Acne

SEATTLE – It used to be thought that acne begins with microcomedones, which go on to develop either inflammatory lesions or noninflammatory lesions, but more recent evidence has changed that perception, according to Linda Stein Gold, MD, director of dermatology research at Henry Ford Hospital, Detroit.

Biopsies of acne-prone areas have found that, before the development of microcomedones, “it appears that there is inflammation around the hair follicles,” Dr. Stein Gold said at the annual Coastal Dermatology Symposium. “All acne is inflammation acne,” and inflammation also persists, she added. Biopsies of scarred lesions, once considered postinflammatory, also have revealed persistent inflammation, she noted.

One study found that persistent scars can evolve from closed comedones, papules, and pustules, but the most common was a papule that turned into a postinflammatory lesion (J Drugs Dermatol 2017 Jun 1;16[6]:566-72). “So when patients come in and they have these red spots on their face, it’s not over. There’s still time to be aggressive because those inflammatory lesions are more likely to lead to scars than anything else,” Dr. Stein Gold said. “And we also know that papules that develop into scars do so because they’re there for a longer period of time. Those that develop scars are present about 10.5 days, compared with 6.6 days for those that don’t develop into scars.”

She went on to review some of the new treatments for acne that can be brought to bear in such cases. These include developments with topical retinoids that are aimed at improving delivery and reducing skin irritation.

A new topical retinoid, trifarotene cream, 0.005%, showed efficacy and tolerability for both the face and trunk in a recent phase 3 trial of patients with moderate facial and truncal acne and was recently approved for patients aged 9 years and older. In the study, about 30%-40% of people aged 9 years and older treated with once-daily trifarotene cream (Aklief) achieved clear or almost-clear status of the face at 12 weeks, vs. about 20% and 26%, of those on the vehicle cream (J Am Acad Dermatol. 2019 Jun;80[6]:1691-9).

The drug can also treat papules and pustules, nearly as well as it treats blackheads and whiteheads, according to Dr. Stein Gold. Like other retinoids, it produces some redness and scaling and rather than letting these adverse events discourage patients, she leans in. “I tell patients they’re going to have some sloughing of the skin the first 2 weeks. I tell them that people pay money for that. It’s called a chemical peel,” said Dr. Stein Gold, noting that patients respond well to this information.

If patients find the treatments too irritating, she advises them to avoid applying it to wet skin. They can also apply it every other night, or even less frequently, and then work up to more frequent use, she said at the meeting, jointly presented by the University of Louisville and Global Academy for Medical Education.

Tazarotene is another topical retinoid that can be very irritating. A new lotion formulation of tazarotene 0.045% contains a lower dose than the 0.1% typically used in creams, and has similar efficacy but reduced irritation, Dr. Stein Gold said. In August, the manufacturer submitted an application for approval with the Food and Drug Administration for treatment of acne.

Dr. Stein Gold also talked about using retinoids to minimize scarring, referring to a study of patients with moderate and severe facial acne, and atrophic acne scars, comparing adapalene 0.3% plus benzoyl peroxide 2.5% gel on one side of the face and vehicle on the other side of the face for 24 weeks, followed by application of the active treatment to both sides of the face for 24 weeks. Treatment was associated with a reduction of atrophic acne scars at 24 weeks, which was maintained for up to 48 weeks (Am J Clin Dermatol. 2019 Oct[5];20:725-32).

“We can now say to patients, ‘Not only can I help you with your acne, but I can potentially even improve your atrophic scarring,’ ” she said.

Finally, she discussed clascoterone, a novel androgen receptor antagonist, which inhibits sebum production and prevents colonization by Cutibacterium acnes (formerly called Propionibacterium acnes) and subsequent inflammation. “It does a lot of good things in terms of the pathogenesis of acne, but more importantly, it is one of the first drugs that topically has been shown to decrease the production of sebum,” Dr. Stein Gold said. A 1% cream formulation is being studied for acne.

Dr. Stein Gold is a consultant, investigator, and/or speaker for Galderma, Ortho Derm, Sol Gel, Foamix, Cassiopea, and Almirall.

This publication and Global Academy for Medical Education are owned by the same parent company.

SEATTLE – It used to be thought that acne begins with microcomedones, which go on to develop either inflammatory lesions or noninflammatory lesions, but more recent evidence has changed that perception, according to Linda Stein Gold, MD, director of dermatology research at Henry Ford Hospital, Detroit.

Biopsies of acne-prone areas have found that, before the development of microcomedones, “it appears that there is inflammation around the hair follicles,” Dr. Stein Gold said at the annual Coastal Dermatology Symposium. “All acne is inflammation acne,” and inflammation also persists, she added. Biopsies of scarred lesions, once considered postinflammatory, also have revealed persistent inflammation, she noted.

One study found that persistent scars can evolve from closed comedones, papules, and pustules, but the most common was a papule that turned into a postinflammatory lesion (J Drugs Dermatol 2017 Jun 1;16[6]:566-72). “So when patients come in and they have these red spots on their face, it’s not over. There’s still time to be aggressive because those inflammatory lesions are more likely to lead to scars than anything else,” Dr. Stein Gold said. “And we also know that papules that develop into scars do so because they’re there for a longer period of time. Those that develop scars are present about 10.5 days, compared with 6.6 days for those that don’t develop into scars.”

She went on to review some of the new treatments for acne that can be brought to bear in such cases. These include developments with topical retinoids that are aimed at improving delivery and reducing skin irritation.

A new topical retinoid, trifarotene cream, 0.005%, showed efficacy and tolerability for both the face and trunk in a recent phase 3 trial of patients with moderate facial and truncal acne and was recently approved for patients aged 9 years and older. In the study, about 30%-40% of people aged 9 years and older treated with once-daily trifarotene cream (Aklief) achieved clear or almost-clear status of the face at 12 weeks, vs. about 20% and 26%, of those on the vehicle cream (J Am Acad Dermatol. 2019 Jun;80[6]:1691-9).

The drug can also treat papules and pustules, nearly as well as it treats blackheads and whiteheads, according to Dr. Stein Gold. Like other retinoids, it produces some redness and scaling and rather than letting these adverse events discourage patients, she leans in. “I tell patients they’re going to have some sloughing of the skin the first 2 weeks. I tell them that people pay money for that. It’s called a chemical peel,” said Dr. Stein Gold, noting that patients respond well to this information.

If patients find the treatments too irritating, she advises them to avoid applying it to wet skin. They can also apply it every other night, or even less frequently, and then work up to more frequent use, she said at the meeting, jointly presented by the University of Louisville and Global Academy for Medical Education.

Tazarotene is another topical retinoid that can be very irritating. A new lotion formulation of tazarotene 0.045% contains a lower dose than the 0.1% typically used in creams, and has similar efficacy but reduced irritation, Dr. Stein Gold said. In August, the manufacturer submitted an application for approval with the Food and Drug Administration for treatment of acne.

Dr. Stein Gold also talked about using retinoids to minimize scarring, referring to a study of patients with moderate and severe facial acne, and atrophic acne scars, comparing adapalene 0.3% plus benzoyl peroxide 2.5% gel on one side of the face and vehicle on the other side of the face for 24 weeks, followed by application of the active treatment to both sides of the face for 24 weeks. Treatment was associated with a reduction of atrophic acne scars at 24 weeks, which was maintained for up to 48 weeks (Am J Clin Dermatol. 2019 Oct[5];20:725-32).

“We can now say to patients, ‘Not only can I help you with your acne, but I can potentially even improve your atrophic scarring,’ ” she said.

Finally, she discussed clascoterone, a novel androgen receptor antagonist, which inhibits sebum production and prevents colonization by Cutibacterium acnes (formerly called Propionibacterium acnes) and subsequent inflammation. “It does a lot of good things in terms of the pathogenesis of acne, but more importantly, it is one of the first drugs that topically has been shown to decrease the production of sebum,” Dr. Stein Gold said. A 1% cream formulation is being studied for acne.

Dr. Stein Gold is a consultant, investigator, and/or speaker for Galderma, Ortho Derm, Sol Gel, Foamix, Cassiopea, and Almirall.

This publication and Global Academy for Medical Education are owned by the same parent company.

SEATTLE – It used to be thought that acne begins with microcomedones, which go on to develop either inflammatory lesions or noninflammatory lesions, but more recent evidence has changed that perception, according to Linda Stein Gold, MD, director of dermatology research at Henry Ford Hospital, Detroit.

Biopsies of acne-prone areas have found that, before the development of microcomedones, “it appears that there is inflammation around the hair follicles,” Dr. Stein Gold said at the annual Coastal Dermatology Symposium. “All acne is inflammation acne,” and inflammation also persists, she added. Biopsies of scarred lesions, once considered postinflammatory, also have revealed persistent inflammation, she noted.

One study found that persistent scars can evolve from closed comedones, papules, and pustules, but the most common was a papule that turned into a postinflammatory lesion (J Drugs Dermatol 2017 Jun 1;16[6]:566-72). “So when patients come in and they have these red spots on their face, it’s not over. There’s still time to be aggressive because those inflammatory lesions are more likely to lead to scars than anything else,” Dr. Stein Gold said. “And we also know that papules that develop into scars do so because they’re there for a longer period of time. Those that develop scars are present about 10.5 days, compared with 6.6 days for those that don’t develop into scars.”

She went on to review some of the new treatments for acne that can be brought to bear in such cases. These include developments with topical retinoids that are aimed at improving delivery and reducing skin irritation.

A new topical retinoid, trifarotene cream, 0.005%, showed efficacy and tolerability for both the face and trunk in a recent phase 3 trial of patients with moderate facial and truncal acne and was recently approved for patients aged 9 years and older. In the study, about 30%-40% of people aged 9 years and older treated with once-daily trifarotene cream (Aklief) achieved clear or almost-clear status of the face at 12 weeks, vs. about 20% and 26%, of those on the vehicle cream (J Am Acad Dermatol. 2019 Jun;80[6]:1691-9).

The drug can also treat papules and pustules, nearly as well as it treats blackheads and whiteheads, according to Dr. Stein Gold. Like other retinoids, it produces some redness and scaling and rather than letting these adverse events discourage patients, she leans in. “I tell patients they’re going to have some sloughing of the skin the first 2 weeks. I tell them that people pay money for that. It’s called a chemical peel,” said Dr. Stein Gold, noting that patients respond well to this information.

If patients find the treatments too irritating, she advises them to avoid applying it to wet skin. They can also apply it every other night, or even less frequently, and then work up to more frequent use, she said at the meeting, jointly presented by the University of Louisville and Global Academy for Medical Education.

Tazarotene is another topical retinoid that can be very irritating. A new lotion formulation of tazarotene 0.045% contains a lower dose than the 0.1% typically used in creams, and has similar efficacy but reduced irritation, Dr. Stein Gold said. In August, the manufacturer submitted an application for approval with the Food and Drug Administration for treatment of acne.

Dr. Stein Gold also talked about using retinoids to minimize scarring, referring to a study of patients with moderate and severe facial acne, and atrophic acne scars, comparing adapalene 0.3% plus benzoyl peroxide 2.5% gel on one side of the face and vehicle on the other side of the face for 24 weeks, followed by application of the active treatment to both sides of the face for 24 weeks. Treatment was associated with a reduction of atrophic acne scars at 24 weeks, which was maintained for up to 48 weeks (Am J Clin Dermatol. 2019 Oct[5];20:725-32).

“We can now say to patients, ‘Not only can I help you with your acne, but I can potentially even improve your atrophic scarring,’ ” she said.

Finally, she discussed clascoterone, a novel androgen receptor antagonist, which inhibits sebum production and prevents colonization by Cutibacterium acnes (formerly called Propionibacterium acnes) and subsequent inflammation. “It does a lot of good things in terms of the pathogenesis of acne, but more importantly, it is one of the first drugs that topically has been shown to decrease the production of sebum,” Dr. Stein Gold said. A 1% cream formulation is being studied for acne.

Dr. Stein Gold is a consultant, investigator, and/or speaker for Galderma, Ortho Derm, Sol Gel, Foamix, Cassiopea, and Almirall.

This publication and Global Academy for Medical Education are owned by the same parent company.

At least three particular species in the Ocimum family have been associated with a wide array of health benefits. This column will briefly discuss the dermatologic effects of Ocimum gratissimum, O. sanctum (also known as O. tenuiflorum), and O. basilicum. Holy basil is used in Ayurvedic medicine as an “adaptogen” to counter life’s stresses. It is called “holy basil” because it is sacred to the Hindus who plant it around shrines.

O. sanctum (O. tenuiflorum)

Known popularly as holy basil in English and Tulsi in Sanskrit (in which the translation is “the incomparable one”), O. tenuiflorum is used for multiple indications in traditional medical practices in Southeast Asia, including Ayurveda, Siddha, and Unani.^1,2

In Ayurvedic medicine, the leaves, stem, flower, root, seeds, and whole plant of O. sanctum have been used to treat various ailments, including skin diseases. Eugenol (1-hydroxy-2-methoxy-4-allylbenzene) is its primary constituent and the wide variety of biological activities associated with the plant (including antifertility, anticancer, antidiabetic, antifungal, antimicrobial, hepatoprotective, cardioprotective, antiemetic, antispasmodic, analgesic, adaptogenic, and diaphoretic) are ascribed to it.³

O. sanctum and its water-soluble flavonoids, orientin, and vicenin – as well as eugenol, its main nonpolar component – have been shown in animal studies and a few small clinical trials to act against various radiation-induced illnesses. Antioxidant, anti-inflammatory, and metal-chelating activity have been linked to these benefits.⁴ Indeed, multiple studies have demonstrated that O. sanctum exerts anti-inflammatory, analgesic, and immunomodulatory activities, among other beneficial functions, with phytochemical constituents such as eugenol, rosmarinic acid, apigenin, myrtenal, luteolin, beta-sitosterol, and carnosic acid playing critical roles.²

Several animal studies have also demonstrated that O. sanctum imparts wound-healing activity, such as increasing the rates of epithelialization and wound contraction and augmenting granulation tissue and hydroxyproline levels, with some evidence of benefits for also healing keloids and hypertrophic scars.^1,5

Yamani et al. studied the antimicrobial activity of the flower spikes, leaves, and essential oil of O. sanctum grown in Australia in 2016. They found that, at concentrations of 4.5% and 2.25%, the oils prevented the growth of Staphylococcus aureus (including methicillin-resistant S. aureus) and Escherichia coli, and partly hindered the growth of Pseudomonas aeruginosa. Further, the investigators identified camphor, eucalyptol, and eugenol as the primary ingredients, among 54 observed, accountable for the antimicrobial activity. They concluded that O. sanctum essential oil has potential as a topical antimicrobial agent.⁶

A 2015 investigation into the antioxidant activities of 10 essential oils and 10 absolutes extracted from Thai aromatic plants revealed that O. sanctum was among four of the essential oils to display robust antioxidant activity in the 2,2-diphenyl-1-1-picrylhydrazyl and thiobarbituric acid reactive species tests. The study by Leelapornpisid et al. suggested that holy basil oil, along with ginger oil, Wan-sao-long leaf oil, and lemongrass oil, appear to have potential for use as natural antioxidants in cosmetic formulations aimed at preventing or treating cutaneous aging.⁷

O. gratissimum

O. gratissimum has been used in traditional medicine to treat a range of conditions, including skin and gastrointestinal infections and wounds.⁸

In 2007, Ajose reported on the results of history questionnaires filed by patients at a dermatology clinic in Lagos, Nigeria and oral interviews with vendors and prescribers of herbal formulations at busy markets in Lagos and Ijebu-Ode in southwest Nigeria, indicating that O. gratissimum was 1 of the 38 plants used for dermatologic purposes.⁹

O. basilicum

Also known as great basil or St. Joseph’s Wort, O. basilicum is native to tropical regions and is found abundantly from Southeast Asia to Africa. In a 2011 single-blind study, Rasul and Akhtar tested a formulation containing 3% basil in the inner aqueous phase and a base devoid of extract. The formulation exhibited significant effects in skin moisturization, and both creams conferred measurable benefits in stemming transepidermal water loss. Skin roughness, scaliness, smoothness, and wrinkles appeared to improve with the formulation as well. The researchers concluded that topically applied O. basilicum can deliver antiaging benefits.¹²

Antioxidant activity from myriad constituents, including quercetin, kaempferol, caffeic acid, rosmarinic acid, ferulic acid, rutin, and catechin, among others, has been cited for the potential of O. basilicum to confer an antiaging result.^13,14

Conclusion

Various species in the Ocimum family have been used in traditional medicine for many years, with several reputed to impart dermatologic benefits. There are compelling reasons to continue to research these species in the continuing search to develop more effective topical formulations in the dermatologic armamentarium. As is often the case with botanical agents, we need to see much more evidence and clinical trials to establish if and how appropriate these Ocimum species are in the skin care realm. The word “adaptogen” is starting to be used frequently in the cosmeceutical world. Holy basil is an adaptogen.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002) and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems. Write to her at [email protected]

References

1. Rupani R, Chavez A. Clin Dermatol. 2018 May-Jun;36(3):306-9.

2. Baliga MS et al. Nutr Cancer. 2013;65 Suppl 1:26-35.

3. Prakash P, Gupta N. Indian J Physiol Pharmacol. 2005 Apr;49(2):125-31.

4. Baliga MS et al. J Cancer Res Ther. 2016 Jan-Mar;12(1):20-7.

5. Pazyar N et al. Skin Pharmacol Physiol. 2014;27(6):303-10.

6. Yamani HA et al. Front Microbiol. 2016 May 17;7:681.

7. Leelapornpisid P et al. J Cosmet Sci. 2015 Jul-Aug:66(4):219-31.

8. Nweze EI, Eze EE. BMC Complement Altern Med. 2009 Sep 28;9:37.

9. Ajose FOA. Int J Dermatol. 2007 Oct;46 Suppl 1:48-55.

10. Tolino E et al. G Ital Dermatol Venereol. 2018 Dec;153(6):866-871.

11. Keziah EA et al. J Insect Sci. 2015 Apr 15. doi: 10.1093/jisesa/iev025.

12. Rasul A, Akhtar N. Daru. 2011;19(5):344-50.

13. Jadoon S et al. Oxid Med Cell Longev. 2015;2015:709628.

14. Marwat SK et al. Asian J Chem. 2011;23(9):3773-82.
 

At least three particular species in the Ocimum family have been associated with a wide array of health benefits. This column will briefly discuss the dermatologic effects of Ocimum gratissimum, O. sanctum (also known as O. tenuiflorum), and O. basilicum. Holy basil is used in Ayurvedic medicine as an “adaptogen” to counter life’s stresses. It is called “holy basil” because it is sacred to the Hindus who plant it around shrines.

O. sanctum (O. tenuiflorum)

Known popularly as holy basil in English and Tulsi in Sanskrit (in which the translation is “the incomparable one”), O. tenuiflorum is used for multiple indications in traditional medical practices in Southeast Asia, including Ayurveda, Siddha, and Unani.^1,2

In Ayurvedic medicine, the leaves, stem, flower, root, seeds, and whole plant of O. sanctum have been used to treat various ailments, including skin diseases. Eugenol (1-hydroxy-2-methoxy-4-allylbenzene) is its primary constituent and the wide variety of biological activities associated with the plant (including antifertility, anticancer, antidiabetic, antifungal, antimicrobial, hepatoprotective, cardioprotective, antiemetic, antispasmodic, analgesic, adaptogenic, and diaphoretic) are ascribed to it.³

O. sanctum and its water-soluble flavonoids, orientin, and vicenin – as well as eugenol, its main nonpolar component – have been shown in animal studies and a few small clinical trials to act against various radiation-induced illnesses. Antioxidant, anti-inflammatory, and metal-chelating activity have been linked to these benefits.⁴ Indeed, multiple studies have demonstrated that O. sanctum exerts anti-inflammatory, analgesic, and immunomodulatory activities, among other beneficial functions, with phytochemical constituents such as eugenol, rosmarinic acid, apigenin, myrtenal, luteolin, beta-sitosterol, and carnosic acid playing critical roles.²

Several animal studies have also demonstrated that O. sanctum imparts wound-healing activity, such as increasing the rates of epithelialization and wound contraction and augmenting granulation tissue and hydroxyproline levels, with some evidence of benefits for also healing keloids and hypertrophic scars.^1,5

Yamani et al. studied the antimicrobial activity of the flower spikes, leaves, and essential oil of O. sanctum grown in Australia in 2016. They found that, at concentrations of 4.5% and 2.25%, the oils prevented the growth of Staphylococcus aureus (including methicillin-resistant S. aureus) and Escherichia coli, and partly hindered the growth of Pseudomonas aeruginosa. Further, the investigators identified camphor, eucalyptol, and eugenol as the primary ingredients, among 54 observed, accountable for the antimicrobial activity. They concluded that O. sanctum essential oil has potential as a topical antimicrobial agent.⁶

A 2015 investigation into the antioxidant activities of 10 essential oils and 10 absolutes extracted from Thai aromatic plants revealed that O. sanctum was among four of the essential oils to display robust antioxidant activity in the 2,2-diphenyl-1-1-picrylhydrazyl and thiobarbituric acid reactive species tests. The study by Leelapornpisid et al. suggested that holy basil oil, along with ginger oil, Wan-sao-long leaf oil, and lemongrass oil, appear to have potential for use as natural antioxidants in cosmetic formulations aimed at preventing or treating cutaneous aging.⁷

O. gratissimum

O. gratissimum has been used in traditional medicine to treat a range of conditions, including skin and gastrointestinal infections and wounds.⁸

In 2007, Ajose reported on the results of history questionnaires filed by patients at a dermatology clinic in Lagos, Nigeria and oral interviews with vendors and prescribers of herbal formulations at busy markets in Lagos and Ijebu-Ode in southwest Nigeria, indicating that O. gratissimum was 1 of the 38 plants used for dermatologic purposes.⁹

O. basilicum

Also known as great basil or St. Joseph’s Wort, O. basilicum is native to tropical regions and is found abundantly from Southeast Asia to Africa. In a 2011 single-blind study, Rasul and Akhtar tested a formulation containing 3% basil in the inner aqueous phase and a base devoid of extract. The formulation exhibited significant effects in skin moisturization, and both creams conferred measurable benefits in stemming transepidermal water loss. Skin roughness, scaliness, smoothness, and wrinkles appeared to improve with the formulation as well. The researchers concluded that topically applied O. basilicum can deliver antiaging benefits.¹²

Antioxidant activity from myriad constituents, including quercetin, kaempferol, caffeic acid, rosmarinic acid, ferulic acid, rutin, and catechin, among others, has been cited for the potential of O. basilicum to confer an antiaging result.^13,14

Conclusion

Various species in the Ocimum family have been used in traditional medicine for many years, with several reputed to impart dermatologic benefits. There are compelling reasons to continue to research these species in the continuing search to develop more effective topical formulations in the dermatologic armamentarium. As is often the case with botanical agents, we need to see much more evidence and clinical trials to establish if and how appropriate these Ocimum species are in the skin care realm. The word “adaptogen” is starting to be used frequently in the cosmeceutical world. Holy basil is an adaptogen.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002) and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems. Write to her at [email protected]

References

1. Rupani R, Chavez A. Clin Dermatol. 2018 May-Jun;36(3):306-9.

2. Baliga MS et al. Nutr Cancer. 2013;65 Suppl 1:26-35.

3. Prakash P, Gupta N. Indian J Physiol Pharmacol. 2005 Apr;49(2):125-31.

4. Baliga MS et al. J Cancer Res Ther. 2016 Jan-Mar;12(1):20-7.

5. Pazyar N et al. Skin Pharmacol Physiol. 2014;27(6):303-10.

6. Yamani HA et al. Front Microbiol. 2016 May 17;7:681.

7. Leelapornpisid P et al. J Cosmet Sci. 2015 Jul-Aug:66(4):219-31.

8. Nweze EI, Eze EE. BMC Complement Altern Med. 2009 Sep 28;9:37.

9. Ajose FOA. Int J Dermatol. 2007 Oct;46 Suppl 1:48-55.

10. Tolino E et al. G Ital Dermatol Venereol. 2018 Dec;153(6):866-871.

11. Keziah EA et al. J Insect Sci. 2015 Apr 15. doi: 10.1093/jisesa/iev025.

12. Rasul A, Akhtar N. Daru. 2011;19(5):344-50.

13. Jadoon S et al. Oxid Med Cell Longev. 2015;2015:709628.

14. Marwat SK et al. Asian J Chem. 2011;23(9):3773-82.
 

At least three particular species in the Ocimum family have been associated with a wide array of health benefits. This column will briefly discuss the dermatologic effects of Ocimum gratissimum, O. sanctum (also known as O. tenuiflorum), and O. basilicum. Holy basil is used in Ayurvedic medicine as an “adaptogen” to counter life’s stresses. It is called “holy basil” because it is sacred to the Hindus who plant it around shrines.

O. sanctum (O. tenuiflorum)

Known popularly as holy basil in English and Tulsi in Sanskrit (in which the translation is “the incomparable one”), O. tenuiflorum is used for multiple indications in traditional medical practices in Southeast Asia, including Ayurveda, Siddha, and Unani.^1,2

In Ayurvedic medicine, the leaves, stem, flower, root, seeds, and whole plant of O. sanctum have been used to treat various ailments, including skin diseases. Eugenol (1-hydroxy-2-methoxy-4-allylbenzene) is its primary constituent and the wide variety of biological activities associated with the plant (including antifertility, anticancer, antidiabetic, antifungal, antimicrobial, hepatoprotective, cardioprotective, antiemetic, antispasmodic, analgesic, adaptogenic, and diaphoretic) are ascribed to it.³

O. sanctum and its water-soluble flavonoids, orientin, and vicenin – as well as eugenol, its main nonpolar component – have been shown in animal studies and a few small clinical trials to act against various radiation-induced illnesses. Antioxidant, anti-inflammatory, and metal-chelating activity have been linked to these benefits.⁴ Indeed, multiple studies have demonstrated that O. sanctum exerts anti-inflammatory, analgesic, and immunomodulatory activities, among other beneficial functions, with phytochemical constituents such as eugenol, rosmarinic acid, apigenin, myrtenal, luteolin, beta-sitosterol, and carnosic acid playing critical roles.²

Several animal studies have also demonstrated that O. sanctum imparts wound-healing activity, such as increasing the rates of epithelialization and wound contraction and augmenting granulation tissue and hydroxyproline levels, with some evidence of benefits for also healing keloids and hypertrophic scars.^1,5

Yamani et al. studied the antimicrobial activity of the flower spikes, leaves, and essential oil of O. sanctum grown in Australia in 2016. They found that, at concentrations of 4.5% and 2.25%, the oils prevented the growth of Staphylococcus aureus (including methicillin-resistant S. aureus) and Escherichia coli, and partly hindered the growth of Pseudomonas aeruginosa. Further, the investigators identified camphor, eucalyptol, and eugenol as the primary ingredients, among 54 observed, accountable for the antimicrobial activity. They concluded that O. sanctum essential oil has potential as a topical antimicrobial agent.⁶

A 2015 investigation into the antioxidant activities of 10 essential oils and 10 absolutes extracted from Thai aromatic plants revealed that O. sanctum was among four of the essential oils to display robust antioxidant activity in the 2,2-diphenyl-1-1-picrylhydrazyl and thiobarbituric acid reactive species tests. The study by Leelapornpisid et al. suggested that holy basil oil, along with ginger oil, Wan-sao-long leaf oil, and lemongrass oil, appear to have potential for use as natural antioxidants in cosmetic formulations aimed at preventing or treating cutaneous aging.⁷

O. gratissimum

O. gratissimum has been used in traditional medicine to treat a range of conditions, including skin and gastrointestinal infections and wounds.⁸

In 2007, Ajose reported on the results of history questionnaires filed by patients at a dermatology clinic in Lagos, Nigeria and oral interviews with vendors and prescribers of herbal formulations at busy markets in Lagos and Ijebu-Ode in southwest Nigeria, indicating that O. gratissimum was 1 of the 38 plants used for dermatologic purposes.⁹

O. basilicum

Also known as great basil or St. Joseph’s Wort, O. basilicum is native to tropical regions and is found abundantly from Southeast Asia to Africa. In a 2011 single-blind study, Rasul and Akhtar tested a formulation containing 3% basil in the inner aqueous phase and a base devoid of extract. The formulation exhibited significant effects in skin moisturization, and both creams conferred measurable benefits in stemming transepidermal water loss. Skin roughness, scaliness, smoothness, and wrinkles appeared to improve with the formulation as well. The researchers concluded that topically applied O. basilicum can deliver antiaging benefits.¹²

Antioxidant activity from myriad constituents, including quercetin, kaempferol, caffeic acid, rosmarinic acid, ferulic acid, rutin, and catechin, among others, has been cited for the potential of O. basilicum to confer an antiaging result.^13,14

Conclusion

Various species in the Ocimum family have been used in traditional medicine for many years, with several reputed to impart dermatologic benefits. There are compelling reasons to continue to research these species in the continuing search to develop more effective topical formulations in the dermatologic armamentarium. As is often the case with botanical agents, we need to see much more evidence and clinical trials to establish if and how appropriate these Ocimum species are in the skin care realm. The word “adaptogen” is starting to be used frequently in the cosmeceutical world. Holy basil is an adaptogen.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002) and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems. Write to her at [email protected]

References

1. Rupani R, Chavez A. Clin Dermatol. 2018 May-Jun;36(3):306-9.

2. Baliga MS et al. Nutr Cancer. 2013;65 Suppl 1:26-35.

3. Prakash P, Gupta N. Indian J Physiol Pharmacol. 2005 Apr;49(2):125-31.

4. Baliga MS et al. J Cancer Res Ther. 2016 Jan-Mar;12(1):20-7.

5. Pazyar N et al. Skin Pharmacol Physiol. 2014;27(6):303-10.

6. Yamani HA et al. Front Microbiol. 2016 May 17;7:681.

7. Leelapornpisid P et al. J Cosmet Sci. 2015 Jul-Aug:66(4):219-31.

8. Nweze EI, Eze EE. BMC Complement Altern Med. 2009 Sep 28;9:37.

9. Ajose FOA. Int J Dermatol. 2007 Oct;46 Suppl 1:48-55.

10. Tolino E et al. G Ital Dermatol Venereol. 2018 Dec;153(6):866-871.

11. Keziah EA et al. J Insect Sci. 2015 Apr 15. doi: 10.1093/jisesa/iev025.

12. Rasul A, Akhtar N. Daru. 2011;19(5):344-50.

13. Jadoon S et al. Oxid Med Cell Longev. 2015;2015:709628.

14. Marwat SK et al. Asian J Chem. 2011;23(9):3773-82.
 

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.

[email protected]

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.

[email protected]

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.

[email protected]

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.