Pediatrics

The U.S. Food and Drug Administration has approved vamorolone oral suspension (Agamree, Santhera) for the treatment of 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.

Olivier Le Moal/Getty Images

“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 .

The U.S. Food and Drug Administration has approved vamorolone oral suspension (Agamree, Santhera) for the treatment of 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.

Olivier Le Moal/Getty Images

“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 .

The U.S. Food and Drug Administration has approved vamorolone oral suspension (Agamree, Santhera) for the treatment of 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.

Olivier Le Moal/Getty Images

“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 .

WASHINGTON – Online vendors of nicotine toothpicks rarely verify the age of purchasers, whereas brick-and-mortar stores are more likely to ask for ID, 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 – Online vendors of nicotine toothpicks rarely verify the age of purchasers, whereas brick-and-mortar stores are more likely to ask for ID, 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 – Online vendors of nicotine toothpicks rarely verify the age of purchasers, whereas brick-and-mortar stores are more likely to ask for ID, 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.

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 populations^6-8 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 populations^6-8 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 populations^6-8 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.

VANCOUVER – New evidence from the phase 3 EoE KIDS trial supports the safety and efficacy of dupilumab (Dupixent) treatment for children aged 1-11 years with eosinophilic esophagitis (EoE).

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 – New evidence from the phase 3 EoE KIDS trial supports the safety and efficacy of dupilumab (Dupixent) treatment for children aged 1-11 years with eosinophilic esophagitis (EoE).

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 – New evidence from the phase 3 EoE KIDS trial supports the safety and efficacy of dupilumab (Dupixent) treatment for children aged 1-11 years with eosinophilic esophagitis (EoE).

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.

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

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

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.

Vitamin B6, vitamin D, green tea, and probiotics are among the oral nutraceuticals that may benefit patients with acne, results from a systematic literature review suggest.

“While many topical and systemic prescription options are available for the treatment of acne, some patients may be interested in natural and complementary therapies as either an adjunctive or an alternative to prescription medications,” researchers led by John S. Barbieri, MD, MBA, of the department of dermatology at Brigham and Women’s Hospital, Boston, wrote in their study, which was published online in JAMA Dermatology. The researchers defined nutraceuticals as products derived from food sources that provide both nutritional and medicinal benefits, such as vitamins, dietary supplements, and herbal products. “Although patients may be interested in nutraceuticals as a potential treatment option for acne, there is uncertainty regarding the efficacy and safety of these products,” they wrote.

For the systematic review, they searched the PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science databases from inception through January 30, 2023, to identify randomized clinical trials that evaluated oral nutraceutical interventions such as vitamins and minerals, botanical extracts, prebiotics, and probiotics in individuals with acne. They extracted clinician-reported outcomes, patient-reported outcomes, and adverse events from the included studies, and used the Cochrane Risk of Bias checklist tool to assess the quality of evidence in randomized clinical trials. Based on this tool, they used Agency for Healthcare Research and Quality standards to categorize the articles as good, fair, or poor quality.

The search yielded 42 unique studies with 3,346 participants. Of these 42 studies, 27 were considered poor quality, 11 were considered fair quality, and 4 were considered good quality. The good-quality studies separately evaluated four interventions: vitamin D, green tea extract, probiotics, and cheongsangbangpoong-tang, an herbal formula approved for use in acne by the Korea Food and Drug Administration.

The 11 fair-quality studies suggested potential effectiveness for pantothenic acid (vitamin B5), the fatty acids omega-3 (eicosapentaenoic acid [EPA] and/or docosahexaenoic acid [DHA]) and omega-6 (gamma-linoleic acid), and probiotics.

Zinc was the most studied nutraceutical identified in the review, but “there was substantial heterogeneity in the results, with only slightly greater than one-half of studies finding zinc to be efficacious,” the authors noted. “Studies using higher doses more often found zinc to be efficacious,” they said, adding that zinc “had the highest rate of adverse effect reporting of any nutraceuticals assessed in this review.”

Dr. Barbieri and colleagues acknowledged limitations of their analysis, including the fact that few of the nutraceuticals considered to have good or fair evidence for their use were evaluated in more than one study. “In addition, some studies had inconsistent results depending on the outcome measure assessed,” they wrote. “For instance, although green tea extract led to statistically significant improvements in lesion counts, it did not result in statistically significant improvements in quality of life, suggesting the observed lesion count differences may not be clinically meaningful to patients.”

And while probiotics had the most studies supporting their efficacy, they were generally of very small sample size.

Dr. Jonette Keri

Asked to comment on the study, Jonette Keri, MD, PhD, a dermatologist who directs the Acne and Rosacea Treatment Center at the University of Miami, who was not involved with the study, said that while the review was exhaustive, more research is needed to better determine the efficacy and side effects of the products studied. “The real strength of this wonderful review is now we have all of this information in one place, and this will serve as a great patient care resource,” she told this news organization.

Dr. Barbieri reported personal fees from Dexcel Pharma for consulting outside the submitted work. Dr. Keri disclosed that she is a consultant for L’Oréal.

Vitamin B6, vitamin D, green tea, and probiotics are among the oral nutraceuticals that may benefit patients with acne, results from a systematic literature review suggest.

“While many topical and systemic prescription options are available for the treatment of acne, some patients may be interested in natural and complementary therapies as either an adjunctive or an alternative to prescription medications,” researchers led by John S. Barbieri, MD, MBA, of the department of dermatology at Brigham and Women’s Hospital, Boston, wrote in their study, which was published online in JAMA Dermatology. The researchers defined nutraceuticals as products derived from food sources that provide both nutritional and medicinal benefits, such as vitamins, dietary supplements, and herbal products. “Although patients may be interested in nutraceuticals as a potential treatment option for acne, there is uncertainty regarding the efficacy and safety of these products,” they wrote.

For the systematic review, they searched the PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science databases from inception through January 30, 2023, to identify randomized clinical trials that evaluated oral nutraceutical interventions such as vitamins and minerals, botanical extracts, prebiotics, and probiotics in individuals with acne. They extracted clinician-reported outcomes, patient-reported outcomes, and adverse events from the included studies, and used the Cochrane Risk of Bias checklist tool to assess the quality of evidence in randomized clinical trials. Based on this tool, they used Agency for Healthcare Research and Quality standards to categorize the articles as good, fair, or poor quality.

The search yielded 42 unique studies with 3,346 participants. Of these 42 studies, 27 were considered poor quality, 11 were considered fair quality, and 4 were considered good quality. The good-quality studies separately evaluated four interventions: vitamin D, green tea extract, probiotics, and cheongsangbangpoong-tang, an herbal formula approved for use in acne by the Korea Food and Drug Administration.

The 11 fair-quality studies suggested potential effectiveness for pantothenic acid (vitamin B5), the fatty acids omega-3 (eicosapentaenoic acid [EPA] and/or docosahexaenoic acid [DHA]) and omega-6 (gamma-linoleic acid), and probiotics.

Zinc was the most studied nutraceutical identified in the review, but “there was substantial heterogeneity in the results, with only slightly greater than one-half of studies finding zinc to be efficacious,” the authors noted. “Studies using higher doses more often found zinc to be efficacious,” they said, adding that zinc “had the highest rate of adverse effect reporting of any nutraceuticals assessed in this review.”

Dr. Barbieri and colleagues acknowledged limitations of their analysis, including the fact that few of the nutraceuticals considered to have good or fair evidence for their use were evaluated in more than one study. “In addition, some studies had inconsistent results depending on the outcome measure assessed,” they wrote. “For instance, although green tea extract led to statistically significant improvements in lesion counts, it did not result in statistically significant improvements in quality of life, suggesting the observed lesion count differences may not be clinically meaningful to patients.”

And while probiotics had the most studies supporting their efficacy, they were generally of very small sample size.

Dr. Jonette Keri

Asked to comment on the study, Jonette Keri, MD, PhD, a dermatologist who directs the Acne and Rosacea Treatment Center at the University of Miami, who was not involved with the study, said that while the review was exhaustive, more research is needed to better determine the efficacy and side effects of the products studied. “The real strength of this wonderful review is now we have all of this information in one place, and this will serve as a great patient care resource,” she told this news organization.

Dr. Barbieri reported personal fees from Dexcel Pharma for consulting outside the submitted work. Dr. Keri disclosed that she is a consultant for L’Oréal.

Vitamin B6, vitamin D, green tea, and probiotics are among the oral nutraceuticals that may benefit patients with acne, results from a systematic literature review suggest.

“While many topical and systemic prescription options are available for the treatment of acne, some patients may be interested in natural and complementary therapies as either an adjunctive or an alternative to prescription medications,” researchers led by John S. Barbieri, MD, MBA, of the department of dermatology at Brigham and Women’s Hospital, Boston, wrote in their study, which was published online in JAMA Dermatology. The researchers defined nutraceuticals as products derived from food sources that provide both nutritional and medicinal benefits, such as vitamins, dietary supplements, and herbal products. “Although patients may be interested in nutraceuticals as a potential treatment option for acne, there is uncertainty regarding the efficacy and safety of these products,” they wrote.

For the systematic review, they searched the PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science databases from inception through January 30, 2023, to identify randomized clinical trials that evaluated oral nutraceutical interventions such as vitamins and minerals, botanical extracts, prebiotics, and probiotics in individuals with acne. They extracted clinician-reported outcomes, patient-reported outcomes, and adverse events from the included studies, and used the Cochrane Risk of Bias checklist tool to assess the quality of evidence in randomized clinical trials. Based on this tool, they used Agency for Healthcare Research and Quality standards to categorize the articles as good, fair, or poor quality.

The search yielded 42 unique studies with 3,346 participants. Of these 42 studies, 27 were considered poor quality, 11 were considered fair quality, and 4 were considered good quality. The good-quality studies separately evaluated four interventions: vitamin D, green tea extract, probiotics, and cheongsangbangpoong-tang, an herbal formula approved for use in acne by the Korea Food and Drug Administration.

The 11 fair-quality studies suggested potential effectiveness for pantothenic acid (vitamin B5), the fatty acids omega-3 (eicosapentaenoic acid [EPA] and/or docosahexaenoic acid [DHA]) and omega-6 (gamma-linoleic acid), and probiotics.

Zinc was the most studied nutraceutical identified in the review, but “there was substantial heterogeneity in the results, with only slightly greater than one-half of studies finding zinc to be efficacious,” the authors noted. “Studies using higher doses more often found zinc to be efficacious,” they said, adding that zinc “had the highest rate of adverse effect reporting of any nutraceuticals assessed in this review.”

Dr. Barbieri and colleagues acknowledged limitations of their analysis, including the fact that few of the nutraceuticals considered to have good or fair evidence for their use were evaluated in more than one study. “In addition, some studies had inconsistent results depending on the outcome measure assessed,” they wrote. “For instance, although green tea extract led to statistically significant improvements in lesion counts, it did not result in statistically significant improvements in quality of life, suggesting the observed lesion count differences may not be clinically meaningful to patients.”

And while probiotics had the most studies supporting their efficacy, they were generally of very small sample size.

Dr. Jonette Keri

Asked to comment on the study, Jonette Keri, MD, PhD, a dermatologist who directs the Acne and Rosacea Treatment Center at the University of Miami, who was not involved with the study, said that while the review was exhaustive, more research is needed to better determine the efficacy and side effects of the products studied. “The real strength of this wonderful review is now we have all of this information in one place, and this will serve as a great patient care resource,” she told this news organization.

Dr. Barbieri reported personal fees from Dexcel Pharma for consulting outside the submitted work. Dr. Keri disclosed that she is a consultant for L’Oréal.

A device that stimulates the median nerve and a D1 receptor antagonist are among the promising new treatment approaches for patients with Tourette syndrome (TS), according to an overview of new therapies presented at the XXVI World Congress of Neurology.

One recent study by University of Nottingham researchers showed a wrist-worn stimulating device significantly reduces the frequency and severity of tics – repetitive movements or vocalizations that can occur several times a day.

“Wearable nerve stimulation holds great promise because it will be good across the age spectrum; adults can wear it to work, and children can go to school with it to help them concentrate on their schoolwork, and then they take it off at night,” Eileen Joyce, PhD, MB BChir, professor of neuropsychiatry at the Institute of Neurology, University College London, told this news organization.

Dr. Joyce, who was not part of the study, discussed this and other new advances in tic therapy at the meeting.

About 24% of children will suffer from tics at some point. The prevalence of Tourette syndrome among males is about four times that of females, Dr. Joyce told delegates. She added the typical age of onset is about 7 years with peak severity at about 12 years.

Predictors of tics persisting into adulthood include comorbid attention deficit hyperactivity disorder (ADHD), obsessive–compulsive disorder, and autism spectrum disorder, said Dr. Joyce, who also discussed the “highly heritable” nature of the syndrome and the numerous related genes identified to date.
 

Current and emerging treatments

Current treatments include psychological therapy, Botox for focal tics, and medications such as antipsychotics. Emerging therapies included deep brain stimulation and the new median nerve stimulation approach.

A study published  earlier this year included 135 patients with moderate to severe tic disorder who were randomly assigned to receive the investigational neuromodulation treatment, a sham treatment, or a wait-list treatment group.

The intervention involves rhythmic pulse trains of median nerve stimulation delivered via a device worn at the wrist. The device was programmed to deliver rhythmic (10 Hz) trains of low-intensity (1-19 mA) electrical stimulation to the median nerve at home once daily, 5 days a week for 4 weeks.

At 4 weeks, tic severity, as measured by the Yale Global Tic Severity Scale-Total Tic Severity Score (YGTSS-TTSS), was reduced by 7.1 points (35% reduction) in the active stimulation group compared to 2.13 points in the sham and 2.11 points in wait-list control groups.

The reduction for active stimulation was substantially larger, clinically meaningful (effect size, 0.5), and statistically significant (P = .02) compared to both the sham stimulation and wait-list control groups, which did not differ from one another.

Tic frequency (tics per minute or TPM) was reduced more in the active than sham stimulation groups (−15.6 TPM vs. −7.7 TPM; P < .03) and the reduction in tic frequency was clinically meaningful (>25% reduction; effect-size, 0.3).

When the active stimulator was turned off, the tics worsened, noted Dr. Joyce.

“The study showed that if you stimulate the median nerve at the wrist, you can train brain oscillations that are linked to the suppression of movement,” Dr. Joyce said. “So based on physiological knowledge, they have developed a median nerve stimulator to entrain cortical rhythms.”
 

Simple and exciting

The new device is “really exciting”, she added. “It’s not invasive and is quite simple to use and could help a lot of people with Tourette syndrome.”

Asked to comment, Alan Carson, MD, consultant neuropsychiatrist and honorary professor of neuropsychiatry, University of Edinburgh, who co-chaired the neuropsychiatry session featuring this presentation, called the device “promising.”

“Deep brain stimulation appears to be very effective but it’s a major procedure, so a simple wearable device seems highly desirable,” Dr. Carson said.

Dr. Joyce also discussed a study on the efficacy of cannabis (nabiximols; Sativex) as an intervention for tic management in males, those with severe tics, and those with comorbid ADHD.

And a new oral medication, ecopipam, a highly selective D1 receptor antagonist, is also raising hopes, said Dr. Joyce, with results from a randomized controlled trial  showing the drug significantly improved tics and had few adverse effects.

Dr. Joyce and Dr. Carson report no relevant financial relationships.

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

A device that stimulates the median nerve and a D1 receptor antagonist are among the promising new treatment approaches for patients with Tourette syndrome (TS), according to an overview of new therapies presented at the XXVI World Congress of Neurology.

One recent study by University of Nottingham researchers showed a wrist-worn stimulating device significantly reduces the frequency and severity of tics – repetitive movements or vocalizations that can occur several times a day.

“Wearable nerve stimulation holds great promise because it will be good across the age spectrum; adults can wear it to work, and children can go to school with it to help them concentrate on their schoolwork, and then they take it off at night,” Eileen Joyce, PhD, MB BChir, professor of neuropsychiatry at the Institute of Neurology, University College London, told this news organization.

Dr. Joyce, who was not part of the study, discussed this and other new advances in tic therapy at the meeting.

About 24% of children will suffer from tics at some point. The prevalence of Tourette syndrome among males is about four times that of females, Dr. Joyce told delegates. She added the typical age of onset is about 7 years with peak severity at about 12 years.

Predictors of tics persisting into adulthood include comorbid attention deficit hyperactivity disorder (ADHD), obsessive–compulsive disorder, and autism spectrum disorder, said Dr. Joyce, who also discussed the “highly heritable” nature of the syndrome and the numerous related genes identified to date.
 

Current and emerging treatments

Current treatments include psychological therapy, Botox for focal tics, and medications such as antipsychotics. Emerging therapies included deep brain stimulation and the new median nerve stimulation approach.

A study published  earlier this year included 135 patients with moderate to severe tic disorder who were randomly assigned to receive the investigational neuromodulation treatment, a sham treatment, or a wait-list treatment group.

The intervention involves rhythmic pulse trains of median nerve stimulation delivered via a device worn at the wrist. The device was programmed to deliver rhythmic (10 Hz) trains of low-intensity (1-19 mA) electrical stimulation to the median nerve at home once daily, 5 days a week for 4 weeks.

At 4 weeks, tic severity, as measured by the Yale Global Tic Severity Scale-Total Tic Severity Score (YGTSS-TTSS), was reduced by 7.1 points (35% reduction) in the active stimulation group compared to 2.13 points in the sham and 2.11 points in wait-list control groups.

The reduction for active stimulation was substantially larger, clinically meaningful (effect size, 0.5), and statistically significant (P = .02) compared to both the sham stimulation and wait-list control groups, which did not differ from one another.

Tic frequency (tics per minute or TPM) was reduced more in the active than sham stimulation groups (−15.6 TPM vs. −7.7 TPM; P < .03) and the reduction in tic frequency was clinically meaningful (>25% reduction; effect-size, 0.3).

When the active stimulator was turned off, the tics worsened, noted Dr. Joyce.

“The study showed that if you stimulate the median nerve at the wrist, you can train brain oscillations that are linked to the suppression of movement,” Dr. Joyce said. “So based on physiological knowledge, they have developed a median nerve stimulator to entrain cortical rhythms.”
 

Simple and exciting

The new device is “really exciting”, she added. “It’s not invasive and is quite simple to use and could help a lot of people with Tourette syndrome.”

Asked to comment, Alan Carson, MD, consultant neuropsychiatrist and honorary professor of neuropsychiatry, University of Edinburgh, who co-chaired the neuropsychiatry session featuring this presentation, called the device “promising.”

“Deep brain stimulation appears to be very effective but it’s a major procedure, so a simple wearable device seems highly desirable,” Dr. Carson said.

Dr. Joyce also discussed a study on the efficacy of cannabis (nabiximols; Sativex) as an intervention for tic management in males, those with severe tics, and those with comorbid ADHD.

And a new oral medication, ecopipam, a highly selective D1 receptor antagonist, is also raising hopes, said Dr. Joyce, with results from a randomized controlled trial  showing the drug significantly improved tics and had few adverse effects.

Dr. Joyce and Dr. Carson report no relevant financial relationships.

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

A device that stimulates the median nerve and a D1 receptor antagonist are among the promising new treatment approaches for patients with Tourette syndrome (TS), according to an overview of new therapies presented at the XXVI World Congress of Neurology.

One recent study by University of Nottingham researchers showed a wrist-worn stimulating device significantly reduces the frequency and severity of tics – repetitive movements or vocalizations that can occur several times a day.

“Wearable nerve stimulation holds great promise because it will be good across the age spectrum; adults can wear it to work, and children can go to school with it to help them concentrate on their schoolwork, and then they take it off at night,” Eileen Joyce, PhD, MB BChir, professor of neuropsychiatry at the Institute of Neurology, University College London, told this news organization.

Dr. Joyce, who was not part of the study, discussed this and other new advances in tic therapy at the meeting.

About 24% of children will suffer from tics at some point. The prevalence of Tourette syndrome among males is about four times that of females, Dr. Joyce told delegates. She added the typical age of onset is about 7 years with peak severity at about 12 years.

Predictors of tics persisting into adulthood include comorbid attention deficit hyperactivity disorder (ADHD), obsessive–compulsive disorder, and autism spectrum disorder, said Dr. Joyce, who also discussed the “highly heritable” nature of the syndrome and the numerous related genes identified to date.
 

Current and emerging treatments

Current treatments include psychological therapy, Botox for focal tics, and medications such as antipsychotics. Emerging therapies included deep brain stimulation and the new median nerve stimulation approach.

A study published  earlier this year included 135 patients with moderate to severe tic disorder who were randomly assigned to receive the investigational neuromodulation treatment, a sham treatment, or a wait-list treatment group.

The intervention involves rhythmic pulse trains of median nerve stimulation delivered via a device worn at the wrist. The device was programmed to deliver rhythmic (10 Hz) trains of low-intensity (1-19 mA) electrical stimulation to the median nerve at home once daily, 5 days a week for 4 weeks.

At 4 weeks, tic severity, as measured by the Yale Global Tic Severity Scale-Total Tic Severity Score (YGTSS-TTSS), was reduced by 7.1 points (35% reduction) in the active stimulation group compared to 2.13 points in the sham and 2.11 points in wait-list control groups.

The reduction for active stimulation was substantially larger, clinically meaningful (effect size, 0.5), and statistically significant (P = .02) compared to both the sham stimulation and wait-list control groups, which did not differ from one another.

Tic frequency (tics per minute or TPM) was reduced more in the active than sham stimulation groups (−15.6 TPM vs. −7.7 TPM; P < .03) and the reduction in tic frequency was clinically meaningful (>25% reduction; effect-size, 0.3).

When the active stimulator was turned off, the tics worsened, noted Dr. Joyce.

“The study showed that if you stimulate the median nerve at the wrist, you can train brain oscillations that are linked to the suppression of movement,” Dr. Joyce said. “So based on physiological knowledge, they have developed a median nerve stimulator to entrain cortical rhythms.”
 

Simple and exciting

The new device is “really exciting”, she added. “It’s not invasive and is quite simple to use and could help a lot of people with Tourette syndrome.”

Asked to comment, Alan Carson, MD, consultant neuropsychiatrist and honorary professor of neuropsychiatry, University of Edinburgh, who co-chaired the neuropsychiatry session featuring this presentation, called the device “promising.”

“Deep brain stimulation appears to be very effective but it’s a major procedure, so a simple wearable device seems highly desirable,” Dr. Carson said.

Dr. Joyce also discussed a study on the efficacy of cannabis (nabiximols; Sativex) as an intervention for tic management in males, those with severe tics, and those with comorbid ADHD.

And a new oral medication, ecopipam, a highly selective D1 receptor antagonist, is also raising hopes, said Dr. Joyce, with results from a randomized controlled trial  showing the drug significantly improved tics and had few adverse effects.

Dr. Joyce and Dr. Carson report no relevant financial relationships.

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

TOPLINE:

Adolescents with atopic dermatitis (AD) experience bullying significantly more often than their peers without AD.

METHODOLOGY:

• Adolescents with AD have reported appearance-based bullying.
• To evaluate the association between AD and the prevalence and frequency of bullying, researchers analyzed cross-sectional data from adult caregivers of U.S. adolescents aged 12-17 years who participated in the 2021 National Health Interview Survey.
• Logistic regression and ordinal logistic regression were used to compare the prevalence of experiencing one or more bullying encounters during the previous 12 months and the frequency of bullying between adolescents with and those without AD.

TAKEAWAY:

• A total of 3,207 adolescents were included in the analysis. The mean age of the participants was 14.5 years, and 11.9% currently had AD. The prevalence of experiencing bullying was significantly higher among adolescents with AD, compared with those without AD (33.2% vs. 19%; P < .001), as was the prevalence of cyberbullying (9.1% vs. 5.8%; P = .04).
• Following adjustment for demographics and atopic comorbidities, adolescents with AD were at increased odds of bullying, compared with their peers without AD (adjusted odds ratio, 1.99; 95% confidence interval, 1.45-2.73).
• Following adjustment for demographics, adolescents with AD were also at increased odds of cyberbullying, compared with their peers without AD (AOR, 1.65; 95% CI, 1.04-2.62), but no association was observed following adjustment for atopic comorbidities (AOR, 1.27; 95% CI, 0.82-1.96).
• Following ordinal logistic regression that was adjusted for demographics and atopic comorbidities, adolescents with AD were at greater odds of being bullied at a higher frequency, compared with their peers without AD (AOR, 1.97; 95% CI, 1.44-2.68).

IN PRACTICE:

“Larger, future studies using clinical AD diagnoses and adolescent self-report can advance understanding of bullying and AD,” the researchers wrote. “Clinicians, families, and schools should address and monitor bullying among adolescents.”

SOURCE:

Howa Yeung, MD, of the department of dermatology at Emory University School of Medicine, Atlanta, led the research. The study was published online  in JAMA Dermatology.

LIMITATIONS:

Limitations include the study’s cross-sectional design. In addition, the investigators could not directly attribute bullying to skin-specific findings, and it was a caregiver report.

DISCLOSURES:

The study was supported by grants from the National Institutes of Health and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. One of the authors, Joy Wan, MD, received grants from Pfizer and personal fees from Janssen and Sun Pharmaceuticals outside of the submitted work.

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

TOPLINE:

Adolescents with atopic dermatitis (AD) experience bullying significantly more often than their peers without AD.

METHODOLOGY:

• Adolescents with AD have reported appearance-based bullying.
• To evaluate the association between AD and the prevalence and frequency of bullying, researchers analyzed cross-sectional data from adult caregivers of U.S. adolescents aged 12-17 years who participated in the 2021 National Health Interview Survey.
• Logistic regression and ordinal logistic regression were used to compare the prevalence of experiencing one or more bullying encounters during the previous 12 months and the frequency of bullying between adolescents with and those without AD.

TAKEAWAY:

• A total of 3,207 adolescents were included in the analysis. The mean age of the participants was 14.5 years, and 11.9% currently had AD. The prevalence of experiencing bullying was significantly higher among adolescents with AD, compared with those without AD (33.2% vs. 19%; P < .001), as was the prevalence of cyberbullying (9.1% vs. 5.8%; P = .04).
• Following adjustment for demographics and atopic comorbidities, adolescents with AD were at increased odds of bullying, compared with their peers without AD (adjusted odds ratio, 1.99; 95% confidence interval, 1.45-2.73).
• Following adjustment for demographics, adolescents with AD were also at increased odds of cyberbullying, compared with their peers without AD (AOR, 1.65; 95% CI, 1.04-2.62), but no association was observed following adjustment for atopic comorbidities (AOR, 1.27; 95% CI, 0.82-1.96).
• Following ordinal logistic regression that was adjusted for demographics and atopic comorbidities, adolescents with AD were at greater odds of being bullied at a higher frequency, compared with their peers without AD (AOR, 1.97; 95% CI, 1.44-2.68).

IN PRACTICE:

“Larger, future studies using clinical AD diagnoses and adolescent self-report can advance understanding of bullying and AD,” the researchers wrote. “Clinicians, families, and schools should address and monitor bullying among adolescents.”

SOURCE:

Howa Yeung, MD, of the department of dermatology at Emory University School of Medicine, Atlanta, led the research. The study was published online  in JAMA Dermatology.

LIMITATIONS:

Limitations include the study’s cross-sectional design. In addition, the investigators could not directly attribute bullying to skin-specific findings, and it was a caregiver report.

DISCLOSURES:

The study was supported by grants from the National Institutes of Health and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. One of the authors, Joy Wan, MD, received grants from Pfizer and personal fees from Janssen and Sun Pharmaceuticals outside of the submitted work.

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

TOPLINE:

Adolescents with atopic dermatitis (AD) experience bullying significantly more often than their peers without AD.

METHODOLOGY:

• Adolescents with AD have reported appearance-based bullying.
• To evaluate the association between AD and the prevalence and frequency of bullying, researchers analyzed cross-sectional data from adult caregivers of U.S. adolescents aged 12-17 years who participated in the 2021 National Health Interview Survey.
• Logistic regression and ordinal logistic regression were used to compare the prevalence of experiencing one or more bullying encounters during the previous 12 months and the frequency of bullying between adolescents with and those without AD.

TAKEAWAY:

• A total of 3,207 adolescents were included in the analysis. The mean age of the participants was 14.5 years, and 11.9% currently had AD. The prevalence of experiencing bullying was significantly higher among adolescents with AD, compared with those without AD (33.2% vs. 19%; P < .001), as was the prevalence of cyberbullying (9.1% vs. 5.8%; P = .04).
• Following adjustment for demographics and atopic comorbidities, adolescents with AD were at increased odds of bullying, compared with their peers without AD (adjusted odds ratio, 1.99; 95% confidence interval, 1.45-2.73).
• Following adjustment for demographics, adolescents with AD were also at increased odds of cyberbullying, compared with their peers without AD (AOR, 1.65; 95% CI, 1.04-2.62), but no association was observed following adjustment for atopic comorbidities (AOR, 1.27; 95% CI, 0.82-1.96).
• Following ordinal logistic regression that was adjusted for demographics and atopic comorbidities, adolescents with AD were at greater odds of being bullied at a higher frequency, compared with their peers without AD (AOR, 1.97; 95% CI, 1.44-2.68).

IN PRACTICE:

“Larger, future studies using clinical AD diagnoses and adolescent self-report can advance understanding of bullying and AD,” the researchers wrote. “Clinicians, families, and schools should address and monitor bullying among adolescents.”

SOURCE:

Howa Yeung, MD, of the department of dermatology at Emory University School of Medicine, Atlanta, led the research. The study was published online  in JAMA Dermatology.

LIMITATIONS:

Limitations include the study’s cross-sectional design. In addition, the investigators could not directly attribute bullying to skin-specific findings, and it was a caregiver report.

DISCLOSURES:

The study was supported by grants from the National Institutes of Health and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. One of the authors, Joy Wan, MD, received grants from Pfizer and personal fees from Janssen and Sun Pharmaceuticals outside of the submitted work.

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

It’s upper respiratory infection (URI) season. The following is a clinical scenario drawn from my own practice. I’ll tell you what I plan to do, but I’m most interested in crowdsourcing a response from all of you to collectively determine best practice. So please answer the polling questions and contribute your thoughts in the comments, whether you agree or disagree with me.

The patient

The patient is a 69-year-old woman with a 3-day history of cough, nasal congestion, malaise, tactile fever, and poor appetite. She has no sick contacts. She denies dyspnea, presyncope, and chest pain. She has tried guaifenesin and ibuprofen for her symptoms, which helped a little.

She is up to date on immunizations, including four doses of COVID-19 vaccine and the influenza vaccine, which she received 2 months ago.

The patient has a history of heart failure with reduced ejection fraction, coronary artery disease, hypertension, chronic kidney disease stage 3aA2, obesity, and osteoarthritis. Current medications include atorvastatin, losartan, metoprolol, and aspirin.

Her weight is stable at 212 lb, and her vital signs today are:

• Temperature: 37.5° C
• Pulse: 60 beats/min
• Blood pressure: 150/88 mm Hg
• Respiration rate: 14 breaths/min
• SpO₂: 93% on room air

What information is most critical before deciding on management?

Your peers chose: 

• The patient’s history of viral URIs

 14%

 

• Whether her cough is productive and the color of the sputum

 38%

 

• How well this season’s flu vaccine matches circulating influenza viruses

 8%

 

• Local epidemiology of major viral pathogens (e.g., SARS-CoV-2, influenza, RSV)

 40%
 

Dr. Vega’s take

To provide the best care for our patients when they are threatened with multiple viral upper respiratory pathogens, it is imperative that clinicians have some idea regarding the epidemiology of viral infections, with as much local data as possible. This knowledge will help direct appropriate testing and treatment.

Modern viral molecular testing platforms are highly accurate, but they are not infallible. Small flaws in specificity and sensitivity of testing are magnified when community viral circulation is low. In a U.K. study conducted during a period of low COVID-19 prevalence, the positive predictive value of reverse-transcriptase polymerase chain reaction (RT-PCR) testing was just 16%. Although the negative predictive value was much higher, the false-positive rate of testing was still 0.5%. The authors of the study describe important potential consequences of false-positive results, such as being temporarily removed from an organ transplant list and unnecessary contact tracing.
 

Testing and treatment

Your county public health department maintains a website describing local activity of SARS-CoV-2 and influenza. Both viruses are in heavy circulation now.

What is the next best step in this patient’s management?

Your peers chose: 

• Treat empirically with ritonavir-boosted nirmatrelvir

 7%

 

• Treat empirically with oseltamivir or baloxavir

 14%

 

• Perform lab-based multiplex RT-PCR testing and wait to treat on the basis of results

 34%

 

• Perform rapid nucleic acid amplification testing (NAAT) and treat on the basis of results

 45%

Every practice has different resources and should use the best means available to treat patients. Ideally, this patient would undergo rapid NAAT with results available within 30 minutes. Test results will help guide not only treatment decisions but also infection-control measures.

The Infectious Diseases Society of America has provided updates for testing for URIs since the onset of the COVID-19 pandemic. Both laboratory-based and point-of-care rapid NAATs are recommended for testing. Rapid NAATs have been demonstrated to have a sensitivity of 96% and specificity of 100% in the detection of SARS-CoV-2. Obviously, they also offer a highly efficient means to make treatment and isolation decisions.

There are multiple platforms for molecular testing available. Laboratory-based platforms can test for dozens of potential pathogens, including bacteria. Rapid NAATs often have the ability to test for SARS-CoV-2, influenza, and respiratory syncytial virus (RSV). This functionality is important, because these infections generally are difficult to discriminate on the basis of clinical information alone.

The IDSA clearly recognizes the challenges of trying to manage cases of URI. For example, they state that testing of the anterior nares (AN) or oropharynx (OP) is acceptable, even though testing from the nasopharynx offers increased sensitivity. However, testing at the AN/OP allows for patient self-collection of samples, which is also recommended as an option by the IDSA. In an analysis of six cohort studies, the pooled sensitivity of patient-collected nasopharyngeal samples from the AN/OP was 88%, whereas the respective value for samples taken by health care providers was 95%.

The U.S. Centers for Disease Control and Prevention also provides recommendations for the management of patients with acute upper respiratory illness. Patients who are sick enough to be hospitalized should be tested at least for SARS-CoV-2 and influenza using molecular assays. Outpatients should be tested for SARS-CoV-2 with either molecular or antigen testing, and influenza testing should be offered if the findings will change decisions regarding treatment or isolation. Practically speaking, the recommendations for influenza testing mean that most individuals should be tested, including patients at high risk for complications of influenza and those who might have exposure to individuals at high risk.

Treatment of COVID-19 should only be provided in cases of a positive test within 5 days of symptom onset. However, clinicians may treat patients with anti-influenza medications presumptively if test results are not immediately available and the patient has worsening symptoms or is in a group at high risk for complications.

What are some of the challenges that you have faced during the COVID-19 pandemic regarding the management of patients with acute URIs? What have you found in terms of solutions, and where do gaps in quality of care persist? Please add your comments. I will review and circle back with a response. Thank you!

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

It’s upper respiratory infection (URI) season. The following is a clinical scenario drawn from my own practice. I’ll tell you what I plan to do, but I’m most interested in crowdsourcing a response from all of you to collectively determine best practice. So please answer the polling questions and contribute your thoughts in the comments, whether you agree or disagree with me.

The patient

The patient is a 69-year-old woman with a 3-day history of cough, nasal congestion, malaise, tactile fever, and poor appetite. She has no sick contacts. She denies dyspnea, presyncope, and chest pain. She has tried guaifenesin and ibuprofen for her symptoms, which helped a little.

She is up to date on immunizations, including four doses of COVID-19 vaccine and the influenza vaccine, which she received 2 months ago.

The patient has a history of heart failure with reduced ejection fraction, coronary artery disease, hypertension, chronic kidney disease stage 3aA2, obesity, and osteoarthritis. Current medications include atorvastatin, losartan, metoprolol, and aspirin.

Her weight is stable at 212 lb, and her vital signs today are:

• Temperature: 37.5° C
• Pulse: 60 beats/min
• Blood pressure: 150/88 mm Hg
• Respiration rate: 14 breaths/min
• SpO₂: 93% on room air

What information is most critical before deciding on management?

Your peers chose: 

• The patient’s history of viral URIs

 14%

 

• Whether her cough is productive and the color of the sputum

 38%

 

• How well this season’s flu vaccine matches circulating influenza viruses

 8%

 

• Local epidemiology of major viral pathogens (e.g., SARS-CoV-2, influenza, RSV)

 40%
 

Dr. Vega’s take

To provide the best care for our patients when they are threatened with multiple viral upper respiratory pathogens, it is imperative that clinicians have some idea regarding the epidemiology of viral infections, with as much local data as possible. This knowledge will help direct appropriate testing and treatment.

Modern viral molecular testing platforms are highly accurate, but they are not infallible. Small flaws in specificity and sensitivity of testing are magnified when community viral circulation is low. In a U.K. study conducted during a period of low COVID-19 prevalence, the positive predictive value of reverse-transcriptase polymerase chain reaction (RT-PCR) testing was just 16%. Although the negative predictive value was much higher, the false-positive rate of testing was still 0.5%. The authors of the study describe important potential consequences of false-positive results, such as being temporarily removed from an organ transplant list and unnecessary contact tracing.
 

Testing and treatment

Your county public health department maintains a website describing local activity of SARS-CoV-2 and influenza. Both viruses are in heavy circulation now.

What is the next best step in this patient’s management?

Your peers chose: 

• Treat empirically with ritonavir-boosted nirmatrelvir

 7%

 

• Treat empirically with oseltamivir or baloxavir

 14%

 

• Perform lab-based multiplex RT-PCR testing and wait to treat on the basis of results

 34%

 

• Perform rapid nucleic acid amplification testing (NAAT) and treat on the basis of results

 45%

Every practice has different resources and should use the best means available to treat patients. Ideally, this patient would undergo rapid NAAT with results available within 30 minutes. Test results will help guide not only treatment decisions but also infection-control measures.

The Infectious Diseases Society of America has provided updates for testing for URIs since the onset of the COVID-19 pandemic. Both laboratory-based and point-of-care rapid NAATs are recommended for testing. Rapid NAATs have been demonstrated to have a sensitivity of 96% and specificity of 100% in the detection of SARS-CoV-2. Obviously, they also offer a highly efficient means to make treatment and isolation decisions.

There are multiple platforms for molecular testing available. Laboratory-based platforms can test for dozens of potential pathogens, including bacteria. Rapid NAATs often have the ability to test for SARS-CoV-2, influenza, and respiratory syncytial virus (RSV). This functionality is important, because these infections generally are difficult to discriminate on the basis of clinical information alone.

The IDSA clearly recognizes the challenges of trying to manage cases of URI. For example, they state that testing of the anterior nares (AN) or oropharynx (OP) is acceptable, even though testing from the nasopharynx offers increased sensitivity. However, testing at the AN/OP allows for patient self-collection of samples, which is also recommended as an option by the IDSA. In an analysis of six cohort studies, the pooled sensitivity of patient-collected nasopharyngeal samples from the AN/OP was 88%, whereas the respective value for samples taken by health care providers was 95%.

The U.S. Centers for Disease Control and Prevention also provides recommendations for the management of patients with acute upper respiratory illness. Patients who are sick enough to be hospitalized should be tested at least for SARS-CoV-2 and influenza using molecular assays. Outpatients should be tested for SARS-CoV-2 with either molecular or antigen testing, and influenza testing should be offered if the findings will change decisions regarding treatment or isolation. Practically speaking, the recommendations for influenza testing mean that most individuals should be tested, including patients at high risk for complications of influenza and those who might have exposure to individuals at high risk.

Treatment of COVID-19 should only be provided in cases of a positive test within 5 days of symptom onset. However, clinicians may treat patients with anti-influenza medications presumptively if test results are not immediately available and the patient has worsening symptoms or is in a group at high risk for complications.

What are some of the challenges that you have faced during the COVID-19 pandemic regarding the management of patients with acute URIs? What have you found in terms of solutions, and where do gaps in quality of care persist? Please add your comments. I will review and circle back with a response. Thank you!

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

It’s upper respiratory infection (URI) season. The following is a clinical scenario drawn from my own practice. I’ll tell you what I plan to do, but I’m most interested in crowdsourcing a response from all of you to collectively determine best practice. So please answer the polling questions and contribute your thoughts in the comments, whether you agree or disagree with me.

The patient

The patient is a 69-year-old woman with a 3-day history of cough, nasal congestion, malaise, tactile fever, and poor appetite. She has no sick contacts. She denies dyspnea, presyncope, and chest pain. She has tried guaifenesin and ibuprofen for her symptoms, which helped a little.

She is up to date on immunizations, including four doses of COVID-19 vaccine and the influenza vaccine, which she received 2 months ago.

The patient has a history of heart failure with reduced ejection fraction, coronary artery disease, hypertension, chronic kidney disease stage 3aA2, obesity, and osteoarthritis. Current medications include atorvastatin, losartan, metoprolol, and aspirin.

Her weight is stable at 212 lb, and her vital signs today are:

• Temperature: 37.5° C
• Pulse: 60 beats/min
• Blood pressure: 150/88 mm Hg
• Respiration rate: 14 breaths/min
• SpO₂: 93% on room air

What information is most critical before deciding on management?

Your peers chose: 

• The patient’s history of viral URIs

 14%

 

• Whether her cough is productive and the color of the sputum

 38%

 

• How well this season’s flu vaccine matches circulating influenza viruses

 8%

 

• Local epidemiology of major viral pathogens (e.g., SARS-CoV-2, influenza, RSV)

 40%
 

Dr. Vega’s take

To provide the best care for our patients when they are threatened with multiple viral upper respiratory pathogens, it is imperative that clinicians have some idea regarding the epidemiology of viral infections, with as much local data as possible. This knowledge will help direct appropriate testing and treatment.

Modern viral molecular testing platforms are highly accurate, but they are not infallible. Small flaws in specificity and sensitivity of testing are magnified when community viral circulation is low. In a U.K. study conducted during a period of low COVID-19 prevalence, the positive predictive value of reverse-transcriptase polymerase chain reaction (RT-PCR) testing was just 16%. Although the negative predictive value was much higher, the false-positive rate of testing was still 0.5%. The authors of the study describe important potential consequences of false-positive results, such as being temporarily removed from an organ transplant list and unnecessary contact tracing.
 

Testing and treatment

Your county public health department maintains a website describing local activity of SARS-CoV-2 and influenza. Both viruses are in heavy circulation now.

What is the next best step in this patient’s management?

Your peers chose: 

• Treat empirically with ritonavir-boosted nirmatrelvir

 7%

 

• Treat empirically with oseltamivir or baloxavir

 14%

 

• Perform lab-based multiplex RT-PCR testing and wait to treat on the basis of results

 34%

 

• Perform rapid nucleic acid amplification testing (NAAT) and treat on the basis of results

 45%

Every practice has different resources and should use the best means available to treat patients. Ideally, this patient would undergo rapid NAAT with results available within 30 minutes. Test results will help guide not only treatment decisions but also infection-control measures.

The Infectious Diseases Society of America has provided updates for testing for URIs since the onset of the COVID-19 pandemic. Both laboratory-based and point-of-care rapid NAATs are recommended for testing. Rapid NAATs have been demonstrated to have a sensitivity of 96% and specificity of 100% in the detection of SARS-CoV-2. Obviously, they also offer a highly efficient means to make treatment and isolation decisions.

There are multiple platforms for molecular testing available. Laboratory-based platforms can test for dozens of potential pathogens, including bacteria. Rapid NAATs often have the ability to test for SARS-CoV-2, influenza, and respiratory syncytial virus (RSV). This functionality is important, because these infections generally are difficult to discriminate on the basis of clinical information alone.

The IDSA clearly recognizes the challenges of trying to manage cases of URI. For example, they state that testing of the anterior nares (AN) or oropharynx (OP) is acceptable, even though testing from the nasopharynx offers increased sensitivity. However, testing at the AN/OP allows for patient self-collection of samples, which is also recommended as an option by the IDSA. In an analysis of six cohort studies, the pooled sensitivity of patient-collected nasopharyngeal samples from the AN/OP was 88%, whereas the respective value for samples taken by health care providers was 95%.

The U.S. Centers for Disease Control and Prevention also provides recommendations for the management of patients with acute upper respiratory illness. Patients who are sick enough to be hospitalized should be tested at least for SARS-CoV-2 and influenza using molecular assays. Outpatients should be tested for SARS-CoV-2 with either molecular or antigen testing, and influenza testing should be offered if the findings will change decisions regarding treatment or isolation. Practically speaking, the recommendations for influenza testing mean that most individuals should be tested, including patients at high risk for complications of influenza and those who might have exposure to individuals at high risk.

Treatment of COVID-19 should only be provided in cases of a positive test within 5 days of symptom onset. However, clinicians may treat patients with anti-influenza medications presumptively if test results are not immediately available and the patient has worsening symptoms or is in a group at high risk for complications.

What are some of the challenges that you have faced during the COVID-19 pandemic regarding the management of patients with acute URIs? What have you found in terms of solutions, and where do gaps in quality of care persist? Please add your comments. I will review and circle back with a response. Thank you!

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