The diagnosis: Self-gratification, which is benign and usually outgrown, although it can become extreme, he said.
By contrast, “absence,” also known as idiopathic generalized epilepsy, presents as brief events of 4-10 seconds that may occur up to hundreds of times a day. This type of epilepsy is associated with the sudden onset of impaired consciousness and unresponsiveness. These events end abruptly, and the child may be unaware. Absence is more common in girls. It usually occurs after age 4 and usually remits by about age 12, Dr. Strunc said.
However, the onset of absence in patients younger than age 3 is associated with increased odds of neurodevelopmental abnormalities “and probably represents another epilepsy syndrome,” he said.
Absence symptoms may mirror those of children who are simply daydreamers, Dr. Strunc noted. One way to confirm absence is by provoking hyperventilation, which will bring on an episode of absence if present, he said. EEGs provide evidence as well.
Acute ataxia in children has a wide differential that sends kids and families to the pediatrician or emergency department, Dr. Strunc said. Acute cerebellar ataxia is characterized by abrupt and symmetric symptoms, with no mental status changes, no fever, no meningitis, and no headache. A wide, unstable gait is a distinguishing feature, Dr. Strunc said.
However, other causes of acute ataxia should be ruled out, including toxic ingestion, tick paralysis, central nervous system infections, vascular conditions, and genetic conditions.
Don’t miss those ticks
Especially during periods when kids are outdoors, clinicians should consider a tick bite as a source of ataxia and neurologic symptoms in children, Dr. Strunc emphasized. Tick paralysis notably resembles many symptoms of Guillain-Barré syndrome (acute inflammatory demyelinating polyneuropathy).
Dr. Strunc described a case involving a 5-year-old girl who developed sudden problems with gait. The problems worsened quickly and prompted an emergency department visit.
The girl had an unremarkable history, she had not experienced mental status changes, her strength was normal, and she had just returned from a Girl Scouts trip. The patient was presumed to have Guillain-Barré. IVIG was initiated when an emergency nurse found a tick on her scalp. The tick was removed, and the patient left the hospital within 24 hours.
Children with tick paralysis are usually symptomatic after 5-7 days with the tick attached, Dr. Strunc said. They recover within a day after tick removal.
Overall, actual seizures are less common than other neurologic events in children, according to Dr. Strunc. Details on history, lack or presence of neurologic feature, and normal child development can help guide evaluation.
Take advantage of videos, he emphasized, as many parents and caregivers record a child’s neurologic events.
“Ataxia is scary, but exam and associated findings will help you with etiology,” he said.
Dr. Strunc has received research support from Jazz and Harmony and has served on the speakers’ bureau for Jazz Pharmaceuticals, Harmony Biosciences, and Avadel, unrelated to his presentation.
A version of this article first appeared on Medscape.com.
WASHINGTON – Get the back story before rushing to diagnose a seizure disorder in a child, Michael Strunc, MD, said in a presentation at the annual meeting of the American Academy of Pediatrics.
Clinicians should ask parents or caregivers about the child’s behavior before the suspected seizure, whether there were any triggers, and if so, what might they have been, according to Dr. Strunc, a child neurologist and sleep medicine specialist at Children’s Hospital of the King’s Daughters, Norfolk, Va.
“Most seizures don’t have triggers,” he said. Rather, patients often become stiff, experience a motor event that builds in intensity then slows and stops, and finally, the patient is sleepy and tired. Clinicians should also find out whether the event had a beginning, middle, and end.
Approximately 0.6% of children younger than 17 years in the United States have active epilepsy, according to the Centers for Disease Control and Prevention.
Dr. Strunc offered a few more tips for diagnosing a child:
- Ask whether the patient’s eyes were open during the event. If the eyes were closed or squished closed, “it is almost never a seizure,” he said.
- Find out whether the patient was awake or asleep, and how, if at all, caregivers attempted to stop the event.
- Ask if the child’s experiences were repeating and predictable, and inquire about a family history of seizures or other events.
- Inquire about any developmental changes and other changes in the child, such as irritability, regression, or ataxia.
The differential diagnosis for a seizure includes nonepileptic events that occur with and without changes in consciousness or sleep. These events range from breath-holding and hyperventilation to night terrors, narcolepsy, migraine, and attention-deficit/hyperactivity disorder, he said.
Is it epilepsy?
Dr. Strunc shared several cases of neurologic “events” ranging from simple to severe.
In one case, a 10-month-old infant girl with a potential tonic/staring seizure presented with a history of events that involved getting stuck in a stiff position, usually while sitting in a car seat or highchair, with adducting of legs, redness of face, and “zoned-out” expression. The infant was healthy, smart, and precocious, with no illness, fever, or trauma, but the mother was very concerned, Dr. Strunc said.
The diagnosis: Self-gratification, which is benign and usually outgrown, although it can become extreme, he said.
By contrast, “absence,” also known as idiopathic generalized epilepsy, presents as brief events of 4-10 seconds that may occur up to hundreds of times a day. This type of epilepsy is associated with the sudden onset of impaired consciousness and unresponsiveness. These events end abruptly, and the child may be unaware. Absence is more common in girls. It usually occurs after age 4 and usually remits by about age 12, Dr. Strunc said.
However, the onset of absence in patients younger than age 3 is associated with increased odds of neurodevelopmental abnormalities “and probably represents another epilepsy syndrome,” he said.
Absence symptoms may mirror those of children who are simply daydreamers, Dr. Strunc noted. One way to confirm absence is by provoking hyperventilation, which will bring on an episode of absence if present, he said. EEGs provide evidence as well.
Acute ataxia in children has a wide differential that sends kids and families to the pediatrician or emergency department, Dr. Strunc said. Acute cerebellar ataxia is characterized by abrupt and symmetric symptoms, with no mental status changes, no fever, no meningitis, and no headache. A wide, unstable gait is a distinguishing feature, Dr. Strunc said.
However, other causes of acute ataxia should be ruled out, including toxic ingestion, tick paralysis, central nervous system infections, vascular conditions, and genetic conditions.
Don’t miss those ticks
Especially during periods when kids are outdoors, clinicians should consider a tick bite as a source of ataxia and neurologic symptoms in children, Dr. Strunc emphasized. Tick paralysis notably resembles many symptoms of Guillain-Barré syndrome (acute inflammatory demyelinating polyneuropathy).
Dr. Strunc described a case involving a 5-year-old girl who developed sudden problems with gait. The problems worsened quickly and prompted an emergency department visit.
The girl had an unremarkable history, she had not experienced mental status changes, her strength was normal, and she had just returned from a Girl Scouts trip. The patient was presumed to have Guillain-Barré. IVIG was initiated when an emergency nurse found a tick on her scalp. The tick was removed, and the patient left the hospital within 24 hours.
Children with tick paralysis are usually symptomatic after 5-7 days with the tick attached, Dr. Strunc said. They recover within a day after tick removal.
Overall, actual seizures are less common than other neurologic events in children, according to Dr. Strunc. Details on history, lack or presence of neurologic feature, and normal child development can help guide evaluation.
Take advantage of videos, he emphasized, as many parents and caregivers record a child’s neurologic events.
“Ataxia is scary, but exam and associated findings will help you with etiology,” he said.
Dr. Strunc has received research support from Jazz and Harmony and has served on the speakers’ bureau for Jazz Pharmaceuticals, Harmony Biosciences, and Avadel, unrelated to his presentation.
A version of this article first appeared on Medscape.com.
FROM AAP 2023