Acne

Potentially life-threatening cutaneous adverse drug reactions (cADRs) are associated with commonly prescribed oral antibiotics, according to a large, population-based, nested case-control study of older adults, spanning two decades.

The findings, published online in JAMA, “underscore the importance of judicious prescribing, with preferential use of antibiotics associated with a lower risk when clinically appropriate,” noted senior author David Juurlink, MD, PhD, professor of medicine; pediatrics; and health policy, management and evaluation at the University of Toronto, and head of the Clinical Pharmacology and Toxicology Division at Sunnybrook Health Sciences Centre, also in Toronto, Ontario, Canada, and coauthors.

“We hope our study raises awareness about the importance of drug allergy and gains support for future studies to improve drug allergy care,” lead author Erika Lee, MD, clinical immunology and allergy lecturer at the University of Toronto’s Drug Allergy Clinic, Sunnybrook Health Sciences Centre, said in an interview. “It is important to recognize symptoms and signs of a severe drug rash and promptly stop culprit drugs to prevent worsening reaction.”

Serious cADRs are “a group of rare but potentially life-threatening drug hypersensitivity reactions involving the skin and, frequently, internal organs,” the authors wrote. “Typically delayed in onset, these reactions include drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) — the most severe cADR, which has a reported mortality of 20%-40%,” they noted.

Speculation Without Data

Although it has been speculated that some oral antibiotics are more likely than others to be associated with serious cADRs, there have been no population-based studies examining this, they added.

The study included adults aged 66 years or older and used administrative health databases in Ontario, spanning from April 1, 2002, to March 31, 2022. Data on antibiotic use were taken from the Ontario Drug Benefit database. The Canadian Institute for Health Information (CIHI) National Ambulatory Care Reporting System was used to obtain data on emergency department (ED) visits for cADRs, while the CIHI Discharge Abstract Database was used to identify hospitalizations for cADRs. Finally, demographic information and outpatient healthcare utilization data were obtained from the Registered Persons Database and the Ontario Health Insurance Plan database, respectively.

A cohort of 21,758 older adults (median age, 75 years; 64.1% women) who had an ED visit or hospitalization for serious cADRs within 60 days of receiving antibiotic therapy was matched by age and sex with 87,025 antibiotic-treated controls who did not have a cutaneous reaction.

The median duration of antibiotic prescription was 7 days among cases and controls, and among the cases, the median latency period between antibiotic prescriptions and hospital visits for cADRs was 14 days. Most of the case patients went to the ED only (86.9%), and the rest were hospitalized.

The most commonly prescribed antibiotic class was penicillins (28.9%), followed by cephalosporins (18.2%), fluoroquinolones (16.5%), macrolides (14.8%), nitrofurantoin (8.6%), and sulfonamides (6.2%). Less commonly used antibiotics (“other” antibiotics) accounted for 6.9%.

Macrolide antibiotics were used as the reference because they are rarely associated with serious cADRs, noted the authors, and the multivariable analysis, adjusted for risk factors associated with serious cADRs, including malignancy, chronic liver disease, chronic kidney disease, and HIV.

After multivariable adjustment, relative to macrolides, sulfonamides were most strongly associated with serious cADRs (adjusted odds ratio [aOR], 2.9) but so were all other antibiotic classes, including cephalosporins (aOR, 2.6), “other” antibiotics (aOR, 2.3), nitrofurantoin (aOR, 2.2), penicillins (aOR, 1.4), and fluoroquinolones (aOR,1.3).

In the secondary analysis, the crude rate of ED visits or hospitalizations for cADRs was highest for cephalosporins (4.92 per 1000 prescriptions), followed by sulfonamides (3.22 per 1000 prescriptions). Among hospitalized patients, the median length of stay was 6 days, with 9.6% requiring transfer to a critical care unit and 5.3% dying in the hospital.
 

Hospitalizations, ED Visits Not Studied Previously

“Notably, the rate of antibiotic-associated serious cADRs leading to an ED visit or hospitalization has not been previously studied,” noted the authors. “We found that at least two hospital encounters for serious cADRs ensued for every 1000 antibiotic prescriptions. This rate is considerably higher than suggested by studies that examine only SJS/TEN and drug reaction with eosinophilia and systemic symptoms.”

Dr. Lee also emphasized the previously unreported findings about nitrofurantoin. “It is surprising to find that nitrofurantoin, a commonly prescribed antibiotic for urinary tract infection, is also associated with an increased risk of severe drug rash,” she said in an interview.

“This finding highlights a potential novel risk at a population-based level and should be further explored in other populations to verify this association,” the authors wrote.

Amesh Adalja, MD, a senior scholar at the Johns Hopkins Center for Health Security in Baltimore, Maryland, and a spokesperson for the Infectious Diseases Society of America, who was not involved in the study, agreed that the nitrofurantoin finding was surprising, but he was not surprised that sulfonamides were high on the list.

“The study reinforces that antibiotics are not benign medications to be dispensed injudiciously,” he said in an interview. “Antibiotics have risks, including serious skin reactions, as well as the fostering of antibiotic resistance. Clinicians should always first ask themselves if their patient actually merits an antibiotic and then assess what is the safest antibiotic for the purpose, bearing in mind that certain antibiotics are more likely to result in adverse reactions than others.”

The study was supported by the Canadian Institutes of Health Research. The study was conducted at ICES, which is funded in part by an annual grant from the Ontario Ministry of Health and Long-Term Care. One coauthor reported receiving compensation from the British Journal of Dermatology as reviewer and section editor, the American Academy of Dermatology as guidelines writer, Canadian Dermatology Today as manuscript writer, and the National Eczema Association and the Canadian Agency for Drugs and Technologies in Health as consultant; as well as receiving research grants to the coauthor’s institution from the National Eczema Association, Eczema Society of Canada, Canadian Dermatology Foundation, Canadian Institutes of Health Research, US National Institutes of Health, and PSI Foundation. Another coauthor reported receiving grants from AbbVie, Bausch Health, Celgene, Lilly, Incyte, Janssen, LEO Pharma, L’Oréal, Novartis, Organon, Pfizer, Sandoz, Amgen, and Boehringer Ingelheim; receiving payment or honoraria for speaking from Sanofi China; participating on advisory boards for LEO Pharma, Novartis, Sanofi, and Union Therapeutics; and receiving equipment donation from L’Oréal. Dr. Adalja reported no relevant disclosures.

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

Potentially life-threatening cutaneous adverse drug reactions (cADRs) are associated with commonly prescribed oral antibiotics, according to a large, population-based, nested case-control study of older adults, spanning two decades.

The findings, published online in JAMA, “underscore the importance of judicious prescribing, with preferential use of antibiotics associated with a lower risk when clinically appropriate,” noted senior author David Juurlink, MD, PhD, professor of medicine; pediatrics; and health policy, management and evaluation at the University of Toronto, and head of the Clinical Pharmacology and Toxicology Division at Sunnybrook Health Sciences Centre, also in Toronto, Ontario, Canada, and coauthors.

“We hope our study raises awareness about the importance of drug allergy and gains support for future studies to improve drug allergy care,” lead author Erika Lee, MD, clinical immunology and allergy lecturer at the University of Toronto’s Drug Allergy Clinic, Sunnybrook Health Sciences Centre, said in an interview. “It is important to recognize symptoms and signs of a severe drug rash and promptly stop culprit drugs to prevent worsening reaction.”

Serious cADRs are “a group of rare but potentially life-threatening drug hypersensitivity reactions involving the skin and, frequently, internal organs,” the authors wrote. “Typically delayed in onset, these reactions include drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) — the most severe cADR, which has a reported mortality of 20%-40%,” they noted.

Speculation Without Data

Although it has been speculated that some oral antibiotics are more likely than others to be associated with serious cADRs, there have been no population-based studies examining this, they added.

The study included adults aged 66 years or older and used administrative health databases in Ontario, spanning from April 1, 2002, to March 31, 2022. Data on antibiotic use were taken from the Ontario Drug Benefit database. The Canadian Institute for Health Information (CIHI) National Ambulatory Care Reporting System was used to obtain data on emergency department (ED) visits for cADRs, while the CIHI Discharge Abstract Database was used to identify hospitalizations for cADRs. Finally, demographic information and outpatient healthcare utilization data were obtained from the Registered Persons Database and the Ontario Health Insurance Plan database, respectively.

A cohort of 21,758 older adults (median age, 75 years; 64.1% women) who had an ED visit or hospitalization for serious cADRs within 60 days of receiving antibiotic therapy was matched by age and sex with 87,025 antibiotic-treated controls who did not have a cutaneous reaction.

The median duration of antibiotic prescription was 7 days among cases and controls, and among the cases, the median latency period between antibiotic prescriptions and hospital visits for cADRs was 14 days. Most of the case patients went to the ED only (86.9%), and the rest were hospitalized.

The most commonly prescribed antibiotic class was penicillins (28.9%), followed by cephalosporins (18.2%), fluoroquinolones (16.5%), macrolides (14.8%), nitrofurantoin (8.6%), and sulfonamides (6.2%). Less commonly used antibiotics (“other” antibiotics) accounted for 6.9%.

Macrolide antibiotics were used as the reference because they are rarely associated with serious cADRs, noted the authors, and the multivariable analysis, adjusted for risk factors associated with serious cADRs, including malignancy, chronic liver disease, chronic kidney disease, and HIV.

After multivariable adjustment, relative to macrolides, sulfonamides were most strongly associated with serious cADRs (adjusted odds ratio [aOR], 2.9) but so were all other antibiotic classes, including cephalosporins (aOR, 2.6), “other” antibiotics (aOR, 2.3), nitrofurantoin (aOR, 2.2), penicillins (aOR, 1.4), and fluoroquinolones (aOR,1.3).

In the secondary analysis, the crude rate of ED visits or hospitalizations for cADRs was highest for cephalosporins (4.92 per 1000 prescriptions), followed by sulfonamides (3.22 per 1000 prescriptions). Among hospitalized patients, the median length of stay was 6 days, with 9.6% requiring transfer to a critical care unit and 5.3% dying in the hospital.
 

Hospitalizations, ED Visits Not Studied Previously

“Notably, the rate of antibiotic-associated serious cADRs leading to an ED visit or hospitalization has not been previously studied,” noted the authors. “We found that at least two hospital encounters for serious cADRs ensued for every 1000 antibiotic prescriptions. This rate is considerably higher than suggested by studies that examine only SJS/TEN and drug reaction with eosinophilia and systemic symptoms.”

Dr. Lee also emphasized the previously unreported findings about nitrofurantoin. “It is surprising to find that nitrofurantoin, a commonly prescribed antibiotic for urinary tract infection, is also associated with an increased risk of severe drug rash,” she said in an interview.

“This finding highlights a potential novel risk at a population-based level and should be further explored in other populations to verify this association,” the authors wrote.

Amesh Adalja, MD, a senior scholar at the Johns Hopkins Center for Health Security in Baltimore, Maryland, and a spokesperson for the Infectious Diseases Society of America, who was not involved in the study, agreed that the nitrofurantoin finding was surprising, but he was not surprised that sulfonamides were high on the list.

“The study reinforces that antibiotics are not benign medications to be dispensed injudiciously,” he said in an interview. “Antibiotics have risks, including serious skin reactions, as well as the fostering of antibiotic resistance. Clinicians should always first ask themselves if their patient actually merits an antibiotic and then assess what is the safest antibiotic for the purpose, bearing in mind that certain antibiotics are more likely to result in adverse reactions than others.”

The study was supported by the Canadian Institutes of Health Research. The study was conducted at ICES, which is funded in part by an annual grant from the Ontario Ministry of Health and Long-Term Care. One coauthor reported receiving compensation from the British Journal of Dermatology as reviewer and section editor, the American Academy of Dermatology as guidelines writer, Canadian Dermatology Today as manuscript writer, and the National Eczema Association and the Canadian Agency for Drugs and Technologies in Health as consultant; as well as receiving research grants to the coauthor’s institution from the National Eczema Association, Eczema Society of Canada, Canadian Dermatology Foundation, Canadian Institutes of Health Research, US National Institutes of Health, and PSI Foundation. Another coauthor reported receiving grants from AbbVie, Bausch Health, Celgene, Lilly, Incyte, Janssen, LEO Pharma, L’Oréal, Novartis, Organon, Pfizer, Sandoz, Amgen, and Boehringer Ingelheim; receiving payment or honoraria for speaking from Sanofi China; participating on advisory boards for LEO Pharma, Novartis, Sanofi, and Union Therapeutics; and receiving equipment donation from L’Oréal. Dr. Adalja reported no relevant disclosures.

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

Potentially life-threatening cutaneous adverse drug reactions (cADRs) are associated with commonly prescribed oral antibiotics, according to a large, population-based, nested case-control study of older adults, spanning two decades.

The findings, published online in JAMA, “underscore the importance of judicious prescribing, with preferential use of antibiotics associated with a lower risk when clinically appropriate,” noted senior author David Juurlink, MD, PhD, professor of medicine; pediatrics; and health policy, management and evaluation at the University of Toronto, and head of the Clinical Pharmacology and Toxicology Division at Sunnybrook Health Sciences Centre, also in Toronto, Ontario, Canada, and coauthors.

“We hope our study raises awareness about the importance of drug allergy and gains support for future studies to improve drug allergy care,” lead author Erika Lee, MD, clinical immunology and allergy lecturer at the University of Toronto’s Drug Allergy Clinic, Sunnybrook Health Sciences Centre, said in an interview. “It is important to recognize symptoms and signs of a severe drug rash and promptly stop culprit drugs to prevent worsening reaction.”

Serious cADRs are “a group of rare but potentially life-threatening drug hypersensitivity reactions involving the skin and, frequently, internal organs,” the authors wrote. “Typically delayed in onset, these reactions include drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) — the most severe cADR, which has a reported mortality of 20%-40%,” they noted.

Speculation Without Data

Although it has been speculated that some oral antibiotics are more likely than others to be associated with serious cADRs, there have been no population-based studies examining this, they added.

The study included adults aged 66 years or older and used administrative health databases in Ontario, spanning from April 1, 2002, to March 31, 2022. Data on antibiotic use were taken from the Ontario Drug Benefit database. The Canadian Institute for Health Information (CIHI) National Ambulatory Care Reporting System was used to obtain data on emergency department (ED) visits for cADRs, while the CIHI Discharge Abstract Database was used to identify hospitalizations for cADRs. Finally, demographic information and outpatient healthcare utilization data were obtained from the Registered Persons Database and the Ontario Health Insurance Plan database, respectively.

A cohort of 21,758 older adults (median age, 75 years; 64.1% women) who had an ED visit or hospitalization for serious cADRs within 60 days of receiving antibiotic therapy was matched by age and sex with 87,025 antibiotic-treated controls who did not have a cutaneous reaction.

The median duration of antibiotic prescription was 7 days among cases and controls, and among the cases, the median latency period between antibiotic prescriptions and hospital visits for cADRs was 14 days. Most of the case patients went to the ED only (86.9%), and the rest were hospitalized.

The most commonly prescribed antibiotic class was penicillins (28.9%), followed by cephalosporins (18.2%), fluoroquinolones (16.5%), macrolides (14.8%), nitrofurantoin (8.6%), and sulfonamides (6.2%). Less commonly used antibiotics (“other” antibiotics) accounted for 6.9%.

Macrolide antibiotics were used as the reference because they are rarely associated with serious cADRs, noted the authors, and the multivariable analysis, adjusted for risk factors associated with serious cADRs, including malignancy, chronic liver disease, chronic kidney disease, and HIV.

After multivariable adjustment, relative to macrolides, sulfonamides were most strongly associated with serious cADRs (adjusted odds ratio [aOR], 2.9) but so were all other antibiotic classes, including cephalosporins (aOR, 2.6), “other” antibiotics (aOR, 2.3), nitrofurantoin (aOR, 2.2), penicillins (aOR, 1.4), and fluoroquinolones (aOR,1.3).

In the secondary analysis, the crude rate of ED visits or hospitalizations for cADRs was highest for cephalosporins (4.92 per 1000 prescriptions), followed by sulfonamides (3.22 per 1000 prescriptions). Among hospitalized patients, the median length of stay was 6 days, with 9.6% requiring transfer to a critical care unit and 5.3% dying in the hospital.
 

Hospitalizations, ED Visits Not Studied Previously

“Notably, the rate of antibiotic-associated serious cADRs leading to an ED visit or hospitalization has not been previously studied,” noted the authors. “We found that at least two hospital encounters for serious cADRs ensued for every 1000 antibiotic prescriptions. This rate is considerably higher than suggested by studies that examine only SJS/TEN and drug reaction with eosinophilia and systemic symptoms.”

Dr. Lee also emphasized the previously unreported findings about nitrofurantoin. “It is surprising to find that nitrofurantoin, a commonly prescribed antibiotic for urinary tract infection, is also associated with an increased risk of severe drug rash,” she said in an interview.

“This finding highlights a potential novel risk at a population-based level and should be further explored in other populations to verify this association,” the authors wrote.

Amesh Adalja, MD, a senior scholar at the Johns Hopkins Center for Health Security in Baltimore, Maryland, and a spokesperson for the Infectious Diseases Society of America, who was not involved in the study, agreed that the nitrofurantoin finding was surprising, but he was not surprised that sulfonamides were high on the list.

“The study reinforces that antibiotics are not benign medications to be dispensed injudiciously,” he said in an interview. “Antibiotics have risks, including serious skin reactions, as well as the fostering of antibiotic resistance. Clinicians should always first ask themselves if their patient actually merits an antibiotic and then assess what is the safest antibiotic for the purpose, bearing in mind that certain antibiotics are more likely to result in adverse reactions than others.”

The study was supported by the Canadian Institutes of Health Research. The study was conducted at ICES, which is funded in part by an annual grant from the Ontario Ministry of Health and Long-Term Care. One coauthor reported receiving compensation from the British Journal of Dermatology as reviewer and section editor, the American Academy of Dermatology as guidelines writer, Canadian Dermatology Today as manuscript writer, and the National Eczema Association and the Canadian Agency for Drugs and Technologies in Health as consultant; as well as receiving research grants to the coauthor’s institution from the National Eczema Association, Eczema Society of Canada, Canadian Dermatology Foundation, Canadian Institutes of Health Research, US National Institutes of Health, and PSI Foundation. Another coauthor reported receiving grants from AbbVie, Bausch Health, Celgene, Lilly, Incyte, Janssen, LEO Pharma, L’Oréal, Novartis, Organon, Pfizer, Sandoz, Amgen, and Boehringer Ingelheim; receiving payment or honoraria for speaking from Sanofi China; participating on advisory boards for LEO Pharma, Novartis, Sanofi, and Union Therapeutics; and receiving equipment donation from L’Oréal. Dr. Adalja reported no relevant disclosures.

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

Gluconolactone, 3,4,5-trihydroxy-6-(hydroxymethyl) oxan-2-one (C₆H₁₀O₆), is known to display antioxidant, moisturizing, and soothing activity as well as enhance skin barrier function and protect elastin fibers from UV-engendered damage.¹ This derivative of oxidized glucose lactone is present naturally in bread, cheese, fruit juices, honey, tofu, and wine, and is used as a food additive in Europe.^1,2 In dermatology, it is most often used in chemical peels.

Polyhydroxy acids (PHAs) were discovered about 3 decades ago to exert similar functions as alpha hydroxy acids without provoking sensory irritation reactions. Gluconolactone along with lactobionic acid were the identified PHAs and further characterized as delivering more humectant and moisturizing activity than alpha hydroxy acids and effective in combination with retinoic acid to treat adult acne and with retinyl acetate to confer antiaging benefits.³ It is typically added to products for its skin-conditioning qualities, resulting in smoother, brighter, more toned skin.⁴ This column focuses on recent studies using this bioactive agent for dermatologic purposes.
 

Split-Face Studies Show Various Benefits

peepo/E+/Getty Images

In 2023, Jarząbek-Perz and colleagues conducted a split-face evaluation to assess the effects on various skin parameters (ie, hydration, pH, sebum, and transepidermal water loss [TEWL]) of gluconolactone and oxybrasion, compared with gluconolactone and microneedling. Twenty-one White women underwent a series of three split-face treatments at 1-week intervals. Chemical peels with 10% gluconolactone were performed on the whole face. The right side of the face was also treated with oxybrasion and the left with microneedle mesotherapy. Skin parameters were measured before the first and third treatments and 2 weeks following the final treatment. Photos were taken before and after the study. Both treatments resulted in improved hydration and reductions in sebum, pH, and TEWL. No statistically significant differences were noted between the treatment protocols. The researchers concluded that gluconolactone peels can be effectively combined with oxybrasion or microneedle mesotherapy to enhance skin hydration and to secure the hydrolipid barrier.⁵

Later that year, the same team evaluated pH, sebum levels, and TEWL before, during, and after several applications of 10% and 30% gluconolactone chemical peels in a split-face model in 16 female participants. The investigators conducted three procedures on both sides of the face, taking measurements on the forehead, periorbital area, on the cheek, and on the nose wing before, during, and 7 days after the final treatment. They found statistically significant improvements in sebum levels in the cheeks after the treatment series. Also, pH values were lower at each measurement site after each procedure. TEWL levels were significantly diminished around the eyes, as well as the left forehead and right cheek, with no significant discrepancy between gluconolactone concentrations. The researchers concluded that gluconolactone plays a major role in reducing cutaneous pH and TEWL and imparts a regulatory effect on sebum.¹

Two years earlier, Jarząbek-Perz and colleagues assessed skin moisture in a split-face model in 16 healthy women after the application of 10% and 30% gluconolactone. Investigators measured skin moisture before and after each of three treatments and a week after the final treatment from the forehead, periorbital area, and on the cheek. They observed no significant discrepancies between the 10% and 30% formulations, but a significant elevation in facial skin hydration was found to be promoted by gluconolactone. The investigators concluded that gluconolactone is an effective moisturizer for care of dry skin.⁶

Topical Formulation

In 2023, Zerbinati and colleagues determined that a gluconolactone-based lotion that they had begun testing 2 years earlier was safe and effective for dermatologic applications, with the noncomedogenic formulation found suitable as an antiaging agent, particularly as it treats aging-related pore dilatation.^7,8

Acne Treatment

In 2019, Kantikosum and colleagues conducted a double-blind, within-person comparative study to assess the efficacy of various cosmeceutical ingredients, including gluconolactone, glycolic acid, licochalcone A, and salicylic acid, combined with the acne treatment adapalene vs adapalene monotherapy for mild to moderate acne. Each of 25 subjects over 28 days applied a product mixed with 0.1% adapalene on one side of the face, and 0.1% adapalene alone on the other side of the face once nightly. The VISIA camera system spot score pointed to a statistically significant improvement on the combination sides. Differences in lesion reduction and severity were within acceptable margins, the authors reported. They concluded that the cosmeceutical combinations yielded similar benefits as adapalene alone, with the combination formulations decreasing acne complications.⁹

Potential Use as an Antifibrotic Agent

Baumann Cosmetic & Research Institute

In 2018, Jayamani and colleagues investigated the antifibrotic characteristics of glucono-delta-lactone, a known acidifier, to ascertain if it could directly suppress collagen fibrils or even cause them to disintegrate. The researchers noted that collagen fibrillation is pH dependent, and that glucono-delta-lactone was found to exert a concentration-dependent suppression of fibrils and disintegration of preformed collagen fibrils with the antifibrotic function of the compound ascribed to its capacity to decrease pH. Further, glucono-delta-lactone appeared to emerge as an ideal antifibrotic agent as it left intact the triple helical structure of collagen after treatment. The investigators concluded that glucono-delta-lactone provides the foundation for developing antifibrotic agents intended to treat disorders characterized by collagen deposition.¹⁰

Conclusion

Gluconolactone emerged in the 1990s as a PHA useful in skin peels as an alternative to alpha hydroxy acids because of its nonirritating qualities. Since then, its soothing, hydrating, and, in particular, antiacne and antiaging qualities have become established. Wider applications of this versatile agent for dermatologic purposes are likely to be further investigated.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur in Miami. She founded the division of cosmetic dermatology at the University of Miami in 1997. The third edition of her bestselling textbook, “Cosmetic Dermatology,” was published in 2022. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Johnson & Johnson, and Burt’s Bees. She is the CEO of Skin Type Solutions, a SaaS company used to generate skin care routines in office and as a ecommerce solution. Write to her at dermnews@mdedge.com.

References

1. Jarząbek-Perz S et al. J Cosmet Dermatol. 2023 Dec;22(12):3305-3312..

2. Qin X et al. Front Physiol. 2022 Mar 14;13:856699.

3. Grimes PE et al. Cutis. 2004 Feb;73(2 Suppl):3-13.

4. Glaser DA. Facial Plast Surg Clin North Am. 2003 May;11(2):219-227.

5. Jarząbek-Perz S et al. Skin Res Technol. 2023 Jun;29(6):e13353.

6. Jarząbek-Perz S et al. Skin Res Technol. 2021 Sep;27(5):925-930.

7. Zerbinati N et al. Molecules. 2021 Dec 15;26(24):7592.

8. Zerbinati Net al. Pharmaceuticals (Basel). 2023 Apr 27;16(5):655.

9. Kantikosum K et al. Clin Cosmet Investig Dermatol. 2019 Feb 19;12:151-161.

10. Jayamani J et al. Int J Biol Macromol. 2018 Feb;107(Pt A):175-185.

Gluconolactone, 3,4,5-trihydroxy-6-(hydroxymethyl) oxan-2-one (C₆H₁₀O₆), is known to display antioxidant, moisturizing, and soothing activity as well as enhance skin barrier function and protect elastin fibers from UV-engendered damage.¹ This derivative of oxidized glucose lactone is present naturally in bread, cheese, fruit juices, honey, tofu, and wine, and is used as a food additive in Europe.^1,2 In dermatology, it is most often used in chemical peels.

Polyhydroxy acids (PHAs) were discovered about 3 decades ago to exert similar functions as alpha hydroxy acids without provoking sensory irritation reactions. Gluconolactone along with lactobionic acid were the identified PHAs and further characterized as delivering more humectant and moisturizing activity than alpha hydroxy acids and effective in combination with retinoic acid to treat adult acne and with retinyl acetate to confer antiaging benefits.³ It is typically added to products for its skin-conditioning qualities, resulting in smoother, brighter, more toned skin.⁴ This column focuses on recent studies using this bioactive agent for dermatologic purposes.
 

Split-Face Studies Show Various Benefits

peepo/E+/Getty Images

In 2023, Jarząbek-Perz and colleagues conducted a split-face evaluation to assess the effects on various skin parameters (ie, hydration, pH, sebum, and transepidermal water loss [TEWL]) of gluconolactone and oxybrasion, compared with gluconolactone and microneedling. Twenty-one White women underwent a series of three split-face treatments at 1-week intervals. Chemical peels with 10% gluconolactone were performed on the whole face. The right side of the face was also treated with oxybrasion and the left with microneedle mesotherapy. Skin parameters were measured before the first and third treatments and 2 weeks following the final treatment. Photos were taken before and after the study. Both treatments resulted in improved hydration and reductions in sebum, pH, and TEWL. No statistically significant differences were noted between the treatment protocols. The researchers concluded that gluconolactone peels can be effectively combined with oxybrasion or microneedle mesotherapy to enhance skin hydration and to secure the hydrolipid barrier.⁵

Later that year, the same team evaluated pH, sebum levels, and TEWL before, during, and after several applications of 10% and 30% gluconolactone chemical peels in a split-face model in 16 female participants. The investigators conducted three procedures on both sides of the face, taking measurements on the forehead, periorbital area, on the cheek, and on the nose wing before, during, and 7 days after the final treatment. They found statistically significant improvements in sebum levels in the cheeks after the treatment series. Also, pH values were lower at each measurement site after each procedure. TEWL levels were significantly diminished around the eyes, as well as the left forehead and right cheek, with no significant discrepancy between gluconolactone concentrations. The researchers concluded that gluconolactone plays a major role in reducing cutaneous pH and TEWL and imparts a regulatory effect on sebum.¹

Two years earlier, Jarząbek-Perz and colleagues assessed skin moisture in a split-face model in 16 healthy women after the application of 10% and 30% gluconolactone. Investigators measured skin moisture before and after each of three treatments and a week after the final treatment from the forehead, periorbital area, and on the cheek. They observed no significant discrepancies between the 10% and 30% formulations, but a significant elevation in facial skin hydration was found to be promoted by gluconolactone. The investigators concluded that gluconolactone is an effective moisturizer for care of dry skin.⁶

Topical Formulation

In 2023, Zerbinati and colleagues determined that a gluconolactone-based lotion that they had begun testing 2 years earlier was safe and effective for dermatologic applications, with the noncomedogenic formulation found suitable as an antiaging agent, particularly as it treats aging-related pore dilatation.^7,8

Acne Treatment

In 2019, Kantikosum and colleagues conducted a double-blind, within-person comparative study to assess the efficacy of various cosmeceutical ingredients, including gluconolactone, glycolic acid, licochalcone A, and salicylic acid, combined with the acne treatment adapalene vs adapalene monotherapy for mild to moderate acne. Each of 25 subjects over 28 days applied a product mixed with 0.1% adapalene on one side of the face, and 0.1% adapalene alone on the other side of the face once nightly. The VISIA camera system spot score pointed to a statistically significant improvement on the combination sides. Differences in lesion reduction and severity were within acceptable margins, the authors reported. They concluded that the cosmeceutical combinations yielded similar benefits as adapalene alone, with the combination formulations decreasing acne complications.⁹

Potential Use as an Antifibrotic Agent

Baumann Cosmetic & Research Institute

In 2018, Jayamani and colleagues investigated the antifibrotic characteristics of glucono-delta-lactone, a known acidifier, to ascertain if it could directly suppress collagen fibrils or even cause them to disintegrate. The researchers noted that collagen fibrillation is pH dependent, and that glucono-delta-lactone was found to exert a concentration-dependent suppression of fibrils and disintegration of preformed collagen fibrils with the antifibrotic function of the compound ascribed to its capacity to decrease pH. Further, glucono-delta-lactone appeared to emerge as an ideal antifibrotic agent as it left intact the triple helical structure of collagen after treatment. The investigators concluded that glucono-delta-lactone provides the foundation for developing antifibrotic agents intended to treat disorders characterized by collagen deposition.¹⁰

Conclusion

Gluconolactone emerged in the 1990s as a PHA useful in skin peels as an alternative to alpha hydroxy acids because of its nonirritating qualities. Since then, its soothing, hydrating, and, in particular, antiacne and antiaging qualities have become established. Wider applications of this versatile agent for dermatologic purposes are likely to be further investigated.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur in Miami. She founded the division of cosmetic dermatology at the University of Miami in 1997. The third edition of her bestselling textbook, “Cosmetic Dermatology,” was published in 2022. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Johnson & Johnson, and Burt’s Bees. She is the CEO of Skin Type Solutions, a SaaS company used to generate skin care routines in office and as a ecommerce solution. Write to her at dermnews@mdedge.com.

References

1. Jarząbek-Perz S et al. J Cosmet Dermatol. 2023 Dec;22(12):3305-3312..

2. Qin X et al. Front Physiol. 2022 Mar 14;13:856699.

3. Grimes PE et al. Cutis. 2004 Feb;73(2 Suppl):3-13.

4. Glaser DA. Facial Plast Surg Clin North Am. 2003 May;11(2):219-227.

5. Jarząbek-Perz S et al. Skin Res Technol. 2023 Jun;29(6):e13353.

6. Jarząbek-Perz S et al. Skin Res Technol. 2021 Sep;27(5):925-930.

7. Zerbinati N et al. Molecules. 2021 Dec 15;26(24):7592.

8. Zerbinati Net al. Pharmaceuticals (Basel). 2023 Apr 27;16(5):655.

9. Kantikosum K et al. Clin Cosmet Investig Dermatol. 2019 Feb 19;12:151-161.

10. Jayamani J et al. Int J Biol Macromol. 2018 Feb;107(Pt A):175-185.

Gluconolactone, 3,4,5-trihydroxy-6-(hydroxymethyl) oxan-2-one (C₆H₁₀O₆), is known to display antioxidant, moisturizing, and soothing activity as well as enhance skin barrier function and protect elastin fibers from UV-engendered damage.¹ This derivative of oxidized glucose lactone is present naturally in bread, cheese, fruit juices, honey, tofu, and wine, and is used as a food additive in Europe.^1,2 In dermatology, it is most often used in chemical peels.

Polyhydroxy acids (PHAs) were discovered about 3 decades ago to exert similar functions as alpha hydroxy acids without provoking sensory irritation reactions. Gluconolactone along with lactobionic acid were the identified PHAs and further characterized as delivering more humectant and moisturizing activity than alpha hydroxy acids and effective in combination with retinoic acid to treat adult acne and with retinyl acetate to confer antiaging benefits.³ It is typically added to products for its skin-conditioning qualities, resulting in smoother, brighter, more toned skin.⁴ This column focuses on recent studies using this bioactive agent for dermatologic purposes.
 

Split-Face Studies Show Various Benefits

peepo/E+/Getty Images

In 2023, Jarząbek-Perz and colleagues conducted a split-face evaluation to assess the effects on various skin parameters (ie, hydration, pH, sebum, and transepidermal water loss [TEWL]) of gluconolactone and oxybrasion, compared with gluconolactone and microneedling. Twenty-one White women underwent a series of three split-face treatments at 1-week intervals. Chemical peels with 10% gluconolactone were performed on the whole face. The right side of the face was also treated with oxybrasion and the left with microneedle mesotherapy. Skin parameters were measured before the first and third treatments and 2 weeks following the final treatment. Photos were taken before and after the study. Both treatments resulted in improved hydration and reductions in sebum, pH, and TEWL. No statistically significant differences were noted between the treatment protocols. The researchers concluded that gluconolactone peels can be effectively combined with oxybrasion or microneedle mesotherapy to enhance skin hydration and to secure the hydrolipid barrier.⁵

Later that year, the same team evaluated pH, sebum levels, and TEWL before, during, and after several applications of 10% and 30% gluconolactone chemical peels in a split-face model in 16 female participants. The investigators conducted three procedures on both sides of the face, taking measurements on the forehead, periorbital area, on the cheek, and on the nose wing before, during, and 7 days after the final treatment. They found statistically significant improvements in sebum levels in the cheeks after the treatment series. Also, pH values were lower at each measurement site after each procedure. TEWL levels were significantly diminished around the eyes, as well as the left forehead and right cheek, with no significant discrepancy between gluconolactone concentrations. The researchers concluded that gluconolactone plays a major role in reducing cutaneous pH and TEWL and imparts a regulatory effect on sebum.¹

Two years earlier, Jarząbek-Perz and colleagues assessed skin moisture in a split-face model in 16 healthy women after the application of 10% and 30% gluconolactone. Investigators measured skin moisture before and after each of three treatments and a week after the final treatment from the forehead, periorbital area, and on the cheek. They observed no significant discrepancies between the 10% and 30% formulations, but a significant elevation in facial skin hydration was found to be promoted by gluconolactone. The investigators concluded that gluconolactone is an effective moisturizer for care of dry skin.⁶

Topical Formulation

In 2023, Zerbinati and colleagues determined that a gluconolactone-based lotion that they had begun testing 2 years earlier was safe and effective for dermatologic applications, with the noncomedogenic formulation found suitable as an antiaging agent, particularly as it treats aging-related pore dilatation.^7,8

Acne Treatment

In 2019, Kantikosum and colleagues conducted a double-blind, within-person comparative study to assess the efficacy of various cosmeceutical ingredients, including gluconolactone, glycolic acid, licochalcone A, and salicylic acid, combined with the acne treatment adapalene vs adapalene monotherapy for mild to moderate acne. Each of 25 subjects over 28 days applied a product mixed with 0.1% adapalene on one side of the face, and 0.1% adapalene alone on the other side of the face once nightly. The VISIA camera system spot score pointed to a statistically significant improvement on the combination sides. Differences in lesion reduction and severity were within acceptable margins, the authors reported. They concluded that the cosmeceutical combinations yielded similar benefits as adapalene alone, with the combination formulations decreasing acne complications.⁹

Potential Use as an Antifibrotic Agent

Baumann Cosmetic & Research Institute

In 2018, Jayamani and colleagues investigated the antifibrotic characteristics of glucono-delta-lactone, a known acidifier, to ascertain if it could directly suppress collagen fibrils or even cause them to disintegrate. The researchers noted that collagen fibrillation is pH dependent, and that glucono-delta-lactone was found to exert a concentration-dependent suppression of fibrils and disintegration of preformed collagen fibrils with the antifibrotic function of the compound ascribed to its capacity to decrease pH. Further, glucono-delta-lactone appeared to emerge as an ideal antifibrotic agent as it left intact the triple helical structure of collagen after treatment. The investigators concluded that glucono-delta-lactone provides the foundation for developing antifibrotic agents intended to treat disorders characterized by collagen deposition.¹⁰

Conclusion

Gluconolactone emerged in the 1990s as a PHA useful in skin peels as an alternative to alpha hydroxy acids because of its nonirritating qualities. Since then, its soothing, hydrating, and, in particular, antiacne and antiaging qualities have become established. Wider applications of this versatile agent for dermatologic purposes are likely to be further investigated.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur in Miami. She founded the division of cosmetic dermatology at the University of Miami in 1997. The third edition of her bestselling textbook, “Cosmetic Dermatology,” was published in 2022. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Johnson & Johnson, and Burt’s Bees. She is the CEO of Skin Type Solutions, a SaaS company used to generate skin care routines in office and as a ecommerce solution. Write to her at dermnews@mdedge.com.

References

1. Jarząbek-Perz S et al. J Cosmet Dermatol. 2023 Dec;22(12):3305-3312..

2. Qin X et al. Front Physiol. 2022 Mar 14;13:856699.

3. Grimes PE et al. Cutis. 2004 Feb;73(2 Suppl):3-13.

4. Glaser DA. Facial Plast Surg Clin North Am. 2003 May;11(2):219-227.

5. Jarząbek-Perz S et al. Skin Res Technol. 2023 Jun;29(6):e13353.

6. Jarząbek-Perz S et al. Skin Res Technol. 2021 Sep;27(5):925-930.

7. Zerbinati N et al. Molecules. 2021 Dec 15;26(24):7592.

8. Zerbinati Net al. Pharmaceuticals (Basel). 2023 Apr 27;16(5):655.

9. Kantikosum K et al. Clin Cosmet Investig Dermatol. 2019 Feb 19;12:151-161.

10. Jayamani J et al. Int J Biol Macromol. 2018 Feb;107(Pt A):175-185.

TORONTO — Dermatologists should prescribe emergency contraception (EC) to adolescent patients being treated with isotretinoin for acne.

That was one of the main messages from Andrea L. Zaenglein, MD, professor of dermatology and pediatrics, Penn State University, Hershey, who discussed hormonal therapies for pediatric acne at the annual meeting of the Society for Pediatric Dermatology.

Many doctors are reluctant to prescribe EC, which refers to contraceptive methods used to prevent unintended pregnancy after unprotected sexual intercourse or contraceptive failure, whether that’s from discomfort with EC or lack of training, Dr. Zaenglein said in an interview.

Isotretinoin, a retinoid marketed as Accutane and other brand names, is an effective treatment for acne but carries serious teratogenicity risks; the iPLEDGE Risk Evaluation and Mitigation Strategy is designed to manage this risk and minimize fetal exposure. Yet from 2011 to 2017, 210-310 pregnancies per year were reported to the Food and Drug Administration, according to a 2019 study.

There is a knowledge gap regarding EC among dermatologists who prescribe isotretinoin, which “is perpetuated by the iPLEDGE program because it is inadequate in guiding clinicians or educating patients about the use of EC,” Dr. Zaenglein and colleagues wrote in a recently published viewpoint on EC prescribing in patients on isotretinoin.

Types of EC include oral levonorgestrel (plan B), available over the counter; oral ulipristal acetate (ella), which requires a prescription; and the copper/hormonal intrauterine device.

Not all teens taking isotretinoin can be trusted to be sexually abstinent. Dr. Zaenglein cited research showing 39% of female high school students have had sexual relations. “In my opinion, these patients should have emergency contraception prescribed to them as a backup,” she said.

Dr. Zaenglein believes there’s a fair amount of “misunderstanding” about EC, with many people thinking it’s an abortion pill. “It’s a totally different medicine. This is contraception; if you’re pregnant, it’s not going to affect your fetus.”

Outgoing SPD President Sheilagh Maguiness, MD, professor of dermatology and pediatrics, University of Minnesota, Minneapolis, agreed that Dr. Zaenglein raised an important issue. “She has identified a practice gap and a knowledge gap that we need to address,” she said in an interview.

When discussing contraception with female patients taking isotretinoin, assume they’re sexually active or could be, Dr. Zaenglein told meeting attendees. Be explicit about the risks to the fetus and consider their past compliance.
 

Complex Disorder

During her presentation, Dr. Zaenglein described acne as a “very complex, multifactorial inflammatory disorder” of the skin. It involves four steps: Increased sebum production, hyperkeratinization, Cutibacterium acnes, and inflammation. External factors such as diet, genes, and the environment play a role.

“But at the heart of all of it is androgens; if you didn’t have androgens, you wouldn’t have acne.” That’s why some acne treatments block androgen receptors.

Clinicians are increasingly using one such therapy, spironolactone, to treat acne in female adolescents. Dr. Zaenglein referred to a Mayo Clinic study of 80 patients (mean age, 19 years), who had moderate to severe acne treated with a mean dose of 100 mg/day, that found 80% had improvement with a favorable side effect profile. This included nearly 23% who had a complete response (90% or more) and 36% who had a partial response (more than 50%); 20% had no response.

However, response rates are higher in adults, said Dr. Zaenglein, noting that spironolactone works “much better” in adult women.

Side effects of spironolactone can include menstrual disturbances, breast enlargement and tenderness, and premenstrual syndrome–like symptoms.

Dermatologists should also consider combined oral contraceptives (COCs) in their adolescent patients with acne. These have an estrogen component as well as a progestin component.

They have proven effectiveness for acne in adolescents, yet a US survey of 170 dermatology residents found only 60% felt comfortable prescribing them to healthy adolescents. The survey also found only 62% of respondents felt adequately trained on the efficacy of COCs, and 42% felt adequately trained on their safety.

Contraindications for COCs include thrombosis, migraine with aura, lupus, seizures, and hypertension. Complex valvular heart disease and liver tumors also need to be ruled out, said Dr. Zaenglein. One of the “newer concerns” with COCs is depression. “There’s biological plausibility because, obviously, hormones impact the brain.”
 

Preventing Drug Interactions

Before prescribing hormonal therapy, clinicians should carry out an acne assessment, aimed in part at preventing drug interactions. “The one we mostly have to watch out for is rifampin,” an antibiotic that could interact with COCs, said Dr. Zaenglein.

The herbal supplement St John’s Wort can reduce the efficacy of COCs. “You also want to make sure that they’re not on any medicines that will increase potassium, such as ACE inhibitors,” said Dr. Zaenglein. But tetracyclines, ampicillin, or metronidazole are usually “all okay” when combined with COCs.

It’s important to get baseline blood pressure levels and to check these along with weight on a regular basis, she added.

Always Consider PCOS

Before starting hormonal therapy, she advises dermatologists to “always consider” polycystic ovary syndrome (PCOS), a condition that’s “probably much underdiagnosed.” Acne is common in adolescents with PCOS. She suggests using a PCOS checklist, a reminder to ask about irregular periods, hirsutism, signs of insulin resistance such as increased body mass index, a history of premature adrenarche, and a family history of PCOS, said Dr. Zaenglein, noting that a person with a sibling who has PCOS has about a 40% chance of developing the condition.

“We play an important role in getting kids diagnosed at an early age so that we can make interventions because the impact of the metabolic syndrome can have lifelong effects on their cardiovascular system, as well as infertility.”

Dr. Zaenglein is a member of the American Academy of Dermatology (AAD) Acne Guidelines work group, the immediate past president of the American Acne and Rosacea Society, a member of the AAD iPLEDGE work group, co–editor in chief of Pediatric Dermatology, an advisory board member of Ortho Dermatologics, and a consultant for Church & Dwight. Dr. Maguiness had no relevant conflicts of interest.

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

TORONTO — Dermatologists should prescribe emergency contraception (EC) to adolescent patients being treated with isotretinoin for acne.

That was one of the main messages from Andrea L. Zaenglein, MD, professor of dermatology and pediatrics, Penn State University, Hershey, who discussed hormonal therapies for pediatric acne at the annual meeting of the Society for Pediatric Dermatology.

Many doctors are reluctant to prescribe EC, which refers to contraceptive methods used to prevent unintended pregnancy after unprotected sexual intercourse or contraceptive failure, whether that’s from discomfort with EC or lack of training, Dr. Zaenglein said in an interview.

Isotretinoin, a retinoid marketed as Accutane and other brand names, is an effective treatment for acne but carries serious teratogenicity risks; the iPLEDGE Risk Evaluation and Mitigation Strategy is designed to manage this risk and minimize fetal exposure. Yet from 2011 to 2017, 210-310 pregnancies per year were reported to the Food and Drug Administration, according to a 2019 study.

There is a knowledge gap regarding EC among dermatologists who prescribe isotretinoin, which “is perpetuated by the iPLEDGE program because it is inadequate in guiding clinicians or educating patients about the use of EC,” Dr. Zaenglein and colleagues wrote in a recently published viewpoint on EC prescribing in patients on isotretinoin.

Types of EC include oral levonorgestrel (plan B), available over the counter; oral ulipristal acetate (ella), which requires a prescription; and the copper/hormonal intrauterine device.

Not all teens taking isotretinoin can be trusted to be sexually abstinent. Dr. Zaenglein cited research showing 39% of female high school students have had sexual relations. “In my opinion, these patients should have emergency contraception prescribed to them as a backup,” she said.

Dr. Zaenglein believes there’s a fair amount of “misunderstanding” about EC, with many people thinking it’s an abortion pill. “It’s a totally different medicine. This is contraception; if you’re pregnant, it’s not going to affect your fetus.”

Outgoing SPD President Sheilagh Maguiness, MD, professor of dermatology and pediatrics, University of Minnesota, Minneapolis, agreed that Dr. Zaenglein raised an important issue. “She has identified a practice gap and a knowledge gap that we need to address,” she said in an interview.

When discussing contraception with female patients taking isotretinoin, assume they’re sexually active or could be, Dr. Zaenglein told meeting attendees. Be explicit about the risks to the fetus and consider their past compliance.
 

Complex Disorder

During her presentation, Dr. Zaenglein described acne as a “very complex, multifactorial inflammatory disorder” of the skin. It involves four steps: Increased sebum production, hyperkeratinization, Cutibacterium acnes, and inflammation. External factors such as diet, genes, and the environment play a role.

“But at the heart of all of it is androgens; if you didn’t have androgens, you wouldn’t have acne.” That’s why some acne treatments block androgen receptors.

Clinicians are increasingly using one such therapy, spironolactone, to treat acne in female adolescents. Dr. Zaenglein referred to a Mayo Clinic study of 80 patients (mean age, 19 years), who had moderate to severe acne treated with a mean dose of 100 mg/day, that found 80% had improvement with a favorable side effect profile. This included nearly 23% who had a complete response (90% or more) and 36% who had a partial response (more than 50%); 20% had no response.

However, response rates are higher in adults, said Dr. Zaenglein, noting that spironolactone works “much better” in adult women.

Side effects of spironolactone can include menstrual disturbances, breast enlargement and tenderness, and premenstrual syndrome–like symptoms.

Dermatologists should also consider combined oral contraceptives (COCs) in their adolescent patients with acne. These have an estrogen component as well as a progestin component.

They have proven effectiveness for acne in adolescents, yet a US survey of 170 dermatology residents found only 60% felt comfortable prescribing them to healthy adolescents. The survey also found only 62% of respondents felt adequately trained on the efficacy of COCs, and 42% felt adequately trained on their safety.

Contraindications for COCs include thrombosis, migraine with aura, lupus, seizures, and hypertension. Complex valvular heart disease and liver tumors also need to be ruled out, said Dr. Zaenglein. One of the “newer concerns” with COCs is depression. “There’s biological plausibility because, obviously, hormones impact the brain.”
 

Preventing Drug Interactions

Before prescribing hormonal therapy, clinicians should carry out an acne assessment, aimed in part at preventing drug interactions. “The one we mostly have to watch out for is rifampin,” an antibiotic that could interact with COCs, said Dr. Zaenglein.

The herbal supplement St John’s Wort can reduce the efficacy of COCs. “You also want to make sure that they’re not on any medicines that will increase potassium, such as ACE inhibitors,” said Dr. Zaenglein. But tetracyclines, ampicillin, or metronidazole are usually “all okay” when combined with COCs.

It’s important to get baseline blood pressure levels and to check these along with weight on a regular basis, she added.

Always Consider PCOS

Before starting hormonal therapy, she advises dermatologists to “always consider” polycystic ovary syndrome (PCOS), a condition that’s “probably much underdiagnosed.” Acne is common in adolescents with PCOS. She suggests using a PCOS checklist, a reminder to ask about irregular periods, hirsutism, signs of insulin resistance such as increased body mass index, a history of premature adrenarche, and a family history of PCOS, said Dr. Zaenglein, noting that a person with a sibling who has PCOS has about a 40% chance of developing the condition.

“We play an important role in getting kids diagnosed at an early age so that we can make interventions because the impact of the metabolic syndrome can have lifelong effects on their cardiovascular system, as well as infertility.”

Dr. Zaenglein is a member of the American Academy of Dermatology (AAD) Acne Guidelines work group, the immediate past president of the American Acne and Rosacea Society, a member of the AAD iPLEDGE work group, co–editor in chief of Pediatric Dermatology, an advisory board member of Ortho Dermatologics, and a consultant for Church & Dwight. Dr. Maguiness had no relevant conflicts of interest.

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

TORONTO — Dermatologists should prescribe emergency contraception (EC) to adolescent patients being treated with isotretinoin for acne.

That was one of the main messages from Andrea L. Zaenglein, MD, professor of dermatology and pediatrics, Penn State University, Hershey, who discussed hormonal therapies for pediatric acne at the annual meeting of the Society for Pediatric Dermatology.

Many doctors are reluctant to prescribe EC, which refers to contraceptive methods used to prevent unintended pregnancy after unprotected sexual intercourse or contraceptive failure, whether that’s from discomfort with EC or lack of training, Dr. Zaenglein said in an interview.

Isotretinoin, a retinoid marketed as Accutane and other brand names, is an effective treatment for acne but carries serious teratogenicity risks; the iPLEDGE Risk Evaluation and Mitigation Strategy is designed to manage this risk and minimize fetal exposure. Yet from 2011 to 2017, 210-310 pregnancies per year were reported to the Food and Drug Administration, according to a 2019 study.

There is a knowledge gap regarding EC among dermatologists who prescribe isotretinoin, which “is perpetuated by the iPLEDGE program because it is inadequate in guiding clinicians or educating patients about the use of EC,” Dr. Zaenglein and colleagues wrote in a recently published viewpoint on EC prescribing in patients on isotretinoin.

Types of EC include oral levonorgestrel (plan B), available over the counter; oral ulipristal acetate (ella), which requires a prescription; and the copper/hormonal intrauterine device.

Not all teens taking isotretinoin can be trusted to be sexually abstinent. Dr. Zaenglein cited research showing 39% of female high school students have had sexual relations. “In my opinion, these patients should have emergency contraception prescribed to them as a backup,” she said.

Dr. Zaenglein believes there’s a fair amount of “misunderstanding” about EC, with many people thinking it’s an abortion pill. “It’s a totally different medicine. This is contraception; if you’re pregnant, it’s not going to affect your fetus.”

Outgoing SPD President Sheilagh Maguiness, MD, professor of dermatology and pediatrics, University of Minnesota, Minneapolis, agreed that Dr. Zaenglein raised an important issue. “She has identified a practice gap and a knowledge gap that we need to address,” she said in an interview.

When discussing contraception with female patients taking isotretinoin, assume they’re sexually active or could be, Dr. Zaenglein told meeting attendees. Be explicit about the risks to the fetus and consider their past compliance.
 

Complex Disorder

During her presentation, Dr. Zaenglein described acne as a “very complex, multifactorial inflammatory disorder” of the skin. It involves four steps: Increased sebum production, hyperkeratinization, Cutibacterium acnes, and inflammation. External factors such as diet, genes, and the environment play a role.

“But at the heart of all of it is androgens; if you didn’t have androgens, you wouldn’t have acne.” That’s why some acne treatments block androgen receptors.

Clinicians are increasingly using one such therapy, spironolactone, to treat acne in female adolescents. Dr. Zaenglein referred to a Mayo Clinic study of 80 patients (mean age, 19 years), who had moderate to severe acne treated with a mean dose of 100 mg/day, that found 80% had improvement with a favorable side effect profile. This included nearly 23% who had a complete response (90% or more) and 36% who had a partial response (more than 50%); 20% had no response.

However, response rates are higher in adults, said Dr. Zaenglein, noting that spironolactone works “much better” in adult women.

Side effects of spironolactone can include menstrual disturbances, breast enlargement and tenderness, and premenstrual syndrome–like symptoms.

Dermatologists should also consider combined oral contraceptives (COCs) in their adolescent patients with acne. These have an estrogen component as well as a progestin component.

They have proven effectiveness for acne in adolescents, yet a US survey of 170 dermatology residents found only 60% felt comfortable prescribing them to healthy adolescents. The survey also found only 62% of respondents felt adequately trained on the efficacy of COCs, and 42% felt adequately trained on their safety.

Contraindications for COCs include thrombosis, migraine with aura, lupus, seizures, and hypertension. Complex valvular heart disease and liver tumors also need to be ruled out, said Dr. Zaenglein. One of the “newer concerns” with COCs is depression. “There’s biological plausibility because, obviously, hormones impact the brain.”
 

Preventing Drug Interactions

Before prescribing hormonal therapy, clinicians should carry out an acne assessment, aimed in part at preventing drug interactions. “The one we mostly have to watch out for is rifampin,” an antibiotic that could interact with COCs, said Dr. Zaenglein.

The herbal supplement St John’s Wort can reduce the efficacy of COCs. “You also want to make sure that they’re not on any medicines that will increase potassium, such as ACE inhibitors,” said Dr. Zaenglein. But tetracyclines, ampicillin, or metronidazole are usually “all okay” when combined with COCs.

It’s important to get baseline blood pressure levels and to check these along with weight on a regular basis, she added.

Always Consider PCOS

Before starting hormonal therapy, she advises dermatologists to “always consider” polycystic ovary syndrome (PCOS), a condition that’s “probably much underdiagnosed.” Acne is common in adolescents with PCOS. She suggests using a PCOS checklist, a reminder to ask about irregular periods, hirsutism, signs of insulin resistance such as increased body mass index, a history of premature adrenarche, and a family history of PCOS, said Dr. Zaenglein, noting that a person with a sibling who has PCOS has about a 40% chance of developing the condition.

“We play an important role in getting kids diagnosed at an early age so that we can make interventions because the impact of the metabolic syndrome can have lifelong effects on their cardiovascular system, as well as infertility.”

Dr. Zaenglein is a member of the American Academy of Dermatology (AAD) Acne Guidelines work group, the immediate past president of the American Acne and Rosacea Society, a member of the AAD iPLEDGE work group, co–editor in chief of Pediatric Dermatology, an advisory board member of Ortho Dermatologics, and a consultant for Church & Dwight. Dr. Maguiness had no relevant conflicts of interest.

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

Two new studies focusing on the safety of benzoyl peroxide (BP)–containing acne products with typical everyday use found no reason for concern about either high blood levels of benzene, a breakdown product of BP, or cancer risk.

Earlier this year, controversy erupted after an independent lab Valisure petitioned the US Food and Drug Administration (FDA) to recall acne products with BP because it found extremely high levels of the carcinogen benzene. In the research, the lab directors contended that the products can form over 800 times the “conditionally restricted” FDA concentration limit of 2 parts per million (ppm) of benzene, with both prescription and over-the-counter (OTC) products affected. The issue, according to the lab’s report, is one of degradation, not contamination; BP can decompose into benzene. Exposures to benzene have been linked with a higher risk for leukemia and other blood cancers.

Kittisak Kaewchalun/iStock/Getty Images

(“Conditionally restricted” means that the maximum of 2 ppm only applies to a drug product in which the use of benzene is unavoidable in order to produce a drug product with a significant therapeutic advance, according to FDA guidance.)

Critics of the report questioned the method used to test the products, calling for more “real-world” use data, and said the temperature used may not be what is expected with everyday use.

Now, both new studies are reassuring about the safety of the products, John Barbieri, MD, MBA, assistant professor of dermatology at Harvard Medical School and director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, said in a telephone interview. He was a coauthor of both studies. A leading dermatologist not involved in the new research reviewed the findings and agreed.

Brigham and Women's Hospital

Dr. Lim

Further Details

Under high temperatures, or over a long period, BP can decompose to benzene, a colorless, flammable liquid with a sweet odor. Benzene is formed from natural processes such as forest fires and volcanoes, according to the American Cancer Society, and is found in the air, cigarette smoke, some foods (at low levels), and contaminated drinking water. It’s one of the 20 widely used chemicals involved in making plastics, resins, detergents, and pesticides, among other products.

In the study evaluating blood levels, the researchers matched 14 people who used BP products currently with 65 controls who did not. Five (36%) of those using the products had detectable blood levels; 21 (32%) of those who did not use them did. There was no association between BP exposure and detectable blood benzene levels (odds ratio, 1.12; P = .80).

In the larger study, the researchers used the TriNetX US Collaborative Network database, comparing more than 27,000 patients treated with BP products for acne with more than 27,000 patients aged 12-40 years who had a diagnosis of nevus or seborrheic keratosis with no exposure to prescribed BP or any diagnosis of acne, hidradenitis suppurativa, or rosacea. The researchers looked at the database over the subsequent 10 years to determine the risk for either blood cancers or internal malignancies.

Compared with patients diagnosed with nevus or seborrheic keratosis, those with acne treated with BP had no significant difference in the risk for lymphoma (hazard ratio [HR], 1.00), leukemia (HR, 0.91), any lymphoma or leukemia (HR, 1.04), and internal malignancies (HR, 0.93).

The findings suggest no increased risk for malignancy, the researchers said, although they acknowledged study limitations, such as possible misclassification of BP exposure due to OTC availability and other issues.

Value of BP Treatments

BP is the “go-to” acne treatment, as Dr. Barbieri pointed out. “It’s probably the number one treatment for acne,” and there’s no substitute for it and it’s one of the most effective topical acne treatments, he noted.

Despite the reassuring findings, Dr. Barbieri repeated advice he gave soon after the Valisure report was released. Use common sense and don’t store BP-containing products in hot cars or other hot environments. In warmer climates, refrigeration could be considered, he said. Discard old products. Manufacturers should use cold-chain storage from the manufacturing site to retail or pharmacy sale sites, he added.
 

FDA and Citizen Petition Status

Asked about the status of the petition from Valisure, an FDA spokesperson said: “The FDA does not comment on the status of pending petitions.”

Dr. Barbieri and Dr. Lim had no relevant disclosures. There were no funding sources for either of the two studies.
 

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

Two new studies focusing on the safety of benzoyl peroxide (BP)–containing acne products with typical everyday use found no reason for concern about either high blood levels of benzene, a breakdown product of BP, or cancer risk.

Earlier this year, controversy erupted after an independent lab Valisure petitioned the US Food and Drug Administration (FDA) to recall acne products with BP because it found extremely high levels of the carcinogen benzene. In the research, the lab directors contended that the products can form over 800 times the “conditionally restricted” FDA concentration limit of 2 parts per million (ppm) of benzene, with both prescription and over-the-counter (OTC) products affected. The issue, according to the lab’s report, is one of degradation, not contamination; BP can decompose into benzene. Exposures to benzene have been linked with a higher risk for leukemia and other blood cancers.

Kittisak Kaewchalun/iStock/Getty Images

(“Conditionally restricted” means that the maximum of 2 ppm only applies to a drug product in which the use of benzene is unavoidable in order to produce a drug product with a significant therapeutic advance, according to FDA guidance.)

Critics of the report questioned the method used to test the products, calling for more “real-world” use data, and said the temperature used may not be what is expected with everyday use.

Now, both new studies are reassuring about the safety of the products, John Barbieri, MD, MBA, assistant professor of dermatology at Harvard Medical School and director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, said in a telephone interview. He was a coauthor of both studies. A leading dermatologist not involved in the new research reviewed the findings and agreed.

Brigham and Women's Hospital

Dr. Lim

Further Details

Under high temperatures, or over a long period, BP can decompose to benzene, a colorless, flammable liquid with a sweet odor. Benzene is formed from natural processes such as forest fires and volcanoes, according to the American Cancer Society, and is found in the air, cigarette smoke, some foods (at low levels), and contaminated drinking water. It’s one of the 20 widely used chemicals involved in making plastics, resins, detergents, and pesticides, among other products.

In the study evaluating blood levels, the researchers matched 14 people who used BP products currently with 65 controls who did not. Five (36%) of those using the products had detectable blood levels; 21 (32%) of those who did not use them did. There was no association between BP exposure and detectable blood benzene levels (odds ratio, 1.12; P = .80).

In the larger study, the researchers used the TriNetX US Collaborative Network database, comparing more than 27,000 patients treated with BP products for acne with more than 27,000 patients aged 12-40 years who had a diagnosis of nevus or seborrheic keratosis with no exposure to prescribed BP or any diagnosis of acne, hidradenitis suppurativa, or rosacea. The researchers looked at the database over the subsequent 10 years to determine the risk for either blood cancers or internal malignancies.

Compared with patients diagnosed with nevus or seborrheic keratosis, those with acne treated with BP had no significant difference in the risk for lymphoma (hazard ratio [HR], 1.00), leukemia (HR, 0.91), any lymphoma or leukemia (HR, 1.04), and internal malignancies (HR, 0.93).

The findings suggest no increased risk for malignancy, the researchers said, although they acknowledged study limitations, such as possible misclassification of BP exposure due to OTC availability and other issues.

Value of BP Treatments

BP is the “go-to” acne treatment, as Dr. Barbieri pointed out. “It’s probably the number one treatment for acne,” and there’s no substitute for it and it’s one of the most effective topical acne treatments, he noted.

Despite the reassuring findings, Dr. Barbieri repeated advice he gave soon after the Valisure report was released. Use common sense and don’t store BP-containing products in hot cars or other hot environments. In warmer climates, refrigeration could be considered, he said. Discard old products. Manufacturers should use cold-chain storage from the manufacturing site to retail or pharmacy sale sites, he added.
 

FDA and Citizen Petition Status

Asked about the status of the petition from Valisure, an FDA spokesperson said: “The FDA does not comment on the status of pending petitions.”

Dr. Barbieri and Dr. Lim had no relevant disclosures. There were no funding sources for either of the two studies.
 

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

Two new studies focusing on the safety of benzoyl peroxide (BP)–containing acne products with typical everyday use found no reason for concern about either high blood levels of benzene, a breakdown product of BP, or cancer risk.

Earlier this year, controversy erupted after an independent lab Valisure petitioned the US Food and Drug Administration (FDA) to recall acne products with BP because it found extremely high levels of the carcinogen benzene. In the research, the lab directors contended that the products can form over 800 times the “conditionally restricted” FDA concentration limit of 2 parts per million (ppm) of benzene, with both prescription and over-the-counter (OTC) products affected. The issue, according to the lab’s report, is one of degradation, not contamination; BP can decompose into benzene. Exposures to benzene have been linked with a higher risk for leukemia and other blood cancers.

Kittisak Kaewchalun/iStock/Getty Images

(“Conditionally restricted” means that the maximum of 2 ppm only applies to a drug product in which the use of benzene is unavoidable in order to produce a drug product with a significant therapeutic advance, according to FDA guidance.)

Critics of the report questioned the method used to test the products, calling for more “real-world” use data, and said the temperature used may not be what is expected with everyday use.

Now, both new studies are reassuring about the safety of the products, John Barbieri, MD, MBA, assistant professor of dermatology at Harvard Medical School and director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, said in a telephone interview. He was a coauthor of both studies. A leading dermatologist not involved in the new research reviewed the findings and agreed.

Brigham and Women's Hospital

Dr. Lim

Further Details

Under high temperatures, or over a long period, BP can decompose to benzene, a colorless, flammable liquid with a sweet odor. Benzene is formed from natural processes such as forest fires and volcanoes, according to the American Cancer Society, and is found in the air, cigarette smoke, some foods (at low levels), and contaminated drinking water. It’s one of the 20 widely used chemicals involved in making plastics, resins, detergents, and pesticides, among other products.

In the study evaluating blood levels, the researchers matched 14 people who used BP products currently with 65 controls who did not. Five (36%) of those using the products had detectable blood levels; 21 (32%) of those who did not use them did. There was no association between BP exposure and detectable blood benzene levels (odds ratio, 1.12; P = .80).

In the larger study, the researchers used the TriNetX US Collaborative Network database, comparing more than 27,000 patients treated with BP products for acne with more than 27,000 patients aged 12-40 years who had a diagnosis of nevus or seborrheic keratosis with no exposure to prescribed BP or any diagnosis of acne, hidradenitis suppurativa, or rosacea. The researchers looked at the database over the subsequent 10 years to determine the risk for either blood cancers or internal malignancies.

Compared with patients diagnosed with nevus or seborrheic keratosis, those with acne treated with BP had no significant difference in the risk for lymphoma (hazard ratio [HR], 1.00), leukemia (HR, 0.91), any lymphoma or leukemia (HR, 1.04), and internal malignancies (HR, 0.93).

The findings suggest no increased risk for malignancy, the researchers said, although they acknowledged study limitations, such as possible misclassification of BP exposure due to OTC availability and other issues.

Value of BP Treatments

BP is the “go-to” acne treatment, as Dr. Barbieri pointed out. “It’s probably the number one treatment for acne,” and there’s no substitute for it and it’s one of the most effective topical acne treatments, he noted.

Despite the reassuring findings, Dr. Barbieri repeated advice he gave soon after the Valisure report was released. Use common sense and don’t store BP-containing products in hot cars or other hot environments. In warmer climates, refrigeration could be considered, he said. Discard old products. Manufacturers should use cold-chain storage from the manufacturing site to retail or pharmacy sale sites, he added.
 

FDA and Citizen Petition Status

Asked about the status of the petition from Valisure, an FDA spokesperson said: “The FDA does not comment on the status of pending petitions.”

Dr. Barbieri and Dr. Lim had no relevant disclosures. There were no funding sources for either of the two studies.
 

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

To the Editor:

Prescriptions for isotretinoin may be influenced by patient demographics, medical comorbidities, and drug safety programs.^1,2 In 1982, isotretinoin was approved by the US Food and Drug Administration for treatment of severe recalcitrant nodulocystic acne that is nonresponsive to conventional therapies such as antibiotics; however, prescriber beliefs regarding the necessity of oral antibiotic failure before isotretinoin is prescribed may be influenced by the provider’s generational age.³ Currently, there is a knowledge gap regarding the impact of provider characteristics, including the year providers completed training, on isotretinoin utilization. The aim of our cross-sectional study was to characterize generational isotretinoin prescribing habits in a large-scale midwestern private practice dermatology group.

Modernizing Medicine (https://www.modmed.com), an electronic medical record software, was queried for all encounters that included both an International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis code L70.0 (acne vulgaris) and a medication prescription from May 2021 to May 2022. Data were collected from a large private practice group with locations across the state of Ohio. Exclusion criteria included provider-patient prescription pairs that included non–acne medication prescriptions, patients seen by multiple providers, and providers who treated fewer than 5 patients with acne during the study period. A mixed-effect multiple logistic regression was performed to analyze whether a patient was ever prescribed isotretinoin, adjusting for individual prescriber, prescriber generation (millennial [1981–1996], Generation X [1965–1980], and baby boomer [1946–1964]),⁴ and patient sex; spironolactone and oral antibiotic prescriptions during the study period were included as additional covariates in a subsequent post hoc analysis. This study utilized data that was fully deidentified in accordance with the US Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule. Approval from an institutional review board was not required.

A total of 18,089 provider-patient prescription pairs were included in our analysis (Table). In our most robust model, female patients were significantly less likely to receive isotretinoin compared with male patients (adjusted OR [aOR], 0.394; P<.01). Millennial providers were significantly more likely to utilize isotretinoin in patients who did not receive antibiotics compared with patients who did receive antibiotics (aOR, 1.693; P<.01). When compared with both Generation X and baby boomers, millennial providers were more likely to prescribe isotretinoin in patients who received antibiotics (aOR, 2.227 [P=.02] and 3.638 [P<.01], respectively).

To the Editor:

Prescriptions for isotretinoin may be influenced by patient demographics, medical comorbidities, and drug safety programs.^1,2 In 1982, isotretinoin was approved by the US Food and Drug Administration for treatment of severe recalcitrant nodulocystic acne that is nonresponsive to conventional therapies such as antibiotics; however, prescriber beliefs regarding the necessity of oral antibiotic failure before isotretinoin is prescribed may be influenced by the provider’s generational age.³ Currently, there is a knowledge gap regarding the impact of provider characteristics, including the year providers completed training, on isotretinoin utilization. The aim of our cross-sectional study was to characterize generational isotretinoin prescribing habits in a large-scale midwestern private practice dermatology group.

Modernizing Medicine (https://www.modmed.com), an electronic medical record software, was queried for all encounters that included both an International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis code L70.0 (acne vulgaris) and a medication prescription from May 2021 to May 2022. Data were collected from a large private practice group with locations across the state of Ohio. Exclusion criteria included provider-patient prescription pairs that included non–acne medication prescriptions, patients seen by multiple providers, and providers who treated fewer than 5 patients with acne during the study period. A mixed-effect multiple logistic regression was performed to analyze whether a patient was ever prescribed isotretinoin, adjusting for individual prescriber, prescriber generation (millennial [1981–1996], Generation X [1965–1980], and baby boomer [1946–1964]),⁴ and patient sex; spironolactone and oral antibiotic prescriptions during the study period were included as additional covariates in a subsequent post hoc analysis. This study utilized data that was fully deidentified in accordance with the US Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule. Approval from an institutional review board was not required.

A total of 18,089 provider-patient prescription pairs were included in our analysis (Table). In our most robust model, female patients were significantly less likely to receive isotretinoin compared with male patients (adjusted OR [aOR], 0.394; P<.01). Millennial providers were significantly more likely to utilize isotretinoin in patients who did not receive antibiotics compared with patients who did receive antibiotics (aOR, 1.693; P<.01). When compared with both Generation X and baby boomers, millennial providers were more likely to prescribe isotretinoin in patients who received antibiotics (aOR, 2.227 [P=.02] and 3.638 [P<.01], respectively).

To the Editor:

Prescriptions for isotretinoin may be influenced by patient demographics, medical comorbidities, and drug safety programs.^1,2 In 1982, isotretinoin was approved by the US Food and Drug Administration for treatment of severe recalcitrant nodulocystic acne that is nonresponsive to conventional therapies such as antibiotics; however, prescriber beliefs regarding the necessity of oral antibiotic failure before isotretinoin is prescribed may be influenced by the provider’s generational age.³ Currently, there is a knowledge gap regarding the impact of provider characteristics, including the year providers completed training, on isotretinoin utilization. The aim of our cross-sectional study was to characterize generational isotretinoin prescribing habits in a large-scale midwestern private practice dermatology group.

Modernizing Medicine (https://www.modmed.com), an electronic medical record software, was queried for all encounters that included both an International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis code L70.0 (acne vulgaris) and a medication prescription from May 2021 to May 2022. Data were collected from a large private practice group with locations across the state of Ohio. Exclusion criteria included provider-patient prescription pairs that included non–acne medication prescriptions, patients seen by multiple providers, and providers who treated fewer than 5 patients with acne during the study period. A mixed-effect multiple logistic regression was performed to analyze whether a patient was ever prescribed isotretinoin, adjusting for individual prescriber, prescriber generation (millennial [1981–1996], Generation X [1965–1980], and baby boomer [1946–1964]),⁴ and patient sex; spironolactone and oral antibiotic prescriptions during the study period were included as additional covariates in a subsequent post hoc analysis. This study utilized data that was fully deidentified in accordance with the US Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule. Approval from an institutional review board was not required.

A total of 18,089 provider-patient prescription pairs were included in our analysis (Table). In our most robust model, female patients were significantly less likely to receive isotretinoin compared with male patients (adjusted OR [aOR], 0.394; P<.01). Millennial providers were significantly more likely to utilize isotretinoin in patients who did not receive antibiotics compared with patients who did receive antibiotics (aOR, 1.693; P<.01). When compared with both Generation X and baby boomers, millennial providers were more likely to prescribe isotretinoin in patients who received antibiotics (aOR, 2.227 [P=.02] and 3.638 [P<.01], respectively).

People whose gender identity differs from the sex assigned at birth are referred to as transgender. For some, gender identity may not fit into the binary constructs of male and female but rather falls between, within, or outside this construct. These people often consider themselves nonbinary or gender diverse. As the terminology continues to evolve, current recommendations include referring to this patient population as transgender and gender diverse (TGD) to ensure the broadest inclusivity.¹ In this article, the following terms are used as defined below:

• The terms transgender woman and trans feminine describe persons who were assigned male gender at birth but their affirmed gender is female or nonmasculine.
• The terms transgender man and trans masculine describe persons who were assigned female gender at birth but their affirmed gender is male or nonfeminine.

The US Military’s policies on the service of TGD persons have evolved considerably over the past decade. Initial military policies barred TGD service members (TSMs) from service all together, leading to challenges in accessing necessary health care. The first official memorandum explicitly allowing military service by TGD persons was released on June 30, 2016.² The intention of this memorandum was 2-fold: (1) to allow TGD persons to serve in the military so long as they meet “the rigorous standards for military service and readiness” by fulfilling the same standards and procedures as other military service members, including medical fitness for duty, physical fitness, uniform and grooming, deployability, and retention, and (2) to direct the establishment of new or updated policies to specific departments and prescribe procedures for retention standards, separation from service, in-service transition, and medical coverage.² Several other official policies were released following this initial memorandum that provided more specific guidance on how to implement these policies at the level of the force, unit, and individual service member.

Modifications to the original 2016 policies had varying impacts on transgender health care provision and access.³ At the time of publication of this article, the current policy—the Department of Defense Instruction 1300.28⁴—among others, establishes standards and procedures for the process by which active and reserve TSMs may medically, socially, and legally transition genders within the military. The current policy applies to all military branches and serves as the framework by which each branch currently organizes their gender-affirmation processes (GAP).⁴

There currently are several different GAP models among the military branches.⁵ Each branch has a different model or approach to implementing the current policy, with varying service-specific processes in place for TSMs to access gender-affirming care; however, this may be changing. The Defense Health Agency is in the process of consolidating and streamlining the GAP across the Department of Defense branches in an effort to optimize costs and ensure uniformity of care. Per the Defense Health Agency Procedural Instruction Number 6025.21 published in May 2023, the proposed consolidated model likely will entail a single central transgender health center that provides oversight and guidance for several regional joint-service gender-affirming medical hubs. Patients would either be managed at the level of the hub or be referred to the central site.⁵

Herein, we discuss the importance of gender-affirming care and how military and civilian dermatologists can contribute. We also review disparities in health care and identify areas of improvement.

Benefits of Gender-Affirming Care

Gender-affirming procedures are critical for aligning physical appearance with gender identity. Physical appearance is essential for psychological well-being, operational readiness, and the safety of TSMs.⁶ It is well documented that TGD persons experience suicidal ideation, depression, stigma, discrimination and violence at higher rates than their cisgender peers.^7,8 It is important to recognize that transgender identity is not a mental illness, and these elevated rates have been linked to complex trauma, societal stigma, violence, and discrimination.¹ Other studies have suggested that increased access to gender-affirming interventions may ameliorate these mental health concerns.^1,7-9

The major components of gender-affirming care include hormone therapy, gender confirmation surgery, and mental health care, if needed. These are covered by TRICARE, the health care program for military service members; however, at the time of publication, many of the dermatologic gender-affirming procedures are not covered by TRICARE because they are considered “cosmetic procedures,” which is a term used by insurance companies but does not accurately indicate whether a procedure is medically necessary or not. Newer literature has demonstrated that gender-affirming care positively affects the lives of TGD patients, strengthening the argument that gender-affirming care is a medical necessity and not just cosmetic.¹

Aesthetic Procedures in Gender-Affirming Care

Surgeons, including those within the specialties of oto-laryngology, oral and maxillofacial surgery, urology, gynecology, and plastic surgery, provide major gender-affirming interventions; however, dermatologists may offer less invasive solutions that can serve as a temporary experience prior to undergoing more permanent procedures.Hormonally driven disorders including acne, hair loss, and melasma also are managed by dermatologists, along with scar treatment following surgeries.

Because human variation is expansive and subjective, what is considered feminine or masculine may vary by person, group, culture, and country; therefore, it is imperative to ask patients about their individual aesthetic goals and tailor their treatment accordingly. Feminine and masculine are terms that will be used to describe prototypical appearances and are not meant to define a patient’s current state or ultimate goals. The following procedures and medical interventions are where dermatologists can play an important role in TGD persons’ GAPs.

Botulinum Toxin Injections—Botulinum toxin injection is the most common nonsurgical aesthetic procedure performed around the world.¹⁰ The selective paralysis afforded by botulinum toxin has several uses for people undergoing transition. Aesthetically, the feminine eyebrow tends to be positioned above the orbital rim and is arched with its apex between the lateral limbus and lateral canthus,¹¹ while the masculine eyebrow tends to be flatter and fuller and runs over the orbital rim without a peak. For people seeking a more feminine appearance, an eyebrow lift with botulinum toxin can help reshape the typical flatter masculine eyebrow to give it lateral lift that often is considered more feminine. The targeted muscle is the superolateral orbicularis oculi, which serves as a depressor on the eyebrow. This can be combined with purposefully avoiding total lateral frontalis paralysis, which leads to a “Spock” brow for extra lift. Conversely, a naturally arched and higher eyebrow can be flattened and lowered by selectively targeting areas of the frontalis muscle.

Broad square jawlines typically are considered a masculine feature and are another area where botulinum toxin can be used to feminize a patient’s facial features. Targeting the masseter muscle induces muscle weakness, which ultimately may result in atrophy after one or more treatment sessions. This atrophy may lead to narrowing of the lower face and thus may lead to a fuller-appearing midface or overall more heart-shaped face. Every individual’s aesthetic goals are unique and therefore should be discussed prior to any treatment.

Dermal Fillers—Dermal fillers are gel-like substances injected under the skin for subtle contouring of the face. Fillers also can be used to help promote a more masculine or feminine appearance. Filler can be placed in the lips to create a fuller, more projected, feminine-appearing lip. Malar cheek and central lower chin filler can be used to help define a heart-shaped face by accentuating the upper portion of the face and creating a more pointed chin, respectively. Alternatively, filler can be used to masculinize the chin by placing it where it can increase jawline squareness and increase anterior jaw projection. Additionally, filler at the angle of the jaw can help accentuate a square facial shape and a more defined jawline. Although not as widely practiced, lateral brow filler can create a heavier-appearing and broader forehead for a more masculine appearance. These procedures can be combined with the previously mentioned botulinum toxin procedures for a synergistic effect.

Deoxycholic Acid—Deoxycholic acid is an injectable product used to selectively remove unwanted fat. It currently is approved by the US Food and Drug Administration for submental fat, but some providers are experimenting with off-label uses. Buccal fat pad removal—or in this case reduction by dissolution—tends to give a thinner, more feminine facial appearance.¹² Reducing fat around the axillae also can help promote a more masculine upper torso.¹³ The safety of deoxycholic acid in these areas has not been adequately tested; thus, caution should be used when discussing these off-label uses with patients.

Hair and Tattoo Removal—Hair removal may be desired by TGD persons for a variety of reasons. Because cisgender females tend to have less body hair overall, transgender people in pursuit of a more feminine appearance often desire removal of facial, neck, and body hair. Although shaving and other modalities such as waxing and chemical depilatories are readily available at-home options, they are not permanent and may lead to folliculitis or pseudofolliculitis barbae. Laser hair removal (LHR) and electrolysis are modalities provided by dermatologists that tend to be more permanent and lead to better outcomes, including less irritation and better aesthetic appearance. It is important to keep in mind that not every person and not every body site can be safely treated with LHR. Patients with lighter skin types and darker hair tend to have the most effective response with a higher margin of safety, as these features allow the laser energy to be selectively absorbed by the melanin in the hair bulb and not by the background skin pigmentation.^14,15 Inappropriate patient selection or improper settings for wavelength, pulse width, or fluences can lead to burns and permanent scarring.^14,15 Electrolysis is an alternative to hair removal within tattoos and is more effective for those individuals with blonde, red, or white hair.¹⁶

Another novel treatment for unwanted hair is eflor­nithine hydrochloride cream, which works by blocking ornithine decarboxylase, the enzyme that stimulates hair growth. It currently is approved to reduce unwanted hair on the face and adjacent areas under the chin; however the effects of this medication are modest and the medication can be expensive.¹⁷

Cosmetic hair and tattoo removal are not currently covered by TRICARE, except in cases of surgical and donor-site preparation for some GAPs. Individuals may desire removal of tattoos at surgery sites to obtain more natural-appearing skin. Currently, GAPs such as vaginoplasty, phalloplasty, and metoidioplasty—often referred to by patients as “bottom surgeries”—include insurance coverage for tattoo removal, LHR, and/or electrolysis.

Management of Hormonal Adverse Effects

Acne—Individuals on testosterone supplementation tend to develop acne for the first several years of treatment, but it may improve with time.¹⁸ Acne is treated in individuals receiving testosterone the same way as it is treated in cisgender men, with numerous options for topical and oral medications. In trans masculine persons, spironolactone therapy typically is avoided because it may interfere with the actions of exogenous testosterone administered as part of gender-affirming medical treatment and may lead to other undesired adverse effects such as impotence and gynecomastia.¹

Although acne typically improves after starting estrogen therapy, patients receiving estrogens may still develop acne. Most trans feminine patients will already be on an estrogen and an antiandrogen, often spironolactone.¹ Spironolactone often is used as monotherapy for acne control in cisgender women. Additionally, an important factor to consider with spironolactone is the possible adverse effect of increased micturition. Currently, the military rarely has gender-inclusive restroom options, which can create a challenge for TSMs who find themselves needing to use the restroom more frequently in the workplace.

If planning therapy with isotretinoin, dermatologists should discuss several important factors with all patients, including TGD patients. One consideration is the patient’s planned future surgeries. Although new literature shows that isotretinoin does not adversely affect wound healing,¹⁹ some surgeons still adhere to an isotretinoin washout period of 6 to 12 months prior to performing any elective procedures due to concerns about wound healing.^20,21 Second, be sure to properly assess and document pregnancy potential in TGD persons. Providers should not assume that a patient is not pregnant or is not trying to become pregnant just because they are trans masculine. It also is important to note that testosterone is not a reliable birth control method.¹ If a patient still has ovaries, fallopian tubes, and a uterus, they are considered medically capable of pregnancy, and providers should keep this in mind regarding all procedures in the TGD population.

Another newer acne treatment modality is the 1762-nm laser, which targets sebaceous glands.²² This device allows for targeted treatment of acne-prone areas without systemic therapy such as retinoids or antiandrogens. The 1762-nm laser is not widely available but may become a regular treatment option once its benefits are proven over time.

Alopecia and Hyperpigmentation—Androgens, whether endogenously or exogenously derived, can lead to androgenetic alopecia (AGA) in genetically susceptible individuals. Trans masculine persons and others receiving androgen therapy are at higher risk for AGA, which often is undesirable and may be considered gender affirming by some TGD persons. Standard AGA treatments for cisgender men also can be used in trans masculine persons. Some of the most common anti-AGA medications are topical minoxidil, oral finasteride, and oral minoxidil. Although Coleman et al¹ recently reported that finasteride may be an appropriate treatment option in trans masculine persons experiencing alopecia, treatment with 5α-reductase inhibitors may impair clitoral growth and the development of facial and body hair. Further studies are needed to assess the efficacy and safety of 5α-reductase inhibitors in transgender populations.¹ Dutasteride may be used off-label and comes with a similar potential adverse-event profile as finasteride, which includes depression, decreased libido, erectile dysfunction, ejaculation disorders, and gynecomastia.

Conversely, AGA tends to improve in trans feminine persons and others receiving estrogen and antiandrogen therapy. Natural testosterone production is suppressed by estrogens and spironolactone as well as in patients who undergo orchiectomy.¹ Although spironolactone is not approved for acne, AGA, or hirsutism, it is a standard treatment of AGA in cisgender women because it functions to block the effects of androgens, including at the hair follicle. Finasteride may be used for AGA in cisgender women but it is not recommended for trans feminine persons.¹

There are many other modalities available for the treatment of AGA that are less commonly used—some may be cost prohibitive or do not have robust supporting evidence, or both. One example is hair transplantation. Although this procedure gives dramatic results, it typically is performed by a specialized dermatologist, is not covered by insurance, and can cost up to tens of thousands of dollars out-of-pocket. Patients typically require continuous medical management of AGA even after the procedure. Examples of treatment modalities with uncertain supporting evidence are platelet-rich plasma injections, laser combs or hats, and microneedling. Additionally, clascoterone is a topical antiandrogen currently approved for acne, but it is under investigation for the treatment of AGA and may become an additional nonsystemic medication available for AGA in the future.²³

Melasma is a hyperpigmentation disorder related to estrogens, UV light exposure, and sometimes medication use (eg, hormonal birth control, spironolactone).²⁴ The mainstay of treatment is prevention, including sun avoidance as well as use of sun-protective clothing and broad-spectrum sunscreens. Dermatologists tend to recommend physical sunscreens containing zinc oxide, titanium dioxide, and/or iron oxide, as they cover a wider UV spectrum and also provide some protection from visible light. Once melasma is present, dermatologists still have several treatment options. Topical hydroquinone is a proven treatment; however, it must be used with caution to avoid ochronosis. With careful patient selection, chemical peels also are effective treatment options for dyspigmentation and hyperpigmentation. Energy devices such as intense pulsed light and tattoo removal lasers—Q-switched lasers and picosecond pulse widths—also can be used to treat hyperpigmentation. Oral, intralesional, and topical tranexamic acid are newer treatment options for melasma that still are being studied and have shown promising results. Further studies are needed to determine long-term safety and optimal treatment regimens.^24,25

Many insurance carriers, including TRICARE, do not routinely cover medical management of AGA or melasma. Patients should be advised that they likely will have to pay for any medications prescribed and procedures undertaken for these purposes; however, some medication costs can be offset by ordering larger prescription quantities, such as a 90-day supply vs a 30-day supply, as well as utilizing pharmacy discount programs.

Scar Management Following Surgery

In TSMs who undergo gender-affirming surgeries, dermatologists play an important role when scar symptoms develop, including pruritus, tenderness, and/or paresthesia. In the military, some common treatment modalities for symptomatic scars include intralesional steroids with or without 5-fluouroruacil and the fractionated CO₂ laser. There also are numerous experimental treatment options for scars, including intralesional or perilesional botulinum toxin, the pulsed dye laser, or nonablative fractionated lasers. These modalities also may be used on hypertrophic scars or keloids. Another option for keloids is scar excision followed by superficial radiation therapy.²⁶

Mental Health Considerations

Providers must take psychological adverse effects into consideration when considering medical therapies for dermatologic conditions in TGD patients. In particular, it is important to consider the risks for increased rates of depression and suicidal ideation formerly associated with the use of isotretinoin and finasteride, though much of the evidence regarding these risks has been called into question in recent years.^27,28 Nonetheless, it remains prominent in lay media and may be a more important consideration in patients at higher baseline risk.²⁷ Although there are no known studies that have expressly assessed rates of depression or suicidal ideation in TGD patients taking isotretinoin or finasteride, it is well established that TGD persons are at higher baseline risk for depression and suicidality.^1,7,8 All patients should be carefully assessed for depression and suicidal ideation as well as counseled regarding these risks prior to initiating these therapies. If concerns for untreated mental health issues arise during screening and counseling, patients should be referred for assessment by a behavioral health specialist prior to starting therapy.

Future Directions

The future of TGD health care in the military could see an expansion of covered benefits and the development of new dermatologic procedures or medications. Research and policy evolution are necessary to bridge the current gaps in care; however, it is unlikely that all procedures currently considered to be cosmetic will become covered benefits.

Facial LHR is a promising candidate for future coverage for trans feminine persons. When cisgender men develop adverse effects from mandatory daily shaving, LHR is already a covered benefit. Two arguments in support of adding LHR for TGD patients revolve around achieving and maintaining an appearance congruent with their gender along with avoiding unwanted adverse effects related to daily shaving. Visual conformity with one’s affirmed gender has been associated with improvements in well-being, quality of life, and some mental health conditions.²⁹

Scar prevention, treatment, and reduction are additional areas under active research in which dermatologists likely will play a crucial role.^30,31 As more dermatologic procedures are performed on TGD persons, the published data and collective knowledge regarding best practices in this population will continue to grow, which will lead to improved cosmetic and safety outcomes.

Final Thoughts

Although dermatologists do not directly perform gender-affirming surgeries or hormone management, they do play an important role in enhancing a TGD person’s desired appearance and managing possible adverse effects resulting from gender-affirming interventions. There have been considerable advancements in TGD health care over the past decade, but there likely are more changes on the way. As policies and understanding of TGD health care needs evolve, it is crucial that the military health care system adapts to provide comprehensive, accessible, and equitable care, which includes expanding the range of covered dermatologic treatments to fully support the health and readiness of TSMs.

Acknowledgment—We would like to extend our sincere appreciation to the invaluable contributions and editorial support provided by Allison Higgins, JD (San Antonio, Texas), throughout the writing of this article.

People whose gender identity differs from the sex assigned at birth are referred to as transgender. For some, gender identity may not fit into the binary constructs of male and female but rather falls between, within, or outside this construct. These people often consider themselves nonbinary or gender diverse. As the terminology continues to evolve, current recommendations include referring to this patient population as transgender and gender diverse (TGD) to ensure the broadest inclusivity.¹ In this article, the following terms are used as defined below:

• The terms transgender woman and trans feminine describe persons who were assigned male gender at birth but their affirmed gender is female or nonmasculine.
• The terms transgender man and trans masculine describe persons who were assigned female gender at birth but their affirmed gender is male or nonfeminine.

The US Military’s policies on the service of TGD persons have evolved considerably over the past decade. Initial military policies barred TGD service members (TSMs) from service all together, leading to challenges in accessing necessary health care. The first official memorandum explicitly allowing military service by TGD persons was released on June 30, 2016.² The intention of this memorandum was 2-fold: (1) to allow TGD persons to serve in the military so long as they meet “the rigorous standards for military service and readiness” by fulfilling the same standards and procedures as other military service members, including medical fitness for duty, physical fitness, uniform and grooming, deployability, and retention, and (2) to direct the establishment of new or updated policies to specific departments and prescribe procedures for retention standards, separation from service, in-service transition, and medical coverage.² Several other official policies were released following this initial memorandum that provided more specific guidance on how to implement these policies at the level of the force, unit, and individual service member.

Modifications to the original 2016 policies had varying impacts on transgender health care provision and access.³ At the time of publication of this article, the current policy—the Department of Defense Instruction 1300.28⁴—among others, establishes standards and procedures for the process by which active and reserve TSMs may medically, socially, and legally transition genders within the military. The current policy applies to all military branches and serves as the framework by which each branch currently organizes their gender-affirmation processes (GAP).⁴

There currently are several different GAP models among the military branches.⁵ Each branch has a different model or approach to implementing the current policy, with varying service-specific processes in place for TSMs to access gender-affirming care; however, this may be changing. The Defense Health Agency is in the process of consolidating and streamlining the GAP across the Department of Defense branches in an effort to optimize costs and ensure uniformity of care. Per the Defense Health Agency Procedural Instruction Number 6025.21 published in May 2023, the proposed consolidated model likely will entail a single central transgender health center that provides oversight and guidance for several regional joint-service gender-affirming medical hubs. Patients would either be managed at the level of the hub or be referred to the central site.⁵

Herein, we discuss the importance of gender-affirming care and how military and civilian dermatologists can contribute. We also review disparities in health care and identify areas of improvement.

Benefits of Gender-Affirming Care

Gender-affirming procedures are critical for aligning physical appearance with gender identity. Physical appearance is essential for psychological well-being, operational readiness, and the safety of TSMs.⁶ It is well documented that TGD persons experience suicidal ideation, depression, stigma, discrimination and violence at higher rates than their cisgender peers.^7,8 It is important to recognize that transgender identity is not a mental illness, and these elevated rates have been linked to complex trauma, societal stigma, violence, and discrimination.¹ Other studies have suggested that increased access to gender-affirming interventions may ameliorate these mental health concerns.^1,7-9

The major components of gender-affirming care include hormone therapy, gender confirmation surgery, and mental health care, if needed. These are covered by TRICARE, the health care program for military service members; however, at the time of publication, many of the dermatologic gender-affirming procedures are not covered by TRICARE because they are considered “cosmetic procedures,” which is a term used by insurance companies but does not accurately indicate whether a procedure is medically necessary or not. Newer literature has demonstrated that gender-affirming care positively affects the lives of TGD patients, strengthening the argument that gender-affirming care is a medical necessity and not just cosmetic.¹

Aesthetic Procedures in Gender-Affirming Care

Surgeons, including those within the specialties of oto-laryngology, oral and maxillofacial surgery, urology, gynecology, and plastic surgery, provide major gender-affirming interventions; however, dermatologists may offer less invasive solutions that can serve as a temporary experience prior to undergoing more permanent procedures.Hormonally driven disorders including acne, hair loss, and melasma also are managed by dermatologists, along with scar treatment following surgeries.

Because human variation is expansive and subjective, what is considered feminine or masculine may vary by person, group, culture, and country; therefore, it is imperative to ask patients about their individual aesthetic goals and tailor their treatment accordingly. Feminine and masculine are terms that will be used to describe prototypical appearances and are not meant to define a patient’s current state or ultimate goals. The following procedures and medical interventions are where dermatologists can play an important role in TGD persons’ GAPs.

Botulinum Toxin Injections—Botulinum toxin injection is the most common nonsurgical aesthetic procedure performed around the world.¹⁰ The selective paralysis afforded by botulinum toxin has several uses for people undergoing transition. Aesthetically, the feminine eyebrow tends to be positioned above the orbital rim and is arched with its apex between the lateral limbus and lateral canthus,¹¹ while the masculine eyebrow tends to be flatter and fuller and runs over the orbital rim without a peak. For people seeking a more feminine appearance, an eyebrow lift with botulinum toxin can help reshape the typical flatter masculine eyebrow to give it lateral lift that often is considered more feminine. The targeted muscle is the superolateral orbicularis oculi, which serves as a depressor on the eyebrow. This can be combined with purposefully avoiding total lateral frontalis paralysis, which leads to a “Spock” brow for extra lift. Conversely, a naturally arched and higher eyebrow can be flattened and lowered by selectively targeting areas of the frontalis muscle.

Broad square jawlines typically are considered a masculine feature and are another area where botulinum toxin can be used to feminize a patient’s facial features. Targeting the masseter muscle induces muscle weakness, which ultimately may result in atrophy after one or more treatment sessions. This atrophy may lead to narrowing of the lower face and thus may lead to a fuller-appearing midface or overall more heart-shaped face. Every individual’s aesthetic goals are unique and therefore should be discussed prior to any treatment.

Dermal Fillers—Dermal fillers are gel-like substances injected under the skin for subtle contouring of the face. Fillers also can be used to help promote a more masculine or feminine appearance. Filler can be placed in the lips to create a fuller, more projected, feminine-appearing lip. Malar cheek and central lower chin filler can be used to help define a heart-shaped face by accentuating the upper portion of the face and creating a more pointed chin, respectively. Alternatively, filler can be used to masculinize the chin by placing it where it can increase jawline squareness and increase anterior jaw projection. Additionally, filler at the angle of the jaw can help accentuate a square facial shape and a more defined jawline. Although not as widely practiced, lateral brow filler can create a heavier-appearing and broader forehead for a more masculine appearance. These procedures can be combined with the previously mentioned botulinum toxin procedures for a synergistic effect.

Deoxycholic Acid—Deoxycholic acid is an injectable product used to selectively remove unwanted fat. It currently is approved by the US Food and Drug Administration for submental fat, but some providers are experimenting with off-label uses. Buccal fat pad removal—or in this case reduction by dissolution—tends to give a thinner, more feminine facial appearance.¹² Reducing fat around the axillae also can help promote a more masculine upper torso.¹³ The safety of deoxycholic acid in these areas has not been adequately tested; thus, caution should be used when discussing these off-label uses with patients.

Hair and Tattoo Removal—Hair removal may be desired by TGD persons for a variety of reasons. Because cisgender females tend to have less body hair overall, transgender people in pursuit of a more feminine appearance often desire removal of facial, neck, and body hair. Although shaving and other modalities such as waxing and chemical depilatories are readily available at-home options, they are not permanent and may lead to folliculitis or pseudofolliculitis barbae. Laser hair removal (LHR) and electrolysis are modalities provided by dermatologists that tend to be more permanent and lead to better outcomes, including less irritation and better aesthetic appearance. It is important to keep in mind that not every person and not every body site can be safely treated with LHR. Patients with lighter skin types and darker hair tend to have the most effective response with a higher margin of safety, as these features allow the laser energy to be selectively absorbed by the melanin in the hair bulb and not by the background skin pigmentation.^14,15 Inappropriate patient selection or improper settings for wavelength, pulse width, or fluences can lead to burns and permanent scarring.^14,15 Electrolysis is an alternative to hair removal within tattoos and is more effective for those individuals with blonde, red, or white hair.¹⁶

Another novel treatment for unwanted hair is eflor­nithine hydrochloride cream, which works by blocking ornithine decarboxylase, the enzyme that stimulates hair growth. It currently is approved to reduce unwanted hair on the face and adjacent areas under the chin; however the effects of this medication are modest and the medication can be expensive.¹⁷

Cosmetic hair and tattoo removal are not currently covered by TRICARE, except in cases of surgical and donor-site preparation for some GAPs. Individuals may desire removal of tattoos at surgery sites to obtain more natural-appearing skin. Currently, GAPs such as vaginoplasty, phalloplasty, and metoidioplasty—often referred to by patients as “bottom surgeries”—include insurance coverage for tattoo removal, LHR, and/or electrolysis.

Management of Hormonal Adverse Effects

Acne—Individuals on testosterone supplementation tend to develop acne for the first several years of treatment, but it may improve with time.¹⁸ Acne is treated in individuals receiving testosterone the same way as it is treated in cisgender men, with numerous options for topical and oral medications. In trans masculine persons, spironolactone therapy typically is avoided because it may interfere with the actions of exogenous testosterone administered as part of gender-affirming medical treatment and may lead to other undesired adverse effects such as impotence and gynecomastia.¹

Although acne typically improves after starting estrogen therapy, patients receiving estrogens may still develop acne. Most trans feminine patients will already be on an estrogen and an antiandrogen, often spironolactone.¹ Spironolactone often is used as monotherapy for acne control in cisgender women. Additionally, an important factor to consider with spironolactone is the possible adverse effect of increased micturition. Currently, the military rarely has gender-inclusive restroom options, which can create a challenge for TSMs who find themselves needing to use the restroom more frequently in the workplace.

If planning therapy with isotretinoin, dermatologists should discuss several important factors with all patients, including TGD patients. One consideration is the patient’s planned future surgeries. Although new literature shows that isotretinoin does not adversely affect wound healing,¹⁹ some surgeons still adhere to an isotretinoin washout period of 6 to 12 months prior to performing any elective procedures due to concerns about wound healing.^20,21 Second, be sure to properly assess and document pregnancy potential in TGD persons. Providers should not assume that a patient is not pregnant or is not trying to become pregnant just because they are trans masculine. It also is important to note that testosterone is not a reliable birth control method.¹ If a patient still has ovaries, fallopian tubes, and a uterus, they are considered medically capable of pregnancy, and providers should keep this in mind regarding all procedures in the TGD population.

Another newer acne treatment modality is the 1762-nm laser, which targets sebaceous glands.²² This device allows for targeted treatment of acne-prone areas without systemic therapy such as retinoids or antiandrogens. The 1762-nm laser is not widely available but may become a regular treatment option once its benefits are proven over time.

Alopecia and Hyperpigmentation—Androgens, whether endogenously or exogenously derived, can lead to androgenetic alopecia (AGA) in genetically susceptible individuals. Trans masculine persons and others receiving androgen therapy are at higher risk for AGA, which often is undesirable and may be considered gender affirming by some TGD persons. Standard AGA treatments for cisgender men also can be used in trans masculine persons. Some of the most common anti-AGA medications are topical minoxidil, oral finasteride, and oral minoxidil. Although Coleman et al¹ recently reported that finasteride may be an appropriate treatment option in trans masculine persons experiencing alopecia, treatment with 5α-reductase inhibitors may impair clitoral growth and the development of facial and body hair. Further studies are needed to assess the efficacy and safety of 5α-reductase inhibitors in transgender populations.¹ Dutasteride may be used off-label and comes with a similar potential adverse-event profile as finasteride, which includes depression, decreased libido, erectile dysfunction, ejaculation disorders, and gynecomastia.

Conversely, AGA tends to improve in trans feminine persons and others receiving estrogen and antiandrogen therapy. Natural testosterone production is suppressed by estrogens and spironolactone as well as in patients who undergo orchiectomy.¹ Although spironolactone is not approved for acne, AGA, or hirsutism, it is a standard treatment of AGA in cisgender women because it functions to block the effects of androgens, including at the hair follicle. Finasteride may be used for AGA in cisgender women but it is not recommended for trans feminine persons.¹

There are many other modalities available for the treatment of AGA that are less commonly used—some may be cost prohibitive or do not have robust supporting evidence, or both. One example is hair transplantation. Although this procedure gives dramatic results, it typically is performed by a specialized dermatologist, is not covered by insurance, and can cost up to tens of thousands of dollars out-of-pocket. Patients typically require continuous medical management of AGA even after the procedure. Examples of treatment modalities with uncertain supporting evidence are platelet-rich plasma injections, laser combs or hats, and microneedling. Additionally, clascoterone is a topical antiandrogen currently approved for acne, but it is under investigation for the treatment of AGA and may become an additional nonsystemic medication available for AGA in the future.²³

Melasma is a hyperpigmentation disorder related to estrogens, UV light exposure, and sometimes medication use (eg, hormonal birth control, spironolactone).²⁴ The mainstay of treatment is prevention, including sun avoidance as well as use of sun-protective clothing and broad-spectrum sunscreens. Dermatologists tend to recommend physical sunscreens containing zinc oxide, titanium dioxide, and/or iron oxide, as they cover a wider UV spectrum and also provide some protection from visible light. Once melasma is present, dermatologists still have several treatment options. Topical hydroquinone is a proven treatment; however, it must be used with caution to avoid ochronosis. With careful patient selection, chemical peels also are effective treatment options for dyspigmentation and hyperpigmentation. Energy devices such as intense pulsed light and tattoo removal lasers—Q-switched lasers and picosecond pulse widths—also can be used to treat hyperpigmentation. Oral, intralesional, and topical tranexamic acid are newer treatment options for melasma that still are being studied and have shown promising results. Further studies are needed to determine long-term safety and optimal treatment regimens.^24,25

Many insurance carriers, including TRICARE, do not routinely cover medical management of AGA or melasma. Patients should be advised that they likely will have to pay for any medications prescribed and procedures undertaken for these purposes; however, some medication costs can be offset by ordering larger prescription quantities, such as a 90-day supply vs a 30-day supply, as well as utilizing pharmacy discount programs.

Scar Management Following Surgery

In TSMs who undergo gender-affirming surgeries, dermatologists play an important role when scar symptoms develop, including pruritus, tenderness, and/or paresthesia. In the military, some common treatment modalities for symptomatic scars include intralesional steroids with or without 5-fluouroruacil and the fractionated CO₂ laser. There also are numerous experimental treatment options for scars, including intralesional or perilesional botulinum toxin, the pulsed dye laser, or nonablative fractionated lasers. These modalities also may be used on hypertrophic scars or keloids. Another option for keloids is scar excision followed by superficial radiation therapy.²⁶

Mental Health Considerations

Providers must take psychological adverse effects into consideration when considering medical therapies for dermatologic conditions in TGD patients. In particular, it is important to consider the risks for increased rates of depression and suicidal ideation formerly associated with the use of isotretinoin and finasteride, though much of the evidence regarding these risks has been called into question in recent years.^27,28 Nonetheless, it remains prominent in lay media and may be a more important consideration in patients at higher baseline risk.²⁷ Although there are no known studies that have expressly assessed rates of depression or suicidal ideation in TGD patients taking isotretinoin or finasteride, it is well established that TGD persons are at higher baseline risk for depression and suicidality.^1,7,8 All patients should be carefully assessed for depression and suicidal ideation as well as counseled regarding these risks prior to initiating these therapies. If concerns for untreated mental health issues arise during screening and counseling, patients should be referred for assessment by a behavioral health specialist prior to starting therapy.

Future Directions

The future of TGD health care in the military could see an expansion of covered benefits and the development of new dermatologic procedures or medications. Research and policy evolution are necessary to bridge the current gaps in care; however, it is unlikely that all procedures currently considered to be cosmetic will become covered benefits.

Facial LHR is a promising candidate for future coverage for trans feminine persons. When cisgender men develop adverse effects from mandatory daily shaving, LHR is already a covered benefit. Two arguments in support of adding LHR for TGD patients revolve around achieving and maintaining an appearance congruent with their gender along with avoiding unwanted adverse effects related to daily shaving. Visual conformity with one’s affirmed gender has been associated with improvements in well-being, quality of life, and some mental health conditions.²⁹

Scar prevention, treatment, and reduction are additional areas under active research in which dermatologists likely will play a crucial role.^30,31 As more dermatologic procedures are performed on TGD persons, the published data and collective knowledge regarding best practices in this population will continue to grow, which will lead to improved cosmetic and safety outcomes.

Final Thoughts

Although dermatologists do not directly perform gender-affirming surgeries or hormone management, they do play an important role in enhancing a TGD person’s desired appearance and managing possible adverse effects resulting from gender-affirming interventions. There have been considerable advancements in TGD health care over the past decade, but there likely are more changes on the way. As policies and understanding of TGD health care needs evolve, it is crucial that the military health care system adapts to provide comprehensive, accessible, and equitable care, which includes expanding the range of covered dermatologic treatments to fully support the health and readiness of TSMs.

Acknowledgment—We would like to extend our sincere appreciation to the invaluable contributions and editorial support provided by Allison Higgins, JD (San Antonio, Texas), throughout the writing of this article.

People whose gender identity differs from the sex assigned at birth are referred to as transgender. For some, gender identity may not fit into the binary constructs of male and female but rather falls between, within, or outside this construct. These people often consider themselves nonbinary or gender diverse. As the terminology continues to evolve, current recommendations include referring to this patient population as transgender and gender diverse (TGD) to ensure the broadest inclusivity.¹ In this article, the following terms are used as defined below:

• The terms transgender woman and trans feminine describe persons who were assigned male gender at birth but their affirmed gender is female or nonmasculine.
• The terms transgender man and trans masculine describe persons who were assigned female gender at birth but their affirmed gender is male or nonfeminine.

The US Military’s policies on the service of TGD persons have evolved considerably over the past decade. Initial military policies barred TGD service members (TSMs) from service all together, leading to challenges in accessing necessary health care. The first official memorandum explicitly allowing military service by TGD persons was released on June 30, 2016.² The intention of this memorandum was 2-fold: (1) to allow TGD persons to serve in the military so long as they meet “the rigorous standards for military service and readiness” by fulfilling the same standards and procedures as other military service members, including medical fitness for duty, physical fitness, uniform and grooming, deployability, and retention, and (2) to direct the establishment of new or updated policies to specific departments and prescribe procedures for retention standards, separation from service, in-service transition, and medical coverage.² Several other official policies were released following this initial memorandum that provided more specific guidance on how to implement these policies at the level of the force, unit, and individual service member.

Modifications to the original 2016 policies had varying impacts on transgender health care provision and access.³ At the time of publication of this article, the current policy—the Department of Defense Instruction 1300.28⁴—among others, establishes standards and procedures for the process by which active and reserve TSMs may medically, socially, and legally transition genders within the military. The current policy applies to all military branches and serves as the framework by which each branch currently organizes their gender-affirmation processes (GAP).⁴

There currently are several different GAP models among the military branches.⁵ Each branch has a different model or approach to implementing the current policy, with varying service-specific processes in place for TSMs to access gender-affirming care; however, this may be changing. The Defense Health Agency is in the process of consolidating and streamlining the GAP across the Department of Defense branches in an effort to optimize costs and ensure uniformity of care. Per the Defense Health Agency Procedural Instruction Number 6025.21 published in May 2023, the proposed consolidated model likely will entail a single central transgender health center that provides oversight and guidance for several regional joint-service gender-affirming medical hubs. Patients would either be managed at the level of the hub or be referred to the central site.⁵

Herein, we discuss the importance of gender-affirming care and how military and civilian dermatologists can contribute. We also review disparities in health care and identify areas of improvement.

Benefits of Gender-Affirming Care

Gender-affirming procedures are critical for aligning physical appearance with gender identity. Physical appearance is essential for psychological well-being, operational readiness, and the safety of TSMs.⁶ It is well documented that TGD persons experience suicidal ideation, depression, stigma, discrimination and violence at higher rates than their cisgender peers.^7,8 It is important to recognize that transgender identity is not a mental illness, and these elevated rates have been linked to complex trauma, societal stigma, violence, and discrimination.¹ Other studies have suggested that increased access to gender-affirming interventions may ameliorate these mental health concerns.^1,7-9

The major components of gender-affirming care include hormone therapy, gender confirmation surgery, and mental health care, if needed. These are covered by TRICARE, the health care program for military service members; however, at the time of publication, many of the dermatologic gender-affirming procedures are not covered by TRICARE because they are considered “cosmetic procedures,” which is a term used by insurance companies but does not accurately indicate whether a procedure is medically necessary or not. Newer literature has demonstrated that gender-affirming care positively affects the lives of TGD patients, strengthening the argument that gender-affirming care is a medical necessity and not just cosmetic.¹

Aesthetic Procedures in Gender-Affirming Care

Surgeons, including those within the specialties of oto-laryngology, oral and maxillofacial surgery, urology, gynecology, and plastic surgery, provide major gender-affirming interventions; however, dermatologists may offer less invasive solutions that can serve as a temporary experience prior to undergoing more permanent procedures.Hormonally driven disorders including acne, hair loss, and melasma also are managed by dermatologists, along with scar treatment following surgeries.

Because human variation is expansive and subjective, what is considered feminine or masculine may vary by person, group, culture, and country; therefore, it is imperative to ask patients about their individual aesthetic goals and tailor their treatment accordingly. Feminine and masculine are terms that will be used to describe prototypical appearances and are not meant to define a patient’s current state or ultimate goals. The following procedures and medical interventions are where dermatologists can play an important role in TGD persons’ GAPs.

Botulinum Toxin Injections—Botulinum toxin injection is the most common nonsurgical aesthetic procedure performed around the world.¹⁰ The selective paralysis afforded by botulinum toxin has several uses for people undergoing transition. Aesthetically, the feminine eyebrow tends to be positioned above the orbital rim and is arched with its apex between the lateral limbus and lateral canthus,¹¹ while the masculine eyebrow tends to be flatter and fuller and runs over the orbital rim without a peak. For people seeking a more feminine appearance, an eyebrow lift with botulinum toxin can help reshape the typical flatter masculine eyebrow to give it lateral lift that often is considered more feminine. The targeted muscle is the superolateral orbicularis oculi, which serves as a depressor on the eyebrow. This can be combined with purposefully avoiding total lateral frontalis paralysis, which leads to a “Spock” brow for extra lift. Conversely, a naturally arched and higher eyebrow can be flattened and lowered by selectively targeting areas of the frontalis muscle.

Broad square jawlines typically are considered a masculine feature and are another area where botulinum toxin can be used to feminize a patient’s facial features. Targeting the masseter muscle induces muscle weakness, which ultimately may result in atrophy after one or more treatment sessions. This atrophy may lead to narrowing of the lower face and thus may lead to a fuller-appearing midface or overall more heart-shaped face. Every individual’s aesthetic goals are unique and therefore should be discussed prior to any treatment.

Dermal Fillers—Dermal fillers are gel-like substances injected under the skin for subtle contouring of the face. Fillers also can be used to help promote a more masculine or feminine appearance. Filler can be placed in the lips to create a fuller, more projected, feminine-appearing lip. Malar cheek and central lower chin filler can be used to help define a heart-shaped face by accentuating the upper portion of the face and creating a more pointed chin, respectively. Alternatively, filler can be used to masculinize the chin by placing it where it can increase jawline squareness and increase anterior jaw projection. Additionally, filler at the angle of the jaw can help accentuate a square facial shape and a more defined jawline. Although not as widely practiced, lateral brow filler can create a heavier-appearing and broader forehead for a more masculine appearance. These procedures can be combined with the previously mentioned botulinum toxin procedures for a synergistic effect.

Deoxycholic Acid—Deoxycholic acid is an injectable product used to selectively remove unwanted fat. It currently is approved by the US Food and Drug Administration for submental fat, but some providers are experimenting with off-label uses. Buccal fat pad removal—or in this case reduction by dissolution—tends to give a thinner, more feminine facial appearance.¹² Reducing fat around the axillae also can help promote a more masculine upper torso.¹³ The safety of deoxycholic acid in these areas has not been adequately tested; thus, caution should be used when discussing these off-label uses with patients.

Hair and Tattoo Removal—Hair removal may be desired by TGD persons for a variety of reasons. Because cisgender females tend to have less body hair overall, transgender people in pursuit of a more feminine appearance often desire removal of facial, neck, and body hair. Although shaving and other modalities such as waxing and chemical depilatories are readily available at-home options, they are not permanent and may lead to folliculitis or pseudofolliculitis barbae. Laser hair removal (LHR) and electrolysis are modalities provided by dermatologists that tend to be more permanent and lead to better outcomes, including less irritation and better aesthetic appearance. It is important to keep in mind that not every person and not every body site can be safely treated with LHR. Patients with lighter skin types and darker hair tend to have the most effective response with a higher margin of safety, as these features allow the laser energy to be selectively absorbed by the melanin in the hair bulb and not by the background skin pigmentation.^14,15 Inappropriate patient selection or improper settings for wavelength, pulse width, or fluences can lead to burns and permanent scarring.^14,15 Electrolysis is an alternative to hair removal within tattoos and is more effective for those individuals with blonde, red, or white hair.¹⁶

Another novel treatment for unwanted hair is eflor­nithine hydrochloride cream, which works by blocking ornithine decarboxylase, the enzyme that stimulates hair growth. It currently is approved to reduce unwanted hair on the face and adjacent areas under the chin; however the effects of this medication are modest and the medication can be expensive.¹⁷

Cosmetic hair and tattoo removal are not currently covered by TRICARE, except in cases of surgical and donor-site preparation for some GAPs. Individuals may desire removal of tattoos at surgery sites to obtain more natural-appearing skin. Currently, GAPs such as vaginoplasty, phalloplasty, and metoidioplasty—often referred to by patients as “bottom surgeries”—include insurance coverage for tattoo removal, LHR, and/or electrolysis.

Management of Hormonal Adverse Effects

Acne—Individuals on testosterone supplementation tend to develop acne for the first several years of treatment, but it may improve with time.¹⁸ Acne is treated in individuals receiving testosterone the same way as it is treated in cisgender men, with numerous options for topical and oral medications. In trans masculine persons, spironolactone therapy typically is avoided because it may interfere with the actions of exogenous testosterone administered as part of gender-affirming medical treatment and may lead to other undesired adverse effects such as impotence and gynecomastia.¹

Although acne typically improves after starting estrogen therapy, patients receiving estrogens may still develop acne. Most trans feminine patients will already be on an estrogen and an antiandrogen, often spironolactone.¹ Spironolactone often is used as monotherapy for acne control in cisgender women. Additionally, an important factor to consider with spironolactone is the possible adverse effect of increased micturition. Currently, the military rarely has gender-inclusive restroom options, which can create a challenge for TSMs who find themselves needing to use the restroom more frequently in the workplace.

If planning therapy with isotretinoin, dermatologists should discuss several important factors with all patients, including TGD patients. One consideration is the patient’s planned future surgeries. Although new literature shows that isotretinoin does not adversely affect wound healing,¹⁹ some surgeons still adhere to an isotretinoin washout period of 6 to 12 months prior to performing any elective procedures due to concerns about wound healing.^20,21 Second, be sure to properly assess and document pregnancy potential in TGD persons. Providers should not assume that a patient is not pregnant or is not trying to become pregnant just because they are trans masculine. It also is important to note that testosterone is not a reliable birth control method.¹ If a patient still has ovaries, fallopian tubes, and a uterus, they are considered medically capable of pregnancy, and providers should keep this in mind regarding all procedures in the TGD population.

Another newer acne treatment modality is the 1762-nm laser, which targets sebaceous glands.²² This device allows for targeted treatment of acne-prone areas without systemic therapy such as retinoids or antiandrogens. The 1762-nm laser is not widely available but may become a regular treatment option once its benefits are proven over time.

Alopecia and Hyperpigmentation—Androgens, whether endogenously or exogenously derived, can lead to androgenetic alopecia (AGA) in genetically susceptible individuals. Trans masculine persons and others receiving androgen therapy are at higher risk for AGA, which often is undesirable and may be considered gender affirming by some TGD persons. Standard AGA treatments for cisgender men also can be used in trans masculine persons. Some of the most common anti-AGA medications are topical minoxidil, oral finasteride, and oral minoxidil. Although Coleman et al¹ recently reported that finasteride may be an appropriate treatment option in trans masculine persons experiencing alopecia, treatment with 5α-reductase inhibitors may impair clitoral growth and the development of facial and body hair. Further studies are needed to assess the efficacy and safety of 5α-reductase inhibitors in transgender populations.¹ Dutasteride may be used off-label and comes with a similar potential adverse-event profile as finasteride, which includes depression, decreased libido, erectile dysfunction, ejaculation disorders, and gynecomastia.

Conversely, AGA tends to improve in trans feminine persons and others receiving estrogen and antiandrogen therapy. Natural testosterone production is suppressed by estrogens and spironolactone as well as in patients who undergo orchiectomy.¹ Although spironolactone is not approved for acne, AGA, or hirsutism, it is a standard treatment of AGA in cisgender women because it functions to block the effects of androgens, including at the hair follicle. Finasteride may be used for AGA in cisgender women but it is not recommended for trans feminine persons.¹

There are many other modalities available for the treatment of AGA that are less commonly used—some may be cost prohibitive or do not have robust supporting evidence, or both. One example is hair transplantation. Although this procedure gives dramatic results, it typically is performed by a specialized dermatologist, is not covered by insurance, and can cost up to tens of thousands of dollars out-of-pocket. Patients typically require continuous medical management of AGA even after the procedure. Examples of treatment modalities with uncertain supporting evidence are platelet-rich plasma injections, laser combs or hats, and microneedling. Additionally, clascoterone is a topical antiandrogen currently approved for acne, but it is under investigation for the treatment of AGA and may become an additional nonsystemic medication available for AGA in the future.²³

Melasma is a hyperpigmentation disorder related to estrogens, UV light exposure, and sometimes medication use (eg, hormonal birth control, spironolactone).²⁴ The mainstay of treatment is prevention, including sun avoidance as well as use of sun-protective clothing and broad-spectrum sunscreens. Dermatologists tend to recommend physical sunscreens containing zinc oxide, titanium dioxide, and/or iron oxide, as they cover a wider UV spectrum and also provide some protection from visible light. Once melasma is present, dermatologists still have several treatment options. Topical hydroquinone is a proven treatment; however, it must be used with caution to avoid ochronosis. With careful patient selection, chemical peels also are effective treatment options for dyspigmentation and hyperpigmentation. Energy devices such as intense pulsed light and tattoo removal lasers—Q-switched lasers and picosecond pulse widths—also can be used to treat hyperpigmentation. Oral, intralesional, and topical tranexamic acid are newer treatment options for melasma that still are being studied and have shown promising results. Further studies are needed to determine long-term safety and optimal treatment regimens.^24,25

Many insurance carriers, including TRICARE, do not routinely cover medical management of AGA or melasma. Patients should be advised that they likely will have to pay for any medications prescribed and procedures undertaken for these purposes; however, some medication costs can be offset by ordering larger prescription quantities, such as a 90-day supply vs a 30-day supply, as well as utilizing pharmacy discount programs.

Scar Management Following Surgery

In TSMs who undergo gender-affirming surgeries, dermatologists play an important role when scar symptoms develop, including pruritus, tenderness, and/or paresthesia. In the military, some common treatment modalities for symptomatic scars include intralesional steroids with or without 5-fluouroruacil and the fractionated CO₂ laser. There also are numerous experimental treatment options for scars, including intralesional or perilesional botulinum toxin, the pulsed dye laser, or nonablative fractionated lasers. These modalities also may be used on hypertrophic scars or keloids. Another option for keloids is scar excision followed by superficial radiation therapy.²⁶

Mental Health Considerations

Providers must take psychological adverse effects into consideration when considering medical therapies for dermatologic conditions in TGD patients. In particular, it is important to consider the risks for increased rates of depression and suicidal ideation formerly associated with the use of isotretinoin and finasteride, though much of the evidence regarding these risks has been called into question in recent years.^27,28 Nonetheless, it remains prominent in lay media and may be a more important consideration in patients at higher baseline risk.²⁷ Although there are no known studies that have expressly assessed rates of depression or suicidal ideation in TGD patients taking isotretinoin or finasteride, it is well established that TGD persons are at higher baseline risk for depression and suicidality.^1,7,8 All patients should be carefully assessed for depression and suicidal ideation as well as counseled regarding these risks prior to initiating these therapies. If concerns for untreated mental health issues arise during screening and counseling, patients should be referred for assessment by a behavioral health specialist prior to starting therapy.

Future Directions

The future of TGD health care in the military could see an expansion of covered benefits and the development of new dermatologic procedures or medications. Research and policy evolution are necessary to bridge the current gaps in care; however, it is unlikely that all procedures currently considered to be cosmetic will become covered benefits.

Facial LHR is a promising candidate for future coverage for trans feminine persons. When cisgender men develop adverse effects from mandatory daily shaving, LHR is already a covered benefit. Two arguments in support of adding LHR for TGD patients revolve around achieving and maintaining an appearance congruent with their gender along with avoiding unwanted adverse effects related to daily shaving. Visual conformity with one’s affirmed gender has been associated with improvements in well-being, quality of life, and some mental health conditions.²⁹

Scar prevention, treatment, and reduction are additional areas under active research in which dermatologists likely will play a crucial role.^30,31 As more dermatologic procedures are performed on TGD persons, the published data and collective knowledge regarding best practices in this population will continue to grow, which will lead to improved cosmetic and safety outcomes.

Final Thoughts

Although dermatologists do not directly perform gender-affirming surgeries or hormone management, they do play an important role in enhancing a TGD person’s desired appearance and managing possible adverse effects resulting from gender-affirming interventions. There have been considerable advancements in TGD health care over the past decade, but there likely are more changes on the way. As policies and understanding of TGD health care needs evolve, it is crucial that the military health care system adapts to provide comprehensive, accessible, and equitable care, which includes expanding the range of covered dermatologic treatments to fully support the health and readiness of TSMs.

Acknowledgment—We would like to extend our sincere appreciation to the invaluable contributions and editorial support provided by Allison Higgins, JD (San Antonio, Texas), throughout the writing of this article.

March 2024 proved to be a busy month for benzoyl peroxide in the media! We are now at almost 4 months since Valisure, an independent analytical laboratory located in Connecticut, filed a Citizen Petition on benzene in benzoyl peroxide drug products with the US Food and Drug Administration (FDA) on March 5, 2024.¹ This petition was filed shortly before the annual meeting of the American Academy of Dermatology was held in San Diego, California, creating quite a stir of concern in the dermatology world. Further information on the degradation of benzoyl peroxide with production of benzene was published in the medical literature in March 2024.² As benzene is recognized as a human carcinogen, manufacturing regulations exist to assure that it does not appear in topical products either through contamination or degradation over the course of a product’s shelf-life.³

As anticipated, several opinions and commentaries appeared quickly, both on video and in various articles. The American Acne & Rosacea Society (AARS) released a statement on this issue on March 20, 2024.⁴ The safety of the public is the overarching primary concern. This AARS statement does include some general suggestions related to benzoyl peroxide use based on the best assessment to date while awaiting further guidance from the FDA on this issue. Benzoyl peroxide is approved for use by the FDA as an over-the-counter (OTC) topical product for acne and also is in several FDA-approved prescription topical products.^5,6

The following reflects my personal viewpoint as both a dermatologist and a grandfather who has grandchildren who use acne products. My views are not necessarily those of AARS. Since early March 2024, I have read several documents and spoken to several dermatologists, scientists, and formulators with knowledge in this area, including contacts at Valisure. I was hoping to get to some reasonable definitive answer but have not been able to achieve this to my full satisfaction. There are many opinions and concerns, and each one makes sense based on the vantage point of the presenter. However, several unanswered questions remain related to what testing and data are currently required of companies to gain FDA approval of a benzoyl peroxide product, including:

• assessment of stability and degradation products (including benzene),
• validation of testing methods,
• the issue of benzoyl peroxide stability in commercial products, and
• the relevant magnitude of resultant benzene exposures, especially as we are all exposed to benzene from several sources each day.

I am certain that companies with benzoyl peroxide products will evaluate their already-approved products and also do further testing. However, in this situation, which impacts millions of people on so many levels, I feel there needs to be an organized approach to evaluate and resolve the issue, otherwise the likelihood of continued confusion and uncertainty is high. As the FDA is the approval body, I am hoping it will provide definitive guidance within a reasonable timeline so that clinicians, patients, and manufacturers of benzoyl peroxide can proceed with full confidence. Right now, we all remain in a state of limbo. It is time for less talk and more definitive action to sort out this issue.

March 2024 proved to be a busy month for benzoyl peroxide in the media! We are now at almost 4 months since Valisure, an independent analytical laboratory located in Connecticut, filed a Citizen Petition on benzene in benzoyl peroxide drug products with the US Food and Drug Administration (FDA) on March 5, 2024.¹ This petition was filed shortly before the annual meeting of the American Academy of Dermatology was held in San Diego, California, creating quite a stir of concern in the dermatology world. Further information on the degradation of benzoyl peroxide with production of benzene was published in the medical literature in March 2024.² As benzene is recognized as a human carcinogen, manufacturing regulations exist to assure that it does not appear in topical products either through contamination or degradation over the course of a product’s shelf-life.³

As anticipated, several opinions and commentaries appeared quickly, both on video and in various articles. The American Acne & Rosacea Society (AARS) released a statement on this issue on March 20, 2024.⁴ The safety of the public is the overarching primary concern. This AARS statement does include some general suggestions related to benzoyl peroxide use based on the best assessment to date while awaiting further guidance from the FDA on this issue. Benzoyl peroxide is approved for use by the FDA as an over-the-counter (OTC) topical product for acne and also is in several FDA-approved prescription topical products.^5,6

The following reflects my personal viewpoint as both a dermatologist and a grandfather who has grandchildren who use acne products. My views are not necessarily those of AARS. Since early March 2024, I have read several documents and spoken to several dermatologists, scientists, and formulators with knowledge in this area, including contacts at Valisure. I was hoping to get to some reasonable definitive answer but have not been able to achieve this to my full satisfaction. There are many opinions and concerns, and each one makes sense based on the vantage point of the presenter. However, several unanswered questions remain related to what testing and data are currently required of companies to gain FDA approval of a benzoyl peroxide product, including:

• assessment of stability and degradation products (including benzene),
• validation of testing methods,
• the issue of benzoyl peroxide stability in commercial products, and
• the relevant magnitude of resultant benzene exposures, especially as we are all exposed to benzene from several sources each day.

I am certain that companies with benzoyl peroxide products will evaluate their already-approved products and also do further testing. However, in this situation, which impacts millions of people on so many levels, I feel there needs to be an organized approach to evaluate and resolve the issue, otherwise the likelihood of continued confusion and uncertainty is high. As the FDA is the approval body, I am hoping it will provide definitive guidance within a reasonable timeline so that clinicians, patients, and manufacturers of benzoyl peroxide can proceed with full confidence. Right now, we all remain in a state of limbo. It is time for less talk and more definitive action to sort out this issue.

March 2024 proved to be a busy month for benzoyl peroxide in the media! We are now at almost 4 months since Valisure, an independent analytical laboratory located in Connecticut, filed a Citizen Petition on benzene in benzoyl peroxide drug products with the US Food and Drug Administration (FDA) on March 5, 2024.¹ This petition was filed shortly before the annual meeting of the American Academy of Dermatology was held in San Diego, California, creating quite a stir of concern in the dermatology world. Further information on the degradation of benzoyl peroxide with production of benzene was published in the medical literature in March 2024.² As benzene is recognized as a human carcinogen, manufacturing regulations exist to assure that it does not appear in topical products either through contamination or degradation over the course of a product’s shelf-life.³

As anticipated, several opinions and commentaries appeared quickly, both on video and in various articles. The American Acne & Rosacea Society (AARS) released a statement on this issue on March 20, 2024.⁴ The safety of the public is the overarching primary concern. This AARS statement does include some general suggestions related to benzoyl peroxide use based on the best assessment to date while awaiting further guidance from the FDA on this issue. Benzoyl peroxide is approved for use by the FDA as an over-the-counter (OTC) topical product for acne and also is in several FDA-approved prescription topical products.^5,6

The following reflects my personal viewpoint as both a dermatologist and a grandfather who has grandchildren who use acne products. My views are not necessarily those of AARS. Since early March 2024, I have read several documents and spoken to several dermatologists, scientists, and formulators with knowledge in this area, including contacts at Valisure. I was hoping to get to some reasonable definitive answer but have not been able to achieve this to my full satisfaction. There are many opinions and concerns, and each one makes sense based on the vantage point of the presenter. However, several unanswered questions remain related to what testing and data are currently required of companies to gain FDA approval of a benzoyl peroxide product, including:

• assessment of stability and degradation products (including benzene),
• validation of testing methods,
• the issue of benzoyl peroxide stability in commercial products, and
• the relevant magnitude of resultant benzene exposures, especially as we are all exposed to benzene from several sources each day.

I am certain that companies with benzoyl peroxide products will evaluate their already-approved products and also do further testing. However, in this situation, which impacts millions of people on so many levels, I feel there needs to be an organized approach to evaluate and resolve the issue, otherwise the likelihood of continued confusion and uncertainty is high. As the FDA is the approval body, I am hoping it will provide definitive guidance within a reasonable timeline so that clinicians, patients, and manufacturers of benzoyl peroxide can proceed with full confidence. Right now, we all remain in a state of limbo. It is time for less talk and more definitive action to sort out this issue.

Isotretinoin was introduced more than 3 decades ago and marked a major advancement in the treatment of severe refractory cystic acne. The most common adverse effects linked to isotretinoin usage are mucocutaneous in nature, manifesting as xerosis and cheilitis.¹ Skin fragility and poor wound healing also have been reported.^2-6 Current recommendations for avoiding these adverse effects include refraining from waxing, laser procedures, and other elective cutaneous procedures for at least 6 months.⁷ We present a case of isotretinoin-induced cutaneous fragility resulting in blistering and erosions on the palms of a competitive aerial trapeze artist.

Case Report

A 25-year-old woman presented for follow-up during week 12 of isotretinoin therapy (40 mg twice daily) prescribed for acne. She reported peeling of the skin on the palms following intense aerial acrobatic workouts. She had been a performing aerialist for many years and had never sustained a similar injury. The wounds were painful and led to decreased activity. She had no notable medical history. Physical examination of the palms revealed erosions in a distribution that corresponded to horizontal bar contact and friction (Figure). The patient was advised on proper wound care, application of emollients, and minimizing friction. She completed the course of isotretinoin and has continued aerialist activity without recurrence of skin fragility.

Comment

Skin fragility is a well-known adverse effect of isotretinoin therapy.⁸ Pavlis and Lieblich⁹ reported skin fragility in a young wrestler who experienced similar skin erosions due to isotretinoin therapy. The proposed mechanism of isotretinoin-induced skin fragility is multifactorial. It involves an apoptotic effect on sebocytes,⁵ which results in reduced stratum corneum hydration and an associated increase in transepidermal water loss.^6,10,11 Retinoids also are known to cause thinning of the skin, likely due to the disadhesion of both the epidermis and the stratum corneum, which was demonstrated by the easy removal of cornified cells through tape stripping in hairless mice treated with isotretinoin.¹² In further investigations, human patients and hairless mice treated with isotretinoin readily developed friction blisters through pencil eraser abrasion.¹³ Examination of the friction blisters using light and electron microscopy revealed fraying or loss of the stratum corneum and viable epidermis as well as loss of desmosomes and tonofilaments. Additionally, intracellular and intercellular deposits of an unidentified amorphous material were noted.¹³

Overall, the origin of skin fragility induced by isotretinoin is supported by its effect on sebocytes, increased transepidermal water loss, and profound disruption of the integrity of the epidermis, resulting in an elevated risk for inadvertent skin damage. Patients were encouraged to avoid cosmetic procedures in prior case reports,^14-16 and because our case demonstrates the risk for cutaneous injury in athletes due to isotretinoin-induced skin fragility, we propose an extension of these warnings to encompass athletes receiving isotretinoin treatment. Offering early guidance on wound prevention is of paramount importance in maintaining athletic performance and minimizing painful injuries.

Isotretinoin was introduced more than 3 decades ago and marked a major advancement in the treatment of severe refractory cystic acne. The most common adverse effects linked to isotretinoin usage are mucocutaneous in nature, manifesting as xerosis and cheilitis.¹ Skin fragility and poor wound healing also have been reported.^2-6 Current recommendations for avoiding these adverse effects include refraining from waxing, laser procedures, and other elective cutaneous procedures for at least 6 months.⁷ We present a case of isotretinoin-induced cutaneous fragility resulting in blistering and erosions on the palms of a competitive aerial trapeze artist.

Case Report

A 25-year-old woman presented for follow-up during week 12 of isotretinoin therapy (40 mg twice daily) prescribed for acne. She reported peeling of the skin on the palms following intense aerial acrobatic workouts. She had been a performing aerialist for many years and had never sustained a similar injury. The wounds were painful and led to decreased activity. She had no notable medical history. Physical examination of the palms revealed erosions in a distribution that corresponded to horizontal bar contact and friction (Figure). The patient was advised on proper wound care, application of emollients, and minimizing friction. She completed the course of isotretinoin and has continued aerialist activity without recurrence of skin fragility.

Comment

Skin fragility is a well-known adverse effect of isotretinoin therapy.⁸ Pavlis and Lieblich⁹ reported skin fragility in a young wrestler who experienced similar skin erosions due to isotretinoin therapy. The proposed mechanism of isotretinoin-induced skin fragility is multifactorial. It involves an apoptotic effect on sebocytes,⁵ which results in reduced stratum corneum hydration and an associated increase in transepidermal water loss.^6,10,11 Retinoids also are known to cause thinning of the skin, likely due to the disadhesion of both the epidermis and the stratum corneum, which was demonstrated by the easy removal of cornified cells through tape stripping in hairless mice treated with isotretinoin.¹² In further investigations, human patients and hairless mice treated with isotretinoin readily developed friction blisters through pencil eraser abrasion.¹³ Examination of the friction blisters using light and electron microscopy revealed fraying or loss of the stratum corneum and viable epidermis as well as loss of desmosomes and tonofilaments. Additionally, intracellular and intercellular deposits of an unidentified amorphous material were noted.¹³

Overall, the origin of skin fragility induced by isotretinoin is supported by its effect on sebocytes, increased transepidermal water loss, and profound disruption of the integrity of the epidermis, resulting in an elevated risk for inadvertent skin damage. Patients were encouraged to avoid cosmetic procedures in prior case reports,^14-16 and because our case demonstrates the risk for cutaneous injury in athletes due to isotretinoin-induced skin fragility, we propose an extension of these warnings to encompass athletes receiving isotretinoin treatment. Offering early guidance on wound prevention is of paramount importance in maintaining athletic performance and minimizing painful injuries.

Isotretinoin was introduced more than 3 decades ago and marked a major advancement in the treatment of severe refractory cystic acne. The most common adverse effects linked to isotretinoin usage are mucocutaneous in nature, manifesting as xerosis and cheilitis.¹ Skin fragility and poor wound healing also have been reported.^2-6 Current recommendations for avoiding these adverse effects include refraining from waxing, laser procedures, and other elective cutaneous procedures for at least 6 months.⁷ We present a case of isotretinoin-induced cutaneous fragility resulting in blistering and erosions on the palms of a competitive aerial trapeze artist.

Case Report

A 25-year-old woman presented for follow-up during week 12 of isotretinoin therapy (40 mg twice daily) prescribed for acne. She reported peeling of the skin on the palms following intense aerial acrobatic workouts. She had been a performing aerialist for many years and had never sustained a similar injury. The wounds were painful and led to decreased activity. She had no notable medical history. Physical examination of the palms revealed erosions in a distribution that corresponded to horizontal bar contact and friction (Figure). The patient was advised on proper wound care, application of emollients, and minimizing friction. She completed the course of isotretinoin and has continued aerialist activity without recurrence of skin fragility.

Comment

Skin fragility is a well-known adverse effect of isotretinoin therapy.⁸ Pavlis and Lieblich⁹ reported skin fragility in a young wrestler who experienced similar skin erosions due to isotretinoin therapy. The proposed mechanism of isotretinoin-induced skin fragility is multifactorial. It involves an apoptotic effect on sebocytes,⁵ which results in reduced stratum corneum hydration and an associated increase in transepidermal water loss.^6,10,11 Retinoids also are known to cause thinning of the skin, likely due to the disadhesion of both the epidermis and the stratum corneum, which was demonstrated by the easy removal of cornified cells through tape stripping in hairless mice treated with isotretinoin.¹² In further investigations, human patients and hairless mice treated with isotretinoin readily developed friction blisters through pencil eraser abrasion.¹³ Examination of the friction blisters using light and electron microscopy revealed fraying or loss of the stratum corneum and viable epidermis as well as loss of desmosomes and tonofilaments. Additionally, intracellular and intercellular deposits of an unidentified amorphous material were noted.¹³

Overall, the origin of skin fragility induced by isotretinoin is supported by its effect on sebocytes, increased transepidermal water loss, and profound disruption of the integrity of the epidermis, resulting in an elevated risk for inadvertent skin damage. Patients were encouraged to avoid cosmetic procedures in prior case reports,^14-16 and because our case demonstrates the risk for cutaneous injury in athletes due to isotretinoin-induced skin fragility, we propose an extension of these warnings to encompass athletes receiving isotretinoin treatment. Offering early guidance on wound prevention is of paramount importance in maintaining athletic performance and minimizing painful injuries.

TOPLINE:

Isotretinoin was effective in treating acne in individuals undergoing masculinizing gender-affirming hormone therapy in a case series, but more information is needed on dosing and barriers to treatment.

METHODOLOGY:

• Acne can be a side effect of masculinizing hormone therapy for transmasculine individuals. While isotretinoin is an effective treatment option for acne, its effectiveness and safety in transgender and gender-diverse individuals are not well understood.
• This retrospective case series included 55 patients (mean age, 25.4 years) undergoing masculinizing hormone therapy at four medical centers, who were prescribed isotretinoin for acne associated with treatment.
• Isotretinoin treatment was started a median of 22.1 months after hormone therapy was initiated and continued for a median of 6 months with a median cumulative dose of 132.7 mg/kg.
• Researchers assessed acne improvement, clearance, recurrence, adverse effects, and reasons for treatment discontinuation.

TAKEAWAY:

• Overall, 48 patients (87.3%) experienced improvement, and 26 (47.3%) achieved clearance during treatment. A higher proportion of patients experienced improvement (97% vs 72.7%) and achieved clearance (63.6% vs 22.7%) with cumulative doses of ≥ 120 mg/kg than those who received cumulative doses < 120 mg/kg.
• The risk for recurrence was 20% (in four patients) among 20 patients who achieved clearance and had any subsequent health care encounters, with a mean follow-up time of 734.3 days.
• Common adverse effects included dryness (80%), joint pain (14.5%), and headaches (10.9%). Other adverse effects included nose bleeds (9.1%) and depression (5.5%).
• Of the 22 patients with a cumulative dose < 120 mg/kg, 14 (63.6%) were lost to follow-up; among those not lost to follow-up, 2 patients discontinued treatment because of transfer of care, 1 because of adverse effects, and 1 because of gender-affirming surgery, with concerns about wound healing.

IN PRACTICE:

“Although isotretinoin appears to be an effective treatment option for acne among individuals undergoing masculinizing hormone therapy, further efforts are needed to understand optimal dosing and treatment barriers to improve outcomes in transgender and gender-diverse individuals receiving testosterone,” the authors concluded.

SOURCE:

The study, led by James Choe, BS, Department of Dermatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, was published online in JAMA Dermatology.

LIMITATIONS:

The study population was limited to four centers, and variability in clinician- and patient-reported acne outcomes and missing information could affect the reliability of data. Because of the small sample size, the association of masculinizing hormone therapy regimens with outcomes could not be evaluated.

DISCLOSURES:

One author is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Three authors reported receiving grants or personal fees from various sources. The other authors declared no conflicts of interest.

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

TOPLINE:

Isotretinoin was effective in treating acne in individuals undergoing masculinizing gender-affirming hormone therapy in a case series, but more information is needed on dosing and barriers to treatment.

METHODOLOGY:

• Acne can be a side effect of masculinizing hormone therapy for transmasculine individuals. While isotretinoin is an effective treatment option for acne, its effectiveness and safety in transgender and gender-diverse individuals are not well understood.
• This retrospective case series included 55 patients (mean age, 25.4 years) undergoing masculinizing hormone therapy at four medical centers, who were prescribed isotretinoin for acne associated with treatment.
• Isotretinoin treatment was started a median of 22.1 months after hormone therapy was initiated and continued for a median of 6 months with a median cumulative dose of 132.7 mg/kg.
• Researchers assessed acne improvement, clearance, recurrence, adverse effects, and reasons for treatment discontinuation.

TAKEAWAY:

• Overall, 48 patients (87.3%) experienced improvement, and 26 (47.3%) achieved clearance during treatment. A higher proportion of patients experienced improvement (97% vs 72.7%) and achieved clearance (63.6% vs 22.7%) with cumulative doses of ≥ 120 mg/kg than those who received cumulative doses < 120 mg/kg.
• The risk for recurrence was 20% (in four patients) among 20 patients who achieved clearance and had any subsequent health care encounters, with a mean follow-up time of 734.3 days.
• Common adverse effects included dryness (80%), joint pain (14.5%), and headaches (10.9%). Other adverse effects included nose bleeds (9.1%) and depression (5.5%).
• Of the 22 patients with a cumulative dose < 120 mg/kg, 14 (63.6%) were lost to follow-up; among those not lost to follow-up, 2 patients discontinued treatment because of transfer of care, 1 because of adverse effects, and 1 because of gender-affirming surgery, with concerns about wound healing.

IN PRACTICE:

“Although isotretinoin appears to be an effective treatment option for acne among individuals undergoing masculinizing hormone therapy, further efforts are needed to understand optimal dosing and treatment barriers to improve outcomes in transgender and gender-diverse individuals receiving testosterone,” the authors concluded.

SOURCE:

The study, led by James Choe, BS, Department of Dermatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, was published online in JAMA Dermatology.

LIMITATIONS:

The study population was limited to four centers, and variability in clinician- and patient-reported acne outcomes and missing information could affect the reliability of data. Because of the small sample size, the association of masculinizing hormone therapy regimens with outcomes could not be evaluated.

DISCLOSURES:

One author is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Three authors reported receiving grants or personal fees from various sources. The other authors declared no conflicts of interest.

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

TOPLINE:

Isotretinoin was effective in treating acne in individuals undergoing masculinizing gender-affirming hormone therapy in a case series, but more information is needed on dosing and barriers to treatment.

METHODOLOGY:

• Acne can be a side effect of masculinizing hormone therapy for transmasculine individuals. While isotretinoin is an effective treatment option for acne, its effectiveness and safety in transgender and gender-diverse individuals are not well understood.
• This retrospective case series included 55 patients (mean age, 25.4 years) undergoing masculinizing hormone therapy at four medical centers, who were prescribed isotretinoin for acne associated with treatment.
• Isotretinoin treatment was started a median of 22.1 months after hormone therapy was initiated and continued for a median of 6 months with a median cumulative dose of 132.7 mg/kg.
• Researchers assessed acne improvement, clearance, recurrence, adverse effects, and reasons for treatment discontinuation.

TAKEAWAY:

• Overall, 48 patients (87.3%) experienced improvement, and 26 (47.3%) achieved clearance during treatment. A higher proportion of patients experienced improvement (97% vs 72.7%) and achieved clearance (63.6% vs 22.7%) with cumulative doses of ≥ 120 mg/kg than those who received cumulative doses < 120 mg/kg.
• The risk for recurrence was 20% (in four patients) among 20 patients who achieved clearance and had any subsequent health care encounters, with a mean follow-up time of 734.3 days.
• Common adverse effects included dryness (80%), joint pain (14.5%), and headaches (10.9%). Other adverse effects included nose bleeds (9.1%) and depression (5.5%).
• Of the 22 patients with a cumulative dose < 120 mg/kg, 14 (63.6%) were lost to follow-up; among those not lost to follow-up, 2 patients discontinued treatment because of transfer of care, 1 because of adverse effects, and 1 because of gender-affirming surgery, with concerns about wound healing.

IN PRACTICE:

“Although isotretinoin appears to be an effective treatment option for acne among individuals undergoing masculinizing hormone therapy, further efforts are needed to understand optimal dosing and treatment barriers to improve outcomes in transgender and gender-diverse individuals receiving testosterone,” the authors concluded.

SOURCE:

The study, led by James Choe, BS, Department of Dermatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, was published online in JAMA Dermatology.

LIMITATIONS:

The study population was limited to four centers, and variability in clinician- and patient-reported acne outcomes and missing information could affect the reliability of data. Because of the small sample size, the association of masculinizing hormone therapy regimens with outcomes could not be evaluated.

DISCLOSURES:

One author is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Three authors reported receiving grants or personal fees from various sources. The other authors declared no conflicts of interest.

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

Dermatologists are well aware of guidelines limiting long-term antibiotic use for acne to 3-4 months, but a perceived lack of supporting data, along with in-office realities unaddressed by guidelines, hinder clinicians’ ability and willingness to follow them, according to the authors of a recently published study.

“This study explored why dermatologists still prescribe a good number of long-term antibiotics for people with acne,” the study’s senior author Howa Yeung, MD, MSc, assistant professor of dermatology at Emory University, Atlanta, said in an interview. “And we found a lot of reasons.” The study was published online in JAMA Dermatology.

Dr. Yeung

Using online surveys and semi-structured video interviews of 30 dermatologists, infectious disease physicians with expertise in antimicrobial stewardship, dermatology residents, and nonphysician clinicians, the investigators assessed respondents’ knowledge and attitudes regarding long-term antibiotics in acne. Salient themes impacting long-term antibiotic prescriptions included the following:

• A perceived dearth of evidence to justify changes in practice.
• Difficulties with iPLEDGE, the Risk Evaluation and Mitigation Strategy (REMS) for managing the teratogenic risks associated with isotretinoin, and with discussing oral contraceptives.
• “Navigating” discussions with about tapering-off of antibiotics.
• Challenging patient demands.
• A lack of effective tools for monitoring progress in antibiotic stewardship.

“It’s surprising there are so many barriers that make it difficult for dermatologists to stick with the guidelines even if they want to,” said Dr. Yeung, a coauthor of the recently released updated American Academy of Dermatology (AAD) acne management guidelines.

A dermatologist who wants to stop systemic antibiotics within 3 months may not know how to do so, he explained, or high demand for appointments may prevent timely follow-ups.

A major reason why dermatologists struggle to limit long-term antibiotic use is that there are very few substitutes that are perceived to work as well, said David J. Margolis, MD, PhD, who was not involved with the study and was asked to comment on the results. He is professor of epidemiology and dermatology at the University of Pennsylvania, Philadelphia.

Dr. Margolis

“Part of the reason antibiotics are being used to treat acne is that they’re effective, and effective for severe disease,” he said. The alternatives, which are mostly topicals, said Dr. Margolis, do not work as well for moderate to severe disease or, with isotretinoin, involve time-consuming hurdles. Dr. Margolis said that he often hears such concerns from individual dermatologists. “But it’s helpful to see these in a well-organized, well-reported qualitative study.”

Infectious disease specialists surveyed considered limiting long-term antibiotic use as extremely important, while several dermatologists “argued that other specialties ‘underestimate the impact acne has on people’s lives,’ ” the authors wrote. Other respondents prioritized making the right choice for the patient at hand.

Although guidelines were never meant to be black and white, Dr. Yeung said, it is crucial to target the goal of tapering off after about 3-4 months — a cutoff with which guidelines from groups including the AAD, the Japanese Dermatological Association in guidelines from 2016, and 2017, respectively, and others concur.

He added, “Some folks believe that if the oral antibiotic is working, why stop? We need to develop evidence to show that reducing oral antibiotic use is important to our patients, not just to a theoretical problem of antibiotic resistance in society.” For example, in a study published in The Lancet in 2004, patients who used strictly topical regimens achieved efficacy similar to that of those who used only oral antibiotics.

In addition, some clinicians worried that limiting antibiotics could reduce patient satisfaction, spurring switches to other providers. However, he and the other authors of the JAMA Dermatology study noted that in a survey of patients with acne published in the Journal of Clinical and Aesthetic Dermatology in 2019, 76.9% said they would be “very or extremely likely” to use effective antibiotic-free treatments if offered.

Because most respondents were highly aware of the importance of antibiotic stewardship, Dr. Yeung said, additional passive education is not necessarily the answer. “It will take a concerted effort by our national societies to come up with resources and solutions for individual dermatologists to overcome some of these larger barriers.” Such solutions could range from training in communication and shared decision-making to implementing systems that provide individualized feedback to support antibiotic stewardship.

Many ongoing studies are examining antibiotic stewardship, Dr. Margolis said in the interview. However, he added, dermatologists’ idea of long-term use is 3 months, versus 1 month or less in other specialties. “Moreover, dermatology patients tend to be much healthier individuals and are rarely hospitalized, so there may be some issues comparing the ongoing studies to individuals with acne.” Future research will need to account for such differences, he said.

The study was funded by an American Acne & Rosacea Society Clinical Research Award. Dr. Yeung is associate editor of JAMA Dermatology. Dr. Margolis has received a National Institutes of Health grant to study doxycycline versus spironolactone in acne.

Dermatologists are well aware of guidelines limiting long-term antibiotic use for acne to 3-4 months, but a perceived lack of supporting data, along with in-office realities unaddressed by guidelines, hinder clinicians’ ability and willingness to follow them, according to the authors of a recently published study.

“This study explored why dermatologists still prescribe a good number of long-term antibiotics for people with acne,” the study’s senior author Howa Yeung, MD, MSc, assistant professor of dermatology at Emory University, Atlanta, said in an interview. “And we found a lot of reasons.” The study was published online in JAMA Dermatology.

Dr. Yeung

Using online surveys and semi-structured video interviews of 30 dermatologists, infectious disease physicians with expertise in antimicrobial stewardship, dermatology residents, and nonphysician clinicians, the investigators assessed respondents’ knowledge and attitudes regarding long-term antibiotics in acne. Salient themes impacting long-term antibiotic prescriptions included the following:

• A perceived dearth of evidence to justify changes in practice.
• Difficulties with iPLEDGE, the Risk Evaluation and Mitigation Strategy (REMS) for managing the teratogenic risks associated with isotretinoin, and with discussing oral contraceptives.
• “Navigating” discussions with about tapering-off of antibiotics.
• Challenging patient demands.
• A lack of effective tools for monitoring progress in antibiotic stewardship.

“It’s surprising there are so many barriers that make it difficult for dermatologists to stick with the guidelines even if they want to,” said Dr. Yeung, a coauthor of the recently released updated American Academy of Dermatology (AAD) acne management guidelines.

A dermatologist who wants to stop systemic antibiotics within 3 months may not know how to do so, he explained, or high demand for appointments may prevent timely follow-ups.

A major reason why dermatologists struggle to limit long-term antibiotic use is that there are very few substitutes that are perceived to work as well, said David J. Margolis, MD, PhD, who was not involved with the study and was asked to comment on the results. He is professor of epidemiology and dermatology at the University of Pennsylvania, Philadelphia.

Dr. Margolis

“Part of the reason antibiotics are being used to treat acne is that they’re effective, and effective for severe disease,” he said. The alternatives, which are mostly topicals, said Dr. Margolis, do not work as well for moderate to severe disease or, with isotretinoin, involve time-consuming hurdles. Dr. Margolis said that he often hears such concerns from individual dermatologists. “But it’s helpful to see these in a well-organized, well-reported qualitative study.”

Infectious disease specialists surveyed considered limiting long-term antibiotic use as extremely important, while several dermatologists “argued that other specialties ‘underestimate the impact acne has on people’s lives,’ ” the authors wrote. Other respondents prioritized making the right choice for the patient at hand.

Although guidelines were never meant to be black and white, Dr. Yeung said, it is crucial to target the goal of tapering off after about 3-4 months — a cutoff with which guidelines from groups including the AAD, the Japanese Dermatological Association in guidelines from 2016, and 2017, respectively, and others concur.

He added, “Some folks believe that if the oral antibiotic is working, why stop? We need to develop evidence to show that reducing oral antibiotic use is important to our patients, not just to a theoretical problem of antibiotic resistance in society.” For example, in a study published in The Lancet in 2004, patients who used strictly topical regimens achieved efficacy similar to that of those who used only oral antibiotics.

In addition, some clinicians worried that limiting antibiotics could reduce patient satisfaction, spurring switches to other providers. However, he and the other authors of the JAMA Dermatology study noted that in a survey of patients with acne published in the Journal of Clinical and Aesthetic Dermatology in 2019, 76.9% said they would be “very or extremely likely” to use effective antibiotic-free treatments if offered.

Because most respondents were highly aware of the importance of antibiotic stewardship, Dr. Yeung said, additional passive education is not necessarily the answer. “It will take a concerted effort by our national societies to come up with resources and solutions for individual dermatologists to overcome some of these larger barriers.” Such solutions could range from training in communication and shared decision-making to implementing systems that provide individualized feedback to support antibiotic stewardship.

Many ongoing studies are examining antibiotic stewardship, Dr. Margolis said in the interview. However, he added, dermatologists’ idea of long-term use is 3 months, versus 1 month or less in other specialties. “Moreover, dermatology patients tend to be much healthier individuals and are rarely hospitalized, so there may be some issues comparing the ongoing studies to individuals with acne.” Future research will need to account for such differences, he said.

The study was funded by an American Acne & Rosacea Society Clinical Research Award. Dr. Yeung is associate editor of JAMA Dermatology. Dr. Margolis has received a National Institutes of Health grant to study doxycycline versus spironolactone in acne.

Dermatologists are well aware of guidelines limiting long-term antibiotic use for acne to 3-4 months, but a perceived lack of supporting data, along with in-office realities unaddressed by guidelines, hinder clinicians’ ability and willingness to follow them, according to the authors of a recently published study.

“This study explored why dermatologists still prescribe a good number of long-term antibiotics for people with acne,” the study’s senior author Howa Yeung, MD, MSc, assistant professor of dermatology at Emory University, Atlanta, said in an interview. “And we found a lot of reasons.” The study was published online in JAMA Dermatology.

Dr. Yeung

Using online surveys and semi-structured video interviews of 30 dermatologists, infectious disease physicians with expertise in antimicrobial stewardship, dermatology residents, and nonphysician clinicians, the investigators assessed respondents’ knowledge and attitudes regarding long-term antibiotics in acne. Salient themes impacting long-term antibiotic prescriptions included the following:

• A perceived dearth of evidence to justify changes in practice.
• Difficulties with iPLEDGE, the Risk Evaluation and Mitigation Strategy (REMS) for managing the teratogenic risks associated with isotretinoin, and with discussing oral contraceptives.
• “Navigating” discussions with about tapering-off of antibiotics.
• Challenging patient demands.
• A lack of effective tools for monitoring progress in antibiotic stewardship.

“It’s surprising there are so many barriers that make it difficult for dermatologists to stick with the guidelines even if they want to,” said Dr. Yeung, a coauthor of the recently released updated American Academy of Dermatology (AAD) acne management guidelines.

A dermatologist who wants to stop systemic antibiotics within 3 months may not know how to do so, he explained, or high demand for appointments may prevent timely follow-ups.

A major reason why dermatologists struggle to limit long-term antibiotic use is that there are very few substitutes that are perceived to work as well, said David J. Margolis, MD, PhD, who was not involved with the study and was asked to comment on the results. He is professor of epidemiology and dermatology at the University of Pennsylvania, Philadelphia.

Dr. Margolis

“Part of the reason antibiotics are being used to treat acne is that they’re effective, and effective for severe disease,” he said. The alternatives, which are mostly topicals, said Dr. Margolis, do not work as well for moderate to severe disease or, with isotretinoin, involve time-consuming hurdles. Dr. Margolis said that he often hears such concerns from individual dermatologists. “But it’s helpful to see these in a well-organized, well-reported qualitative study.”

Infectious disease specialists surveyed considered limiting long-term antibiotic use as extremely important, while several dermatologists “argued that other specialties ‘underestimate the impact acne has on people’s lives,’ ” the authors wrote. Other respondents prioritized making the right choice for the patient at hand.

Although guidelines were never meant to be black and white, Dr. Yeung said, it is crucial to target the goal of tapering off after about 3-4 months — a cutoff with which guidelines from groups including the AAD, the Japanese Dermatological Association in guidelines from 2016, and 2017, respectively, and others concur.

He added, “Some folks believe that if the oral antibiotic is working, why stop? We need to develop evidence to show that reducing oral antibiotic use is important to our patients, not just to a theoretical problem of antibiotic resistance in society.” For example, in a study published in The Lancet in 2004, patients who used strictly topical regimens achieved efficacy similar to that of those who used only oral antibiotics.

In addition, some clinicians worried that limiting antibiotics could reduce patient satisfaction, spurring switches to other providers. However, he and the other authors of the JAMA Dermatology study noted that in a survey of patients with acne published in the Journal of Clinical and Aesthetic Dermatology in 2019, 76.9% said they would be “very or extremely likely” to use effective antibiotic-free treatments if offered.

Because most respondents were highly aware of the importance of antibiotic stewardship, Dr. Yeung said, additional passive education is not necessarily the answer. “It will take a concerted effort by our national societies to come up with resources and solutions for individual dermatologists to overcome some of these larger barriers.” Such solutions could range from training in communication and shared decision-making to implementing systems that provide individualized feedback to support antibiotic stewardship.

Many ongoing studies are examining antibiotic stewardship, Dr. Margolis said in the interview. However, he added, dermatologists’ idea of long-term use is 3 months, versus 1 month or less in other specialties. “Moreover, dermatology patients tend to be much healthier individuals and are rarely hospitalized, so there may be some issues comparing the ongoing studies to individuals with acne.” Future research will need to account for such differences, he said.

The study was funded by an American Acne & Rosacea Society Clinical Research Award. Dr. Yeung is associate editor of JAMA Dermatology. Dr. Margolis has received a National Institutes of Health grant to study doxycycline versus spironolactone in acne.