Acne

The Food and Drug Administration has approved trifarotene cream 0.005% for the treatment of acne vulgaris. The product is manufactured by Galderma under the brand name Aklief.

Olivier Le Moal/Getty Images

The approval was based on data from a pair of phase 3, randomized trials including 2,420 patients aged 9 years and older. The trials evaluated the effectiveness of the cream in a once-daily topical dose for facial and truncal acne at 12 weeks. Patients showed a significant reduction in the number of inflammatory lesions as early as 2 weeks on the face (including forehead cheeks, nose, and chin) and as early as 4 weeks on the trunk (including back, chest, and shoulders), compared with a control cream. The most common treatment-emergent adverse events were pain, dryness, discoloration, or rash at the site of application. Some patients also reported sunburn.

The complete study findings were published in the June issue of the Journal of the American Academy of Dermatology.

The studies, funded by Galderma, “showed that once-daily trifarotene cream appears effective and safe, with manageable local tolerability, for the treatment for facial and truncal acne,” wrote lead author Jerry Tan, MD, of the University of Western Ontario, London, and colleagues. “The studies provide substantial evidence to support use of this new topical retinoid in facial and truncal acne,” the researchers wrote.

Trifarotene is designed to target the retinoic acid receptor gamma, the most common retinoic acid receptor in the skin, and is the first new retinoid to be approved by the FDA in approximately 2 decades, according to a press release from Galderma.

The product is expected to be available in the United States in November 2019 in a 45-g pump.

The Food and Drug Administration has approved trifarotene cream 0.005% for the treatment of acne vulgaris. The product is manufactured by Galderma under the brand name Aklief.

Olivier Le Moal/Getty Images

The approval was based on data from a pair of phase 3, randomized trials including 2,420 patients aged 9 years and older. The trials evaluated the effectiveness of the cream in a once-daily topical dose for facial and truncal acne at 12 weeks. Patients showed a significant reduction in the number of inflammatory lesions as early as 2 weeks on the face (including forehead cheeks, nose, and chin) and as early as 4 weeks on the trunk (including back, chest, and shoulders), compared with a control cream. The most common treatment-emergent adverse events were pain, dryness, discoloration, or rash at the site of application. Some patients also reported sunburn.

The complete study findings were published in the June issue of the Journal of the American Academy of Dermatology.

The studies, funded by Galderma, “showed that once-daily trifarotene cream appears effective and safe, with manageable local tolerability, for the treatment for facial and truncal acne,” wrote lead author Jerry Tan, MD, of the University of Western Ontario, London, and colleagues. “The studies provide substantial evidence to support use of this new topical retinoid in facial and truncal acne,” the researchers wrote.

Trifarotene is designed to target the retinoic acid receptor gamma, the most common retinoic acid receptor in the skin, and is the first new retinoid to be approved by the FDA in approximately 2 decades, according to a press release from Galderma.

The product is expected to be available in the United States in November 2019 in a 45-g pump.

The Food and Drug Administration has approved trifarotene cream 0.005% for the treatment of acne vulgaris. The product is manufactured by Galderma under the brand name Aklief.

Olivier Le Moal/Getty Images

The approval was based on data from a pair of phase 3, randomized trials including 2,420 patients aged 9 years and older. The trials evaluated the effectiveness of the cream in a once-daily topical dose for facial and truncal acne at 12 weeks. Patients showed a significant reduction in the number of inflammatory lesions as early as 2 weeks on the face (including forehead cheeks, nose, and chin) and as early as 4 weeks on the trunk (including back, chest, and shoulders), compared with a control cream. The most common treatment-emergent adverse events were pain, dryness, discoloration, or rash at the site of application. Some patients also reported sunburn.

The complete study findings were published in the June issue of the Journal of the American Academy of Dermatology.

The studies, funded by Galderma, “showed that once-daily trifarotene cream appears effective and safe, with manageable local tolerability, for the treatment for facial and truncal acne,” wrote lead author Jerry Tan, MD, of the University of Western Ontario, London, and colleagues. “The studies provide substantial evidence to support use of this new topical retinoid in facial and truncal acne,” the researchers wrote.

Trifarotene is designed to target the retinoic acid receptor gamma, the most common retinoic acid receptor in the skin, and is the first new retinoid to be approved by the FDA in approximately 2 decades, according to a press release from Galderma.

The product is expected to be available in the United States in November 2019 in a 45-g pump.

James Q. Del Rosso, DO, answers important questions on antibiotic resistance and what it means for the practicing dermatologist.

Questions include:

• What is the potential magnitude of concern regarding antibiotic resistance? Is it clinically relevant to dermatologists in their day-to-day practice?

• What can dermatologists do to slow the development of antibiotic resistance?

• What is the mutant selection window?

• How does the mutant selection window apply to topical antibiotics?

Click here to read the article

James Q. Del Rosso, DO, answers important questions on antibiotic resistance and what it means for the practicing dermatologist.

Questions include:

• What is the potential magnitude of concern regarding antibiotic resistance? Is it clinically relevant to dermatologists in their day-to-day practice?

• What can dermatologists do to slow the development of antibiotic resistance?

• What is the mutant selection window?

• How does the mutant selection window apply to topical antibiotics?

Click here to read the article

James Q. Del Rosso, DO, answers important questions on antibiotic resistance and what it means for the practicing dermatologist.

Questions include:

• What is the potential magnitude of concern regarding antibiotic resistance? Is it clinically relevant to dermatologists in their day-to-day practice?

• What can dermatologists do to slow the development of antibiotic resistance?

• What is the mutant selection window?

• How does the mutant selection window apply to topical antibiotics?

Click here to read the article

NEW YORK – The most recently approved therapy for acne, sarecycline, as well as several agents in late stages of clinical testing, might represent a particular advance for treating black patients or others with darker skin tones due to a reduced risk of irritation, according to a review presented at the Skin of Color Update 2019.

Hulldude30/Getty Images

Acne is an inflammatory skin disease, but patients with darker skin tones are at a high risk of postinflammatory hyperpigmentation (PIH), a complication many consider worse than the acne itself, according to Andrew Alexis, MD, director of the Skin of Color Center and chair of the department of dermatology at Mount Sinai St. Luke’s, New York.

“The importance of PIH is that it alters our endpoint in patients of color. Not only are we treating the pustules, comedones, and other classic features of acne, but we have to treat all the way through to the resolution of the PIH if we want a satisfied patient,” he said.

There are data to back this up. In one of the surveys cited by Dr. Alexis, 42% of nonwhite patients identified resolution of PIH as the most important goal in the treatment of their acne.

As in those with light skin, acute acne lesions in darker skin can resolve relatively rapidly after initiating an effective regimen that includes established therapies such as retinoids or antibiotics. However, PIH, once it develops, might take 6-12 months to resolve, according to Dr. Alexis, who is a professor of dermatology at the Icahn School of Medicine at Mount Sinai, New York.

Ted Bosworth/MDedge News

“You have to keep in mind the subclinical inflammation, which can be a slow burning process beneath the surface of the skin,” he said. He cited a biopsy study that demonstrated inflammation even in nonlesional skin of black patients with acne.

Because of the slow reversal of PIH, it is imperative in skin of color patients to employ therapies with the least risk of exacerbating PIH. While this includes judicious use of currently available agents, Dr. Alexis believes that newer agents might have a larger therapeutic window, reducing the potential for inflammation at effective doses.

This advantage has yet to be confirmed in head-to-head studies, but Dr. Alexis is optimistic. In the case of sarecycline, which became the first antibiotic approved specifically for acne when it was approved by the Food and Drug Administration in 2018, about 20% of those included in the phase 3 registration trial were nonwhite, he said.

The results were “impressive” regardless of skin color in the phase 3 study, according to Dr. Alexis. He conceded that this is not the only antibiotic with anti-inflammatory activity, but he suggested that a high degree of efficacy might be relevant for early acne control and a reduced risk of PIH.

The same can be said for trifarotene, a novel topical retinoid that was associated with highly significant reductions in both inflammatory and noninflammatory lesion counts in a recently published phase 3 trial (J Am Acad Dermatol. 2019 Jun;80[6]:1691-9). According to Dr. Alexis, the impact of this therapy on PIH has not been specifically tested, but he expects those data to be forthcoming.

A new 0.045% lotion formulation of tazarotene might also widen the therapeutic window relative to current tazarotene formulations based on clinical trials he cited. Despite a concentration that is about half that of the currently available tazarotene cream, the efficacy of this product appeared to be at least as good “without the baggage of a greater potential for irritation,” he said.

After “a few years of drought” regarding new options for treatment of acne, these are not the only promising agents in clinical trials, according to Dr. Alexis. If these agents prove to offer greater efficacy with less irritation, their increased clinical value might prove most meaningful to patients with darker skin.

“There is a delicate balance between maximizing efficacy without causing irritation that leads to PIH in patients with skin of color,” he cautioned. He is hopeful that the newer agents will make this balance easier to achieve.

Dr. Alexis has financial relationships with many pharmaceutical companies, including many that market drugs for acne.


 

NEW YORK – The most recently approved therapy for acne, sarecycline, as well as several agents in late stages of clinical testing, might represent a particular advance for treating black patients or others with darker skin tones due to a reduced risk of irritation, according to a review presented at the Skin of Color Update 2019.

Hulldude30/Getty Images

Acne is an inflammatory skin disease, but patients with darker skin tones are at a high risk of postinflammatory hyperpigmentation (PIH), a complication many consider worse than the acne itself, according to Andrew Alexis, MD, director of the Skin of Color Center and chair of the department of dermatology at Mount Sinai St. Luke’s, New York.

“The importance of PIH is that it alters our endpoint in patients of color. Not only are we treating the pustules, comedones, and other classic features of acne, but we have to treat all the way through to the resolution of the PIH if we want a satisfied patient,” he said.

There are data to back this up. In one of the surveys cited by Dr. Alexis, 42% of nonwhite patients identified resolution of PIH as the most important goal in the treatment of their acne.

As in those with light skin, acute acne lesions in darker skin can resolve relatively rapidly after initiating an effective regimen that includes established therapies such as retinoids or antibiotics. However, PIH, once it develops, might take 6-12 months to resolve, according to Dr. Alexis, who is a professor of dermatology at the Icahn School of Medicine at Mount Sinai, New York.

Ted Bosworth/MDedge News

“You have to keep in mind the subclinical inflammation, which can be a slow burning process beneath the surface of the skin,” he said. He cited a biopsy study that demonstrated inflammation even in nonlesional skin of black patients with acne.

Because of the slow reversal of PIH, it is imperative in skin of color patients to employ therapies with the least risk of exacerbating PIH. While this includes judicious use of currently available agents, Dr. Alexis believes that newer agents might have a larger therapeutic window, reducing the potential for inflammation at effective doses.

This advantage has yet to be confirmed in head-to-head studies, but Dr. Alexis is optimistic. In the case of sarecycline, which became the first antibiotic approved specifically for acne when it was approved by the Food and Drug Administration in 2018, about 20% of those included in the phase 3 registration trial were nonwhite, he said.

The results were “impressive” regardless of skin color in the phase 3 study, according to Dr. Alexis. He conceded that this is not the only antibiotic with anti-inflammatory activity, but he suggested that a high degree of efficacy might be relevant for early acne control and a reduced risk of PIH.

The same can be said for trifarotene, a novel topical retinoid that was associated with highly significant reductions in both inflammatory and noninflammatory lesion counts in a recently published phase 3 trial (J Am Acad Dermatol. 2019 Jun;80[6]:1691-9). According to Dr. Alexis, the impact of this therapy on PIH has not been specifically tested, but he expects those data to be forthcoming.

A new 0.045% lotion formulation of tazarotene might also widen the therapeutic window relative to current tazarotene formulations based on clinical trials he cited. Despite a concentration that is about half that of the currently available tazarotene cream, the efficacy of this product appeared to be at least as good “without the baggage of a greater potential for irritation,” he said.

After “a few years of drought” regarding new options for treatment of acne, these are not the only promising agents in clinical trials, according to Dr. Alexis. If these agents prove to offer greater efficacy with less irritation, their increased clinical value might prove most meaningful to patients with darker skin.

“There is a delicate balance between maximizing efficacy without causing irritation that leads to PIH in patients with skin of color,” he cautioned. He is hopeful that the newer agents will make this balance easier to achieve.

Dr. Alexis has financial relationships with many pharmaceutical companies, including many that market drugs for acne.


 

NEW YORK – The most recently approved therapy for acne, sarecycline, as well as several agents in late stages of clinical testing, might represent a particular advance for treating black patients or others with darker skin tones due to a reduced risk of irritation, according to a review presented at the Skin of Color Update 2019.

Hulldude30/Getty Images

Acne is an inflammatory skin disease, but patients with darker skin tones are at a high risk of postinflammatory hyperpigmentation (PIH), a complication many consider worse than the acne itself, according to Andrew Alexis, MD, director of the Skin of Color Center and chair of the department of dermatology at Mount Sinai St. Luke’s, New York.

“The importance of PIH is that it alters our endpoint in patients of color. Not only are we treating the pustules, comedones, and other classic features of acne, but we have to treat all the way through to the resolution of the PIH if we want a satisfied patient,” he said.

There are data to back this up. In one of the surveys cited by Dr. Alexis, 42% of nonwhite patients identified resolution of PIH as the most important goal in the treatment of their acne.

As in those with light skin, acute acne lesions in darker skin can resolve relatively rapidly after initiating an effective regimen that includes established therapies such as retinoids or antibiotics. However, PIH, once it develops, might take 6-12 months to resolve, according to Dr. Alexis, who is a professor of dermatology at the Icahn School of Medicine at Mount Sinai, New York.

Ted Bosworth/MDedge News

“You have to keep in mind the subclinical inflammation, which can be a slow burning process beneath the surface of the skin,” he said. He cited a biopsy study that demonstrated inflammation even in nonlesional skin of black patients with acne.

Because of the slow reversal of PIH, it is imperative in skin of color patients to employ therapies with the least risk of exacerbating PIH. While this includes judicious use of currently available agents, Dr. Alexis believes that newer agents might have a larger therapeutic window, reducing the potential for inflammation at effective doses.

This advantage has yet to be confirmed in head-to-head studies, but Dr. Alexis is optimistic. In the case of sarecycline, which became the first antibiotic approved specifically for acne when it was approved by the Food and Drug Administration in 2018, about 20% of those included in the phase 3 registration trial were nonwhite, he said.

The results were “impressive” regardless of skin color in the phase 3 study, according to Dr. Alexis. He conceded that this is not the only antibiotic with anti-inflammatory activity, but he suggested that a high degree of efficacy might be relevant for early acne control and a reduced risk of PIH.

The same can be said for trifarotene, a novel topical retinoid that was associated with highly significant reductions in both inflammatory and noninflammatory lesion counts in a recently published phase 3 trial (J Am Acad Dermatol. 2019 Jun;80[6]:1691-9). According to Dr. Alexis, the impact of this therapy on PIH has not been specifically tested, but he expects those data to be forthcoming.

A new 0.045% lotion formulation of tazarotene might also widen the therapeutic window relative to current tazarotene formulations based on clinical trials he cited. Despite a concentration that is about half that of the currently available tazarotene cream, the efficacy of this product appeared to be at least as good “without the baggage of a greater potential for irritation,” he said.

After “a few years of drought” regarding new options for treatment of acne, these are not the only promising agents in clinical trials, according to Dr. Alexis. If these agents prove to offer greater efficacy with less irritation, their increased clinical value might prove most meaningful to patients with darker skin.

“There is a delicate balance between maximizing efficacy without causing irritation that leads to PIH in patients with skin of color,” he cautioned. He is hopeful that the newer agents will make this balance easier to achieve.

Dr. Alexis has financial relationships with many pharmaceutical companies, including many that market drugs for acne.


 

To improve patient care and outcomes, leading dermatologists from the Cutis and Dermatology News Editorial Boards answered 5 questions on monitoring acne patients on oral therapy. Here’s what we found.

Do you check potassium levels for patients taking spironolactone for acne?

Half of dermatologists surveyed never check potassium levels for patients taking spironolactone for acne. For those who do check levels, 8% do it at baseline only, 8% at baseline and every 6 months, 23% at baseline and yearly, and 13% at baseline and for dosing changes.

Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)

Although some dermatologists are still checking for potassium levels in patients taking spironolactone for acne, there is a clear trend toward foregoing laboratory monitoring. This change was likely spurred by a retrospective study of healthy young women taking spironolactone for acne that found a hyperkalemia rate of 0.72%, which is practically equivalent to the 0.76% baseline rate of hyperkalemia in this age group. Furthermore, since repeat testing in 6 of 13 patients showed normal values, the original potassium measurements may have been erroneous. Based on this study, routine potassium monitoring is likely unnecessary for healthy young women taking spironolactone for acne (Plovanich et al). In another retrospective study of women aged 18 to 65 years taking spironolactone for acne, women aged 46 to 65 years had a significantly higher rate of hyperkalemia with spironolactone compared with women aged 18 to 45 years (2/12 women [16.7%] vs 1/112 women [<1%]; P=.0245). Based on this study, potassium monitoring may be indicated for women older than 45 years taking spironolactone for acne (Thiede et al). 

Next page: Cholesterol levels

Do you monitor cholesterol levels in patients taking isotretinoin?

Almost two-thirds of dermatologists indicated that they monitor all cholesterol levels in patients taking isotretinoin, including low-density lipoprotein, high-density lipoprotein, very low-density lipoprotein, and triglycerides, but almost one-third monitor triglycerides only. Five percent do not monitor cholesterol levels.

Do you routinely monitor cholesterol levels in patients taking isotretinoin?

More than 80% of dermatologists surveyed routinely monitor cholesterol levels in patients taking isotretinoin, with almost half (45%) at baseline and every 2 to 3 months. Eight percent check levels at baseline only, 28% at baseline and monthly, and 3% at baseline and end of therapy. Eighteen percent indicated they do not routinely monitor cholesterol levels. 

Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)

In this survey, dermatologists most often check cholesterol levels at baseline and then every 2 to 3 months, with most monitoring all cholesterol types. Elevations in cholesterol are by far the most common laboratory abnormality seen with isotretinoin therapy. In a retrospective study of 515 patients undergoing isotretinoin treatment of acne, mild to moderate triglyceride elevations were seen in 23.5% of patients (Hansen et al). At least in part, these elevations are likely due to the fact the levels were not drawn during fasting. Keep in mind that triglyceride-induced pancreatitis due to isotretinoin is remarkably rare, so monthly screening for triglycerides is likely not warranted. It is reasonable to monitor triglyceride levels during isotretinoin dose adjustments and for patients whose values are trending upward. 

Next page: Monitoring CBC

Do you routinely monitor complete blood cell count (CBC) in patients taking isotretinoin?

More than half (55%) of dermatologists surveyed routinely monitor complete blood cell (CBC) counts in patients taking isotretinoin, while 45% do not. Of those who do monitor CBC, 13% do so at baseline only, 26% at baseline and monthly, 13% at baseline only and every 2 to 3 months, and only 3% at baseline and end of therapy.

Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)

Slightly more than half of dermatologists in this survey are obtaining CBC for their patients taking isotretinoin for acne and many of those are performing the test at baseline and monthly. Multiple studies as well as American Academy of Dermatology guidelines have substantiated that routine CBC monitoring is unwarranted in healthy patients, as abnormal values usually resolve or remain stable with therapy (American Academy of Dermatology, Isotretinoin: Recommendations). Therefore, it is worthwhile to consider foregoing CBC testing or obtaining just a baseline CBC in healthy patients being treated with isotretinoin.

Next page: Pregnancy testing

Which pregnancy test do you perform on female patients taking isotretinoin?

More than 40% of dermatologists surveyed use the urine β-human chorionic gonadotropin (hCG) pregnancy test for female patients taking isotretinoin, while 30% use the serum B-hCG test; 28% indicated that they use both tests.

Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)

The iPLEDGE program was implemented in 2006 to avoid fetal exposure to isotretinoin and requires pregnancy testing (urine or serum) for females of childbearing potential taking isotretinoin. In a study of pregnancy-related adverse events associated with isotretinoin reported to the US Food and Drug Administration, 6740 total pregnancies were reported from 1997 to 2017. The rate peaked with 768 pregnancies in 2006 and then decreased. Because several hundred pregnancies in women taking isotretinoin have been reported yearly in the last 10 years, there is a clear need to have better systems in place and patient education to prevent fetal exposure to isotretinoin. 

Next page: More tips from derms

More Tips From Dermatologists

The dermatologists we polled had the following advice for their peers:

I see lab monitoring as an opportunity to engage patients and families in co-directing their care (ie, practice patient- and family-centered care). Some families and patients like frequent monitoring and some want as few blood draws as possible. I do my best to make sure the decision includes components of the patients’ preferences, medical evidence and my best clinical judgement.—Craig Burkhart, MD, MS, MPH (Chapel Hill, North Caroline)

Being familiar with and following the standard of care guidelines for the individual oral therapies used in the treatment of acne is very important. However, it is equally as important to assure the individual patient (medical history, physical examination, social history, etc) is taken into consideration to determine if additional monitoring is required.—Fran E. Cook-Bolden, MD (New York, New York)

The trend seems to be towards less routine monitoring other than pregnancy. Baseline tests may pick out the occasional patient with comorbidities that would preclude or delay treatment, but the majority of patients may not need the repetitive and costly testing that we have done in the past.—Richard Glogau, MD (San Francisco, California)
I have loosened my lab monitoring with isotretinoin over the past few years. If a patient has normal lipid values, comprehensive panel and complete blood cell count for the first 3 months of tests, I skip labs until the end of therapy.—Lawrence J. Green, MD (Washington, DC)

Interestingly, we focus quite a bit of attention on the risk of pregnancy with isotretinoin, and often don't focus enough on the risk with spironolactone. In our practice, we are careful to warn the patients on spironolactone about pregnancy prevention.—Stephen Stone, MD (Springfield, Illinois)

About This Survey

The survey was fielded electronically to Cutis and Dermatology News Editorial Board Members within the United States from May 5, 2019, to June 23, 2019. A total of 40 usable responses were received.

To improve patient care and outcomes, leading dermatologists from the Cutis and Dermatology News Editorial Boards answered 5 questions on monitoring acne patients on oral therapy. Here’s what we found.

Do you check potassium levels for patients taking spironolactone for acne?

Half of dermatologists surveyed never check potassium levels for patients taking spironolactone for acne. For those who do check levels, 8% do it at baseline only, 8% at baseline and every 6 months, 23% at baseline and yearly, and 13% at baseline and for dosing changes.

Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)

Although some dermatologists are still checking for potassium levels in patients taking spironolactone for acne, there is a clear trend toward foregoing laboratory monitoring. This change was likely spurred by a retrospective study of healthy young women taking spironolactone for acne that found a hyperkalemia rate of 0.72%, which is practically equivalent to the 0.76% baseline rate of hyperkalemia in this age group. Furthermore, since repeat testing in 6 of 13 patients showed normal values, the original potassium measurements may have been erroneous. Based on this study, routine potassium monitoring is likely unnecessary for healthy young women taking spironolactone for acne (Plovanich et al). In another retrospective study of women aged 18 to 65 years taking spironolactone for acne, women aged 46 to 65 years had a significantly higher rate of hyperkalemia with spironolactone compared with women aged 18 to 45 years (2/12 women [16.7%] vs 1/112 women [<1%]; P=.0245). Based on this study, potassium monitoring may be indicated for women older than 45 years taking spironolactone for acne (Thiede et al). 

Next page: Cholesterol levels

Do you monitor cholesterol levels in patients taking isotretinoin?

Almost two-thirds of dermatologists indicated that they monitor all cholesterol levels in patients taking isotretinoin, including low-density lipoprotein, high-density lipoprotein, very low-density lipoprotein, and triglycerides, but almost one-third monitor triglycerides only. Five percent do not monitor cholesterol levels.

Do you routinely monitor cholesterol levels in patients taking isotretinoin?

More than 80% of dermatologists surveyed routinely monitor cholesterol levels in patients taking isotretinoin, with almost half (45%) at baseline and every 2 to 3 months. Eight percent check levels at baseline only, 28% at baseline and monthly, and 3% at baseline and end of therapy. Eighteen percent indicated they do not routinely monitor cholesterol levels. 

Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)

In this survey, dermatologists most often check cholesterol levels at baseline and then every 2 to 3 months, with most monitoring all cholesterol types. Elevations in cholesterol are by far the most common laboratory abnormality seen with isotretinoin therapy. In a retrospective study of 515 patients undergoing isotretinoin treatment of acne, mild to moderate triglyceride elevations were seen in 23.5% of patients (Hansen et al). At least in part, these elevations are likely due to the fact the levels were not drawn during fasting. Keep in mind that triglyceride-induced pancreatitis due to isotretinoin is remarkably rare, so monthly screening for triglycerides is likely not warranted. It is reasonable to monitor triglyceride levels during isotretinoin dose adjustments and for patients whose values are trending upward. 

Next page: Monitoring CBC

Do you routinely monitor complete blood cell count (CBC) in patients taking isotretinoin?

More than half (55%) of dermatologists surveyed routinely monitor complete blood cell (CBC) counts in patients taking isotretinoin, while 45% do not. Of those who do monitor CBC, 13% do so at baseline only, 26% at baseline and monthly, 13% at baseline only and every 2 to 3 months, and only 3% at baseline and end of therapy.

Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)

Slightly more than half of dermatologists in this survey are obtaining CBC for their patients taking isotretinoin for acne and many of those are performing the test at baseline and monthly. Multiple studies as well as American Academy of Dermatology guidelines have substantiated that routine CBC monitoring is unwarranted in healthy patients, as abnormal values usually resolve or remain stable with therapy (American Academy of Dermatology, Isotretinoin: Recommendations). Therefore, it is worthwhile to consider foregoing CBC testing or obtaining just a baseline CBC in healthy patients being treated with isotretinoin.

Next page: Pregnancy testing

Which pregnancy test do you perform on female patients taking isotretinoin?

More than 40% of dermatologists surveyed use the urine β-human chorionic gonadotropin (hCG) pregnancy test for female patients taking isotretinoin, while 30% use the serum B-hCG test; 28% indicated that they use both tests.

Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)

The iPLEDGE program was implemented in 2006 to avoid fetal exposure to isotretinoin and requires pregnancy testing (urine or serum) for females of childbearing potential taking isotretinoin. In a study of pregnancy-related adverse events associated with isotretinoin reported to the US Food and Drug Administration, 6740 total pregnancies were reported from 1997 to 2017. The rate peaked with 768 pregnancies in 2006 and then decreased. Because several hundred pregnancies in women taking isotretinoin have been reported yearly in the last 10 years, there is a clear need to have better systems in place and patient education to prevent fetal exposure to isotretinoin. 

Next page: More tips from derms

More Tips From Dermatologists

The dermatologists we polled had the following advice for their peers:

I see lab monitoring as an opportunity to engage patients and families in co-directing their care (ie, practice patient- and family-centered care). Some families and patients like frequent monitoring and some want as few blood draws as possible. I do my best to make sure the decision includes components of the patients’ preferences, medical evidence and my best clinical judgement.—Craig Burkhart, MD, MS, MPH (Chapel Hill, North Caroline)

Being familiar with and following the standard of care guidelines for the individual oral therapies used in the treatment of acne is very important. However, it is equally as important to assure the individual patient (medical history, physical examination, social history, etc) is taken into consideration to determine if additional monitoring is required.—Fran E. Cook-Bolden, MD (New York, New York)

The trend seems to be towards less routine monitoring other than pregnancy. Baseline tests may pick out the occasional patient with comorbidities that would preclude or delay treatment, but the majority of patients may not need the repetitive and costly testing that we have done in the past.—Richard Glogau, MD (San Francisco, California)
I have loosened my lab monitoring with isotretinoin over the past few years. If a patient has normal lipid values, comprehensive panel and complete blood cell count for the first 3 months of tests, I skip labs until the end of therapy.—Lawrence J. Green, MD (Washington, DC)

Interestingly, we focus quite a bit of attention on the risk of pregnancy with isotretinoin, and often don't focus enough on the risk with spironolactone. In our practice, we are careful to warn the patients on spironolactone about pregnancy prevention.—Stephen Stone, MD (Springfield, Illinois)

About This Survey

The survey was fielded electronically to Cutis and Dermatology News Editorial Board Members within the United States from May 5, 2019, to June 23, 2019. A total of 40 usable responses were received.

To improve patient care and outcomes, leading dermatologists from the Cutis and Dermatology News Editorial Boards answered 5 questions on monitoring acne patients on oral therapy. Here’s what we found.

Do you check potassium levels for patients taking spironolactone for acne?

Half of dermatologists surveyed never check potassium levels for patients taking spironolactone for acne. For those who do check levels, 8% do it at baseline only, 8% at baseline and every 6 months, 23% at baseline and yearly, and 13% at baseline and for dosing changes.

Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)

Although some dermatologists are still checking for potassium levels in patients taking spironolactone for acne, there is a clear trend toward foregoing laboratory monitoring. This change was likely spurred by a retrospective study of healthy young women taking spironolactone for acne that found a hyperkalemia rate of 0.72%, which is practically equivalent to the 0.76% baseline rate of hyperkalemia in this age group. Furthermore, since repeat testing in 6 of 13 patients showed normal values, the original potassium measurements may have been erroneous. Based on this study, routine potassium monitoring is likely unnecessary for healthy young women taking spironolactone for acne (Plovanich et al). In another retrospective study of women aged 18 to 65 years taking spironolactone for acne, women aged 46 to 65 years had a significantly higher rate of hyperkalemia with spironolactone compared with women aged 18 to 45 years (2/12 women [16.7%] vs 1/112 women [<1%]; P=.0245). Based on this study, potassium monitoring may be indicated for women older than 45 years taking spironolactone for acne (Thiede et al). 

Next page: Cholesterol levels

Do you monitor cholesterol levels in patients taking isotretinoin?

Almost two-thirds of dermatologists indicated that they monitor all cholesterol levels in patients taking isotretinoin, including low-density lipoprotein, high-density lipoprotein, very low-density lipoprotein, and triglycerides, but almost one-third monitor triglycerides only. Five percent do not monitor cholesterol levels.

Do you routinely monitor cholesterol levels in patients taking isotretinoin?

More than 80% of dermatologists surveyed routinely monitor cholesterol levels in patients taking isotretinoin, with almost half (45%) at baseline and every 2 to 3 months. Eight percent check levels at baseline only, 28% at baseline and monthly, and 3% at baseline and end of therapy. Eighteen percent indicated they do not routinely monitor cholesterol levels. 

Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)

In this survey, dermatologists most often check cholesterol levels at baseline and then every 2 to 3 months, with most monitoring all cholesterol types. Elevations in cholesterol are by far the most common laboratory abnormality seen with isotretinoin therapy. In a retrospective study of 515 patients undergoing isotretinoin treatment of acne, mild to moderate triglyceride elevations were seen in 23.5% of patients (Hansen et al). At least in part, these elevations are likely due to the fact the levels were not drawn during fasting. Keep in mind that triglyceride-induced pancreatitis due to isotretinoin is remarkably rare, so monthly screening for triglycerides is likely not warranted. It is reasonable to monitor triglyceride levels during isotretinoin dose adjustments and for patients whose values are trending upward. 

Next page: Monitoring CBC

Do you routinely monitor complete blood cell count (CBC) in patients taking isotretinoin?

More than half (55%) of dermatologists surveyed routinely monitor complete blood cell (CBC) counts in patients taking isotretinoin, while 45% do not. Of those who do monitor CBC, 13% do so at baseline only, 26% at baseline and monthly, 13% at baseline only and every 2 to 3 months, and only 3% at baseline and end of therapy.

Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)

Slightly more than half of dermatologists in this survey are obtaining CBC for their patients taking isotretinoin for acne and many of those are performing the test at baseline and monthly. Multiple studies as well as American Academy of Dermatology guidelines have substantiated that routine CBC monitoring is unwarranted in healthy patients, as abnormal values usually resolve or remain stable with therapy (American Academy of Dermatology, Isotretinoin: Recommendations). Therefore, it is worthwhile to consider foregoing CBC testing or obtaining just a baseline CBC in healthy patients being treated with isotretinoin.

Next page: Pregnancy testing

Which pregnancy test do you perform on female patients taking isotretinoin?

More than 40% of dermatologists surveyed use the urine β-human chorionic gonadotropin (hCG) pregnancy test for female patients taking isotretinoin, while 30% use the serum B-hCG test; 28% indicated that they use both tests.

Expert Commentary
Provided by Shari R. Lipner, MD, PhD (New York, New York)

The iPLEDGE program was implemented in 2006 to avoid fetal exposure to isotretinoin and requires pregnancy testing (urine or serum) for females of childbearing potential taking isotretinoin. In a study of pregnancy-related adverse events associated with isotretinoin reported to the US Food and Drug Administration, 6740 total pregnancies were reported from 1997 to 2017. The rate peaked with 768 pregnancies in 2006 and then decreased. Because several hundred pregnancies in women taking isotretinoin have been reported yearly in the last 10 years, there is a clear need to have better systems in place and patient education to prevent fetal exposure to isotretinoin. 

Next page: More tips from derms

More Tips From Dermatologists

The dermatologists we polled had the following advice for their peers:

I see lab monitoring as an opportunity to engage patients and families in co-directing their care (ie, practice patient- and family-centered care). Some families and patients like frequent monitoring and some want as few blood draws as possible. I do my best to make sure the decision includes components of the patients’ preferences, medical evidence and my best clinical judgement.—Craig Burkhart, MD, MS, MPH (Chapel Hill, North Caroline)

Being familiar with and following the standard of care guidelines for the individual oral therapies used in the treatment of acne is very important. However, it is equally as important to assure the individual patient (medical history, physical examination, social history, etc) is taken into consideration to determine if additional monitoring is required.—Fran E. Cook-Bolden, MD (New York, New York)

The trend seems to be towards less routine monitoring other than pregnancy. Baseline tests may pick out the occasional patient with comorbidities that would preclude or delay treatment, but the majority of patients may not need the repetitive and costly testing that we have done in the past.—Richard Glogau, MD (San Francisco, California)
I have loosened my lab monitoring with isotretinoin over the past few years. If a patient has normal lipid values, comprehensive panel and complete blood cell count for the first 3 months of tests, I skip labs until the end of therapy.—Lawrence J. Green, MD (Washington, DC)

Interestingly, we focus quite a bit of attention on the risk of pregnancy with isotretinoin, and often don't focus enough on the risk with spironolactone. In our practice, we are careful to warn the patients on spironolactone about pregnancy prevention.—Stephen Stone, MD (Springfield, Illinois)

About This Survey

The survey was fielded electronically to Cutis and Dermatology News Editorial Board Members within the United States from May 5, 2019, to June 23, 2019. A total of 40 usable responses were received.

MILAN – Chemical peels are effective for many medical indications, but a mild peel can really shine as a treatment for acne, according to Dee Anna Glaser, MD.

Speaking at the World Congress of Dermatology, Dr. Glaser, director of clinical research and interim chair of the department of dermatology at Saint Louis University, said that in her practice, acne and actinic keratosis are the most common medical indications for chemical peels and that “acne is just a winner all the way around.”

For acne, she added: “Chemical peels can help both the comedonal and the inflammatory component. It should probably be combined with other therapies, and it does produce both an exfoliative and an anti-inflammatory benefit,.”

A variety of chemical peel formulations can be considered for acne, Dr. Glaser noted. “Typically, you’re going to use a light chemical peel,” such as glycolic or salicylic acid. Other options include Jessner’s solution or a light trichloroacetic acid formulation, she said, adding that tretinoin alone can also be considered.

In choosing between glycolic and salicylic acid, Dr. Glaser said, “salicylic acid should theoretically be the best agent because it is lipophilic and the glycolic acid is hydrophilic.” The reality of how these agents perform clinically, though, may sort out differently.

Dr. Glaser pointed to a double-blind, randomized controlled trial of the two agents in 20 women with facial acne. The severity of participants’ inflammatory acne was mild to moderate, with an average of 27 inflammatory lesions, and they had been on a stable prescription or over-the-counter acne regimen for at least 2 months (Dermatol Surg. 2008 Jan;34[1]:45-50).

Patients received six peels – one every 2 weeks – with 30% glycolic acid (an alpha-hydroxy acid) and 30% salicylic acid (a beta-hydroxy acid) in the split-face study.

All participants started at 4 minutes of exposure and increased up to 5 minutes as tolerated, although timing is only really important for glycolic acid, the same duration of exposure was maintained for each agent for the sake of consistency between arms, said Dr. Glaser, one of the investigators.

Sharing photographs of study participants, she observed that after six peels, “there really isn’t a significant difference.” Therefore, she added, “even though salicylic acid should be better, you can see that glycolic acid really held its own in this study.”

Dr. Glaser pointed out that a trend was seen for slightly better results with salicylic acid and results with this agent were more durable than those seen with glycolic acid. Patients reported fewer side effects on the beta-hydroxy–treated side as well.

She referred to another study, conducted in Japan, that used a double-blind, split-face design to compare 40% glycolic acid with a placebo that had a similarly low pH of 2.0. The 26 patients with moderate acne received five peels on a biweekly schedule, with glycolic acid significantly outperforming placebo. Among acne subtypes, noninflammatory acne improved more than inflammatory acne with glycolic acid (Dermatol Surg. 2014 Mar;40[3]:314-22).

Dr. Glaser said that in her own practice, she still tries to use salicylic acid for her acne patients,” though some patients prefer the experience of a glycolic acid peel, with which there’s likely to be less pain. “So if you have a preference, or your patient has a preference, you will probably be able to use the acid that works best for you,” she said.


Whatever peel is chosen, it should be considered an adjuvant to other topical and systemic acne therapies, Dr. Glaser stressed. “To maintain the results, you really do need to maintain the patient on some sort of standard acne therapy that you would normally do.”

Peels can also be an effective part of a multipronged approach that includes laser therapy and intralesional steroids, she said. However, peels can be considered for monotherapy in patients who don’t tolerate other acne therapies, and they can be used safely in pregnancy, she said.

As with all such treatments, dermatologists should remember to consider and counsel about herpes simplex virus prophylaxis and sun protection.

Dr. Glaser reported financial relationships with Galderma, Ulthera, Ortho, Allergan, Cellgene, and other pharmaceutical companies.

koakes@mdedge.com

MILAN – Chemical peels are effective for many medical indications, but a mild peel can really shine as a treatment for acne, according to Dee Anna Glaser, MD.

Speaking at the World Congress of Dermatology, Dr. Glaser, director of clinical research and interim chair of the department of dermatology at Saint Louis University, said that in her practice, acne and actinic keratosis are the most common medical indications for chemical peels and that “acne is just a winner all the way around.”

For acne, she added: “Chemical peels can help both the comedonal and the inflammatory component. It should probably be combined with other therapies, and it does produce both an exfoliative and an anti-inflammatory benefit,.”

A variety of chemical peel formulations can be considered for acne, Dr. Glaser noted. “Typically, you’re going to use a light chemical peel,” such as glycolic or salicylic acid. Other options include Jessner’s solution or a light trichloroacetic acid formulation, she said, adding that tretinoin alone can also be considered.

In choosing between glycolic and salicylic acid, Dr. Glaser said, “salicylic acid should theoretically be the best agent because it is lipophilic and the glycolic acid is hydrophilic.” The reality of how these agents perform clinically, though, may sort out differently.

Dr. Glaser pointed to a double-blind, randomized controlled trial of the two agents in 20 women with facial acne. The severity of participants’ inflammatory acne was mild to moderate, with an average of 27 inflammatory lesions, and they had been on a stable prescription or over-the-counter acne regimen for at least 2 months (Dermatol Surg. 2008 Jan;34[1]:45-50).

Patients received six peels – one every 2 weeks – with 30% glycolic acid (an alpha-hydroxy acid) and 30% salicylic acid (a beta-hydroxy acid) in the split-face study.

All participants started at 4 minutes of exposure and increased up to 5 minutes as tolerated, although timing is only really important for glycolic acid, the same duration of exposure was maintained for each agent for the sake of consistency between arms, said Dr. Glaser, one of the investigators.

Sharing photographs of study participants, she observed that after six peels, “there really isn’t a significant difference.” Therefore, she added, “even though salicylic acid should be better, you can see that glycolic acid really held its own in this study.”

Dr. Glaser pointed out that a trend was seen for slightly better results with salicylic acid and results with this agent were more durable than those seen with glycolic acid. Patients reported fewer side effects on the beta-hydroxy–treated side as well.

She referred to another study, conducted in Japan, that used a double-blind, split-face design to compare 40% glycolic acid with a placebo that had a similarly low pH of 2.0. The 26 patients with moderate acne received five peels on a biweekly schedule, with glycolic acid significantly outperforming placebo. Among acne subtypes, noninflammatory acne improved more than inflammatory acne with glycolic acid (Dermatol Surg. 2014 Mar;40[3]:314-22).

Dr. Glaser said that in her own practice, she still tries to use salicylic acid for her acne patients,” though some patients prefer the experience of a glycolic acid peel, with which there’s likely to be less pain. “So if you have a preference, or your patient has a preference, you will probably be able to use the acid that works best for you,” she said.


Whatever peel is chosen, it should be considered an adjuvant to other topical and systemic acne therapies, Dr. Glaser stressed. “To maintain the results, you really do need to maintain the patient on some sort of standard acne therapy that you would normally do.”

Peels can also be an effective part of a multipronged approach that includes laser therapy and intralesional steroids, she said. However, peels can be considered for monotherapy in patients who don’t tolerate other acne therapies, and they can be used safely in pregnancy, she said.

As with all such treatments, dermatologists should remember to consider and counsel about herpes simplex virus prophylaxis and sun protection.

Dr. Glaser reported financial relationships with Galderma, Ulthera, Ortho, Allergan, Cellgene, and other pharmaceutical companies.

koakes@mdedge.com

MILAN – Chemical peels are effective for many medical indications, but a mild peel can really shine as a treatment for acne, according to Dee Anna Glaser, MD.

Speaking at the World Congress of Dermatology, Dr. Glaser, director of clinical research and interim chair of the department of dermatology at Saint Louis University, said that in her practice, acne and actinic keratosis are the most common medical indications for chemical peels and that “acne is just a winner all the way around.”

For acne, she added: “Chemical peels can help both the comedonal and the inflammatory component. It should probably be combined with other therapies, and it does produce both an exfoliative and an anti-inflammatory benefit,.”

A variety of chemical peel formulations can be considered for acne, Dr. Glaser noted. “Typically, you’re going to use a light chemical peel,” such as glycolic or salicylic acid. Other options include Jessner’s solution or a light trichloroacetic acid formulation, she said, adding that tretinoin alone can also be considered.

In choosing between glycolic and salicylic acid, Dr. Glaser said, “salicylic acid should theoretically be the best agent because it is lipophilic and the glycolic acid is hydrophilic.” The reality of how these agents perform clinically, though, may sort out differently.

Dr. Glaser pointed to a double-blind, randomized controlled trial of the two agents in 20 women with facial acne. The severity of participants’ inflammatory acne was mild to moderate, with an average of 27 inflammatory lesions, and they had been on a stable prescription or over-the-counter acne regimen for at least 2 months (Dermatol Surg. 2008 Jan;34[1]:45-50).

Patients received six peels – one every 2 weeks – with 30% glycolic acid (an alpha-hydroxy acid) and 30% salicylic acid (a beta-hydroxy acid) in the split-face study.

All participants started at 4 minutes of exposure and increased up to 5 minutes as tolerated, although timing is only really important for glycolic acid, the same duration of exposure was maintained for each agent for the sake of consistency between arms, said Dr. Glaser, one of the investigators.

Sharing photographs of study participants, she observed that after six peels, “there really isn’t a significant difference.” Therefore, she added, “even though salicylic acid should be better, you can see that glycolic acid really held its own in this study.”

Dr. Glaser pointed out that a trend was seen for slightly better results with salicylic acid and results with this agent were more durable than those seen with glycolic acid. Patients reported fewer side effects on the beta-hydroxy–treated side as well.

She referred to another study, conducted in Japan, that used a double-blind, split-face design to compare 40% glycolic acid with a placebo that had a similarly low pH of 2.0. The 26 patients with moderate acne received five peels on a biweekly schedule, with glycolic acid significantly outperforming placebo. Among acne subtypes, noninflammatory acne improved more than inflammatory acne with glycolic acid (Dermatol Surg. 2014 Mar;40[3]:314-22).

Dr. Glaser said that in her own practice, she still tries to use salicylic acid for her acne patients,” though some patients prefer the experience of a glycolic acid peel, with which there’s likely to be less pain. “So if you have a preference, or your patient has a preference, you will probably be able to use the acid that works best for you,” she said.


Whatever peel is chosen, it should be considered an adjuvant to other topical and systemic acne therapies, Dr. Glaser stressed. “To maintain the results, you really do need to maintain the patient on some sort of standard acne therapy that you would normally do.”

Peels can also be an effective part of a multipronged approach that includes laser therapy and intralesional steroids, she said. However, peels can be considered for monotherapy in patients who don’t tolerate other acne therapies, and they can be used safely in pregnancy, she said.

As with all such treatments, dermatologists should remember to consider and counsel about herpes simplex virus prophylaxis and sun protection.

Dr. Glaser reported financial relationships with Galderma, Ulthera, Ortho, Allergan, Cellgene, and other pharmaceutical companies.

koakes@mdedge.com

The American Academy of Dermatology confers combined oral contraceptives (COCs) a strength A recommendation for the treatment of acne based on level I evidence, and 4 COCs are approved for the treatment of acne by the US Food and Drug Administration (FDA).¹ Furthermore, when dermatologists prescribe isotretinoin and thalidomide to women of reproductive potential, the iPLEDGE and THALOMID Risk Evaluation and Mitigation Strategy (REMS) programs require 2 concurrent methods of contraception, one of which may be a COC. In addition, COCs have several potential off-label indications in dermatology including idiopathic hirsutism, female pattern hair loss, hidradenitis suppurativa, and autoimmune progesterone dermatitis.

Despite this evidence and opportunity, research suggests that dermatologists underprescribe COCs. The National Ambulatory Medical Care Survey found that between 1993 and 2008, dermatologists in the United States prescribed COCs to only 2.03% of women presenting for acne treatment, which was less often than obstetricians/gynecologists (36.03%) and internists (10.76%).² More recently, in a survey of 130 US dermatologists conducted from 2014 to 2015, only 55.4% reported prescribing COCs. This survey also found that only 45.8% of dermatologists who prescribed COCs felt very comfortable counseling on how to begin taking them, only 48.6% felt very comfortable counseling patients on side effects, and only 22.2% felt very comfortable managing side effects.³

In light of these data, this article reviews the basics of COCs for dermatology residents, from assessing patient eligibility and selecting a COC to counseling on use and managing risks and side effects. Because there are different approaches to prescribing COCs, readers are encouraged to integrate the information in this article with what they have learned from other sources.

Assess Patient Eligibility

In general, patients should be at least 14 years of age and have waited 2 years after menarche to start COCs. They can be taken until menopause.^1,4 Contraindications can be screened for by taking a medical history and measuring a baseline blood pressure (Tables 1 and 2).⁵ In addition, pregnancy should be excluded with a urine or serum pregnancy test or criteria provided in Box 2 of the 2016 US Selected Practice Recommendations for Contraceptive Use from the Centers for Disease Control and Prevention (CDC).⁴ Although important for women’s overall health, a pelvic examination is not required to start COCs according to the CDC and the American Academy of Dermatology.^1,4

Select the COC

Combined oral contraceptives combine estrogen, usually in the form of ethinyl estradiol, with a progestin. Data suggest that all COCs effectively treat acne, but 4 are specifically FDA approved for acne: ethinyl estradiol–norethindrone acetate–ferrous fumarate, ethinyl estradiol–norgestimate, ethinyl estradiol–drospirenone, and ethinyl estradiol–drospirenone–levomefolate.¹ Ethinyl estradiol–desogestrel and ethinyl estradiol–drospirenone are 2 go-to COCs for some of the attending physicians at my residency program. All COCs are FDA approved for contraception. When selecting a COC, one approach is to start with the patient’s drug formulary, then consider the following characteristics.

Monophasic vs Multiphasic
All the hormonally active pills in a monophasic formulation contain the same dose of estrogen and progestin; however, these doses change per pill in a multiphasic formulation, which requires that patients take the pills in a specific order. Given this greater complexity and the fact that multiphasic formulations often are more expensive and lack evidence of superiority, a 2011 Cochrane review recommended monophasic formulations as first line.⁶ In addition, monophasic formulations are preferred for autoimmune progesterone dermatitis because of the stable progestin dose.

Hormone-Free Interval
Some COCs include placebo pills during which hormone withdrawal symptoms such as bleeding, pelvic pain, mood changes, and headache may occur. If a patient is concerned about these symptoms, choose a COC with no or fewer placebo pills, or have the patient skip the hormone-free interval altogether and start the next pack early⁷; in this case, the prescription should be written with instructions to allow the patient to get earlier refills from the pharmacy.

Estrogen Dose
To minimize estrogen-related side effects, the lowest possible dose of ethinyl estradiol that is effective and tolerable should be prescribed^7,8; 20 μg of ethinyl estradiol generally is the lowest dose available, but it may be associated with more frequent breakthrough bleeding.⁹ The International Planned Parenthood Federation recommends starting with COCs that contain 30 to 35 μg of estrogen.¹⁰ Synthesizing this information, one option is to start with 20 μg of ethinyl estradiol and increase the dose if breakthrough bleeding persists after 3 cycles.

Progestin Type
First-generation progestins (eg, norethindrone), second-generation progestins (eg, norgestrel, levonorgestrel), and third-generation progestins (eg, norgestimate, desogestrel) are derived from testosterone and therefore are variably androgenic; second-generation progestins are the most androgenic, and third-generation progestins are the least. On the other hand, drospirenone, the fourth-generation progestin available in the United States, is derived from 17α-spironolactone and thus is mildly antiandrogenic (3 mg of drospirenone is considered equivalent to 25 mg of spironolactone).

Although COCs with less androgenic progestins should theoretically treat acne better, a 2012 Cochrane review of COCs and acne concluded that “differences in the comparative effectiveness of COCs containing varying progestin types and dosages were less clear, and data were limited for any particular comparison.”¹¹ As a result, regardless of the progestin, all COCs are believed to have a net antiandrogenic effect due to their estrogen component.¹

Counsel on Use

Combined oral contraceptives can be started on any day of the menstrual cycle, including the day the prescription is given. If a patient begins a COC within 5 days of the first day of her most recent period, backup contraception is not needed.⁴ If she begins the COC more than 5 days after the first day of her most recent period, she needs to use backup contraception or abstain from sexual intercourse for the next 7 days.⁴ In general, at least 3 months of therapy are required to evaluate the effectiveness of COCs for acne.¹

Manage Risks and Side Effects

Breakthrough Bleeding
The most common side effect of breakthrough bleeding can be minimized by taking COCs at approximately the same time every day and avoiding missed pills. If breakthrough bleeding does not stop after 3 cycles, consider increasing the estrogen dose to 30 to 35 μg and/or referring to an obstetrician/gynecologist to rule out other etiologies of bleeding.^7,8

Nausea, Headache, Bloating, and Breast Tenderness
These symptoms typically resolve after the first 3 months. To minimize nausea, patients should take COCs in the early evening and eat breakfast the next morning.^7,8 For headaches that occur during the hormone-free interval, consider skipping the placebo pills and starting the next pack early. Switching the progestin to drospirenone, which has a mild diuretic effect, can help with bloating as well as breast tenderness.⁷ For persistent symptoms, consider a lower estrogen dose.^7,8

Changes in Libido
In a systemic review including 8422 COC users, 64% reported no change in libido, 22% reported an increase, and 15% reported a decrease.¹²

Weight Gain
Although patients may be concerned that COCs cause weight gain, a 2014 Cochrane review concluded that “available evidence is insufficient to determine the effect of combination contraceptives on weight, but no large effect is evident.”¹³ If weight gain does occur, anecdotal evidence suggests it tends to be not more than 5 pounds. If weight gain is an issue, consider a less androgenic progestin.⁸

Venous Thromboembolism
Use the 3-6-9-12 model to contextualize venous thromboembolism (VTE) risk: a woman’s annual VTE risk is 3 per 10,000 women at baseline, 6 per 10,000 women with nondrospirenone COCs, 9 per 10,000 women with drospirenone-containing COCs, and 12 per 10,000 women when pregnant.¹⁴ Patients should be counseled on the signs and symptoms of VTE such as unilateral or bilateral leg or arm swelling, pain, warmth, redness, and/or shortness of breath. The British Society for Haematology recommends maintaining mobility as a reasonable precaution when traveling for more than 3 hours.¹⁵

Cardiovascular Disease
A 2015 Cochrane review found that the risk for myocardial infarction or ischemic stroke is increased 1.6‐fold in COC users.¹⁶ Despite this increased relative risk, the increased absolute annual risk of myocardial infarction in nonsmoking women remains low: increased from 0.83 to 3.53 per 10,000,000 women younger than 35 years and from 9.45 to 40.4 per 10,000,000 women 35 years and older.¹⁷

Breast Cancer and Cervical Cancer
Data are mixed on the effect of COCs on the risk for breast cancer and cervical cancer.¹ According to the CDC, COC use for 5 or more years might increase the risk of cervical carcinoma in situ and invasive cervical carcinoma in women with persistent human papillomavirus infection.⁵ Regardless of COC use, women should undergo age-appropriate screening for breast cancer and cervical cancer.

Melasma
Melasma is an estrogen-mediated side effect of COCs.⁸ A study from 1967 found that 29% of COC users (N=212) developed melasma; however, they were taking COCs with much higher ethinyl estradiol doses (50–100 μg) than typically used today.¹⁸ Nevertheless, as part of an overall skin care regimen, photoprotection should be encouraged with a broad-spectrum, water-resistant sunscreen that has a sun protection factor of at least 30. In addition, sunscreens with iron oxides have been shown to better prevent melasma relapse by protecting against the shorter wavelengths of visible light.¹⁹

The American Academy of Dermatology confers combined oral contraceptives (COCs) a strength A recommendation for the treatment of acne based on level I evidence, and 4 COCs are approved for the treatment of acne by the US Food and Drug Administration (FDA).¹ Furthermore, when dermatologists prescribe isotretinoin and thalidomide to women of reproductive potential, the iPLEDGE and THALOMID Risk Evaluation and Mitigation Strategy (REMS) programs require 2 concurrent methods of contraception, one of which may be a COC. In addition, COCs have several potential off-label indications in dermatology including idiopathic hirsutism, female pattern hair loss, hidradenitis suppurativa, and autoimmune progesterone dermatitis.

Despite this evidence and opportunity, research suggests that dermatologists underprescribe COCs. The National Ambulatory Medical Care Survey found that between 1993 and 2008, dermatologists in the United States prescribed COCs to only 2.03% of women presenting for acne treatment, which was less often than obstetricians/gynecologists (36.03%) and internists (10.76%).² More recently, in a survey of 130 US dermatologists conducted from 2014 to 2015, only 55.4% reported prescribing COCs. This survey also found that only 45.8% of dermatologists who prescribed COCs felt very comfortable counseling on how to begin taking them, only 48.6% felt very comfortable counseling patients on side effects, and only 22.2% felt very comfortable managing side effects.³

In light of these data, this article reviews the basics of COCs for dermatology residents, from assessing patient eligibility and selecting a COC to counseling on use and managing risks and side effects. Because there are different approaches to prescribing COCs, readers are encouraged to integrate the information in this article with what they have learned from other sources.

Assess Patient Eligibility

In general, patients should be at least 14 years of age and have waited 2 years after menarche to start COCs. They can be taken until menopause.^1,4 Contraindications can be screened for by taking a medical history and measuring a baseline blood pressure (Tables 1 and 2).⁵ In addition, pregnancy should be excluded with a urine or serum pregnancy test or criteria provided in Box 2 of the 2016 US Selected Practice Recommendations for Contraceptive Use from the Centers for Disease Control and Prevention (CDC).⁴ Although important for women’s overall health, a pelvic examination is not required to start COCs according to the CDC and the American Academy of Dermatology.^1,4

Select the COC

Combined oral contraceptives combine estrogen, usually in the form of ethinyl estradiol, with a progestin. Data suggest that all COCs effectively treat acne, but 4 are specifically FDA approved for acne: ethinyl estradiol–norethindrone acetate–ferrous fumarate, ethinyl estradiol–norgestimate, ethinyl estradiol–drospirenone, and ethinyl estradiol–drospirenone–levomefolate.¹ Ethinyl estradiol–desogestrel and ethinyl estradiol–drospirenone are 2 go-to COCs for some of the attending physicians at my residency program. All COCs are FDA approved for contraception. When selecting a COC, one approach is to start with the patient’s drug formulary, then consider the following characteristics.

Monophasic vs Multiphasic
All the hormonally active pills in a monophasic formulation contain the same dose of estrogen and progestin; however, these doses change per pill in a multiphasic formulation, which requires that patients take the pills in a specific order. Given this greater complexity and the fact that multiphasic formulations often are more expensive and lack evidence of superiority, a 2011 Cochrane review recommended monophasic formulations as first line.⁶ In addition, monophasic formulations are preferred for autoimmune progesterone dermatitis because of the stable progestin dose.

Hormone-Free Interval
Some COCs include placebo pills during which hormone withdrawal symptoms such as bleeding, pelvic pain, mood changes, and headache may occur. If a patient is concerned about these symptoms, choose a COC with no or fewer placebo pills, or have the patient skip the hormone-free interval altogether and start the next pack early⁷; in this case, the prescription should be written with instructions to allow the patient to get earlier refills from the pharmacy.

Estrogen Dose
To minimize estrogen-related side effects, the lowest possible dose of ethinyl estradiol that is effective and tolerable should be prescribed^7,8; 20 μg of ethinyl estradiol generally is the lowest dose available, but it may be associated with more frequent breakthrough bleeding.⁹ The International Planned Parenthood Federation recommends starting with COCs that contain 30 to 35 μg of estrogen.¹⁰ Synthesizing this information, one option is to start with 20 μg of ethinyl estradiol and increase the dose if breakthrough bleeding persists after 3 cycles.

Progestin Type
First-generation progestins (eg, norethindrone), second-generation progestins (eg, norgestrel, levonorgestrel), and third-generation progestins (eg, norgestimate, desogestrel) are derived from testosterone and therefore are variably androgenic; second-generation progestins are the most androgenic, and third-generation progestins are the least. On the other hand, drospirenone, the fourth-generation progestin available in the United States, is derived from 17α-spironolactone and thus is mildly antiandrogenic (3 mg of drospirenone is considered equivalent to 25 mg of spironolactone).

Although COCs with less androgenic progestins should theoretically treat acne better, a 2012 Cochrane review of COCs and acne concluded that “differences in the comparative effectiveness of COCs containing varying progestin types and dosages were less clear, and data were limited for any particular comparison.”¹¹ As a result, regardless of the progestin, all COCs are believed to have a net antiandrogenic effect due to their estrogen component.¹

Counsel on Use

Combined oral contraceptives can be started on any day of the menstrual cycle, including the day the prescription is given. If a patient begins a COC within 5 days of the first day of her most recent period, backup contraception is not needed.⁴ If she begins the COC more than 5 days after the first day of her most recent period, she needs to use backup contraception or abstain from sexual intercourse for the next 7 days.⁴ In general, at least 3 months of therapy are required to evaluate the effectiveness of COCs for acne.¹

Manage Risks and Side Effects

Breakthrough Bleeding
The most common side effect of breakthrough bleeding can be minimized by taking COCs at approximately the same time every day and avoiding missed pills. If breakthrough bleeding does not stop after 3 cycles, consider increasing the estrogen dose to 30 to 35 μg and/or referring to an obstetrician/gynecologist to rule out other etiologies of bleeding.^7,8

Nausea, Headache, Bloating, and Breast Tenderness
These symptoms typically resolve after the first 3 months. To minimize nausea, patients should take COCs in the early evening and eat breakfast the next morning.^7,8 For headaches that occur during the hormone-free interval, consider skipping the placebo pills and starting the next pack early. Switching the progestin to drospirenone, which has a mild diuretic effect, can help with bloating as well as breast tenderness.⁷ For persistent symptoms, consider a lower estrogen dose.^7,8

Changes in Libido
In a systemic review including 8422 COC users, 64% reported no change in libido, 22% reported an increase, and 15% reported a decrease.¹²

Weight Gain
Although patients may be concerned that COCs cause weight gain, a 2014 Cochrane review concluded that “available evidence is insufficient to determine the effect of combination contraceptives on weight, but no large effect is evident.”¹³ If weight gain does occur, anecdotal evidence suggests it tends to be not more than 5 pounds. If weight gain is an issue, consider a less androgenic progestin.⁸

Venous Thromboembolism
Use the 3-6-9-12 model to contextualize venous thromboembolism (VTE) risk: a woman’s annual VTE risk is 3 per 10,000 women at baseline, 6 per 10,000 women with nondrospirenone COCs, 9 per 10,000 women with drospirenone-containing COCs, and 12 per 10,000 women when pregnant.¹⁴ Patients should be counseled on the signs and symptoms of VTE such as unilateral or bilateral leg or arm swelling, pain, warmth, redness, and/or shortness of breath. The British Society for Haematology recommends maintaining mobility as a reasonable precaution when traveling for more than 3 hours.¹⁵

Cardiovascular Disease
A 2015 Cochrane review found that the risk for myocardial infarction or ischemic stroke is increased 1.6‐fold in COC users.¹⁶ Despite this increased relative risk, the increased absolute annual risk of myocardial infarction in nonsmoking women remains low: increased from 0.83 to 3.53 per 10,000,000 women younger than 35 years and from 9.45 to 40.4 per 10,000,000 women 35 years and older.¹⁷

Breast Cancer and Cervical Cancer
Data are mixed on the effect of COCs on the risk for breast cancer and cervical cancer.¹ According to the CDC, COC use for 5 or more years might increase the risk of cervical carcinoma in situ and invasive cervical carcinoma in women with persistent human papillomavirus infection.⁵ Regardless of COC use, women should undergo age-appropriate screening for breast cancer and cervical cancer.

Melasma
Melasma is an estrogen-mediated side effect of COCs.⁸ A study from 1967 found that 29% of COC users (N=212) developed melasma; however, they were taking COCs with much higher ethinyl estradiol doses (50–100 μg) than typically used today.¹⁸ Nevertheless, as part of an overall skin care regimen, photoprotection should be encouraged with a broad-spectrum, water-resistant sunscreen that has a sun protection factor of at least 30. In addition, sunscreens with iron oxides have been shown to better prevent melasma relapse by protecting against the shorter wavelengths of visible light.¹⁹

The American Academy of Dermatology confers combined oral contraceptives (COCs) a strength A recommendation for the treatment of acne based on level I evidence, and 4 COCs are approved for the treatment of acne by the US Food and Drug Administration (FDA).¹ Furthermore, when dermatologists prescribe isotretinoin and thalidomide to women of reproductive potential, the iPLEDGE and THALOMID Risk Evaluation and Mitigation Strategy (REMS) programs require 2 concurrent methods of contraception, one of which may be a COC. In addition, COCs have several potential off-label indications in dermatology including idiopathic hirsutism, female pattern hair loss, hidradenitis suppurativa, and autoimmune progesterone dermatitis.

Despite this evidence and opportunity, research suggests that dermatologists underprescribe COCs. The National Ambulatory Medical Care Survey found that between 1993 and 2008, dermatologists in the United States prescribed COCs to only 2.03% of women presenting for acne treatment, which was less often than obstetricians/gynecologists (36.03%) and internists (10.76%).² More recently, in a survey of 130 US dermatologists conducted from 2014 to 2015, only 55.4% reported prescribing COCs. This survey also found that only 45.8% of dermatologists who prescribed COCs felt very comfortable counseling on how to begin taking them, only 48.6% felt very comfortable counseling patients on side effects, and only 22.2% felt very comfortable managing side effects.³

In light of these data, this article reviews the basics of COCs for dermatology residents, from assessing patient eligibility and selecting a COC to counseling on use and managing risks and side effects. Because there are different approaches to prescribing COCs, readers are encouraged to integrate the information in this article with what they have learned from other sources.

Assess Patient Eligibility

In general, patients should be at least 14 years of age and have waited 2 years after menarche to start COCs. They can be taken until menopause.^1,4 Contraindications can be screened for by taking a medical history and measuring a baseline blood pressure (Tables 1 and 2).⁵ In addition, pregnancy should be excluded with a urine or serum pregnancy test or criteria provided in Box 2 of the 2016 US Selected Practice Recommendations for Contraceptive Use from the Centers for Disease Control and Prevention (CDC).⁴ Although important for women’s overall health, a pelvic examination is not required to start COCs according to the CDC and the American Academy of Dermatology.^1,4

Select the COC

Combined oral contraceptives combine estrogen, usually in the form of ethinyl estradiol, with a progestin. Data suggest that all COCs effectively treat acne, but 4 are specifically FDA approved for acne: ethinyl estradiol–norethindrone acetate–ferrous fumarate, ethinyl estradiol–norgestimate, ethinyl estradiol–drospirenone, and ethinyl estradiol–drospirenone–levomefolate.¹ Ethinyl estradiol–desogestrel and ethinyl estradiol–drospirenone are 2 go-to COCs for some of the attending physicians at my residency program. All COCs are FDA approved for contraception. When selecting a COC, one approach is to start with the patient’s drug formulary, then consider the following characteristics.

Monophasic vs Multiphasic
All the hormonally active pills in a monophasic formulation contain the same dose of estrogen and progestin; however, these doses change per pill in a multiphasic formulation, which requires that patients take the pills in a specific order. Given this greater complexity and the fact that multiphasic formulations often are more expensive and lack evidence of superiority, a 2011 Cochrane review recommended monophasic formulations as first line.⁶ In addition, monophasic formulations are preferred for autoimmune progesterone dermatitis because of the stable progestin dose.

Hormone-Free Interval
Some COCs include placebo pills during which hormone withdrawal symptoms such as bleeding, pelvic pain, mood changes, and headache may occur. If a patient is concerned about these symptoms, choose a COC with no or fewer placebo pills, or have the patient skip the hormone-free interval altogether and start the next pack early⁷; in this case, the prescription should be written with instructions to allow the patient to get earlier refills from the pharmacy.

Estrogen Dose
To minimize estrogen-related side effects, the lowest possible dose of ethinyl estradiol that is effective and tolerable should be prescribed^7,8; 20 μg of ethinyl estradiol generally is the lowest dose available, but it may be associated with more frequent breakthrough bleeding.⁹ The International Planned Parenthood Federation recommends starting with COCs that contain 30 to 35 μg of estrogen.¹⁰ Synthesizing this information, one option is to start with 20 μg of ethinyl estradiol and increase the dose if breakthrough bleeding persists after 3 cycles.

Progestin Type
First-generation progestins (eg, norethindrone), second-generation progestins (eg, norgestrel, levonorgestrel), and third-generation progestins (eg, norgestimate, desogestrel) are derived from testosterone and therefore are variably androgenic; second-generation progestins are the most androgenic, and third-generation progestins are the least. On the other hand, drospirenone, the fourth-generation progestin available in the United States, is derived from 17α-spironolactone and thus is mildly antiandrogenic (3 mg of drospirenone is considered equivalent to 25 mg of spironolactone).

Although COCs with less androgenic progestins should theoretically treat acne better, a 2012 Cochrane review of COCs and acne concluded that “differences in the comparative effectiveness of COCs containing varying progestin types and dosages were less clear, and data were limited for any particular comparison.”¹¹ As a result, regardless of the progestin, all COCs are believed to have a net antiandrogenic effect due to their estrogen component.¹

Counsel on Use

Combined oral contraceptives can be started on any day of the menstrual cycle, including the day the prescription is given. If a patient begins a COC within 5 days of the first day of her most recent period, backup contraception is not needed.⁴ If she begins the COC more than 5 days after the first day of her most recent period, she needs to use backup contraception or abstain from sexual intercourse for the next 7 days.⁴ In general, at least 3 months of therapy are required to evaluate the effectiveness of COCs for acne.¹

Manage Risks and Side Effects

Breakthrough Bleeding
The most common side effect of breakthrough bleeding can be minimized by taking COCs at approximately the same time every day and avoiding missed pills. If breakthrough bleeding does not stop after 3 cycles, consider increasing the estrogen dose to 30 to 35 μg and/or referring to an obstetrician/gynecologist to rule out other etiologies of bleeding.^7,8

Nausea, Headache, Bloating, and Breast Tenderness
These symptoms typically resolve after the first 3 months. To minimize nausea, patients should take COCs in the early evening and eat breakfast the next morning.^7,8 For headaches that occur during the hormone-free interval, consider skipping the placebo pills and starting the next pack early. Switching the progestin to drospirenone, which has a mild diuretic effect, can help with bloating as well as breast tenderness.⁷ For persistent symptoms, consider a lower estrogen dose.^7,8

Changes in Libido
In a systemic review including 8422 COC users, 64% reported no change in libido, 22% reported an increase, and 15% reported a decrease.¹²

Weight Gain
Although patients may be concerned that COCs cause weight gain, a 2014 Cochrane review concluded that “available evidence is insufficient to determine the effect of combination contraceptives on weight, but no large effect is evident.”¹³ If weight gain does occur, anecdotal evidence suggests it tends to be not more than 5 pounds. If weight gain is an issue, consider a less androgenic progestin.⁸

Venous Thromboembolism
Use the 3-6-9-12 model to contextualize venous thromboembolism (VTE) risk: a woman’s annual VTE risk is 3 per 10,000 women at baseline, 6 per 10,000 women with nondrospirenone COCs, 9 per 10,000 women with drospirenone-containing COCs, and 12 per 10,000 women when pregnant.¹⁴ Patients should be counseled on the signs and symptoms of VTE such as unilateral or bilateral leg or arm swelling, pain, warmth, redness, and/or shortness of breath. The British Society for Haematology recommends maintaining mobility as a reasonable precaution when traveling for more than 3 hours.¹⁵

Cardiovascular Disease
A 2015 Cochrane review found that the risk for myocardial infarction or ischemic stroke is increased 1.6‐fold in COC users.¹⁶ Despite this increased relative risk, the increased absolute annual risk of myocardial infarction in nonsmoking women remains low: increased from 0.83 to 3.53 per 10,000,000 women younger than 35 years and from 9.45 to 40.4 per 10,000,000 women 35 years and older.¹⁷

Breast Cancer and Cervical Cancer
Data are mixed on the effect of COCs on the risk for breast cancer and cervical cancer.¹ According to the CDC, COC use for 5 or more years might increase the risk of cervical carcinoma in situ and invasive cervical carcinoma in women with persistent human papillomavirus infection.⁵ Regardless of COC use, women should undergo age-appropriate screening for breast cancer and cervical cancer.

Melasma
Melasma is an estrogen-mediated side effect of COCs.⁸ A study from 1967 found that 29% of COC users (N=212) developed melasma; however, they were taking COCs with much higher ethinyl estradiol doses (50–100 μg) than typically used today.¹⁸ Nevertheless, as part of an overall skin care regimen, photoprotection should be encouraged with a broad-spectrum, water-resistant sunscreen that has a sun protection factor of at least 30. In addition, sunscreens with iron oxides have been shown to better prevent melasma relapse by protecting against the shorter wavelengths of visible light.¹⁹

The number of pregnancies among women taking isotretinoin has decreased since the introduction of the iPledge program, but pregnancy, abortions, and fetal defects associated with isotretinoin exposure are still occurring in women of reproductive age, according to a retrospective study published in JAMA Dermatology.

In 2006, the Food and Drug Administration implemented the iPledge program, with requirements that include women of childbearing age having a negative pregnancy test and evidence of using two forms of contraception monthly to use isotretinoin, a teratogen. “Although the number of pregnancy-related adverse events for patients taking isotretinoin has decreased since 2006, pregnancies, abortions, and fetal defects associated with isotretinoin exposure continue to be a problem,” Elizabeth Tkachenko, BS, from the University of Massachusetts Medical School, Worcester, and coauthors concluded. “Further research is required to determine the most efficacious system to reduce complications for patients and administrative requirements for physicians while at the same time maintaining access to this important drug.” (iPledge followed other Risk Evaluation and Mitigation Strategy systems for isotretinoin.)

She and her colleagues performed a retrospective evaluation of pregnancy-related adverse events related to isotretinoin that had occurred between January 1997 and December 2017 using the FDA Adverse Event Reporting System (FAERS), which receives reports from prescribers, consumers, and pharmaceutical manufacturers. While there could be many different classification terms for each individual, any number of adverse events reported by an individual was counted as one pregnancy. Ms. Tkachenko and colleagues classified abortions, pregnancies during contraception use, and pregnancy-related defects into separate subgroups for analysis.

From 1997 to 2017, there were 6,740 pregnancies among women (mean age, 24.6 years) during treatment with isotretinoin reported to FAERS, with 7 reports in 1997, and a peak of 768 pregnancies in 2006. Almost 70% (4,647) of the pregnancies were reported after iPledge was introduced. Between 2011 and 2017, there were 218-310 pregnancy reports each year.

Of the total number of pregnancy reports during the study period, 1,896 were abortions (28.1% of the total); 10.9% of the total number of pregnancy reports were spontaneous abortions (733). The number of abortions peaked in 2008, with 291 reports, of which 85% were therapeutic abortions. Also peaking in 2008 was the number of reports of pregnancies while taking a contraceptive (64). After 2008, pregnancies and abortions dropped.

Fetal defects peaked in 2000, with 34 cases reported, and dropped to four or fewer reports annually after 2008.

“Our findings demonstrate that reports of pregnancy among women taking isotretinoin are concentrated among those aged 20 to 29 years, peaked in 2006, and have been consistent since 2011,” the authors wrote.

Limitations of the study, they noted, include limitations of FAERS data and possible reporting fatigue among doctors and patients. The total number of isotretinoin courses prescribed to this patient population is also unknown, which affected their ability to determine the true rate of pregnancy-related adverse events, they noted.

The other authors for this study were from Harvard Medical School and the departments of dermatology at Brigham and Women’s Hospital, both in Boston, as well as the University of Pennsylvania, Philadelphia. One author reported support from an award by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health and salary support from a Pfizer Fellowship in Dermatology Patient Oriented Research grant to the trustees of the University of Pennsylvania. The other authors reported no relevant conflicts of interest.

SOURCE: Tkachenko E et al. JAMA Dermatol. 2019. doi: 10.1001/jamadermatol.2019.1388.

The number of pregnancies among women taking isotretinoin has decreased since the introduction of the iPledge program, but pregnancy, abortions, and fetal defects associated with isotretinoin exposure are still occurring in women of reproductive age, according to a retrospective study published in JAMA Dermatology.

In 2006, the Food and Drug Administration implemented the iPledge program, with requirements that include women of childbearing age having a negative pregnancy test and evidence of using two forms of contraception monthly to use isotretinoin, a teratogen. “Although the number of pregnancy-related adverse events for patients taking isotretinoin has decreased since 2006, pregnancies, abortions, and fetal defects associated with isotretinoin exposure continue to be a problem,” Elizabeth Tkachenko, BS, from the University of Massachusetts Medical School, Worcester, and coauthors concluded. “Further research is required to determine the most efficacious system to reduce complications for patients and administrative requirements for physicians while at the same time maintaining access to this important drug.” (iPledge followed other Risk Evaluation and Mitigation Strategy systems for isotretinoin.)

She and her colleagues performed a retrospective evaluation of pregnancy-related adverse events related to isotretinoin that had occurred between January 1997 and December 2017 using the FDA Adverse Event Reporting System (FAERS), which receives reports from prescribers, consumers, and pharmaceutical manufacturers. While there could be many different classification terms for each individual, any number of adverse events reported by an individual was counted as one pregnancy. Ms. Tkachenko and colleagues classified abortions, pregnancies during contraception use, and pregnancy-related defects into separate subgroups for analysis.

From 1997 to 2017, there were 6,740 pregnancies among women (mean age, 24.6 years) during treatment with isotretinoin reported to FAERS, with 7 reports in 1997, and a peak of 768 pregnancies in 2006. Almost 70% (4,647) of the pregnancies were reported after iPledge was introduced. Between 2011 and 2017, there were 218-310 pregnancy reports each year.

Of the total number of pregnancy reports during the study period, 1,896 were abortions (28.1% of the total); 10.9% of the total number of pregnancy reports were spontaneous abortions (733). The number of abortions peaked in 2008, with 291 reports, of which 85% were therapeutic abortions. Also peaking in 2008 was the number of reports of pregnancies while taking a contraceptive (64). After 2008, pregnancies and abortions dropped.

Fetal defects peaked in 2000, with 34 cases reported, and dropped to four or fewer reports annually after 2008.

“Our findings demonstrate that reports of pregnancy among women taking isotretinoin are concentrated among those aged 20 to 29 years, peaked in 2006, and have been consistent since 2011,” the authors wrote.

Limitations of the study, they noted, include limitations of FAERS data and possible reporting fatigue among doctors and patients. The total number of isotretinoin courses prescribed to this patient population is also unknown, which affected their ability to determine the true rate of pregnancy-related adverse events, they noted.

The other authors for this study were from Harvard Medical School and the departments of dermatology at Brigham and Women’s Hospital, both in Boston, as well as the University of Pennsylvania, Philadelphia. One author reported support from an award by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health and salary support from a Pfizer Fellowship in Dermatology Patient Oriented Research grant to the trustees of the University of Pennsylvania. The other authors reported no relevant conflicts of interest.

SOURCE: Tkachenko E et al. JAMA Dermatol. 2019. doi: 10.1001/jamadermatol.2019.1388.

The number of pregnancies among women taking isotretinoin has decreased since the introduction of the iPledge program, but pregnancy, abortions, and fetal defects associated with isotretinoin exposure are still occurring in women of reproductive age, according to a retrospective study published in JAMA Dermatology.

In 2006, the Food and Drug Administration implemented the iPledge program, with requirements that include women of childbearing age having a negative pregnancy test and evidence of using two forms of contraception monthly to use isotretinoin, a teratogen. “Although the number of pregnancy-related adverse events for patients taking isotretinoin has decreased since 2006, pregnancies, abortions, and fetal defects associated with isotretinoin exposure continue to be a problem,” Elizabeth Tkachenko, BS, from the University of Massachusetts Medical School, Worcester, and coauthors concluded. “Further research is required to determine the most efficacious system to reduce complications for patients and administrative requirements for physicians while at the same time maintaining access to this important drug.” (iPledge followed other Risk Evaluation and Mitigation Strategy systems for isotretinoin.)

She and her colleagues performed a retrospective evaluation of pregnancy-related adverse events related to isotretinoin that had occurred between January 1997 and December 2017 using the FDA Adverse Event Reporting System (FAERS), which receives reports from prescribers, consumers, and pharmaceutical manufacturers. While there could be many different classification terms for each individual, any number of adverse events reported by an individual was counted as one pregnancy. Ms. Tkachenko and colleagues classified abortions, pregnancies during contraception use, and pregnancy-related defects into separate subgroups for analysis.

From 1997 to 2017, there were 6,740 pregnancies among women (mean age, 24.6 years) during treatment with isotretinoin reported to FAERS, with 7 reports in 1997, and a peak of 768 pregnancies in 2006. Almost 70% (4,647) of the pregnancies were reported after iPledge was introduced. Between 2011 and 2017, there were 218-310 pregnancy reports each year.

Of the total number of pregnancy reports during the study period, 1,896 were abortions (28.1% of the total); 10.9% of the total number of pregnancy reports were spontaneous abortions (733). The number of abortions peaked in 2008, with 291 reports, of which 85% were therapeutic abortions. Also peaking in 2008 was the number of reports of pregnancies while taking a contraceptive (64). After 2008, pregnancies and abortions dropped.

Fetal defects peaked in 2000, with 34 cases reported, and dropped to four or fewer reports annually after 2008.

“Our findings demonstrate that reports of pregnancy among women taking isotretinoin are concentrated among those aged 20 to 29 years, peaked in 2006, and have been consistent since 2011,” the authors wrote.

Limitations of the study, they noted, include limitations of FAERS data and possible reporting fatigue among doctors and patients. The total number of isotretinoin courses prescribed to this patient population is also unknown, which affected their ability to determine the true rate of pregnancy-related adverse events, they noted.

The other authors for this study were from Harvard Medical School and the departments of dermatology at Brigham and Women’s Hospital, both in Boston, as well as the University of Pennsylvania, Philadelphia. One author reported support from an award by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health and salary support from a Pfizer Fellowship in Dermatology Patient Oriented Research grant to the trustees of the University of Pennsylvania. The other authors reported no relevant conflicts of interest.

SOURCE: Tkachenko E et al. JAMA Dermatol. 2019. doi: 10.1001/jamadermatol.2019.1388.

NEWPORT BEACH, CALIF. – Acne – which can appear anytime from the neonatal period to puberty – is most worrisome when it appears during the midchildhood years, from ages 1-7 years, according to Sheila Fallon Friedlander, MD.

“This is something you are going to see in your practice,” said Dr. Friedlander, a pediatric dermatologists at Rady Children’s Hospital–San Diego. It’s important to know when it’s time to be concerned and when another condition may be masquerading as acne, she said at the at Skin Disease Education Foundation’s Women’s & Pediatric Dermatology Seminar.

Dr. Friedlander, who is professor of dermatology and pediatrics at the University of California, San Diego, talked about treating acne in the following prepubertal age groups:
 

Neonatal acne (ages birth to 4 weeks)

Acne appears in this population up to 20% of the time, according to research, and it is much more common in males than in females, at a ratio of five to one.

The cause is “most likely the relationship between placental androgens and the baby’s adrenal glands,” Dr. Friedlander said. However, something more serious could be going on. “Look at the child and see if he’s sick. If he looks sick, then we need to worry.”

Hormonal abnormalities also could be a cause, she said. Refer a baby to a specialist if there are other signs of hyperandrogenism. However, “the likelihood is very low,” and she’s never needed to refer a neonate with acne for evaluation.

As for treatment, she said, “Mainly, I’m using tincture of time.” However, “many of my mothers have told me that topical yogurt application will work.” Why yogurt? It’s possible that its bacteria could play a role in combating acne, she said.

Masquerader alert! Beware of neonatal cephalic pustulosis, Dr. Friedlander cautioned, which may be an inflammatory response to yeast. Ketoconazole cream may be helpful.
 

Infantile acne (ages 0-12 months)

This form of acne is more common in males and may hint at the future development of severe adolescent acne. It does resolve but it may take months or years, Dr. Friedlander said.

In general, this acne isn’t a sign of something more serious. “You do not need to go crazy with the work-up,” she said. “With mild to moderate disease, with nothing else suspicious, I don’t do a big work-up.”

However, do consider whether the child is undergoing precocious puberty, Dr. Friedlander said. Signs include axillary hair, pubic hair, and body odor.

As for treatment of infantile acne, “start out topically” and consider options such as Bactrim (sulfamethoxazole/trimethoprim) and erythromycin.

Masquerader alert! Idiopathic facial aseptic granuloma can be mistaken for acne and abscess, and ultrasound is helpful to confirm it. “It’s not so easy to treat,” she said. “Ivermectin may be helpful. Sometimes you do cultures and make sure something else isn’t going on.”
 

Midchildhood (ages 1-7 years)

“It’s not as common to have acne develop in this age group, but when it develops you need to be concerned,” Dr. Friedlander said. “This is the age period when there is more often something really wrong.”

Be on the lookout for a family history of hormonal abnormalities, and check if the child is on medication. “You need to look carefully,” she said, adding that it’s important to check for signs of premature puberty such as giant spikes in growth, abnormally large hands and feet, genital changes, and body odor. Check blood pressure if you’re worried about an adrenal tumor.

It’s possible for children to develop precocious puberty – with acne – because of exposure to testosterone gel used by a father. Dehydroepiandrosterone (DHEA) creams also may cause the condition. “The more creams out there with androgenic effects, the more we may see it,” Dr. Friedlander said. “This is something to ask about because families may not be forthcoming.”

Masquerader alert! Perioral dermatitis may look like acne, and it may be linked to inhaled or topical steroids, she said.

Other masqueraders include demodex folliculitis, angiofibromas (think tuberous sclerosis), and keratosis pilaris (the most common type of bump on a children aged 1-7 years). The latter condition “is not the end of the world,” said Dr. Friedlander, who added that “I’ve never cured anyone of it.”
 

Prepubertal acne (ages 7 years to puberty)

Acne in this group is generally not worrisome, Dr. Friedlander said, but investigate further if there’s significant inflammation and signs of early sexual development or virilization.

Benzoyl peroxide wash may be enough to help the condition initially, and consider topical clindamycin or a combination product. “Start out slow,” she said. Twice a week to start might be appropriate. Moisturizers can be helpful, as can topical adapalene.

Also, keep in mind that even mild acne can be emotionally devastating to a child in this age group and worthy of treatment. “Your assessment may be very different than hers,” she said. It’s possible that “she has a few lesions, but she feels like an outcast.”

Dr. Friedlander reported no relevant financial disclosures. SDEF and this news organization are owned by the same parent company.

NEWPORT BEACH, CALIF. – Acne – which can appear anytime from the neonatal period to puberty – is most worrisome when it appears during the midchildhood years, from ages 1-7 years, according to Sheila Fallon Friedlander, MD.

“This is something you are going to see in your practice,” said Dr. Friedlander, a pediatric dermatologists at Rady Children’s Hospital–San Diego. It’s important to know when it’s time to be concerned and when another condition may be masquerading as acne, she said at the at Skin Disease Education Foundation’s Women’s & Pediatric Dermatology Seminar.

Dr. Friedlander, who is professor of dermatology and pediatrics at the University of California, San Diego, talked about treating acne in the following prepubertal age groups:
 

Neonatal acne (ages birth to 4 weeks)

Acne appears in this population up to 20% of the time, according to research, and it is much more common in males than in females, at a ratio of five to one.

The cause is “most likely the relationship between placental androgens and the baby’s adrenal glands,” Dr. Friedlander said. However, something more serious could be going on. “Look at the child and see if he’s sick. If he looks sick, then we need to worry.”

Hormonal abnormalities also could be a cause, she said. Refer a baby to a specialist if there are other signs of hyperandrogenism. However, “the likelihood is very low,” and she’s never needed to refer a neonate with acne for evaluation.

As for treatment, she said, “Mainly, I’m using tincture of time.” However, “many of my mothers have told me that topical yogurt application will work.” Why yogurt? It’s possible that its bacteria could play a role in combating acne, she said.

Masquerader alert! Beware of neonatal cephalic pustulosis, Dr. Friedlander cautioned, which may be an inflammatory response to yeast. Ketoconazole cream may be helpful.
 

Infantile acne (ages 0-12 months)

This form of acne is more common in males and may hint at the future development of severe adolescent acne. It does resolve but it may take months or years, Dr. Friedlander said.

In general, this acne isn’t a sign of something more serious. “You do not need to go crazy with the work-up,” she said. “With mild to moderate disease, with nothing else suspicious, I don’t do a big work-up.”

However, do consider whether the child is undergoing precocious puberty, Dr. Friedlander said. Signs include axillary hair, pubic hair, and body odor.

As for treatment of infantile acne, “start out topically” and consider options such as Bactrim (sulfamethoxazole/trimethoprim) and erythromycin.

Masquerader alert! Idiopathic facial aseptic granuloma can be mistaken for acne and abscess, and ultrasound is helpful to confirm it. “It’s not so easy to treat,” she said. “Ivermectin may be helpful. Sometimes you do cultures and make sure something else isn’t going on.”
 

Midchildhood (ages 1-7 years)

“It’s not as common to have acne develop in this age group, but when it develops you need to be concerned,” Dr. Friedlander said. “This is the age period when there is more often something really wrong.”

Be on the lookout for a family history of hormonal abnormalities, and check if the child is on medication. “You need to look carefully,” she said, adding that it’s important to check for signs of premature puberty such as giant spikes in growth, abnormally large hands and feet, genital changes, and body odor. Check blood pressure if you’re worried about an adrenal tumor.

It’s possible for children to develop precocious puberty – with acne – because of exposure to testosterone gel used by a father. Dehydroepiandrosterone (DHEA) creams also may cause the condition. “The more creams out there with androgenic effects, the more we may see it,” Dr. Friedlander said. “This is something to ask about because families may not be forthcoming.”

Masquerader alert! Perioral dermatitis may look like acne, and it may be linked to inhaled or topical steroids, she said.

Other masqueraders include demodex folliculitis, angiofibromas (think tuberous sclerosis), and keratosis pilaris (the most common type of bump on a children aged 1-7 years). The latter condition “is not the end of the world,” said Dr. Friedlander, who added that “I’ve never cured anyone of it.”
 

Prepubertal acne (ages 7 years to puberty)

Acne in this group is generally not worrisome, Dr. Friedlander said, but investigate further if there’s significant inflammation and signs of early sexual development or virilization.

Benzoyl peroxide wash may be enough to help the condition initially, and consider topical clindamycin or a combination product. “Start out slow,” she said. Twice a week to start might be appropriate. Moisturizers can be helpful, as can topical adapalene.

Also, keep in mind that even mild acne can be emotionally devastating to a child in this age group and worthy of treatment. “Your assessment may be very different than hers,” she said. It’s possible that “she has a few lesions, but she feels like an outcast.”

Dr. Friedlander reported no relevant financial disclosures. SDEF and this news organization are owned by the same parent company.

NEWPORT BEACH, CALIF. – Acne – which can appear anytime from the neonatal period to puberty – is most worrisome when it appears during the midchildhood years, from ages 1-7 years, according to Sheila Fallon Friedlander, MD.

“This is something you are going to see in your practice,” said Dr. Friedlander, a pediatric dermatologists at Rady Children’s Hospital–San Diego. It’s important to know when it’s time to be concerned and when another condition may be masquerading as acne, she said at the at Skin Disease Education Foundation’s Women’s & Pediatric Dermatology Seminar.

Dr. Friedlander, who is professor of dermatology and pediatrics at the University of California, San Diego, talked about treating acne in the following prepubertal age groups:
 

Neonatal acne (ages birth to 4 weeks)

Acne appears in this population up to 20% of the time, according to research, and it is much more common in males than in females, at a ratio of five to one.

The cause is “most likely the relationship between placental androgens and the baby’s adrenal glands,” Dr. Friedlander said. However, something more serious could be going on. “Look at the child and see if he’s sick. If he looks sick, then we need to worry.”

Hormonal abnormalities also could be a cause, she said. Refer a baby to a specialist if there are other signs of hyperandrogenism. However, “the likelihood is very low,” and she’s never needed to refer a neonate with acne for evaluation.

As for treatment, she said, “Mainly, I’m using tincture of time.” However, “many of my mothers have told me that topical yogurt application will work.” Why yogurt? It’s possible that its bacteria could play a role in combating acne, she said.

Masquerader alert! Beware of neonatal cephalic pustulosis, Dr. Friedlander cautioned, which may be an inflammatory response to yeast. Ketoconazole cream may be helpful.
 

Infantile acne (ages 0-12 months)

This form of acne is more common in males and may hint at the future development of severe adolescent acne. It does resolve but it may take months or years, Dr. Friedlander said.

In general, this acne isn’t a sign of something more serious. “You do not need to go crazy with the work-up,” she said. “With mild to moderate disease, with nothing else suspicious, I don’t do a big work-up.”

However, do consider whether the child is undergoing precocious puberty, Dr. Friedlander said. Signs include axillary hair, pubic hair, and body odor.

As for treatment of infantile acne, “start out topically” and consider options such as Bactrim (sulfamethoxazole/trimethoprim) and erythromycin.

Masquerader alert! Idiopathic facial aseptic granuloma can be mistaken for acne and abscess, and ultrasound is helpful to confirm it. “It’s not so easy to treat,” she said. “Ivermectin may be helpful. Sometimes you do cultures and make sure something else isn’t going on.”
 

Midchildhood (ages 1-7 years)

“It’s not as common to have acne develop in this age group, but when it develops you need to be concerned,” Dr. Friedlander said. “This is the age period when there is more often something really wrong.”

Be on the lookout for a family history of hormonal abnormalities, and check if the child is on medication. “You need to look carefully,” she said, adding that it’s important to check for signs of premature puberty such as giant spikes in growth, abnormally large hands and feet, genital changes, and body odor. Check blood pressure if you’re worried about an adrenal tumor.

It’s possible for children to develop precocious puberty – with acne – because of exposure to testosterone gel used by a father. Dehydroepiandrosterone (DHEA) creams also may cause the condition. “The more creams out there with androgenic effects, the more we may see it,” Dr. Friedlander said. “This is something to ask about because families may not be forthcoming.”

Masquerader alert! Perioral dermatitis may look like acne, and it may be linked to inhaled or topical steroids, she said.

Other masqueraders include demodex folliculitis, angiofibromas (think tuberous sclerosis), and keratosis pilaris (the most common type of bump on a children aged 1-7 years). The latter condition “is not the end of the world,” said Dr. Friedlander, who added that “I’ve never cured anyone of it.”
 

Prepubertal acne (ages 7 years to puberty)

Acne in this group is generally not worrisome, Dr. Friedlander said, but investigate further if there’s significant inflammation and signs of early sexual development or virilization.

Benzoyl peroxide wash may be enough to help the condition initially, and consider topical clindamycin or a combination product. “Start out slow,” she said. Twice a week to start might be appropriate. Moisturizers can be helpful, as can topical adapalene.

Also, keep in mind that even mild acne can be emotionally devastating to a child in this age group and worthy of treatment. “Your assessment may be very different than hers,” she said. It’s possible that “she has a few lesions, but she feels like an outcast.”

Dr. Friedlander reported no relevant financial disclosures. SDEF and this news organization are owned by the same parent company.

Acne is a common condition that most often affects adolescents but is not uncommon in adults. It can result in considerable anxiety, depression, and medical and pharmaceutical costs. Additionally, oral antibiotics, the standard treatment for acne, are increasingly under suspicion for causing bacterial resistance as well as disruption of the cutaneous and gut microbiomes.^1,2 These factors are among those that often drive patients and physicians to search for alternative and complementary treatments, including dietary modification.

Over the last few decades, the interaction between diet and acne has been one of the most fluid areas of research in dermatology. The role of diet in acne incidence and presentation has evolved from the general view in the 1970s that there was no connection to today’s more data-driven understanding that the acne disease course likely is modified by specific dietary components. Better designed and more rigorous studies have supported a link between acne severity and glycemic index (GI)/glycemic load (GL) and possibly dairy consumption. The ability to use data-driven evidence to counsel patients regarding dietary treatment of acne is increasingly important to counteract the pseudoadvice that patients can easily find on the Internet.

This article summarizes the history of beliefs about diet and acne, reviews more recent published data regarding dietary components that can modify acne severity, and outlines the current American Academy of Dermatology (AAD) guidelines and recommendations for diet and acne.

History of Diet and Acne

In most of the current literature, acne frequently is referred to as a disease of modern civilization or a consequence of the typical Western diet.³ For clarity, the Western diet is most commonly described as “a dietary regimen characterized by high amounts of sugary desserts, refined grains, high protein, high-fat dairy products, and high-sugar drinks.”⁴ The role of dairy in the etiology of acne typically is discussed separately from the Western diet. It has been reported that acne is not found in nonwesternized populations where a Paleolithic diet, which does not include consumption of high-GI carbohydrates, milk, or other dairy products, is common.⁵

Extending this line of argument, acne vulgaris has been called a metabolic syndrome of the sebaceous follicle and one of the mammalian target of rapamycin complex 1–driven diseases of civilization, along with cancer, obesity, and diabetes mellitus.³ This view seems somewhat extreme and discounts other drivers of acne incidence and severity. Twin studies have shown that acne is highly heritable, with 81% of the population variance attributed to genetic factors.⁶ Similar incidence numbers for acne vulgaris have been reported worldwide, and global incidence in late adolescence is rising; however, it is unknown whether this increase is a result of the adoption of the Western diet, which is thought to encourage early onset of puberty; genetic drift; changes in regional and cultural understanding and reporting of acne; or a byproduct of unknown environmental factors.⁴ More nuanced views acknowledge that acne is a multifactorial disease,⁷ and therefore genetic and possibly epigenetic factors as well as the cutaneous and gut microbiomes also must be taken into account. An interesting historical perspective on acne by Mahmood and Shipman⁸ outlined acne descriptions, diagnoses, topical treatments, and dietary advice going back to ancient Greek and Egyptian civilizations. They also cited recommendations from the 1930s that suggested avoiding “starchy foods, bread rolls, noodles, spaghetti, potatoes, oily nuts, chop suey, chow mein, and waffles” and listed the following foods as suitable to cure acne: “cooked and raw fruit, farina, rice, wheat, oatmeal, green vegetables, boiled or broiled meat and poultry, clear soup, vegetable soup, and an abundance of water.”⁸

More Recent Evidence of Dietary Influence on Acne

Importantly, the available research does not demonstrate that diet causes acne but rather that it may influence or aggravate existing acne. Data collection for acne studies also can be confounded by the interplay of many factors, such as increased access to health care, socioeconomic status, and shifting cultural perceptions of skin care and beauty.⁴ An important facet of any therapeutic recommendation is that it should be supported by confirmable mechanistic pathways.

GI and GL
Over the last few decades, a number of observational and intervention studies have focused on the possible influence of the GI/GL of foods on acne incidence and/or severity. A high GI diet is characterized by a relatively high intake of carbohydrate-containing foods that are quickly digested and absorbed, increasing blood glucose and insulin concentrations. Glycemic load takes the portion size of dietary carbohydrates into consideration and therefore is a measure of both the quality and quantity of carbohydrate-containing foods.⁹ TheGI/GL values of more than 2480 food items are available in the literature.¹⁰

Evidence from several studies supports the role of high GI/GL diets in exacerbating acne and suggests that transitioning to low GI/GL diets may lead to decreased lesion counts after 12 weeks.^11-13 In one randomized controlled trial, male participants aged 15 to 25 years with mild to moderate facial acne were instructed either to eat a high protein/low GI diet or a conventional high GL control diet.¹³ After 12 weeks, total lesion counts had decreased more in the low GI diet group than the control. As partial confirmation of a mechanistic pathway for a high GI diet and acne, the low GI group demonstrated lower free androgen index and insulin levels than the control group.¹³ In a Korean study, a 10-week low GL regimen led to a reduction in acne lesion count, a decrease in sebaceous gland size, decreased inflammation, and reduced expression of sterol regulatory element-binding protein 1 and IL-8.¹⁴

More recent studies have further solidified the role of high GI/GL diets in acne severity.^9,15,16 High GI/GL diets are believed to stimulate acne pathways by stimulating insulinlike growth factor 1 (IGF-1), which induces proliferation of both keratinocytes and sebocytes and simulates androgen production.¹⁷ An excellent diagram showing the connection between high GI diets (and dairy) and IGF-1, insulin and its receptors, androgen and its receptors, mammalian target of rapamycin, and the pilosebaceous unit was published in the literature in 2016.⁴ Interestingly, metformin has been shown to be an effective adjunctive therapy in the treatment of moderate to severe acne vulgaris.^18,19

Milk and Dairy Consumption
Milk consumption also has been examined for its potential role in the pathogenesis of acne, including its ability to increase insulin and IGF-1 levels and bind to the human IGF-1 receptor as well as the fact that it contains bovine IGF-1 and dihydrotestosterone precursors.²⁰ Although not studied quite as extensively or rigorously as GI/GL, consumption of milk and dairy products does appear to have the potential to exacerbate acne lesions. Beginning with a series of retrospective and prospective epidemiologic studies published from 2005 to 2008,^21-23 a link between clinical acne and milk or dairy consumption in adolescent subjects was reported. A recent meta-analysis found a positive relationship between dairy, total milk, whole milk, low-fat milk, and skim milk consumption and acne occurrence but no significant association between yogurt/cheese consumption and acne development.²⁴

AAD Guidelines

In their public forum, the AAD has advised that a low-glycemic diet may reduce the number of lesions in acne patients and highlighted data from around the world that support the concept that a high-glycemic diet and dairy are correlated with acne severity. They stated that consumption of milk—whole, low fat, and skim—may be linked to an increase in acne breakouts but that no studies have found that products made from milk, such as yogurt or cheese, lead to more breakouts.²⁵

Other Considerations

Acne can be a serious quality-of-life issue with considerable psychological distress, physical morbidity, and social prejudice.⁹ Consequently, acne patients may be more willing to accept nonprofessional treatment advice, and there is no shortage of non–health care “experts” willing to provide an array of unfounded and fantastical advice. Dietary recommendations found online range from specific “miracle” foods to the more data-driven suggestions to “avoid dairy” or “eat low GI foods.” An important study recently published in Cutis concluded that most of the information found online regarding diet and acne is unfounded and/or misleading.²⁶A quick perusal of results from a Google search conducted on May 28, 2019, using the terms diet and acne included claims such as “salty and oily foods cause acne,” as well as lists provided by so-called experts of “superfoods” that supposedly cure or fight acne, including coconut and olive oil, avocados, oranges, lemons, and kiwis. Problems can arise when this advice is taken seriously.

Two additional reasons for recommending that acne patients consider dietary modification are not directly related to the disease: (1) the general health benefits of a lower GI/GL diet, and (2) the potential for decreasing the use of antibiotics. Antibiotic resistance is a growing problem across medicine, and dermatologists prescribe more antibiotics per provider than any other specialty.¹⁷ Dietary modification, where appropriate, could provide an approach to limiting the use of antibiotics in acne.

Final Thoughts

When advising acne patients, dermatologists can refer to the Table for general guidelines that incorporate the most current data-driven information on the relationship between diet and acne. Dietary modification, of course, will not work for all but can be safely recommended in cases of mild to moderate acne.

Acne is a common condition that most often affects adolescents but is not uncommon in adults. It can result in considerable anxiety, depression, and medical and pharmaceutical costs. Additionally, oral antibiotics, the standard treatment for acne, are increasingly under suspicion for causing bacterial resistance as well as disruption of the cutaneous and gut microbiomes.^1,2 These factors are among those that often drive patients and physicians to search for alternative and complementary treatments, including dietary modification.

Over the last few decades, the interaction between diet and acne has been one of the most fluid areas of research in dermatology. The role of diet in acne incidence and presentation has evolved from the general view in the 1970s that there was no connection to today’s more data-driven understanding that the acne disease course likely is modified by specific dietary components. Better designed and more rigorous studies have supported a link between acne severity and glycemic index (GI)/glycemic load (GL) and possibly dairy consumption. The ability to use data-driven evidence to counsel patients regarding dietary treatment of acne is increasingly important to counteract the pseudoadvice that patients can easily find on the Internet.

This article summarizes the history of beliefs about diet and acne, reviews more recent published data regarding dietary components that can modify acne severity, and outlines the current American Academy of Dermatology (AAD) guidelines and recommendations for diet and acne.

History of Diet and Acne

In most of the current literature, acne frequently is referred to as a disease of modern civilization or a consequence of the typical Western diet.³ For clarity, the Western diet is most commonly described as “a dietary regimen characterized by high amounts of sugary desserts, refined grains, high protein, high-fat dairy products, and high-sugar drinks.”⁴ The role of dairy in the etiology of acne typically is discussed separately from the Western diet. It has been reported that acne is not found in nonwesternized populations where a Paleolithic diet, which does not include consumption of high-GI carbohydrates, milk, or other dairy products, is common.⁵

Extending this line of argument, acne vulgaris has been called a metabolic syndrome of the sebaceous follicle and one of the mammalian target of rapamycin complex 1–driven diseases of civilization, along with cancer, obesity, and diabetes mellitus.³ This view seems somewhat extreme and discounts other drivers of acne incidence and severity. Twin studies have shown that acne is highly heritable, with 81% of the population variance attributed to genetic factors.⁶ Similar incidence numbers for acne vulgaris have been reported worldwide, and global incidence in late adolescence is rising; however, it is unknown whether this increase is a result of the adoption of the Western diet, which is thought to encourage early onset of puberty; genetic drift; changes in regional and cultural understanding and reporting of acne; or a byproduct of unknown environmental factors.⁴ More nuanced views acknowledge that acne is a multifactorial disease,⁷ and therefore genetic and possibly epigenetic factors as well as the cutaneous and gut microbiomes also must be taken into account. An interesting historical perspective on acne by Mahmood and Shipman⁸ outlined acne descriptions, diagnoses, topical treatments, and dietary advice going back to ancient Greek and Egyptian civilizations. They also cited recommendations from the 1930s that suggested avoiding “starchy foods, bread rolls, noodles, spaghetti, potatoes, oily nuts, chop suey, chow mein, and waffles” and listed the following foods as suitable to cure acne: “cooked and raw fruit, farina, rice, wheat, oatmeal, green vegetables, boiled or broiled meat and poultry, clear soup, vegetable soup, and an abundance of water.”⁸

More Recent Evidence of Dietary Influence on Acne

Importantly, the available research does not demonstrate that diet causes acne but rather that it may influence or aggravate existing acne. Data collection for acne studies also can be confounded by the interplay of many factors, such as increased access to health care, socioeconomic status, and shifting cultural perceptions of skin care and beauty.⁴ An important facet of any therapeutic recommendation is that it should be supported by confirmable mechanistic pathways.

GI and GL
Over the last few decades, a number of observational and intervention studies have focused on the possible influence of the GI/GL of foods on acne incidence and/or severity. A high GI diet is characterized by a relatively high intake of carbohydrate-containing foods that are quickly digested and absorbed, increasing blood glucose and insulin concentrations. Glycemic load takes the portion size of dietary carbohydrates into consideration and therefore is a measure of both the quality and quantity of carbohydrate-containing foods.⁹ TheGI/GL values of more than 2480 food items are available in the literature.¹⁰

Evidence from several studies supports the role of high GI/GL diets in exacerbating acne and suggests that transitioning to low GI/GL diets may lead to decreased lesion counts after 12 weeks.^11-13 In one randomized controlled trial, male participants aged 15 to 25 years with mild to moderate facial acne were instructed either to eat a high protein/low GI diet or a conventional high GL control diet.¹³ After 12 weeks, total lesion counts had decreased more in the low GI diet group than the control. As partial confirmation of a mechanistic pathway for a high GI diet and acne, the low GI group demonstrated lower free androgen index and insulin levels than the control group.¹³ In a Korean study, a 10-week low GL regimen led to a reduction in acne lesion count, a decrease in sebaceous gland size, decreased inflammation, and reduced expression of sterol regulatory element-binding protein 1 and IL-8.¹⁴

More recent studies have further solidified the role of high GI/GL diets in acne severity.^9,15,16 High GI/GL diets are believed to stimulate acne pathways by stimulating insulinlike growth factor 1 (IGF-1), which induces proliferation of both keratinocytes and sebocytes and simulates androgen production.¹⁷ An excellent diagram showing the connection between high GI diets (and dairy) and IGF-1, insulin and its receptors, androgen and its receptors, mammalian target of rapamycin, and the pilosebaceous unit was published in the literature in 2016.⁴ Interestingly, metformin has been shown to be an effective adjunctive therapy in the treatment of moderate to severe acne vulgaris.^18,19

Milk and Dairy Consumption
Milk consumption also has been examined for its potential role in the pathogenesis of acne, including its ability to increase insulin and IGF-1 levels and bind to the human IGF-1 receptor as well as the fact that it contains bovine IGF-1 and dihydrotestosterone precursors.²⁰ Although not studied quite as extensively or rigorously as GI/GL, consumption of milk and dairy products does appear to have the potential to exacerbate acne lesions. Beginning with a series of retrospective and prospective epidemiologic studies published from 2005 to 2008,^21-23 a link between clinical acne and milk or dairy consumption in adolescent subjects was reported. A recent meta-analysis found a positive relationship between dairy, total milk, whole milk, low-fat milk, and skim milk consumption and acne occurrence but no significant association between yogurt/cheese consumption and acne development.²⁴

AAD Guidelines

In their public forum, the AAD has advised that a low-glycemic diet may reduce the number of lesions in acne patients and highlighted data from around the world that support the concept that a high-glycemic diet and dairy are correlated with acne severity. They stated that consumption of milk—whole, low fat, and skim—may be linked to an increase in acne breakouts but that no studies have found that products made from milk, such as yogurt or cheese, lead to more breakouts.²⁵

Other Considerations

Acne can be a serious quality-of-life issue with considerable psychological distress, physical morbidity, and social prejudice.⁹ Consequently, acne patients may be more willing to accept nonprofessional treatment advice, and there is no shortage of non–health care “experts” willing to provide an array of unfounded and fantastical advice. Dietary recommendations found online range from specific “miracle” foods to the more data-driven suggestions to “avoid dairy” or “eat low GI foods.” An important study recently published in Cutis concluded that most of the information found online regarding diet and acne is unfounded and/or misleading.²⁶A quick perusal of results from a Google search conducted on May 28, 2019, using the terms diet and acne included claims such as “salty and oily foods cause acne,” as well as lists provided by so-called experts of “superfoods” that supposedly cure or fight acne, including coconut and olive oil, avocados, oranges, lemons, and kiwis. Problems can arise when this advice is taken seriously.

Two additional reasons for recommending that acne patients consider dietary modification are not directly related to the disease: (1) the general health benefits of a lower GI/GL diet, and (2) the potential for decreasing the use of antibiotics. Antibiotic resistance is a growing problem across medicine, and dermatologists prescribe more antibiotics per provider than any other specialty.¹⁷ Dietary modification, where appropriate, could provide an approach to limiting the use of antibiotics in acne.

Final Thoughts

When advising acne patients, dermatologists can refer to the Table for general guidelines that incorporate the most current data-driven information on the relationship between diet and acne. Dietary modification, of course, will not work for all but can be safely recommended in cases of mild to moderate acne.

Acne is a common condition that most often affects adolescents but is not uncommon in adults. It can result in considerable anxiety, depression, and medical and pharmaceutical costs. Additionally, oral antibiotics, the standard treatment for acne, are increasingly under suspicion for causing bacterial resistance as well as disruption of the cutaneous and gut microbiomes.^1,2 These factors are among those that often drive patients and physicians to search for alternative and complementary treatments, including dietary modification.

Over the last few decades, the interaction between diet and acne has been one of the most fluid areas of research in dermatology. The role of diet in acne incidence and presentation has evolved from the general view in the 1970s that there was no connection to today’s more data-driven understanding that the acne disease course likely is modified by specific dietary components. Better designed and more rigorous studies have supported a link between acne severity and glycemic index (GI)/glycemic load (GL) and possibly dairy consumption. The ability to use data-driven evidence to counsel patients regarding dietary treatment of acne is increasingly important to counteract the pseudoadvice that patients can easily find on the Internet.

This article summarizes the history of beliefs about diet and acne, reviews more recent published data regarding dietary components that can modify acne severity, and outlines the current American Academy of Dermatology (AAD) guidelines and recommendations for diet and acne.

History of Diet and Acne

In most of the current literature, acne frequently is referred to as a disease of modern civilization or a consequence of the typical Western diet.³ For clarity, the Western diet is most commonly described as “a dietary regimen characterized by high amounts of sugary desserts, refined grains, high protein, high-fat dairy products, and high-sugar drinks.”⁴ The role of dairy in the etiology of acne typically is discussed separately from the Western diet. It has been reported that acne is not found in nonwesternized populations where a Paleolithic diet, which does not include consumption of high-GI carbohydrates, milk, or other dairy products, is common.⁵

Extending this line of argument, acne vulgaris has been called a metabolic syndrome of the sebaceous follicle and one of the mammalian target of rapamycin complex 1–driven diseases of civilization, along with cancer, obesity, and diabetes mellitus.³ This view seems somewhat extreme and discounts other drivers of acne incidence and severity. Twin studies have shown that acne is highly heritable, with 81% of the population variance attributed to genetic factors.⁶ Similar incidence numbers for acne vulgaris have been reported worldwide, and global incidence in late adolescence is rising; however, it is unknown whether this increase is a result of the adoption of the Western diet, which is thought to encourage early onset of puberty; genetic drift; changes in regional and cultural understanding and reporting of acne; or a byproduct of unknown environmental factors.⁴ More nuanced views acknowledge that acne is a multifactorial disease,⁷ and therefore genetic and possibly epigenetic factors as well as the cutaneous and gut microbiomes also must be taken into account. An interesting historical perspective on acne by Mahmood and Shipman⁸ outlined acne descriptions, diagnoses, topical treatments, and dietary advice going back to ancient Greek and Egyptian civilizations. They also cited recommendations from the 1930s that suggested avoiding “starchy foods, bread rolls, noodles, spaghetti, potatoes, oily nuts, chop suey, chow mein, and waffles” and listed the following foods as suitable to cure acne: “cooked and raw fruit, farina, rice, wheat, oatmeal, green vegetables, boiled or broiled meat and poultry, clear soup, vegetable soup, and an abundance of water.”⁸

More Recent Evidence of Dietary Influence on Acne

Importantly, the available research does not demonstrate that diet causes acne but rather that it may influence or aggravate existing acne. Data collection for acne studies also can be confounded by the interplay of many factors, such as increased access to health care, socioeconomic status, and shifting cultural perceptions of skin care and beauty.⁴ An important facet of any therapeutic recommendation is that it should be supported by confirmable mechanistic pathways.

GI and GL
Over the last few decades, a number of observational and intervention studies have focused on the possible influence of the GI/GL of foods on acne incidence and/or severity. A high GI diet is characterized by a relatively high intake of carbohydrate-containing foods that are quickly digested and absorbed, increasing blood glucose and insulin concentrations. Glycemic load takes the portion size of dietary carbohydrates into consideration and therefore is a measure of both the quality and quantity of carbohydrate-containing foods.⁹ TheGI/GL values of more than 2480 food items are available in the literature.¹⁰

Evidence from several studies supports the role of high GI/GL diets in exacerbating acne and suggests that transitioning to low GI/GL diets may lead to decreased lesion counts after 12 weeks.^11-13 In one randomized controlled trial, male participants aged 15 to 25 years with mild to moderate facial acne were instructed either to eat a high protein/low GI diet or a conventional high GL control diet.¹³ After 12 weeks, total lesion counts had decreased more in the low GI diet group than the control. As partial confirmation of a mechanistic pathway for a high GI diet and acne, the low GI group demonstrated lower free androgen index and insulin levels than the control group.¹³ In a Korean study, a 10-week low GL regimen led to a reduction in acne lesion count, a decrease in sebaceous gland size, decreased inflammation, and reduced expression of sterol regulatory element-binding protein 1 and IL-8.¹⁴

More recent studies have further solidified the role of high GI/GL diets in acne severity.^9,15,16 High GI/GL diets are believed to stimulate acne pathways by stimulating insulinlike growth factor 1 (IGF-1), which induces proliferation of both keratinocytes and sebocytes and simulates androgen production.¹⁷ An excellent diagram showing the connection between high GI diets (and dairy) and IGF-1, insulin and its receptors, androgen and its receptors, mammalian target of rapamycin, and the pilosebaceous unit was published in the literature in 2016.⁴ Interestingly, metformin has been shown to be an effective adjunctive therapy in the treatment of moderate to severe acne vulgaris.^18,19

Milk and Dairy Consumption
Milk consumption also has been examined for its potential role in the pathogenesis of acne, including its ability to increase insulin and IGF-1 levels and bind to the human IGF-1 receptor as well as the fact that it contains bovine IGF-1 and dihydrotestosterone precursors.²⁰ Although not studied quite as extensively or rigorously as GI/GL, consumption of milk and dairy products does appear to have the potential to exacerbate acne lesions. Beginning with a series of retrospective and prospective epidemiologic studies published from 2005 to 2008,^21-23 a link between clinical acne and milk or dairy consumption in adolescent subjects was reported. A recent meta-analysis found a positive relationship between dairy, total milk, whole milk, low-fat milk, and skim milk consumption and acne occurrence but no significant association between yogurt/cheese consumption and acne development.²⁴

AAD Guidelines

In their public forum, the AAD has advised that a low-glycemic diet may reduce the number of lesions in acne patients and highlighted data from around the world that support the concept that a high-glycemic diet and dairy are correlated with acne severity. They stated that consumption of milk—whole, low fat, and skim—may be linked to an increase in acne breakouts but that no studies have found that products made from milk, such as yogurt or cheese, lead to more breakouts.²⁵

Other Considerations

Acne can be a serious quality-of-life issue with considerable psychological distress, physical morbidity, and social prejudice.⁹ Consequently, acne patients may be more willing to accept nonprofessional treatment advice, and there is no shortage of non–health care “experts” willing to provide an array of unfounded and fantastical advice. Dietary recommendations found online range from specific “miracle” foods to the more data-driven suggestions to “avoid dairy” or “eat low GI foods.” An important study recently published in Cutis concluded that most of the information found online regarding diet and acne is unfounded and/or misleading.²⁶A quick perusal of results from a Google search conducted on May 28, 2019, using the terms diet and acne included claims such as “salty and oily foods cause acne,” as well as lists provided by so-called experts of “superfoods” that supposedly cure or fight acne, including coconut and olive oil, avocados, oranges, lemons, and kiwis. Problems can arise when this advice is taken seriously.

Two additional reasons for recommending that acne patients consider dietary modification are not directly related to the disease: (1) the general health benefits of a lower GI/GL diet, and (2) the potential for decreasing the use of antibiotics. Antibiotic resistance is a growing problem across medicine, and dermatologists prescribe more antibiotics per provider than any other specialty.¹⁷ Dietary modification, where appropriate, could provide an approach to limiting the use of antibiotics in acne.

Final Thoughts

When advising acne patients, dermatologists can refer to the Table for general guidelines that incorporate the most current data-driven information on the relationship between diet and acne. Dietary modification, of course, will not work for all but can be safely recommended in cases of mild to moderate acne.