Aesthetic Dermatology

Parabens were named nonallergen of the year! It is time that we help consumers understand that the substitutes for parabens are often worse than parabens, and parabens are not as sensitizing as we thought. Preservatives are essential parts of most cosmetics and cosmeceuticals. (I say “most” because many organic products do not have them and consequently have shorter shelf lives.) Without them, products are vulnerable to rapid decomposition and infiltration by bacteria, fungi, and molds. The preservatives that are used in the place of parabens often are sensitizers. What do we tell our patients about the safety of parabens with all of these conflicting reports? This column will focus on current thoughts regarding the safety of parabens used as preservatives. I would love to hear your thoughts.

Background

monticelllo/iStock/Getty Images Plus

Parabens are alkyl esters of p-hydroxybenzoic acid and have been used as a class of preservatives since the late 1920s and early 1930s. Parabens are found naturally in raspberries, blackberries, carrots, and cucumbers and are common ingredients in food and pharmaceuticals. They are still widely used in skin, hair, and body care products, despite the public outcry against them.^1-4

There are many kinds of parabens such as butylparaben, isobutylparaben, ethylparaben, methylparaben, propylparaben, isopropylparaben, and benzylparaben, each with its own characteristics.⁵ Parabens are considered ideal preservative ingredients because they exhibit a broad spectrum of antimicrobial activity, stability over a large pH and temperature range, have no odor, do not change color, and are water soluble enough to yield an effective concentration in a hydrophilic formulation.³ As the alkyl chain length of parabens increases, they become less water soluble and more oil soluble. Parabens penetrate the skin barrier in inverse relation to its ester chain length.⁶ Often, several parabens will be combined to take advantage of each paraben’s solubility characteristics.

Many patients avoid parabens because of “health risks.” Now other preservatives are being substituted for parabens, even though these ingredients may be less studied or even less safe than parabens. It is important not to lump all parabens together as they each have different characteristics. Methylparaben and propylparaben are the most commonly used parabens in skin care products.⁷ Combinations of parabens are notably more effective than the use of single parabens.^3,8 High concentrations of any type of paraben can cause an irritant reaction on the skin, but those with longer ester chain lengths are more likely to cause irritation.

Methylparaben

The methyl ester of p-hydroxybenzoic acid is found in many skin care products. It is readily absorbed through the skin and gastrointestinal tract. It is quickly hydrolyzed and excreted in the urine and does not accumulate in the body. Studies have shown it is nontoxic, nonirritating, and nonsensitizing. It is not teratogenic, embryotoxic, or carcinogenic. Methylparaben, because of its shorter side chain groups and greater lipophilicity, has been shown to be more readily absorbed by the skin than other paraben chemicals.^8,9 It is also on the low order of ingredients provoking acute and chronic toxicity.³

Propylparaben

Propylparaben is the ester form of p-hydroxybenzoic acid that has been esterified with n-propanol. It is the most commonly used antimicrobial preservative in foods, cosmetics, and drugs. It is readily absorbed through the skin and GI tract. It is quickly hydrolyzed and excreted in the urine and does not accumulate in the body.

Estrogenic activity of parabens

In a 2004 study, Darbre et al. reported on the discovery of parabens-like substances in breast tissue and published these findings in the Journal of Applied Toxicology.¹⁰ The media and public panicked, saying that parabens have estrogenic activity and can cause breast cancer. However, many studies have shown that certain parabens do not have estrogenic activity. Although some parabens have been shown to impart estrogenic effects in vitro, these are very weak. The four most commonly used parabens in cosmetic products are 10,000-fold or less potent than 17beta-estradiol.¹¹ The potential to result in an adverse effect mediated via an estrogen mode of action has not been established in humans.⁶ Paraben exposure differs geographically. No correlation has been found between the amount of parabens in a geographic location and the incidence of breast cancer. Current scientific knowledge is insufficient to demonstrate a clear cancer risk caused by the topical application of cosmetics that contain parabens on normal intact skin.¹¹

Parabens and contact dermatitis

Paraben compounds are capable of minimal penetrance through intact skin.¹² When they are able to penetrate the skin – a capacity that varies among the class – parabens are rapidly metabolized to p-hydroxybenzoic acid and promptly excreted in the urine.^3,11 Parabens for many years were thought to cause contact dermatitis, and there are many reports of this. However, the incidence is much lower than previously thought. In fact, parabens were named “Nonallergen of the Year in 2018” because of the low incidence of reactions in patch tests.¹³ Higher concentrations of parabens applied topically to skin – especially “nonintact” skin – have been shown to cause mild irritant reactions. It is likely that many of these reported cases of “contact dermatitis” were actually irritant dermatitis. Longstanding concerns about the allergenicity of parabens in relation to the skin have been rendered insignificant, as the wealth of evidence reveals little to no support for the cutaneous toxicity of these substances.¹¹ Yim et al. add that parabens remain far less sensitizing than agents newly introduced for use in personal care products.⁴

Daily average exposure to parabens

It is estimated that parabens are found in 10% of personal care products. In most cases, these products contain 1% or less of parabens. If the average patient uses 50 g of personal care products a day, then the average daily exposure to parabens topically is 0.05 g. Parabens also are found in food and drugs, so the total paraben exposure per day is assumed to be about 1 mg/day. (See the 2002 Food and Chemical Toxicology article for details of how this was calculated.)⁷ When food, personal care products, and drug exposure rates are added, the average person is exposed to 1.29 mg/kg per day or 77.5 mg/day for a 60-kg individual. You can see that personal care products account for a fraction of exposure, as most paraben exposure comes from food.

Government opinion on the safety of parabens for the skin

Parabens long have been assessed as safe for use in cosmetic products in many countries. The European Commission stipulated a maximum concentration of 0.4% for each paraben and 0.8% for total mixture of paraben esters.^4,6 While the Federal Food, Drug, and Cosmetic Act of 1938 prohibits the Food and Drug Administration from ruling on cosmetic ingredients, the industry-sponsored Cosmetic Ingredient Review expert panel has endorsed the European guidelines.^4,6 Further, the North American Contact Dermatitis Group has pointed out that parabens continue to demonstrate the lowest prevalence of positivity (0.6%) of any major preservative available on the North American market, which includes over 10,000 cosmetic and personal care products, and remain one of the safest classes of preservatives for the skin.¹⁴ Further, the FDA has listed or classified parabens as generally regarded as safe.⁸

Safety of parabens

Parabens do not accumulate in tissues or organs for any appreciable length of time.^6,8 In addition, carcinogenicity, cytotoxicity, or mutagenicity has not been proven in relation to parabens.⁸ Indeed, classical assays have shown no activity from parabens in terms of mutagenicity or carcinogenicity.^11,15 Some estrogenic effects or activity that mimics estrogen have been associated with parabens in vitro, but this activity has been noted as very weak and there are no established reports of human cases in which parabens have elicited an estrogen-mediated adverse event.^6,11

Concerns about a possible link between parabens and breast cancer have been largely diminished or relegated to the status of unknown and difficult to ascertain.¹³ Further, present knowledge provides no established link between the topical application of parabens-containing skin care formulations on healthy skin and cancer risk.¹⁰ Only intact skin should come in touch with products containing parabens to prevent irritant reactions.

Conclusion

Despite the fearful hype and reaction to one report 15 years ago, parabens continue to be safely used in numerous topical formulations. Their widespread use and lack of association with adverse events are a testament to their safety. There are no data to support discouraging patients from using parabens-containing products, which often are safer than other preservative alternatives. From a dermatologic perspective, this nonallergen of the year deserves a better reputation.

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. “Goodman and Gilman’s The Pharmacological Basis of Therapeutics,” 6th ed. (New York: Macmillan, 1980, p. 969).

2. Toxicity: The Butyl, Ethyl, Methyl, and Propyl Esters have been found to promote allergic sensitization in humans, in “Dangerous Properties of Industrial Materials,” 4th ed. (New York: Van Nostrand Reinhold, 1975, p. 929).

3. Food Chem Toxicol. 2001 Jun;39(6):513-32.

4. Dermatitis. 2014 Sep-Oct;25(5):215-31.

5. Crit Rev Toxicol. 2005 Jun;35(5):435-58.

6. Int J Toxicol. 2008;27 Suppl 4:1-82.

7. Food Chem Toxicol. 2002 Oct;40(10):1335-73.

8. Dermatitis. 2019 Jan/Feb;30(1):3-31.

9. Exp Dermatol. 2007 Oct;16(10):830-6.

10. J Appl Toxicol. 2004 Jan-Feb;24(1):5-13.

11. Dermatitis. 2019 Jan/Feb;30(1):32-45.

12. Food Chem Toxicol. 2005 Feb;43(2):279-91.

13. Dermatitis. 2018 Dec 18. doi: 10.1097/DER.0000000000000429.

14. Dermatitis. 2018 Nov/Dec;29(6):297-309.

15. Food Chem Toxicol. 2005 Jul;43(7):985-1015.

Parabens were named nonallergen of the year! It is time that we help consumers understand that the substitutes for parabens are often worse than parabens, and parabens are not as sensitizing as we thought. Preservatives are essential parts of most cosmetics and cosmeceuticals. (I say “most” because many organic products do not have them and consequently have shorter shelf lives.) Without them, products are vulnerable to rapid decomposition and infiltration by bacteria, fungi, and molds. The preservatives that are used in the place of parabens often are sensitizers. What do we tell our patients about the safety of parabens with all of these conflicting reports? This column will focus on current thoughts regarding the safety of parabens used as preservatives. I would love to hear your thoughts.

Background

monticelllo/iStock/Getty Images Plus

Parabens are alkyl esters of p-hydroxybenzoic acid and have been used as a class of preservatives since the late 1920s and early 1930s. Parabens are found naturally in raspberries, blackberries, carrots, and cucumbers and are common ingredients in food and pharmaceuticals. They are still widely used in skin, hair, and body care products, despite the public outcry against them.^1-4

There are many kinds of parabens such as butylparaben, isobutylparaben, ethylparaben, methylparaben, propylparaben, isopropylparaben, and benzylparaben, each with its own characteristics.⁵ Parabens are considered ideal preservative ingredients because they exhibit a broad spectrum of antimicrobial activity, stability over a large pH and temperature range, have no odor, do not change color, and are water soluble enough to yield an effective concentration in a hydrophilic formulation.³ As the alkyl chain length of parabens increases, they become less water soluble and more oil soluble. Parabens penetrate the skin barrier in inverse relation to its ester chain length.⁶ Often, several parabens will be combined to take advantage of each paraben’s solubility characteristics.

Many patients avoid parabens because of “health risks.” Now other preservatives are being substituted for parabens, even though these ingredients may be less studied or even less safe than parabens. It is important not to lump all parabens together as they each have different characteristics. Methylparaben and propylparaben are the most commonly used parabens in skin care products.⁷ Combinations of parabens are notably more effective than the use of single parabens.^3,8 High concentrations of any type of paraben can cause an irritant reaction on the skin, but those with longer ester chain lengths are more likely to cause irritation.

Methylparaben

The methyl ester of p-hydroxybenzoic acid is found in many skin care products. It is readily absorbed through the skin and gastrointestinal tract. It is quickly hydrolyzed and excreted in the urine and does not accumulate in the body. Studies have shown it is nontoxic, nonirritating, and nonsensitizing. It is not teratogenic, embryotoxic, or carcinogenic. Methylparaben, because of its shorter side chain groups and greater lipophilicity, has been shown to be more readily absorbed by the skin than other paraben chemicals.^8,9 It is also on the low order of ingredients provoking acute and chronic toxicity.³

Propylparaben

Propylparaben is the ester form of p-hydroxybenzoic acid that has been esterified with n-propanol. It is the most commonly used antimicrobial preservative in foods, cosmetics, and drugs. It is readily absorbed through the skin and GI tract. It is quickly hydrolyzed and excreted in the urine and does not accumulate in the body.

Estrogenic activity of parabens

In a 2004 study, Darbre et al. reported on the discovery of parabens-like substances in breast tissue and published these findings in the Journal of Applied Toxicology.¹⁰ The media and public panicked, saying that parabens have estrogenic activity and can cause breast cancer. However, many studies have shown that certain parabens do not have estrogenic activity. Although some parabens have been shown to impart estrogenic effects in vitro, these are very weak. The four most commonly used parabens in cosmetic products are 10,000-fold or less potent than 17beta-estradiol.¹¹ The potential to result in an adverse effect mediated via an estrogen mode of action has not been established in humans.⁶ Paraben exposure differs geographically. No correlation has been found between the amount of parabens in a geographic location and the incidence of breast cancer. Current scientific knowledge is insufficient to demonstrate a clear cancer risk caused by the topical application of cosmetics that contain parabens on normal intact skin.¹¹

Parabens and contact dermatitis

Paraben compounds are capable of minimal penetrance through intact skin.¹² When they are able to penetrate the skin – a capacity that varies among the class – parabens are rapidly metabolized to p-hydroxybenzoic acid and promptly excreted in the urine.^3,11 Parabens for many years were thought to cause contact dermatitis, and there are many reports of this. However, the incidence is much lower than previously thought. In fact, parabens were named “Nonallergen of the Year in 2018” because of the low incidence of reactions in patch tests.¹³ Higher concentrations of parabens applied topically to skin – especially “nonintact” skin – have been shown to cause mild irritant reactions. It is likely that many of these reported cases of “contact dermatitis” were actually irritant dermatitis. Longstanding concerns about the allergenicity of parabens in relation to the skin have been rendered insignificant, as the wealth of evidence reveals little to no support for the cutaneous toxicity of these substances.¹¹ Yim et al. add that parabens remain far less sensitizing than agents newly introduced for use in personal care products.⁴

Daily average exposure to parabens

It is estimated that parabens are found in 10% of personal care products. In most cases, these products contain 1% or less of parabens. If the average patient uses 50 g of personal care products a day, then the average daily exposure to parabens topically is 0.05 g. Parabens also are found in food and drugs, so the total paraben exposure per day is assumed to be about 1 mg/day. (See the 2002 Food and Chemical Toxicology article for details of how this was calculated.)⁷ When food, personal care products, and drug exposure rates are added, the average person is exposed to 1.29 mg/kg per day or 77.5 mg/day for a 60-kg individual. You can see that personal care products account for a fraction of exposure, as most paraben exposure comes from food.

Government opinion on the safety of parabens for the skin

Parabens long have been assessed as safe for use in cosmetic products in many countries. The European Commission stipulated a maximum concentration of 0.4% for each paraben and 0.8% for total mixture of paraben esters.^4,6 While the Federal Food, Drug, and Cosmetic Act of 1938 prohibits the Food and Drug Administration from ruling on cosmetic ingredients, the industry-sponsored Cosmetic Ingredient Review expert panel has endorsed the European guidelines.^4,6 Further, the North American Contact Dermatitis Group has pointed out that parabens continue to demonstrate the lowest prevalence of positivity (0.6%) of any major preservative available on the North American market, which includes over 10,000 cosmetic and personal care products, and remain one of the safest classes of preservatives for the skin.¹⁴ Further, the FDA has listed or classified parabens as generally regarded as safe.⁸

Safety of parabens

Parabens do not accumulate in tissues or organs for any appreciable length of time.^6,8 In addition, carcinogenicity, cytotoxicity, or mutagenicity has not been proven in relation to parabens.⁸ Indeed, classical assays have shown no activity from parabens in terms of mutagenicity or carcinogenicity.^11,15 Some estrogenic effects or activity that mimics estrogen have been associated with parabens in vitro, but this activity has been noted as very weak and there are no established reports of human cases in which parabens have elicited an estrogen-mediated adverse event.^6,11

Concerns about a possible link between parabens and breast cancer have been largely diminished or relegated to the status of unknown and difficult to ascertain.¹³ Further, present knowledge provides no established link between the topical application of parabens-containing skin care formulations on healthy skin and cancer risk.¹⁰ Only intact skin should come in touch with products containing parabens to prevent irritant reactions.

Conclusion

Despite the fearful hype and reaction to one report 15 years ago, parabens continue to be safely used in numerous topical formulations. Their widespread use and lack of association with adverse events are a testament to their safety. There are no data to support discouraging patients from using parabens-containing products, which often are safer than other preservative alternatives. From a dermatologic perspective, this nonallergen of the year deserves a better reputation.

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. “Goodman and Gilman’s The Pharmacological Basis of Therapeutics,” 6th ed. (New York: Macmillan, 1980, p. 969).

2. Toxicity: The Butyl, Ethyl, Methyl, and Propyl Esters have been found to promote allergic sensitization in humans, in “Dangerous Properties of Industrial Materials,” 4th ed. (New York: Van Nostrand Reinhold, 1975, p. 929).

3. Food Chem Toxicol. 2001 Jun;39(6):513-32.

4. Dermatitis. 2014 Sep-Oct;25(5):215-31.

5. Crit Rev Toxicol. 2005 Jun;35(5):435-58.

6. Int J Toxicol. 2008;27 Suppl 4:1-82.

7. Food Chem Toxicol. 2002 Oct;40(10):1335-73.

8. Dermatitis. 2019 Jan/Feb;30(1):3-31.

9. Exp Dermatol. 2007 Oct;16(10):830-6.

10. J Appl Toxicol. 2004 Jan-Feb;24(1):5-13.

11. Dermatitis. 2019 Jan/Feb;30(1):32-45.

12. Food Chem Toxicol. 2005 Feb;43(2):279-91.

13. Dermatitis. 2018 Dec 18. doi: 10.1097/DER.0000000000000429.

14. Dermatitis. 2018 Nov/Dec;29(6):297-309.

15. Food Chem Toxicol. 2005 Jul;43(7):985-1015.

Parabens were named nonallergen of the year! It is time that we help consumers understand that the substitutes for parabens are often worse than parabens, and parabens are not as sensitizing as we thought. Preservatives are essential parts of most cosmetics and cosmeceuticals. (I say “most” because many organic products do not have them and consequently have shorter shelf lives.) Without them, products are vulnerable to rapid decomposition and infiltration by bacteria, fungi, and molds. The preservatives that are used in the place of parabens often are sensitizers. What do we tell our patients about the safety of parabens with all of these conflicting reports? This column will focus on current thoughts regarding the safety of parabens used as preservatives. I would love to hear your thoughts.

Background

monticelllo/iStock/Getty Images Plus

Parabens are alkyl esters of p-hydroxybenzoic acid and have been used as a class of preservatives since the late 1920s and early 1930s. Parabens are found naturally in raspberries, blackberries, carrots, and cucumbers and are common ingredients in food and pharmaceuticals. They are still widely used in skin, hair, and body care products, despite the public outcry against them.^1-4

There are many kinds of parabens such as butylparaben, isobutylparaben, ethylparaben, methylparaben, propylparaben, isopropylparaben, and benzylparaben, each with its own characteristics.⁵ Parabens are considered ideal preservative ingredients because they exhibit a broad spectrum of antimicrobial activity, stability over a large pH and temperature range, have no odor, do not change color, and are water soluble enough to yield an effective concentration in a hydrophilic formulation.³ As the alkyl chain length of parabens increases, they become less water soluble and more oil soluble. Parabens penetrate the skin barrier in inverse relation to its ester chain length.⁶ Often, several parabens will be combined to take advantage of each paraben’s solubility characteristics.

Many patients avoid parabens because of “health risks.” Now other preservatives are being substituted for parabens, even though these ingredients may be less studied or even less safe than parabens. It is important not to lump all parabens together as they each have different characteristics. Methylparaben and propylparaben are the most commonly used parabens in skin care products.⁷ Combinations of parabens are notably more effective than the use of single parabens.^3,8 High concentrations of any type of paraben can cause an irritant reaction on the skin, but those with longer ester chain lengths are more likely to cause irritation.

Methylparaben

The methyl ester of p-hydroxybenzoic acid is found in many skin care products. It is readily absorbed through the skin and gastrointestinal tract. It is quickly hydrolyzed and excreted in the urine and does not accumulate in the body. Studies have shown it is nontoxic, nonirritating, and nonsensitizing. It is not teratogenic, embryotoxic, or carcinogenic. Methylparaben, because of its shorter side chain groups and greater lipophilicity, has been shown to be more readily absorbed by the skin than other paraben chemicals.^8,9 It is also on the low order of ingredients provoking acute and chronic toxicity.³

Propylparaben

Propylparaben is the ester form of p-hydroxybenzoic acid that has been esterified with n-propanol. It is the most commonly used antimicrobial preservative in foods, cosmetics, and drugs. It is readily absorbed through the skin and GI tract. It is quickly hydrolyzed and excreted in the urine and does not accumulate in the body.

Estrogenic activity of parabens

In a 2004 study, Darbre et al. reported on the discovery of parabens-like substances in breast tissue and published these findings in the Journal of Applied Toxicology.¹⁰ The media and public panicked, saying that parabens have estrogenic activity and can cause breast cancer. However, many studies have shown that certain parabens do not have estrogenic activity. Although some parabens have been shown to impart estrogenic effects in vitro, these are very weak. The four most commonly used parabens in cosmetic products are 10,000-fold or less potent than 17beta-estradiol.¹¹ The potential to result in an adverse effect mediated via an estrogen mode of action has not been established in humans.⁶ Paraben exposure differs geographically. No correlation has been found between the amount of parabens in a geographic location and the incidence of breast cancer. Current scientific knowledge is insufficient to demonstrate a clear cancer risk caused by the topical application of cosmetics that contain parabens on normal intact skin.¹¹

Parabens and contact dermatitis

Paraben compounds are capable of minimal penetrance through intact skin.¹² When they are able to penetrate the skin – a capacity that varies among the class – parabens are rapidly metabolized to p-hydroxybenzoic acid and promptly excreted in the urine.^3,11 Parabens for many years were thought to cause contact dermatitis, and there are many reports of this. However, the incidence is much lower than previously thought. In fact, parabens were named “Nonallergen of the Year in 2018” because of the low incidence of reactions in patch tests.¹³ Higher concentrations of parabens applied topically to skin – especially “nonintact” skin – have been shown to cause mild irritant reactions. It is likely that many of these reported cases of “contact dermatitis” were actually irritant dermatitis. Longstanding concerns about the allergenicity of parabens in relation to the skin have been rendered insignificant, as the wealth of evidence reveals little to no support for the cutaneous toxicity of these substances.¹¹ Yim et al. add that parabens remain far less sensitizing than agents newly introduced for use in personal care products.⁴

Daily average exposure to parabens

It is estimated that parabens are found in 10% of personal care products. In most cases, these products contain 1% or less of parabens. If the average patient uses 50 g of personal care products a day, then the average daily exposure to parabens topically is 0.05 g. Parabens also are found in food and drugs, so the total paraben exposure per day is assumed to be about 1 mg/day. (See the 2002 Food and Chemical Toxicology article for details of how this was calculated.)⁷ When food, personal care products, and drug exposure rates are added, the average person is exposed to 1.29 mg/kg per day or 77.5 mg/day for a 60-kg individual. You can see that personal care products account for a fraction of exposure, as most paraben exposure comes from food.

Government opinion on the safety of parabens for the skin

Parabens long have been assessed as safe for use in cosmetic products in many countries. The European Commission stipulated a maximum concentration of 0.4% for each paraben and 0.8% for total mixture of paraben esters.^4,6 While the Federal Food, Drug, and Cosmetic Act of 1938 prohibits the Food and Drug Administration from ruling on cosmetic ingredients, the industry-sponsored Cosmetic Ingredient Review expert panel has endorsed the European guidelines.^4,6 Further, the North American Contact Dermatitis Group has pointed out that parabens continue to demonstrate the lowest prevalence of positivity (0.6%) of any major preservative available on the North American market, which includes over 10,000 cosmetic and personal care products, and remain one of the safest classes of preservatives for the skin.¹⁴ Further, the FDA has listed or classified parabens as generally regarded as safe.⁸

Safety of parabens

Parabens do not accumulate in tissues or organs for any appreciable length of time.^6,8 In addition, carcinogenicity, cytotoxicity, or mutagenicity has not been proven in relation to parabens.⁸ Indeed, classical assays have shown no activity from parabens in terms of mutagenicity or carcinogenicity.^11,15 Some estrogenic effects or activity that mimics estrogen have been associated with parabens in vitro, but this activity has been noted as very weak and there are no established reports of human cases in which parabens have elicited an estrogen-mediated adverse event.^6,11

Concerns about a possible link between parabens and breast cancer have been largely diminished or relegated to the status of unknown and difficult to ascertain.¹³ Further, present knowledge provides no established link between the topical application of parabens-containing skin care formulations on healthy skin and cancer risk.¹⁰ Only intact skin should come in touch with products containing parabens to prevent irritant reactions.

Conclusion

Despite the fearful hype and reaction to one report 15 years ago, parabens continue to be safely used in numerous topical formulations. Their widespread use and lack of association with adverse events are a testament to their safety. There are no data to support discouraging patients from using parabens-containing products, which often are safer than other preservative alternatives. From a dermatologic perspective, this nonallergen of the year deserves a better reputation.

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. “Goodman and Gilman’s The Pharmacological Basis of Therapeutics,” 6th ed. (New York: Macmillan, 1980, p. 969).

2. Toxicity: The Butyl, Ethyl, Methyl, and Propyl Esters have been found to promote allergic sensitization in humans, in “Dangerous Properties of Industrial Materials,” 4th ed. (New York: Van Nostrand Reinhold, 1975, p. 929).

3. Food Chem Toxicol. 2001 Jun;39(6):513-32.

4. Dermatitis. 2014 Sep-Oct;25(5):215-31.

5. Crit Rev Toxicol. 2005 Jun;35(5):435-58.

6. Int J Toxicol. 2008;27 Suppl 4:1-82.

7. Food Chem Toxicol. 2002 Oct;40(10):1335-73.

8. Dermatitis. 2019 Jan/Feb;30(1):3-31.

9. Exp Dermatol. 2007 Oct;16(10):830-6.

10. J Appl Toxicol. 2004 Jan-Feb;24(1):5-13.

11. Dermatitis. 2019 Jan/Feb;30(1):32-45.

12. Food Chem Toxicol. 2005 Feb;43(2):279-91.

13. Dermatitis. 2018 Dec 18. doi: 10.1097/DER.0000000000000429.

14. Dermatitis. 2018 Nov/Dec;29(6):297-309.

15. Food Chem Toxicol. 2005 Jul;43(7):985-1015.

Case Report

A 32-year-old woman presented to the dermatology clinic with a tender lump overlying the right maxilla of 6 weeks’ duration. The lesion developed acutely 1 to 2 months after the patient began using an at-home microdermabrasion device, which she routinely cleaned with tap water. The physical examination was notable for a 1.5-cm, soft, superficially indurated plaque on the right cheek without associated lymphadenopathy (Figure).

A punch biopsy revealed underlying necrotic fat. Computed tomography of the neck showed 20-mm skin thickening overlying the right zygomatic arch, with minimal adjacent subcutaneous soft tissue stranding and reactive lymph nodes. Further histologic examination of the biopsy specimen revealed inflamed granulation tissue with granulomatous inflammation.

Acid-fast bacterial culture was positive. Subsequent speciation revealed the causal agent to be multidrug-resistant Mycobacterium abscessus. The patient was initially treated with trimethoprim-sulfamethoxazole, which was switched to a combination of doxycycline and levofloxacin a few days later after initial culture returned. The following week, after the specific microorganism was confirmed with specific sensitivity, treatment was changed to intravenous (IV) tigecycline and amikacin. This regimen was continued for 2 more months through a peripherally inserted central catheter, then discontinued after complete resolution of the skin lesion.

Comment

Mycobacterial Infection
Nontuberculous mycobacteria were not identified as human pathogens until the 1950s. They are known to cause skin disease, lymphadenitis, skeletal infection, pulmonary disease, and disseminated infection, with pulmonary disease being the most common clinical form overall.¹Mycobacterium abscessus is a member of a more specific group known as rapidly growing nontuberculous mycobacteria, which also includes Mycobacterium fortuitum and Mycobacterium chelonae.² Commonly found in water, soil, and dust, M abscessus causes skin and soft tissue infection after skin injury by inoculation, minor trauma, or surgery.^2-4 An increased rate of infections recently has been attributed to an increase in cosmetic procedures such as tattooing, liposuction, mesotherapy, pedicures, and body piercing. Mycobacterial infections transmitted through acupuncture also have been documented.^5,6

Causes of Skin and Soft Tissue Infections
Skin and soft tissue infections due to rapidly growing mycobacteria often are associated with systemic comorbidities that cause immunosuppression and with immunosuppressive medications.⁷ Our patient did not have a preexisting comorbidity and did not take any long-term medication. When multiple lesions have been reported, patients were more likely to either have a systemic comorbidity or be taking immunosuppressive medication compared to patients with a single lesion. A history of penetrating trauma or an invasive surgical procedure has been reported more often in patients with a single lesion.⁷

Our patient had a solitary lesion on the face; improper sterile technique while using an at-home microdermabrasion device was thought to be the cause of infection. Although generally considered a minimally abrasive treatment modality, microdermabrasion caused enough trauma to create a nidus of infection in our patient.

Presentation
Cutaneous infection from rapidly growing mycobacteria can manifest as a nonhealing ulceration, subcutaneous abscess, draining sinus, or subcutaneous fluctuant or firm nodules. Erythema may be found in association with ulcers or chronic drainage from a surgical wound.^2,7

Histopathologic appearance varies, depending on the evolution of the disease and host immunologic status. Tuberculoid, palisading, and sarcoidlike granulomas; a diffuse infiltrate of histiocytic foamy cells; acute and chronic panniculitis; nonspecific chronic inflammation; cutaneous abscess; suppurative granuloma; and necrotizing folliculitis all can be seen.⁸ Immunosuppressed patients are less likely to form granulomas.⁶ Diagnosis often is delayed because acid-fast bacterial culture is not typically performed on skin biopsy specimens or surgical wound infections.⁷ Fortunately, a high index of suspicion in our patient’s case allowed for prompt diagnosis and expeditious management.

Management
Mycobacterium abscessus tends to be resistant to conventional antituberculous medications; overall, it is considered a highly drug-resistant pathogen that is difficult to treat.^9,10 Treatment usually requires 3 to 6 months of therapy, with oral clarithromycin considered the first-line agent for localized infection.⁵ Because cases of clarithromycin resistance have been reported in patients with M chelonae infection, caution is warranted when deciding between monotherapy or combination therapy.⁷ Multidrug resistance often necessitates prolonged IV therapy. Amikacin is the mostly commonly used IV agent for M abscessus infection. Adverse effects of treatment are common, often leading to a change in or discontinuation of therapy.¹¹

Our patient was initially given trimethoprim-sulfamethoxazole before being switched to doxycycline and levofloxacin prior to final results of susceptibility testing. Ultimately, due to the multidrug-resistant nature of M abscessus, clarithromycin was not a viable option. Therefore, the patient was administered tigecycline and amikacin through a peripherally inserted central catheter until symptoms fully resolved.

Surgery can be an important adjunctive measure for certain patients, especially those with a single lesion.⁷ Our patient did well with medical treatment alone.

Conclusion

Given the difficulty of treating skin and soft tissue infections caused by M abscessus and related mycobacteria, it is worth noting that these infections are increasingly caused by procedures generally considered to be minimally invasive. Microdermabrasion—performed at home in an unsterile environment and not by a trained medical professional—was the causal procedure in this case. An important consideration is whether clinicians can be comfortable with the use of these treatments at home or whether they should be advising patients against at-home treatments that have potentially serious complications.

Case Report

A 32-year-old woman presented to the dermatology clinic with a tender lump overlying the right maxilla of 6 weeks’ duration. The lesion developed acutely 1 to 2 months after the patient began using an at-home microdermabrasion device, which she routinely cleaned with tap water. The physical examination was notable for a 1.5-cm, soft, superficially indurated plaque on the right cheek without associated lymphadenopathy (Figure).

A punch biopsy revealed underlying necrotic fat. Computed tomography of the neck showed 20-mm skin thickening overlying the right zygomatic arch, with minimal adjacent subcutaneous soft tissue stranding and reactive lymph nodes. Further histologic examination of the biopsy specimen revealed inflamed granulation tissue with granulomatous inflammation.

Acid-fast bacterial culture was positive. Subsequent speciation revealed the causal agent to be multidrug-resistant Mycobacterium abscessus. The patient was initially treated with trimethoprim-sulfamethoxazole, which was switched to a combination of doxycycline and levofloxacin a few days later after initial culture returned. The following week, after the specific microorganism was confirmed with specific sensitivity, treatment was changed to intravenous (IV) tigecycline and amikacin. This regimen was continued for 2 more months through a peripherally inserted central catheter, then discontinued after complete resolution of the skin lesion.

Comment

Mycobacterial Infection
Nontuberculous mycobacteria were not identified as human pathogens until the 1950s. They are known to cause skin disease, lymphadenitis, skeletal infection, pulmonary disease, and disseminated infection, with pulmonary disease being the most common clinical form overall.¹Mycobacterium abscessus is a member of a more specific group known as rapidly growing nontuberculous mycobacteria, which also includes Mycobacterium fortuitum and Mycobacterium chelonae.² Commonly found in water, soil, and dust, M abscessus causes skin and soft tissue infection after skin injury by inoculation, minor trauma, or surgery.^2-4 An increased rate of infections recently has been attributed to an increase in cosmetic procedures such as tattooing, liposuction, mesotherapy, pedicures, and body piercing. Mycobacterial infections transmitted through acupuncture also have been documented.^5,6

Causes of Skin and Soft Tissue Infections
Skin and soft tissue infections due to rapidly growing mycobacteria often are associated with systemic comorbidities that cause immunosuppression and with immunosuppressive medications.⁷ Our patient did not have a preexisting comorbidity and did not take any long-term medication. When multiple lesions have been reported, patients were more likely to either have a systemic comorbidity or be taking immunosuppressive medication compared to patients with a single lesion. A history of penetrating trauma or an invasive surgical procedure has been reported more often in patients with a single lesion.⁷

Our patient had a solitary lesion on the face; improper sterile technique while using an at-home microdermabrasion device was thought to be the cause of infection. Although generally considered a minimally abrasive treatment modality, microdermabrasion caused enough trauma to create a nidus of infection in our patient.

Presentation
Cutaneous infection from rapidly growing mycobacteria can manifest as a nonhealing ulceration, subcutaneous abscess, draining sinus, or subcutaneous fluctuant or firm nodules. Erythema may be found in association with ulcers or chronic drainage from a surgical wound.^2,7

Histopathologic appearance varies, depending on the evolution of the disease and host immunologic status. Tuberculoid, palisading, and sarcoidlike granulomas; a diffuse infiltrate of histiocytic foamy cells; acute and chronic panniculitis; nonspecific chronic inflammation; cutaneous abscess; suppurative granuloma; and necrotizing folliculitis all can be seen.⁸ Immunosuppressed patients are less likely to form granulomas.⁶ Diagnosis often is delayed because acid-fast bacterial culture is not typically performed on skin biopsy specimens or surgical wound infections.⁷ Fortunately, a high index of suspicion in our patient’s case allowed for prompt diagnosis and expeditious management.

Management
Mycobacterium abscessus tends to be resistant to conventional antituberculous medications; overall, it is considered a highly drug-resistant pathogen that is difficult to treat.^9,10 Treatment usually requires 3 to 6 months of therapy, with oral clarithromycin considered the first-line agent for localized infection.⁵ Because cases of clarithromycin resistance have been reported in patients with M chelonae infection, caution is warranted when deciding between monotherapy or combination therapy.⁷ Multidrug resistance often necessitates prolonged IV therapy. Amikacin is the mostly commonly used IV agent for M abscessus infection. Adverse effects of treatment are common, often leading to a change in or discontinuation of therapy.¹¹

Our patient was initially given trimethoprim-sulfamethoxazole before being switched to doxycycline and levofloxacin prior to final results of susceptibility testing. Ultimately, due to the multidrug-resistant nature of M abscessus, clarithromycin was not a viable option. Therefore, the patient was administered tigecycline and amikacin through a peripherally inserted central catheter until symptoms fully resolved.

Surgery can be an important adjunctive measure for certain patients, especially those with a single lesion.⁷ Our patient did well with medical treatment alone.

Conclusion

Given the difficulty of treating skin and soft tissue infections caused by M abscessus and related mycobacteria, it is worth noting that these infections are increasingly caused by procedures generally considered to be minimally invasive. Microdermabrasion—performed at home in an unsterile environment and not by a trained medical professional—was the causal procedure in this case. An important consideration is whether clinicians can be comfortable with the use of these treatments at home or whether they should be advising patients against at-home treatments that have potentially serious complications.

Case Report

A 32-year-old woman presented to the dermatology clinic with a tender lump overlying the right maxilla of 6 weeks’ duration. The lesion developed acutely 1 to 2 months after the patient began using an at-home microdermabrasion device, which she routinely cleaned with tap water. The physical examination was notable for a 1.5-cm, soft, superficially indurated plaque on the right cheek without associated lymphadenopathy (Figure).

A punch biopsy revealed underlying necrotic fat. Computed tomography of the neck showed 20-mm skin thickening overlying the right zygomatic arch, with minimal adjacent subcutaneous soft tissue stranding and reactive lymph nodes. Further histologic examination of the biopsy specimen revealed inflamed granulation tissue with granulomatous inflammation.

Acid-fast bacterial culture was positive. Subsequent speciation revealed the causal agent to be multidrug-resistant Mycobacterium abscessus. The patient was initially treated with trimethoprim-sulfamethoxazole, which was switched to a combination of doxycycline and levofloxacin a few days later after initial culture returned. The following week, after the specific microorganism was confirmed with specific sensitivity, treatment was changed to intravenous (IV) tigecycline and amikacin. This regimen was continued for 2 more months through a peripherally inserted central catheter, then discontinued after complete resolution of the skin lesion.

Comment

Mycobacterial Infection
Nontuberculous mycobacteria were not identified as human pathogens until the 1950s. They are known to cause skin disease, lymphadenitis, skeletal infection, pulmonary disease, and disseminated infection, with pulmonary disease being the most common clinical form overall.¹Mycobacterium abscessus is a member of a more specific group known as rapidly growing nontuberculous mycobacteria, which also includes Mycobacterium fortuitum and Mycobacterium chelonae.² Commonly found in water, soil, and dust, M abscessus causes skin and soft tissue infection after skin injury by inoculation, minor trauma, or surgery.^2-4 An increased rate of infections recently has been attributed to an increase in cosmetic procedures such as tattooing, liposuction, mesotherapy, pedicures, and body piercing. Mycobacterial infections transmitted through acupuncture also have been documented.^5,6

Causes of Skin and Soft Tissue Infections
Skin and soft tissue infections due to rapidly growing mycobacteria often are associated with systemic comorbidities that cause immunosuppression and with immunosuppressive medications.⁷ Our patient did not have a preexisting comorbidity and did not take any long-term medication. When multiple lesions have been reported, patients were more likely to either have a systemic comorbidity or be taking immunosuppressive medication compared to patients with a single lesion. A history of penetrating trauma or an invasive surgical procedure has been reported more often in patients with a single lesion.⁷

Our patient had a solitary lesion on the face; improper sterile technique while using an at-home microdermabrasion device was thought to be the cause of infection. Although generally considered a minimally abrasive treatment modality, microdermabrasion caused enough trauma to create a nidus of infection in our patient.

Presentation
Cutaneous infection from rapidly growing mycobacteria can manifest as a nonhealing ulceration, subcutaneous abscess, draining sinus, or subcutaneous fluctuant or firm nodules. Erythema may be found in association with ulcers or chronic drainage from a surgical wound.^2,7

Histopathologic appearance varies, depending on the evolution of the disease and host immunologic status. Tuberculoid, palisading, and sarcoidlike granulomas; a diffuse infiltrate of histiocytic foamy cells; acute and chronic panniculitis; nonspecific chronic inflammation; cutaneous abscess; suppurative granuloma; and necrotizing folliculitis all can be seen.⁸ Immunosuppressed patients are less likely to form granulomas.⁶ Diagnosis often is delayed because acid-fast bacterial culture is not typically performed on skin biopsy specimens or surgical wound infections.⁷ Fortunately, a high index of suspicion in our patient’s case allowed for prompt diagnosis and expeditious management.

Management
Mycobacterium abscessus tends to be resistant to conventional antituberculous medications; overall, it is considered a highly drug-resistant pathogen that is difficult to treat.^9,10 Treatment usually requires 3 to 6 months of therapy, with oral clarithromycin considered the first-line agent for localized infection.⁵ Because cases of clarithromycin resistance have been reported in patients with M chelonae infection, caution is warranted when deciding between monotherapy or combination therapy.⁷ Multidrug resistance often necessitates prolonged IV therapy. Amikacin is the mostly commonly used IV agent for M abscessus infection. Adverse effects of treatment are common, often leading to a change in or discontinuation of therapy.¹¹

Our patient was initially given trimethoprim-sulfamethoxazole before being switched to doxycycline and levofloxacin prior to final results of susceptibility testing. Ultimately, due to the multidrug-resistant nature of M abscessus, clarithromycin was not a viable option. Therefore, the patient was administered tigecycline and amikacin through a peripherally inserted central catheter until symptoms fully resolved.

Surgery can be an important adjunctive measure for certain patients, especially those with a single lesion.⁷ Our patient did well with medical treatment alone.

Conclusion

Given the difficulty of treating skin and soft tissue infections caused by M abscessus and related mycobacteria, it is worth noting that these infections are increasingly caused by procedures generally considered to be minimally invasive. Microdermabrasion—performed at home in an unsterile environment and not by a trained medical professional—was the causal procedure in this case. An important consideration is whether clinicians can be comfortable with the use of these treatments at home or whether they should be advising patients against at-home treatments that have potentially serious complications.

Hair plays an important role in identity, self-perception, and psychosocial functioning. Hair loss can be a devastating experience that decreases self-esteem and feelings of personal attractiveness while also leading to depression and anxiety.^1,2 Although increasingly popular, surgical hair restoration, including hair transplantation, is costly and carries considerable risk.

Results of nonsurgical hair restoration are not immediate and may not be as dramatic; however, they do not carry the risks or recovery associated with surgical options. Treatments such as sex steroid hormone and biologic response modifiers have been used to inhibit hair miniaturization and stabilize hair loss in cases of androgenic alopecia (AGA).³ Currently, minoxidil and finasteride are the only US Food and Drug Administration (FDA)–approved medications for the treatment of hair loss; however, other nonsurgical treatment options have gained popularity, including dutasteride, spironolactone, low-level laser therapy (LLLT), platelet-rich plasma (PRP), microneedling, stem cells, and nutraceutical supplements. We provide an overview of these treatment options to help dermatologists select appropriate therapies for the treatment of alopecia (Table).

Minoxidil

Minoxidil has been known to improve hair growth for more than 40 years. Oral minoxidil was first introduced for hypertension in the 1970s with a common adverse effect of hypertrichosis; the 2% solution was marketed for AGA shortly thereafter in 1986.⁴ Minoxidil is a biologic response modifier that is thought to promote hair growth through vasodilation and stimulation of hair follicles into the growth phase.⁵ In animal studies, topical minoxidil has been shown to shorten telogen, prolong anagen, and increase hair follicle size.^6,7 More recently, topical minoxidil was shown to have anti-inflammatory effects by downregulating IL-1, which may confer an additional role in combatting alopecia.⁸

Minoxidil is FDA approved for treatment of AGA in men and women and often is used as first-line therapy.⁹ In 3 separate meta-analyses of topical minoxidil, it was shown to be more effective than placebo for treating AGA in men and women, with a notable increase in target area hair growth.¹⁰ A study of 777 male patients treated with topical minoxidil 2% found that 45% subjectively experienced new hair growth.¹¹ However, results may vary, and research indicates that higher concentrations are more effective. In a randomized, double-blind, placebo-controlled trial of 381 women with female pattern hair loss (FPHL), minoxidil solution 2% was found to be superior to placebo after 48 weeks, with average changes in nonvellus hair counts of 20.7/cm² in the minoxidil group vs 9.4/cm² in the placebo group.¹² In a separate meta-analysis, minoxidil solution 5% demonstrated superiority to both the 2% formulation and placebo with a mean change in nonvellus hair counts of 26.0/cm^2.13

Minoxidil also has demonstrated promising benefits in preventing chemotherapy-induced alopecia. Although oncologists most often use the scalp cooling method to prevent hair loss by decreasing perfusion and uptake of cytotoxic agents, cost may be prohibitive, as it is often not reimbursable by insurance companies.^14,15 On the other hand, minoxidil is easily procured over-the-counter and has been successfully used to decrease the duration of alopecia caused by chemotherapeutic agents such as fluorouracil, doxorubicin, and cyclophosphamide, as well as endocrine therapies used to treat breast cancer in women.^16-18 Minoxidil also has been used off label to treat other forms of alopecia, including alopecia areata, telogen effluvium, eyebrow hypotrichosis, and monilethrix; however, there is inconclusive evidence for its efficacy.^5,13,19

Compared to other nonsurgical treatments for hair loss, a meta-analysis found that minoxidil was associated with the highest rate of adverse effects (AEs).^16,17 Potential side effects include pruritus or burning at the application site; irritant or allergic contact dermatitis; hypertrichosis; and cardiovascular effects, which may be due to the vasodilatory mechanism of action of minoxidil.²⁰ One randomized double-blind study found that while topical minoxidil did not affect blood pressure, it increased heart rate by 3 to 5 beats per minute, caused considerable increases in left ventricular end-diastolic volume, an increase in cardiac output (by 0.751 min^-1), and an increase in left ventricular mass (by 5 g m^-2). The authors concluded that short-term use is safe in healthy individuals, but providers should ask about history of coronary artery disease to avoid potential cardiac side effects.²¹

Patients also should be advised that at least 6 months of minoxidil therapy may be necessary.¹¹ Furthermore, measurable hair changes may disappear within 3 months if the patient chooses to discontinue treatment.²² Finally, providers must consider patient perception of improvement and hair growth while on this medication. In one study, although investigator assessments of hair growth and hair count were increased with the use of minoxidil solution 5% compared to placebo, differences in patient assessment of hair growth were not significant at 48 weeks.²² Therefore, dermatologists should address patient expectations and consider additional treatments if necessary.

Finasteride

Finasteride is an oral medication that is FDA approved at a dose of 1 mg daily for the treatment of AGA in men. It competitively inhibits the type I and type II 5α-reductase enzymes, with a strong affinity for the type II enzyme, thereby inhibiting the conversion of testosterone to dihydrotestosterone (DHT), the potent androgen responsible for terminal hair follicle miniaturization and transformation of terminal hair into vellus hair.^21,23

Finasteride has demonstrated efficacy and high tolerability in large-scale, placebo-controlled, randomized trials with only rare complications of sexual dysfunction, supporting its status as a first-line agent.^24,25 One study found that in a population of 3177 Japanese men, an overall increase in hair growth was seen in 87.1% of men receiving oral finasteride 1 mg daily, with AEs such as decreased libido occurring in only 0.7% of patients.²⁶ However, postmarketing studies described more severe complications in men taking finasteride to treat AGA or benign prostatic hyperplasia, even after the discontinuation of medication, described as postfinasteride syndrome.^27,28 These side effects include decreased libido, reduction in penis size, gynecomastia, erectile dysfunction, and ejaculation disorder, in addition to psychologic impairments, including decreased concentration, depression, and suicidal ideation, presumably due to the role of 5α-reductase interacting with the γ-aminobutyric acid (GABA_A) receptor within the central nervous system.²⁹ The incidence of persistent erectile dysfunction was reported to be as low as 1.4% in a study assessing 11,909 men prescribed up to 5 mg once daily of finasteride to treat benign prostatic hyperplasia and AGA. The incidence was higher in patients using higher doses of finasteride and longer treatment courses as well as in patients with prostate disease.²⁹ These potential side effects should be discussed with male patients prior to prescribing finasteride.

Finasteride is not FDA approved for use in women and is considered category X in pregnancy due to animal studies that demonstrated external genital abnormalities in male fetuses exposed to type II 5α-reductase inhibitors.³⁰ Despite this potential teratogenicity, finasteride is prescribed off label to treat FPHL and hirsutism. A meta-analysis of 2683 women participating in 65 studies found that finasteride, when used at dosages of 0.5 to 5 mg daily, may improve FPHL and frontal fibrosing alopecia after 6 to 12 months.³⁰ However, available studies have used varying treatment methods, yielding differing results. For example, one randomized trial of 137 postmenopausal women with FPHL and normal androgen levels found no benefit with 1 mg daily³¹; however, another trial of 87 women with normal levels of androgens found that 5 mg daily of finasteride showed significant improvements in hair quantity and thickness after 12 months (P<.01).³² Further studies are needed to assess the appropriate female population that may benefit from use of finasteride. Premenopausal women interested in this therapy should be counseled about the risk of teratogenicity, as well as potential breast tenderness, loss of libido, and menstrual irregularities.³³ Furthermore, finasteride use in women may pose a theoretical risk of breast cancer, as DHT inhibition results in conversion of excess testosterone to estrogen, thereby altering the estrogen to androgen ratio.³⁴

Dutasteride

Dutasteride is 100-times more potent than finasteride as an inhibitor of type I 5α-reductase enzyme and 3-times more potent as an inhibitor of type I 5α-reductase enzyme.³⁵ Therefore, it has been hypothesized that dutasteride may be more effective than finasteride for restoring hair loss, though it is not yet FDA approved for this indication.

Research evaluating the efficacy of dutasteride is emerging. Randomized controlled trials in men with AGA are promising and suggest reversed hair miniaturization.³⁶ One randomized trial of 153 men found that dutasteride 0.5 mg daily was superior to placebo for the treatment of hair loss, as evidenced by an increase in hair counts in dutasteride patients (12.2/cm²) compared to controls (4.7/cm²). Furthermore, 0.5-mg dutasteride resulted in significantly increased new hair growth after 24 weeks compared to a placebo control (23/cm² vs 4/cm²; P<.05).³⁷

Dutasteride also is now being used off label to treat FPHL. Little evidence-based research exists regarding the use of dutasteride in women, though 1 case report described successful treatment of FPHL after 6 months of treatment with 0.5 mg daily of dutasteride in a 46-year-old woman who showed only minimal improvement on oral finasteride.³⁸

The side-effect profile is similar to finasteride, and research in the urologic literature demonstrated that the rate of AEs is comparable between the 2 drugs, with reports of sexual side effects occurring in 11% of patients taking dutasteride 0.5 mg daily vs 14% of patients taking finasteride 5 mg daily.³⁹ In the dermatologic literature, there was no statistically significant difference between the rate of AEs, specifically sexual AEs, in patients taking dutasteride 0.5 mg daily vs finasteride 1 mg daily.³⁶ Safety of dutasteride in women is not well established. The side-effect profile described for finasteride, including the risk of potential fetal anomalies, should be discussed with women receiving dutasteride therapy.

Spironolactone

Although topical minoxidil is still considered first-line therapy for women experiencing hair loss, spironolactone is growing in popularity as an off-label treatment of FPHL, though it is not FDA approved for this indication. Spironolactone is a synthetic steroid that has been used as a potassium-sparing diuretic for more than 60 years. Its primary metabolite, canrenone, competitively inhibits aldosterone.³⁷ It is FDA approved for the treatment of essential hypertension (25–100 mg), congestive heart failure (25 mg), diuretic-induced hypokalemia (25–100 mg), and primary hyperaldosteronism (100–400 mg).^37,40 Spironolactone was serendipitously discovered to treat hirsutism, acne, and seborrhea associated with polycystic ovary syndrome.⁴¹

Androgens are well studied in male pattern hair loss, and their role in FPHL is now becoming evident, with new research supporting the role of spironolactone as a useful antiandrogen.^42,43 An Australian open-label trial randomized 80 women with biopsy-proven FPHL to receive either spironolactone 200 mg daily or cyproterone acetate, an antiandrogen used abroad, including in European countries, in conjunction with an oral contraceptive pill for premenopausal women.⁴² Spironolactone was found to be as effective as the alternate regimen, with 44% of patients experiencing hair regrowth, 44% experiencing no progression of hair loss, and only 12% experiencing continued hair loss.⁴⁴ Spironolactone used in combination with minoxidil has been shown to demonstrate greater efficacy when compared to spironolactone alone.⁴⁵ One observational study of 100 women with FPHL found that once-daily capsules of minoxidil 0.25 mg combined with once daily spironolactone 25 mg was a safe and effective treatment of FPHL.⁴⁴ Spironolactone also is considered safe and effective to treat FPHL in postmenopausal women by inhibiting the relative androgen excess.⁴⁶

The starting dose for spironolactone usually is 25 mg twice daily and increased by 50 mg daily up to 200 mg daily as tolerated. Furthermore, results should be monitored for at least 6 months to assess efficacy accurately.⁴⁷ Side effects include headache, decreased libido, menstrual irregularities, orthostatic hypotension, fatigue, and hyperkalemia. Although hyperkalemia is a known side effect of spironolactone, one study of 974 male and female participants receiving spironolactone found that only 0.72% of participants experienced mild hyperkalemia (5.1–6.0 mEq/L) with no patients experiencing moderate or severe hyperkalemia. Regardless, providers may consider checking potassium levels within 4 to 8 weeks of initiating treatment with spironolactone.⁴⁸ Other potential AEs include gynecomastia and feminization; therefore, it is not recommended for use in men.⁴² Oral contraception is recommended to prevent pregnancy in premenopausal women, as spironolactone may cause feminization of the male fetus. Because of the antiandrogenic and progestogenic effects of spironolactone, there has been a theoretical concern for risk of inducing breast cancer, especially in postmenopausal women. However, a study conducted in the United Kingdom of more than 1 million female patients older than 55 years found that there was no increased risk of breast cancer in postmenopausal women.⁴⁹

Low-Level Laser Light Therapy

Low-level laser light therapy has been used to reduce pain, treat edema, and promote would healing for almost 50 years and is now one of the few FDA-cleared devices to treat alopecia. Low-level laser light therapy uses red beam or near-infrared nonthermal lasers at a wavelength of 600 to 1000 nm and from 5 to 500 mW. The exact mechanism of hair growth stimulation is not known; however, it is believed that LLLT accelerates mitosis, stimulates hair follicle stem cells to activate follicular keratinocytes, and alters cellular metabolism by inhibiting nitric oxide from cytochrome c oxidase.⁵⁰

Trials evaluating the efficacy of LLLT laser combs for the treatment of AGA have demonstrated notable improvements in hair density. For example, one sham device–controlled, double-blind clinical trial randomized 334 men and women to treatment with either an FDA-cleared laser comb vs sham devices.⁵¹ The treatment devices were used 3 times weekly for 26 weeks. Hair counts for those treated with the 7-, 9-, and 12-beam LLLT laser combs were significantly higher than the sham after 26 weeks (P<.05), without any serious AEs being reported.⁵¹ Another study in men with AGA proved similarly efficacious results using at-home LLLT therapy of 655 nm to the scalp every other day for 16 weeks (60 treatments).⁵² However, a 24-week randomized, double-blind, sham device–controlled, multicenter trial evaluating the LLLT helmet (combining 650-nm laser with 630- and 660-nm light-emitting diodes) among male and female patients with AGA failed to show promising results. Although mean (SD) hair thickness (12.6 [9.4] in LLLT group vs 3.9 [7.3] in control group [P=.01]) and hair density (17.2 [12.1] in LLLT group vs –2.1 [18.3] in control group [P=.003]) increased significantly, there was no significant difference in subject assessment of global appearance between the 2 groups.⁵³

Low-level laser light therapy devices are available both for use at home and in office, with 650- to 900-nm wavelengths at 5 mW being the recommended dose for men and women.⁵¹ With regard to AEs, the safety profile for LLLT is relatively favorable. Adverse events can include dry skin, pruritus, scalp tenderness, irritation, and a warm sensation at the treatment site.⁵²

Platelet-Rich Plasma

Originally used in the orthopedic literature to stimulate collagen growth, PRP has since been used in dermatology to promote hair regrowth by releasing platelet-derived growth factors, vascular endothelial growth factor, epidermal growth factor, insulinlike growth factor, and fibroblast growth factors to stimulate vascularization to the dermal papillary cells.^54,55 Platelet-rich plasma is derived from the supernatant of centrifuged whole blood and then injected in the dermis of the scalp to stimulate hair growth.

Although use of PRP is not approved or cleared by the FDA for treatment of hair loss, several studies have demonstrated the efficacy of autologous PRP use for treating AGA.⁵⁶ One pilot study of 19 male and female participants given a total of 5 PRP injections monthly for 3 months and subsequently at months 4 and 7 found a statistically significant improvement in mean hair density, hair diameter, and terminal-vellus hair ratio at 1-year follow-up (P<.05). Furthermore, histomorphometric evaluation demonstrated a decrease in perivascular inflammatory infiltrate.⁵⁷ On the other hand, 2 separate studies failed to show statistically significant improvements in hair growth after use of PRP.^58,59 Varying levels of success may be due in part to lack of a standard protocol for performing PRP injections. Studies comparing efficacy of different PRP administration regimens are emerging. A trial of 40 men and women found that subdermal PRP injections administered 3 times per month with booster injections administered 3 months later was more effective than other injection regimens, including once monthly injections.^58,59 Activators such as collagen, thrombin, 10% calcium chloride, and calcium gluconate may be added to the PRP serum to promote further growth factor secretion upon platelet activation.⁶⁰ However, different means of activation are used in different trials, potentially leading to varying results in clinical trials, with no one proven superior method.^61-63 The main drawback of PRP use is that there is no consensus regarding exact concentration, utility of activators, dosing parameters, depth of injection, or frequency of sessions.⁶⁰ Transient pain and erythema are the most common side effects of PRP injections, with no major AEs reported in the literature.⁶⁴

Microneedling

Microneedling is a minimally invasive procedure that uses needles to puncture the stratum corneum of the skin.⁶⁵ It was first used cosmetically more than 20 years ago due to its ability to increase collagen and elastin formation.⁵¹ Since its discovery, microneedling has been used to reduce the appearance of scars; augment transdermal drug delivery; and treat active acne vulgaris, melasma, hyperhidrosis, and alopecia.⁶⁵ Although there are numerous at-home and professional microneedling devices on the market, only one device has been FDA cleared thus far.

Microneedling is proposed to increase hair regrowth by triggering the wound healing response, which ultimately augments the release of platelet-derived and epidermal growth factors while also activating the hair bulge.⁶⁶ Treatment often is performed with a roller instrument that uses needles 0.5- to 2.5-mm long. Topical anesthetic cream may be applied prior to treatment.⁶⁷ The treated area is then washed and an antibiotic ointment is applied.⁵⁵ Management regimens typically require daily to weekly treatments with a total of 12 to 28 weeks to demonstrate an effect.

Microneedling has demonstrated efficacy in the treatment of hair loss, especially when combined with minoxidil. One study randomized 68 patients to undergo microneedling with minoxidil solution 5% twice daily compared to a control group of minoxidil solution 5% twice daily alone. After 12 weeks, patients treated with microneedling and minoxidil had significantly higher hair counts than the control group (P<.05).⁶⁸ It is speculated that microneedling increases penetration of topical medications, including minoxidil across the skin barrier, thereby enhancing absorption of large molecules.⁶⁶

Topical PRP has been used synergistically to augment the effects of microneedling. A trial randomized 93 patients with alopecia to receive minoxidil solution 5% alone, minoxidil solution 5% plus PRP, or microneedling with PRP.⁶⁹ Hair growth was appreciated in 26 of 31 patients treated with microneedling and PRP compared to 10 of 31 and 17 of 31 in the other 2 groups, respectively. However, when hair growth occurred in the minoxidil-treated group, it occurred faster, with changes in hair growth at 12 weeks compared to 26 weeks in the microneedling group.⁶⁹ When evaluating the efficacy of microneedling and PRP, it must be noted that there is no established leading protocol for treating hair loss, which may affect the success of the treatment.

The reported side-effect profile for microneedling and PRP injections has been favorable without any major AEs noted in clinical trials.^56,64,70 The possibility of bleeding, pain, erythema, and infection should be discussed with the patient nonetheless. More severe side effects such as allergic granulomatous reactions have been reported in the literature with the use of microneedling for facial rejuvenation.⁷¹

Stem Cells

Stem cell hair therapy is a new and promising area of research with the potential to treat alopecia. Although not yet FDA approved for this indication, human umbilical cord blood–derived mesenchymal stem cells (HUCB-MSCs) have received particular attention due to their proposed ability to promote tissue differentiation and repair, to replace aged and damaged hair cells, and to promote secretion of multiple growth factors.⁷² More recently, HUCB-MSCs have been shown to successfully differentiate into human hair follicles in vitro after 3 weeks of cell culture, establishing a method for high-speed and high-purity hair follicle cell differentiation with the hope of future injections to affected areas with hair loss.⁷³ Another study found that HUCB-MSCs enhanced growth of human follicular stem cells in vitro; the authors proposed an altered Wnt/β‐catenin and JAK/STAT pathway was responsible for improved growth of hair follicular cells.⁷⁴

Although umbilical cord blood is replete with the most rapidly dividing stem cells, autologous stem cells derived from the hair follicle or mononuclear cells also may be used to treat alopecia. One recent study randomized 40 patients with AGA and alopecia areata to receive 1 session of either autologous hair follicle or mononuclear cell–derived stem cell injections to the scalp.⁷⁵ Mononuclear cells were acquired from the upper iliac crest bone marrow of patients who were treated with granulocyte colony-stimulating factor 3 days prior to the procedure. Follicular stem cells were taken from 4-mm punch biopsies of the unaffected scalp. After 6 months, there was a notable improvement in hair growth confirmed by immunostaining and dermoscopy, without a significant difference between the forms of autologous stem cell source. Of note, 45% of study patients with alopecia areata showed recurrence of disease at 1-year follow-up. The most common AEs were scalp dermatitis in 20% of participants. Participants who underwent bone marrow biopsy experienced bone pain, hematoma, and granulocyte colony-stimulating factor–induced fatigue and chills.⁷⁵

Furthermore, the cost of stem cell therapy may be prohibitive. Therefore, although stem cell therapy is a novel and promising treatment for hair loss, future research is necessary to establish safety, efficacy, best practices, and accessibility.

Supplements

Patients failing routine treatments for alopecia may turn to holistic therapies. Nutrafol (Nutraceutical Wellness Inc), a novel nutraceutical product, is one such option that has been described for its anti-inflammatory, adaptogenic, antioxidant, and DHT-inhibiting properties. This supplement is not FDA approved or cleared, and large-scale clinical trials are lacking; however, one randomized controlled trial of 40 women with self-reported hair loss found a statistically significant increase in the number of terminal and vellus hair based on phototrichograms performed after 90 and 180 days (P=.009), with no AEs reported. This study, however, was limited by a small sample size.⁷⁶

Lamdapil (ISDIN) is another oral supplement being investigated for hair loss. It contains L-cystine amino acids; zinc; vitamins B₃, B₅, B₆; biotin; and the plant extract Serenoa repens.⁷¹Serenoa repens has reported activity inhibiting the enzyme 5α-reductase with the other vitamins, and amino acids are thought to maintain keratin and collagen growth in normal hair.⁷⁷ One randomized trial investigated use of Lamdapil capsules in a total of 70 patients, which included men with AGA and women experiencing telogen effluvium. For men, the anagen-telogen ratio increased in the Lamdapil-treated group by 23.4%, indicating that more hair was in the growing phase compared to placebo (P<.05). Women with telogen effluvium experienced a significantly greater improvement in the hair-pull test compared to placebo (P<.05).⁷⁷

Marine-derived nutraceutical substances also have been investigated for their role in treating hair loss. Viviscal, originally marketed under the name Hairgain, is one such supplement, which was shown to significantly reduce hair shedding at 3 and 6 months in a group of 96 premenopausal women diagnosed with subclinical hair thinning (P<.05). Additionally, phototrichogram images demonstrated a statistically significant increase in the mean velluslike hair diameter at 6 months compared to baseline.⁷⁸

Although nutraceutical products are not first-line therapy for hair loss, dermatologists may recommend these treatments in patients refusing prescription medications, specifically requesting a natural treatment, or in addition to a first-line agent such as minoxidil. It must be noted, however, that both supplements are new, and there is need for further investigation on their efficacy, safety, and dosing, as neither is FDA regulated.

Conclusion

Hair loss affects millions of Americans each year and has detrimental effects on self-esteem and psychosocial functioning. Nonsurgical treatment options will undoubtedly continue to intrigue patients, as they are often less costly and do not carry risks associated with surgery. Minoxidil, finasteride, and LLLT remain staples of therapy, with the strongest evidence supporting their safety and efficacy. Numerous other treatment options are emerging, including PRP, microneedling, mesenchymal and autologous stem cell therapy, and oral supplements, though further research must be conducted to establish dosing, safety, and best practices. Physicians must discuss patient preference and anticipated length of treatment when discussing alopecia treatment to maximize patient satisfaction.

Hair plays an important role in identity, self-perception, and psychosocial functioning. Hair loss can be a devastating experience that decreases self-esteem and feelings of personal attractiveness while also leading to depression and anxiety.^1,2 Although increasingly popular, surgical hair restoration, including hair transplantation, is costly and carries considerable risk.

Results of nonsurgical hair restoration are not immediate and may not be as dramatic; however, they do not carry the risks or recovery associated with surgical options. Treatments such as sex steroid hormone and biologic response modifiers have been used to inhibit hair miniaturization and stabilize hair loss in cases of androgenic alopecia (AGA).³ Currently, minoxidil and finasteride are the only US Food and Drug Administration (FDA)–approved medications for the treatment of hair loss; however, other nonsurgical treatment options have gained popularity, including dutasteride, spironolactone, low-level laser therapy (LLLT), platelet-rich plasma (PRP), microneedling, stem cells, and nutraceutical supplements. We provide an overview of these treatment options to help dermatologists select appropriate therapies for the treatment of alopecia (Table).

Minoxidil

Minoxidil has been known to improve hair growth for more than 40 years. Oral minoxidil was first introduced for hypertension in the 1970s with a common adverse effect of hypertrichosis; the 2% solution was marketed for AGA shortly thereafter in 1986.⁴ Minoxidil is a biologic response modifier that is thought to promote hair growth through vasodilation and stimulation of hair follicles into the growth phase.⁵ In animal studies, topical minoxidil has been shown to shorten telogen, prolong anagen, and increase hair follicle size.^6,7 More recently, topical minoxidil was shown to have anti-inflammatory effects by downregulating IL-1, which may confer an additional role in combatting alopecia.⁸

Minoxidil is FDA approved for treatment of AGA in men and women and often is used as first-line therapy.⁹ In 3 separate meta-analyses of topical minoxidil, it was shown to be more effective than placebo for treating AGA in men and women, with a notable increase in target area hair growth.¹⁰ A study of 777 male patients treated with topical minoxidil 2% found that 45% subjectively experienced new hair growth.¹¹ However, results may vary, and research indicates that higher concentrations are more effective. In a randomized, double-blind, placebo-controlled trial of 381 women with female pattern hair loss (FPHL), minoxidil solution 2% was found to be superior to placebo after 48 weeks, with average changes in nonvellus hair counts of 20.7/cm² in the minoxidil group vs 9.4/cm² in the placebo group.¹² In a separate meta-analysis, minoxidil solution 5% demonstrated superiority to both the 2% formulation and placebo with a mean change in nonvellus hair counts of 26.0/cm^2.13

Minoxidil also has demonstrated promising benefits in preventing chemotherapy-induced alopecia. Although oncologists most often use the scalp cooling method to prevent hair loss by decreasing perfusion and uptake of cytotoxic agents, cost may be prohibitive, as it is often not reimbursable by insurance companies.^14,15 On the other hand, minoxidil is easily procured over-the-counter and has been successfully used to decrease the duration of alopecia caused by chemotherapeutic agents such as fluorouracil, doxorubicin, and cyclophosphamide, as well as endocrine therapies used to treat breast cancer in women.^16-18 Minoxidil also has been used off label to treat other forms of alopecia, including alopecia areata, telogen effluvium, eyebrow hypotrichosis, and monilethrix; however, there is inconclusive evidence for its efficacy.^5,13,19

Compared to other nonsurgical treatments for hair loss, a meta-analysis found that minoxidil was associated with the highest rate of adverse effects (AEs).^16,17 Potential side effects include pruritus or burning at the application site; irritant or allergic contact dermatitis; hypertrichosis; and cardiovascular effects, which may be due to the vasodilatory mechanism of action of minoxidil.²⁰ One randomized double-blind study found that while topical minoxidil did not affect blood pressure, it increased heart rate by 3 to 5 beats per minute, caused considerable increases in left ventricular end-diastolic volume, an increase in cardiac output (by 0.751 min^-1), and an increase in left ventricular mass (by 5 g m^-2). The authors concluded that short-term use is safe in healthy individuals, but providers should ask about history of coronary artery disease to avoid potential cardiac side effects.²¹

Patients also should be advised that at least 6 months of minoxidil therapy may be necessary.¹¹ Furthermore, measurable hair changes may disappear within 3 months if the patient chooses to discontinue treatment.²² Finally, providers must consider patient perception of improvement and hair growth while on this medication. In one study, although investigator assessments of hair growth and hair count were increased with the use of minoxidil solution 5% compared to placebo, differences in patient assessment of hair growth were not significant at 48 weeks.²² Therefore, dermatologists should address patient expectations and consider additional treatments if necessary.

Finasteride

Finasteride is an oral medication that is FDA approved at a dose of 1 mg daily for the treatment of AGA in men. It competitively inhibits the type I and type II 5α-reductase enzymes, with a strong affinity for the type II enzyme, thereby inhibiting the conversion of testosterone to dihydrotestosterone (DHT), the potent androgen responsible for terminal hair follicle miniaturization and transformation of terminal hair into vellus hair.^21,23

Finasteride has demonstrated efficacy and high tolerability in large-scale, placebo-controlled, randomized trials with only rare complications of sexual dysfunction, supporting its status as a first-line agent.^24,25 One study found that in a population of 3177 Japanese men, an overall increase in hair growth was seen in 87.1% of men receiving oral finasteride 1 mg daily, with AEs such as decreased libido occurring in only 0.7% of patients.²⁶ However, postmarketing studies described more severe complications in men taking finasteride to treat AGA or benign prostatic hyperplasia, even after the discontinuation of medication, described as postfinasteride syndrome.^27,28 These side effects include decreased libido, reduction in penis size, gynecomastia, erectile dysfunction, and ejaculation disorder, in addition to psychologic impairments, including decreased concentration, depression, and suicidal ideation, presumably due to the role of 5α-reductase interacting with the γ-aminobutyric acid (GABA_A) receptor within the central nervous system.²⁹ The incidence of persistent erectile dysfunction was reported to be as low as 1.4% in a study assessing 11,909 men prescribed up to 5 mg once daily of finasteride to treat benign prostatic hyperplasia and AGA. The incidence was higher in patients using higher doses of finasteride and longer treatment courses as well as in patients with prostate disease.²⁹ These potential side effects should be discussed with male patients prior to prescribing finasteride.

Finasteride is not FDA approved for use in women and is considered category X in pregnancy due to animal studies that demonstrated external genital abnormalities in male fetuses exposed to type II 5α-reductase inhibitors.³⁰ Despite this potential teratogenicity, finasteride is prescribed off label to treat FPHL and hirsutism. A meta-analysis of 2683 women participating in 65 studies found that finasteride, when used at dosages of 0.5 to 5 mg daily, may improve FPHL and frontal fibrosing alopecia after 6 to 12 months.³⁰ However, available studies have used varying treatment methods, yielding differing results. For example, one randomized trial of 137 postmenopausal women with FPHL and normal androgen levels found no benefit with 1 mg daily³¹; however, another trial of 87 women with normal levels of androgens found that 5 mg daily of finasteride showed significant improvements in hair quantity and thickness after 12 months (P<.01).³² Further studies are needed to assess the appropriate female population that may benefit from use of finasteride. Premenopausal women interested in this therapy should be counseled about the risk of teratogenicity, as well as potential breast tenderness, loss of libido, and menstrual irregularities.³³ Furthermore, finasteride use in women may pose a theoretical risk of breast cancer, as DHT inhibition results in conversion of excess testosterone to estrogen, thereby altering the estrogen to androgen ratio.³⁴

Dutasteride

Dutasteride is 100-times more potent than finasteride as an inhibitor of type I 5α-reductase enzyme and 3-times more potent as an inhibitor of type I 5α-reductase enzyme.³⁵ Therefore, it has been hypothesized that dutasteride may be more effective than finasteride for restoring hair loss, though it is not yet FDA approved for this indication.

Research evaluating the efficacy of dutasteride is emerging. Randomized controlled trials in men with AGA are promising and suggest reversed hair miniaturization.³⁶ One randomized trial of 153 men found that dutasteride 0.5 mg daily was superior to placebo for the treatment of hair loss, as evidenced by an increase in hair counts in dutasteride patients (12.2/cm²) compared to controls (4.7/cm²). Furthermore, 0.5-mg dutasteride resulted in significantly increased new hair growth after 24 weeks compared to a placebo control (23/cm² vs 4/cm²; P<.05).³⁷

Dutasteride also is now being used off label to treat FPHL. Little evidence-based research exists regarding the use of dutasteride in women, though 1 case report described successful treatment of FPHL after 6 months of treatment with 0.5 mg daily of dutasteride in a 46-year-old woman who showed only minimal improvement on oral finasteride.³⁸

The side-effect profile is similar to finasteride, and research in the urologic literature demonstrated that the rate of AEs is comparable between the 2 drugs, with reports of sexual side effects occurring in 11% of patients taking dutasteride 0.5 mg daily vs 14% of patients taking finasteride 5 mg daily.³⁹ In the dermatologic literature, there was no statistically significant difference between the rate of AEs, specifically sexual AEs, in patients taking dutasteride 0.5 mg daily vs finasteride 1 mg daily.³⁶ Safety of dutasteride in women is not well established. The side-effect profile described for finasteride, including the risk of potential fetal anomalies, should be discussed with women receiving dutasteride therapy.

Spironolactone

Although topical minoxidil is still considered first-line therapy for women experiencing hair loss, spironolactone is growing in popularity as an off-label treatment of FPHL, though it is not FDA approved for this indication. Spironolactone is a synthetic steroid that has been used as a potassium-sparing diuretic for more than 60 years. Its primary metabolite, canrenone, competitively inhibits aldosterone.³⁷ It is FDA approved for the treatment of essential hypertension (25–100 mg), congestive heart failure (25 mg), diuretic-induced hypokalemia (25–100 mg), and primary hyperaldosteronism (100–400 mg).^37,40 Spironolactone was serendipitously discovered to treat hirsutism, acne, and seborrhea associated with polycystic ovary syndrome.⁴¹

Androgens are well studied in male pattern hair loss, and their role in FPHL is now becoming evident, with new research supporting the role of spironolactone as a useful antiandrogen.^42,43 An Australian open-label trial randomized 80 women with biopsy-proven FPHL to receive either spironolactone 200 mg daily or cyproterone acetate, an antiandrogen used abroad, including in European countries, in conjunction with an oral contraceptive pill for premenopausal women.⁴² Spironolactone was found to be as effective as the alternate regimen, with 44% of patients experiencing hair regrowth, 44% experiencing no progression of hair loss, and only 12% experiencing continued hair loss.⁴⁴ Spironolactone used in combination with minoxidil has been shown to demonstrate greater efficacy when compared to spironolactone alone.⁴⁵ One observational study of 100 women with FPHL found that once-daily capsules of minoxidil 0.25 mg combined with once daily spironolactone 25 mg was a safe and effective treatment of FPHL.⁴⁴ Spironolactone also is considered safe and effective to treat FPHL in postmenopausal women by inhibiting the relative androgen excess.⁴⁶

The starting dose for spironolactone usually is 25 mg twice daily and increased by 50 mg daily up to 200 mg daily as tolerated. Furthermore, results should be monitored for at least 6 months to assess efficacy accurately.⁴⁷ Side effects include headache, decreased libido, menstrual irregularities, orthostatic hypotension, fatigue, and hyperkalemia. Although hyperkalemia is a known side effect of spironolactone, one study of 974 male and female participants receiving spironolactone found that only 0.72% of participants experienced mild hyperkalemia (5.1–6.0 mEq/L) with no patients experiencing moderate or severe hyperkalemia. Regardless, providers may consider checking potassium levels within 4 to 8 weeks of initiating treatment with spironolactone.⁴⁸ Other potential AEs include gynecomastia and feminization; therefore, it is not recommended for use in men.⁴² Oral contraception is recommended to prevent pregnancy in premenopausal women, as spironolactone may cause feminization of the male fetus. Because of the antiandrogenic and progestogenic effects of spironolactone, there has been a theoretical concern for risk of inducing breast cancer, especially in postmenopausal women. However, a study conducted in the United Kingdom of more than 1 million female patients older than 55 years found that there was no increased risk of breast cancer in postmenopausal women.⁴⁹

Low-Level Laser Light Therapy

Low-level laser light therapy has been used to reduce pain, treat edema, and promote would healing for almost 50 years and is now one of the few FDA-cleared devices to treat alopecia. Low-level laser light therapy uses red beam or near-infrared nonthermal lasers at a wavelength of 600 to 1000 nm and from 5 to 500 mW. The exact mechanism of hair growth stimulation is not known; however, it is believed that LLLT accelerates mitosis, stimulates hair follicle stem cells to activate follicular keratinocytes, and alters cellular metabolism by inhibiting nitric oxide from cytochrome c oxidase.⁵⁰

Trials evaluating the efficacy of LLLT laser combs for the treatment of AGA have demonstrated notable improvements in hair density. For example, one sham device–controlled, double-blind clinical trial randomized 334 men and women to treatment with either an FDA-cleared laser comb vs sham devices.⁵¹ The treatment devices were used 3 times weekly for 26 weeks. Hair counts for those treated with the 7-, 9-, and 12-beam LLLT laser combs were significantly higher than the sham after 26 weeks (P<.05), without any serious AEs being reported.⁵¹ Another study in men with AGA proved similarly efficacious results using at-home LLLT therapy of 655 nm to the scalp every other day for 16 weeks (60 treatments).⁵² However, a 24-week randomized, double-blind, sham device–controlled, multicenter trial evaluating the LLLT helmet (combining 650-nm laser with 630- and 660-nm light-emitting diodes) among male and female patients with AGA failed to show promising results. Although mean (SD) hair thickness (12.6 [9.4] in LLLT group vs 3.9 [7.3] in control group [P=.01]) and hair density (17.2 [12.1] in LLLT group vs –2.1 [18.3] in control group [P=.003]) increased significantly, there was no significant difference in subject assessment of global appearance between the 2 groups.⁵³

Low-level laser light therapy devices are available both for use at home and in office, with 650- to 900-nm wavelengths at 5 mW being the recommended dose for men and women.⁵¹ With regard to AEs, the safety profile for LLLT is relatively favorable. Adverse events can include dry skin, pruritus, scalp tenderness, irritation, and a warm sensation at the treatment site.⁵²

Platelet-Rich Plasma

Originally used in the orthopedic literature to stimulate collagen growth, PRP has since been used in dermatology to promote hair regrowth by releasing platelet-derived growth factors, vascular endothelial growth factor, epidermal growth factor, insulinlike growth factor, and fibroblast growth factors to stimulate vascularization to the dermal papillary cells.^54,55 Platelet-rich plasma is derived from the supernatant of centrifuged whole blood and then injected in the dermis of the scalp to stimulate hair growth.

Although use of PRP is not approved or cleared by the FDA for treatment of hair loss, several studies have demonstrated the efficacy of autologous PRP use for treating AGA.⁵⁶ One pilot study of 19 male and female participants given a total of 5 PRP injections monthly for 3 months and subsequently at months 4 and 7 found a statistically significant improvement in mean hair density, hair diameter, and terminal-vellus hair ratio at 1-year follow-up (P<.05). Furthermore, histomorphometric evaluation demonstrated a decrease in perivascular inflammatory infiltrate.⁵⁷ On the other hand, 2 separate studies failed to show statistically significant improvements in hair growth after use of PRP.^58,59 Varying levels of success may be due in part to lack of a standard protocol for performing PRP injections. Studies comparing efficacy of different PRP administration regimens are emerging. A trial of 40 men and women found that subdermal PRP injections administered 3 times per month with booster injections administered 3 months later was more effective than other injection regimens, including once monthly injections.^58,59 Activators such as collagen, thrombin, 10% calcium chloride, and calcium gluconate may be added to the PRP serum to promote further growth factor secretion upon platelet activation.⁶⁰ However, different means of activation are used in different trials, potentially leading to varying results in clinical trials, with no one proven superior method.^61-63 The main drawback of PRP use is that there is no consensus regarding exact concentration, utility of activators, dosing parameters, depth of injection, or frequency of sessions.⁶⁰ Transient pain and erythema are the most common side effects of PRP injections, with no major AEs reported in the literature.⁶⁴

Microneedling

Microneedling is a minimally invasive procedure that uses needles to puncture the stratum corneum of the skin.⁶⁵ It was first used cosmetically more than 20 years ago due to its ability to increase collagen and elastin formation.⁵¹ Since its discovery, microneedling has been used to reduce the appearance of scars; augment transdermal drug delivery; and treat active acne vulgaris, melasma, hyperhidrosis, and alopecia.⁶⁵ Although there are numerous at-home and professional microneedling devices on the market, only one device has been FDA cleared thus far.

Microneedling is proposed to increase hair regrowth by triggering the wound healing response, which ultimately augments the release of platelet-derived and epidermal growth factors while also activating the hair bulge.⁶⁶ Treatment often is performed with a roller instrument that uses needles 0.5- to 2.5-mm long. Topical anesthetic cream may be applied prior to treatment.⁶⁷ The treated area is then washed and an antibiotic ointment is applied.⁵⁵ Management regimens typically require daily to weekly treatments with a total of 12 to 28 weeks to demonstrate an effect.

Microneedling has demonstrated efficacy in the treatment of hair loss, especially when combined with minoxidil. One study randomized 68 patients to undergo microneedling with minoxidil solution 5% twice daily compared to a control group of minoxidil solution 5% twice daily alone. After 12 weeks, patients treated with microneedling and minoxidil had significantly higher hair counts than the control group (P<.05).⁶⁸ It is speculated that microneedling increases penetration of topical medications, including minoxidil across the skin barrier, thereby enhancing absorption of large molecules.⁶⁶

Topical PRP has been used synergistically to augment the effects of microneedling. A trial randomized 93 patients with alopecia to receive minoxidil solution 5% alone, minoxidil solution 5% plus PRP, or microneedling with PRP.⁶⁹ Hair growth was appreciated in 26 of 31 patients treated with microneedling and PRP compared to 10 of 31 and 17 of 31 in the other 2 groups, respectively. However, when hair growth occurred in the minoxidil-treated group, it occurred faster, with changes in hair growth at 12 weeks compared to 26 weeks in the microneedling group.⁶⁹ When evaluating the efficacy of microneedling and PRP, it must be noted that there is no established leading protocol for treating hair loss, which may affect the success of the treatment.

The reported side-effect profile for microneedling and PRP injections has been favorable without any major AEs noted in clinical trials.^56,64,70 The possibility of bleeding, pain, erythema, and infection should be discussed with the patient nonetheless. More severe side effects such as allergic granulomatous reactions have been reported in the literature with the use of microneedling for facial rejuvenation.⁷¹

Stem Cells

Stem cell hair therapy is a new and promising area of research with the potential to treat alopecia. Although not yet FDA approved for this indication, human umbilical cord blood–derived mesenchymal stem cells (HUCB-MSCs) have received particular attention due to their proposed ability to promote tissue differentiation and repair, to replace aged and damaged hair cells, and to promote secretion of multiple growth factors.⁷² More recently, HUCB-MSCs have been shown to successfully differentiate into human hair follicles in vitro after 3 weeks of cell culture, establishing a method for high-speed and high-purity hair follicle cell differentiation with the hope of future injections to affected areas with hair loss.⁷³ Another study found that HUCB-MSCs enhanced growth of human follicular stem cells in vitro; the authors proposed an altered Wnt/β‐catenin and JAK/STAT pathway was responsible for improved growth of hair follicular cells.⁷⁴

Although umbilical cord blood is replete with the most rapidly dividing stem cells, autologous stem cells derived from the hair follicle or mononuclear cells also may be used to treat alopecia. One recent study randomized 40 patients with AGA and alopecia areata to receive 1 session of either autologous hair follicle or mononuclear cell–derived stem cell injections to the scalp.⁷⁵ Mononuclear cells were acquired from the upper iliac crest bone marrow of patients who were treated with granulocyte colony-stimulating factor 3 days prior to the procedure. Follicular stem cells were taken from 4-mm punch biopsies of the unaffected scalp. After 6 months, there was a notable improvement in hair growth confirmed by immunostaining and dermoscopy, without a significant difference between the forms of autologous stem cell source. Of note, 45% of study patients with alopecia areata showed recurrence of disease at 1-year follow-up. The most common AEs were scalp dermatitis in 20% of participants. Participants who underwent bone marrow biopsy experienced bone pain, hematoma, and granulocyte colony-stimulating factor–induced fatigue and chills.⁷⁵

Furthermore, the cost of stem cell therapy may be prohibitive. Therefore, although stem cell therapy is a novel and promising treatment for hair loss, future research is necessary to establish safety, efficacy, best practices, and accessibility.

Supplements

Patients failing routine treatments for alopecia may turn to holistic therapies. Nutrafol (Nutraceutical Wellness Inc), a novel nutraceutical product, is one such option that has been described for its anti-inflammatory, adaptogenic, antioxidant, and DHT-inhibiting properties. This supplement is not FDA approved or cleared, and large-scale clinical trials are lacking; however, one randomized controlled trial of 40 women with self-reported hair loss found a statistically significant increase in the number of terminal and vellus hair based on phototrichograms performed after 90 and 180 days (P=.009), with no AEs reported. This study, however, was limited by a small sample size.⁷⁶

Lamdapil (ISDIN) is another oral supplement being investigated for hair loss. It contains L-cystine amino acids; zinc; vitamins B₃, B₅, B₆; biotin; and the plant extract Serenoa repens.⁷¹Serenoa repens has reported activity inhibiting the enzyme 5α-reductase with the other vitamins, and amino acids are thought to maintain keratin and collagen growth in normal hair.⁷⁷ One randomized trial investigated use of Lamdapil capsules in a total of 70 patients, which included men with AGA and women experiencing telogen effluvium. For men, the anagen-telogen ratio increased in the Lamdapil-treated group by 23.4%, indicating that more hair was in the growing phase compared to placebo (P<.05). Women with telogen effluvium experienced a significantly greater improvement in the hair-pull test compared to placebo (P<.05).⁷⁷

Marine-derived nutraceutical substances also have been investigated for their role in treating hair loss. Viviscal, originally marketed under the name Hairgain, is one such supplement, which was shown to significantly reduce hair shedding at 3 and 6 months in a group of 96 premenopausal women diagnosed with subclinical hair thinning (P<.05). Additionally, phototrichogram images demonstrated a statistically significant increase in the mean velluslike hair diameter at 6 months compared to baseline.⁷⁸

Although nutraceutical products are not first-line therapy for hair loss, dermatologists may recommend these treatments in patients refusing prescription medications, specifically requesting a natural treatment, or in addition to a first-line agent such as minoxidil. It must be noted, however, that both supplements are new, and there is need for further investigation on their efficacy, safety, and dosing, as neither is FDA regulated.

Conclusion

Hair loss affects millions of Americans each year and has detrimental effects on self-esteem and psychosocial functioning. Nonsurgical treatment options will undoubtedly continue to intrigue patients, as they are often less costly and do not carry risks associated with surgery. Minoxidil, finasteride, and LLLT remain staples of therapy, with the strongest evidence supporting their safety and efficacy. Numerous other treatment options are emerging, including PRP, microneedling, mesenchymal and autologous stem cell therapy, and oral supplements, though further research must be conducted to establish dosing, safety, and best practices. Physicians must discuss patient preference and anticipated length of treatment when discussing alopecia treatment to maximize patient satisfaction.

Hair plays an important role in identity, self-perception, and psychosocial functioning. Hair loss can be a devastating experience that decreases self-esteem and feelings of personal attractiveness while also leading to depression and anxiety.^1,2 Although increasingly popular, surgical hair restoration, including hair transplantation, is costly and carries considerable risk.

Results of nonsurgical hair restoration are not immediate and may not be as dramatic; however, they do not carry the risks or recovery associated with surgical options. Treatments such as sex steroid hormone and biologic response modifiers have been used to inhibit hair miniaturization and stabilize hair loss in cases of androgenic alopecia (AGA).³ Currently, minoxidil and finasteride are the only US Food and Drug Administration (FDA)–approved medications for the treatment of hair loss; however, other nonsurgical treatment options have gained popularity, including dutasteride, spironolactone, low-level laser therapy (LLLT), platelet-rich plasma (PRP), microneedling, stem cells, and nutraceutical supplements. We provide an overview of these treatment options to help dermatologists select appropriate therapies for the treatment of alopecia (Table).

Minoxidil

Minoxidil has been known to improve hair growth for more than 40 years. Oral minoxidil was first introduced for hypertension in the 1970s with a common adverse effect of hypertrichosis; the 2% solution was marketed for AGA shortly thereafter in 1986.⁴ Minoxidil is a biologic response modifier that is thought to promote hair growth through vasodilation and stimulation of hair follicles into the growth phase.⁵ In animal studies, topical minoxidil has been shown to shorten telogen, prolong anagen, and increase hair follicle size.^6,7 More recently, topical minoxidil was shown to have anti-inflammatory effects by downregulating IL-1, which may confer an additional role in combatting alopecia.⁸

Minoxidil is FDA approved for treatment of AGA in men and women and often is used as first-line therapy.⁹ In 3 separate meta-analyses of topical minoxidil, it was shown to be more effective than placebo for treating AGA in men and women, with a notable increase in target area hair growth.¹⁰ A study of 777 male patients treated with topical minoxidil 2% found that 45% subjectively experienced new hair growth.¹¹ However, results may vary, and research indicates that higher concentrations are more effective. In a randomized, double-blind, placebo-controlled trial of 381 women with female pattern hair loss (FPHL), minoxidil solution 2% was found to be superior to placebo after 48 weeks, with average changes in nonvellus hair counts of 20.7/cm² in the minoxidil group vs 9.4/cm² in the placebo group.¹² In a separate meta-analysis, minoxidil solution 5% demonstrated superiority to both the 2% formulation and placebo with a mean change in nonvellus hair counts of 26.0/cm^2.13

Minoxidil also has demonstrated promising benefits in preventing chemotherapy-induced alopecia. Although oncologists most often use the scalp cooling method to prevent hair loss by decreasing perfusion and uptake of cytotoxic agents, cost may be prohibitive, as it is often not reimbursable by insurance companies.^14,15 On the other hand, minoxidil is easily procured over-the-counter and has been successfully used to decrease the duration of alopecia caused by chemotherapeutic agents such as fluorouracil, doxorubicin, and cyclophosphamide, as well as endocrine therapies used to treat breast cancer in women.^16-18 Minoxidil also has been used off label to treat other forms of alopecia, including alopecia areata, telogen effluvium, eyebrow hypotrichosis, and monilethrix; however, there is inconclusive evidence for its efficacy.^5,13,19

Compared to other nonsurgical treatments for hair loss, a meta-analysis found that minoxidil was associated with the highest rate of adverse effects (AEs).^16,17 Potential side effects include pruritus or burning at the application site; irritant or allergic contact dermatitis; hypertrichosis; and cardiovascular effects, which may be due to the vasodilatory mechanism of action of minoxidil.²⁰ One randomized double-blind study found that while topical minoxidil did not affect blood pressure, it increased heart rate by 3 to 5 beats per minute, caused considerable increases in left ventricular end-diastolic volume, an increase in cardiac output (by 0.751 min^-1), and an increase in left ventricular mass (by 5 g m^-2). The authors concluded that short-term use is safe in healthy individuals, but providers should ask about history of coronary artery disease to avoid potential cardiac side effects.²¹

Patients also should be advised that at least 6 months of minoxidil therapy may be necessary.¹¹ Furthermore, measurable hair changes may disappear within 3 months if the patient chooses to discontinue treatment.²² Finally, providers must consider patient perception of improvement and hair growth while on this medication. In one study, although investigator assessments of hair growth and hair count were increased with the use of minoxidil solution 5% compared to placebo, differences in patient assessment of hair growth were not significant at 48 weeks.²² Therefore, dermatologists should address patient expectations and consider additional treatments if necessary.

Finasteride

Finasteride is an oral medication that is FDA approved at a dose of 1 mg daily for the treatment of AGA in men. It competitively inhibits the type I and type II 5α-reductase enzymes, with a strong affinity for the type II enzyme, thereby inhibiting the conversion of testosterone to dihydrotestosterone (DHT), the potent androgen responsible for terminal hair follicle miniaturization and transformation of terminal hair into vellus hair.^21,23

Finasteride has demonstrated efficacy and high tolerability in large-scale, placebo-controlled, randomized trials with only rare complications of sexual dysfunction, supporting its status as a first-line agent.^24,25 One study found that in a population of 3177 Japanese men, an overall increase in hair growth was seen in 87.1% of men receiving oral finasteride 1 mg daily, with AEs such as decreased libido occurring in only 0.7% of patients.²⁶ However, postmarketing studies described more severe complications in men taking finasteride to treat AGA or benign prostatic hyperplasia, even after the discontinuation of medication, described as postfinasteride syndrome.^27,28 These side effects include decreased libido, reduction in penis size, gynecomastia, erectile dysfunction, and ejaculation disorder, in addition to psychologic impairments, including decreased concentration, depression, and suicidal ideation, presumably due to the role of 5α-reductase interacting with the γ-aminobutyric acid (GABA_A) receptor within the central nervous system.²⁹ The incidence of persistent erectile dysfunction was reported to be as low as 1.4% in a study assessing 11,909 men prescribed up to 5 mg once daily of finasteride to treat benign prostatic hyperplasia and AGA. The incidence was higher in patients using higher doses of finasteride and longer treatment courses as well as in patients with prostate disease.²⁹ These potential side effects should be discussed with male patients prior to prescribing finasteride.

Finasteride is not FDA approved for use in women and is considered category X in pregnancy due to animal studies that demonstrated external genital abnormalities in male fetuses exposed to type II 5α-reductase inhibitors.³⁰ Despite this potential teratogenicity, finasteride is prescribed off label to treat FPHL and hirsutism. A meta-analysis of 2683 women participating in 65 studies found that finasteride, when used at dosages of 0.5 to 5 mg daily, may improve FPHL and frontal fibrosing alopecia after 6 to 12 months.³⁰ However, available studies have used varying treatment methods, yielding differing results. For example, one randomized trial of 137 postmenopausal women with FPHL and normal androgen levels found no benefit with 1 mg daily³¹; however, another trial of 87 women with normal levels of androgens found that 5 mg daily of finasteride showed significant improvements in hair quantity and thickness after 12 months (P<.01).³² Further studies are needed to assess the appropriate female population that may benefit from use of finasteride. Premenopausal women interested in this therapy should be counseled about the risk of teratogenicity, as well as potential breast tenderness, loss of libido, and menstrual irregularities.³³ Furthermore, finasteride use in women may pose a theoretical risk of breast cancer, as DHT inhibition results in conversion of excess testosterone to estrogen, thereby altering the estrogen to androgen ratio.³⁴

Dutasteride

Dutasteride is 100-times more potent than finasteride as an inhibitor of type I 5α-reductase enzyme and 3-times more potent as an inhibitor of type I 5α-reductase enzyme.³⁵ Therefore, it has been hypothesized that dutasteride may be more effective than finasteride for restoring hair loss, though it is not yet FDA approved for this indication.

Research evaluating the efficacy of dutasteride is emerging. Randomized controlled trials in men with AGA are promising and suggest reversed hair miniaturization.³⁶ One randomized trial of 153 men found that dutasteride 0.5 mg daily was superior to placebo for the treatment of hair loss, as evidenced by an increase in hair counts in dutasteride patients (12.2/cm²) compared to controls (4.7/cm²). Furthermore, 0.5-mg dutasteride resulted in significantly increased new hair growth after 24 weeks compared to a placebo control (23/cm² vs 4/cm²; P<.05).³⁷

Dutasteride also is now being used off label to treat FPHL. Little evidence-based research exists regarding the use of dutasteride in women, though 1 case report described successful treatment of FPHL after 6 months of treatment with 0.5 mg daily of dutasteride in a 46-year-old woman who showed only minimal improvement on oral finasteride.³⁸

The side-effect profile is similar to finasteride, and research in the urologic literature demonstrated that the rate of AEs is comparable between the 2 drugs, with reports of sexual side effects occurring in 11% of patients taking dutasteride 0.5 mg daily vs 14% of patients taking finasteride 5 mg daily.³⁹ In the dermatologic literature, there was no statistically significant difference between the rate of AEs, specifically sexual AEs, in patients taking dutasteride 0.5 mg daily vs finasteride 1 mg daily.³⁶ Safety of dutasteride in women is not well established. The side-effect profile described for finasteride, including the risk of potential fetal anomalies, should be discussed with women receiving dutasteride therapy.

Spironolactone

Although topical minoxidil is still considered first-line therapy for women experiencing hair loss, spironolactone is growing in popularity as an off-label treatment of FPHL, though it is not FDA approved for this indication. Spironolactone is a synthetic steroid that has been used as a potassium-sparing diuretic for more than 60 years. Its primary metabolite, canrenone, competitively inhibits aldosterone.³⁷ It is FDA approved for the treatment of essential hypertension (25–100 mg), congestive heart failure (25 mg), diuretic-induced hypokalemia (25–100 mg), and primary hyperaldosteronism (100–400 mg).^37,40 Spironolactone was serendipitously discovered to treat hirsutism, acne, and seborrhea associated with polycystic ovary syndrome.⁴¹

Androgens are well studied in male pattern hair loss, and their role in FPHL is now becoming evident, with new research supporting the role of spironolactone as a useful antiandrogen.^42,43 An Australian open-label trial randomized 80 women with biopsy-proven FPHL to receive either spironolactone 200 mg daily or cyproterone acetate, an antiandrogen used abroad, including in European countries, in conjunction with an oral contraceptive pill for premenopausal women.⁴² Spironolactone was found to be as effective as the alternate regimen, with 44% of patients experiencing hair regrowth, 44% experiencing no progression of hair loss, and only 12% experiencing continued hair loss.⁴⁴ Spironolactone used in combination with minoxidil has been shown to demonstrate greater efficacy when compared to spironolactone alone.⁴⁵ One observational study of 100 women with FPHL found that once-daily capsules of minoxidil 0.25 mg combined with once daily spironolactone 25 mg was a safe and effective treatment of FPHL.⁴⁴ Spironolactone also is considered safe and effective to treat FPHL in postmenopausal women by inhibiting the relative androgen excess.⁴⁶

The starting dose for spironolactone usually is 25 mg twice daily and increased by 50 mg daily up to 200 mg daily as tolerated. Furthermore, results should be monitored for at least 6 months to assess efficacy accurately.⁴⁷ Side effects include headache, decreased libido, menstrual irregularities, orthostatic hypotension, fatigue, and hyperkalemia. Although hyperkalemia is a known side effect of spironolactone, one study of 974 male and female participants receiving spironolactone found that only 0.72% of participants experienced mild hyperkalemia (5.1–6.0 mEq/L) with no patients experiencing moderate or severe hyperkalemia. Regardless, providers may consider checking potassium levels within 4 to 8 weeks of initiating treatment with spironolactone.⁴⁸ Other potential AEs include gynecomastia and feminization; therefore, it is not recommended for use in men.⁴² Oral contraception is recommended to prevent pregnancy in premenopausal women, as spironolactone may cause feminization of the male fetus. Because of the antiandrogenic and progestogenic effects of spironolactone, there has been a theoretical concern for risk of inducing breast cancer, especially in postmenopausal women. However, a study conducted in the United Kingdom of more than 1 million female patients older than 55 years found that there was no increased risk of breast cancer in postmenopausal women.⁴⁹

Low-Level Laser Light Therapy

Low-level laser light therapy has been used to reduce pain, treat edema, and promote would healing for almost 50 years and is now one of the few FDA-cleared devices to treat alopecia. Low-level laser light therapy uses red beam or near-infrared nonthermal lasers at a wavelength of 600 to 1000 nm and from 5 to 500 mW. The exact mechanism of hair growth stimulation is not known; however, it is believed that LLLT accelerates mitosis, stimulates hair follicle stem cells to activate follicular keratinocytes, and alters cellular metabolism by inhibiting nitric oxide from cytochrome c oxidase.⁵⁰

Trials evaluating the efficacy of LLLT laser combs for the treatment of AGA have demonstrated notable improvements in hair density. For example, one sham device–controlled, double-blind clinical trial randomized 334 men and women to treatment with either an FDA-cleared laser comb vs sham devices.⁵¹ The treatment devices were used 3 times weekly for 26 weeks. Hair counts for those treated with the 7-, 9-, and 12-beam LLLT laser combs were significantly higher than the sham after 26 weeks (P<.05), without any serious AEs being reported.⁵¹ Another study in men with AGA proved similarly efficacious results using at-home LLLT therapy of 655 nm to the scalp every other day for 16 weeks (60 treatments).⁵² However, a 24-week randomized, double-blind, sham device–controlled, multicenter trial evaluating the LLLT helmet (combining 650-nm laser with 630- and 660-nm light-emitting diodes) among male and female patients with AGA failed to show promising results. Although mean (SD) hair thickness (12.6 [9.4] in LLLT group vs 3.9 [7.3] in control group [P=.01]) and hair density (17.2 [12.1] in LLLT group vs –2.1 [18.3] in control group [P=.003]) increased significantly, there was no significant difference in subject assessment of global appearance between the 2 groups.⁵³

Low-level laser light therapy devices are available both for use at home and in office, with 650- to 900-nm wavelengths at 5 mW being the recommended dose for men and women.⁵¹ With regard to AEs, the safety profile for LLLT is relatively favorable. Adverse events can include dry skin, pruritus, scalp tenderness, irritation, and a warm sensation at the treatment site.⁵²

Platelet-Rich Plasma

Originally used in the orthopedic literature to stimulate collagen growth, PRP has since been used in dermatology to promote hair regrowth by releasing platelet-derived growth factors, vascular endothelial growth factor, epidermal growth factor, insulinlike growth factor, and fibroblast growth factors to stimulate vascularization to the dermal papillary cells.^54,55 Platelet-rich plasma is derived from the supernatant of centrifuged whole blood and then injected in the dermis of the scalp to stimulate hair growth.

Although use of PRP is not approved or cleared by the FDA for treatment of hair loss, several studies have demonstrated the efficacy of autologous PRP use for treating AGA.⁵⁶ One pilot study of 19 male and female participants given a total of 5 PRP injections monthly for 3 months and subsequently at months 4 and 7 found a statistically significant improvement in mean hair density, hair diameter, and terminal-vellus hair ratio at 1-year follow-up (P<.05). Furthermore, histomorphometric evaluation demonstrated a decrease in perivascular inflammatory infiltrate.⁵⁷ On the other hand, 2 separate studies failed to show statistically significant improvements in hair growth after use of PRP.^58,59 Varying levels of success may be due in part to lack of a standard protocol for performing PRP injections. Studies comparing efficacy of different PRP administration regimens are emerging. A trial of 40 men and women found that subdermal PRP injections administered 3 times per month with booster injections administered 3 months later was more effective than other injection regimens, including once monthly injections.^58,59 Activators such as collagen, thrombin, 10% calcium chloride, and calcium gluconate may be added to the PRP serum to promote further growth factor secretion upon platelet activation.⁶⁰ However, different means of activation are used in different trials, potentially leading to varying results in clinical trials, with no one proven superior method.^61-63 The main drawback of PRP use is that there is no consensus regarding exact concentration, utility of activators, dosing parameters, depth of injection, or frequency of sessions.⁶⁰ Transient pain and erythema are the most common side effects of PRP injections, with no major AEs reported in the literature.⁶⁴

Microneedling

Microneedling is a minimally invasive procedure that uses needles to puncture the stratum corneum of the skin.⁶⁵ It was first used cosmetically more than 20 years ago due to its ability to increase collagen and elastin formation.⁵¹ Since its discovery, microneedling has been used to reduce the appearance of scars; augment transdermal drug delivery; and treat active acne vulgaris, melasma, hyperhidrosis, and alopecia.⁶⁵ Although there are numerous at-home and professional microneedling devices on the market, only one device has been FDA cleared thus far.

Microneedling is proposed to increase hair regrowth by triggering the wound healing response, which ultimately augments the release of platelet-derived and epidermal growth factors while also activating the hair bulge.⁶⁶ Treatment often is performed with a roller instrument that uses needles 0.5- to 2.5-mm long. Topical anesthetic cream may be applied prior to treatment.⁶⁷ The treated area is then washed and an antibiotic ointment is applied.⁵⁵ Management regimens typically require daily to weekly treatments with a total of 12 to 28 weeks to demonstrate an effect.

Microneedling has demonstrated efficacy in the treatment of hair loss, especially when combined with minoxidil. One study randomized 68 patients to undergo microneedling with minoxidil solution 5% twice daily compared to a control group of minoxidil solution 5% twice daily alone. After 12 weeks, patients treated with microneedling and minoxidil had significantly higher hair counts than the control group (P<.05).⁶⁸ It is speculated that microneedling increases penetration of topical medications, including minoxidil across the skin barrier, thereby enhancing absorption of large molecules.⁶⁶

Topical PRP has been used synergistically to augment the effects of microneedling. A trial randomized 93 patients with alopecia to receive minoxidil solution 5% alone, minoxidil solution 5% plus PRP, or microneedling with PRP.⁶⁹ Hair growth was appreciated in 26 of 31 patients treated with microneedling and PRP compared to 10 of 31 and 17 of 31 in the other 2 groups, respectively. However, when hair growth occurred in the minoxidil-treated group, it occurred faster, with changes in hair growth at 12 weeks compared to 26 weeks in the microneedling group.⁶⁹ When evaluating the efficacy of microneedling and PRP, it must be noted that there is no established leading protocol for treating hair loss, which may affect the success of the treatment.

The reported side-effect profile for microneedling and PRP injections has been favorable without any major AEs noted in clinical trials.^56,64,70 The possibility of bleeding, pain, erythema, and infection should be discussed with the patient nonetheless. More severe side effects such as allergic granulomatous reactions have been reported in the literature with the use of microneedling for facial rejuvenation.⁷¹

Stem Cells

Stem cell hair therapy is a new and promising area of research with the potential to treat alopecia. Although not yet FDA approved for this indication, human umbilical cord blood–derived mesenchymal stem cells (HUCB-MSCs) have received particular attention due to their proposed ability to promote tissue differentiation and repair, to replace aged and damaged hair cells, and to promote secretion of multiple growth factors.⁷² More recently, HUCB-MSCs have been shown to successfully differentiate into human hair follicles in vitro after 3 weeks of cell culture, establishing a method for high-speed and high-purity hair follicle cell differentiation with the hope of future injections to affected areas with hair loss.⁷³ Another study found that HUCB-MSCs enhanced growth of human follicular stem cells in vitro; the authors proposed an altered Wnt/β‐catenin and JAK/STAT pathway was responsible for improved growth of hair follicular cells.⁷⁴

Although umbilical cord blood is replete with the most rapidly dividing stem cells, autologous stem cells derived from the hair follicle or mononuclear cells also may be used to treat alopecia. One recent study randomized 40 patients with AGA and alopecia areata to receive 1 session of either autologous hair follicle or mononuclear cell–derived stem cell injections to the scalp.⁷⁵ Mononuclear cells were acquired from the upper iliac crest bone marrow of patients who were treated with granulocyte colony-stimulating factor 3 days prior to the procedure. Follicular stem cells were taken from 4-mm punch biopsies of the unaffected scalp. After 6 months, there was a notable improvement in hair growth confirmed by immunostaining and dermoscopy, without a significant difference between the forms of autologous stem cell source. Of note, 45% of study patients with alopecia areata showed recurrence of disease at 1-year follow-up. The most common AEs were scalp dermatitis in 20% of participants. Participants who underwent bone marrow biopsy experienced bone pain, hematoma, and granulocyte colony-stimulating factor–induced fatigue and chills.⁷⁵

Furthermore, the cost of stem cell therapy may be prohibitive. Therefore, although stem cell therapy is a novel and promising treatment for hair loss, future research is necessary to establish safety, efficacy, best practices, and accessibility.

Supplements

Patients failing routine treatments for alopecia may turn to holistic therapies. Nutrafol (Nutraceutical Wellness Inc), a novel nutraceutical product, is one such option that has been described for its anti-inflammatory, adaptogenic, antioxidant, and DHT-inhibiting properties. This supplement is not FDA approved or cleared, and large-scale clinical trials are lacking; however, one randomized controlled trial of 40 women with self-reported hair loss found a statistically significant increase in the number of terminal and vellus hair based on phototrichograms performed after 90 and 180 days (P=.009), with no AEs reported. This study, however, was limited by a small sample size.⁷⁶

Lamdapil (ISDIN) is another oral supplement being investigated for hair loss. It contains L-cystine amino acids; zinc; vitamins B₃, B₅, B₆; biotin; and the plant extract Serenoa repens.⁷¹Serenoa repens has reported activity inhibiting the enzyme 5α-reductase with the other vitamins, and amino acids are thought to maintain keratin and collagen growth in normal hair.⁷⁷ One randomized trial investigated use of Lamdapil capsules in a total of 70 patients, which included men with AGA and women experiencing telogen effluvium. For men, the anagen-telogen ratio increased in the Lamdapil-treated group by 23.4%, indicating that more hair was in the growing phase compared to placebo (P<.05). Women with telogen effluvium experienced a significantly greater improvement in the hair-pull test compared to placebo (P<.05).⁷⁷

Marine-derived nutraceutical substances also have been investigated for their role in treating hair loss. Viviscal, originally marketed under the name Hairgain, is one such supplement, which was shown to significantly reduce hair shedding at 3 and 6 months in a group of 96 premenopausal women diagnosed with subclinical hair thinning (P<.05). Additionally, phototrichogram images demonstrated a statistically significant increase in the mean velluslike hair diameter at 6 months compared to baseline.⁷⁸

Although nutraceutical products are not first-line therapy for hair loss, dermatologists may recommend these treatments in patients refusing prescription medications, specifically requesting a natural treatment, or in addition to a first-line agent such as minoxidil. It must be noted, however, that both supplements are new, and there is need for further investigation on their efficacy, safety, and dosing, as neither is FDA regulated.

Conclusion

Hair loss affects millions of Americans each year and has detrimental effects on self-esteem and psychosocial functioning. Nonsurgical treatment options will undoubtedly continue to intrigue patients, as they are often less costly and do not carry risks associated with surgery. Minoxidil, finasteride, and LLLT remain staples of therapy, with the strongest evidence supporting their safety and efficacy. Numerous other treatment options are emerging, including PRP, microneedling, mesenchymal and autologous stem cell therapy, and oral supplements, though further research must be conducted to establish dosing, safety, and best practices. Physicians must discuss patient preference and anticipated length of treatment when discussing alopecia treatment to maximize patient satisfaction.

Bakuchiol [(1E,3S)-3-ethenyl-3,7-dimethyl-1,6-octadien-1-yl]phenol, a prenylated phenolic monoterpene found in the seeds and leaves of various plants, particularly Psoralea corylifolia, has been used to treat a broad array of disorders, including skin conditions, in the traditional medical practices of China, Japan, and Korea, as well as Ayurvedic medicine in India.^1-6 Specifically, the seeds of Psoralea corylifolia have also been used in traditional Chinese medicine to treat leukoderma, psoriasis, vitiligo, chronic graft-versus-host disease, and other skin disorders, as well as cardiovascular diseases, nephritis, osteoporosis, and cancer.^7-9

Anna Gorbacheva / iStock / Getty Images Plus

This primary active ingredient is reputed to exert antioxidant, antibacterial, anti-inflammatory, antiaging, and estrogen-like functions, and recent data suggest anticancer activity, including activity against skin cancer. Its antiaging properties manifest via preservation of cutaneous collagen.⁴ The plant itself has displayed a wide range of biological functions, such as antibacterial, anticancer, cytotoxic, cardiac, diaphoretic, diuretic, stimulant, aphrodisiac, and tonifying activities.^8,9 A 2016 quantitative analysis of Psoralea corylifolia and seven of its standard constituents (psoralen, angelicin, neobavaisoflavone, psoralidin, isobavachalcone, bavachinin, and bakuchiol) using high-performance liquid chromatography revealed that bakuchiol is the strongest phytochemical ingredient in the plant, which the investigators found also confers neuroprotective and antineuroinflammatory benefits.³

Other species contain bakuchiol, and its biological activities have been harnessed in other folk medical traditions. The monoterpene is an important constituent found in Ulmus davidiana var. japonica, which is used for its anti-inflammatory properties in traditional Korean medicine.¹⁰ Further, bakuchiol and 3-hydroxy-bakuchiol have been identified as key components isolated from Psoralea glandulosa, which is a shrub used in Chilean folk medicine to treat cutaneous disorders engendered by bacteria and fungus.¹¹ Topical applications of bakuchiol have been demonstrated to confer antiaging benefits.¹² This column briefly identifies some of the various uses emerging for this compelling botanical agent.
 

Antiaging activities

In 2014, Yu et al. found that bakuchiol may impart antiaging benefits by supporting the cellular activity of the expression level of human skin fibroblasts (ESF-1), as well as production of collagen types I and III, while reducing the matrix metalloproteinase-1 mRNA expression.¹³

The same year, Chaudhuri et al. compared the skin care–related activities of retinol and bakuchiol, finding their gene expression profiles very similar. In addition, they observed that bakuchiol up-regulated collagen types I and IV in a DNA microarray study and stimulated type III collagen production in a model of mature fibroblasts. Further, the investigators formulated bakuchiol into a skin care product and tested it clinically, with twice daily applications over 12 weeks yielding significant amelioration in lines and wrinkles, pigmentation, elasticity, and firmness, as well as overall diminished photodamage without provoking redness. They concluded that bakuchiol can act as an antiaging agent through regulation of gene expression comparable to retinol.¹

Retinoids without reactions?

In 2017, Ma et al. set out to synthesize and test in psoriatic cytokine–treated cultures of keratinocytes and organotypic skin substitutes a new substance created by combining two skin-active compounds (bakuchiol and salicylic acid) into bakuchiol salicylate (bakusylan), with the intention of rendering a novel functional retinoid. The researchers reported that the gene expression profile showed elimination of various retinoid-like proinflammatory responses, without a loss of normalizing activity. They concluded that their work may result in a new class of functional retinoids.¹⁴

Early this year, Dhaliwal et al. reported on a randomized, double-blind, 12-week study of 44 patients who applied either bakuchiol 0.5% cream twice daily or retinol 0.5% cream daily. Facial photographs were evaluated at baseline, 4, 8, and 12 weeks, and a blinded dermatologist rated pigmentation and erythema. Side effects were also noted by subjects in tolerability assessment questionnaires. Both compounds significantly reduced wrinkles and hyperpigmentation, with no statistical variance found between the two. More facial skin scaling and stinging was experienced by the retinol group. The investigators concluded that bakuchiol exhibits photoaging activity comparable with retinol and appears to be an emerging alternative to retinol because it is better tolerated.¹² Notably, there is one report to date of an allergic reaction to topical bakuchiol.¹⁵
 

Topical combination therapies for hyperpigmentation, photodamage, and acne

Bakuchiol was a key ingredient incorporated into a 0.5% retinol treatment evaluated in a 12-week, open-label, single-center clinical-usage trial of 44 women with mild to moderate hyperpigmentation and photodamaged facial skin who took a dual product regimen. This 2016 study showed that the retinol and vitamin C facial regimen yielded a statistically significant amelioration in clinical grading of all parameters.¹⁶

A 2015 randomized controlled clinical trial in 111 subjects evaluated the use of adapalene 0.1% gel and a formulation containing bakuchiol, Ginkgo biloba extract, and mannitol in patients with acne. Patients were randomized to the adapalene and botanical formulation or adapalene and vehicle cream for 2 months. Both treatment groups experienced improvements according to all measured outcomes. The botanical formulation was associated with a statistically significant edge over the vehicle combination in reducing inflammatory lesions, investigator global assessment, and intensity of seborrhea. Quality of life was also perceived to be better with the combination of adapalene and the bakuchiol-containing product, which was deemed to be safe with good local tolerability.¹⁷

A subsequent evaluation by a different team also considered the antibacterial, anti-inflammatory, and antioxidative potential of this combination product via in vitro, ex vivo, and clinical studies. The work by Trompezinski et al. revealed that bakuchiol displays nearly twice the antioxidative potential asthat of vitamin E. The bakuchiol-containing cream was shown in acne patients to successfully regulate sebum composition by raising linolenic and sapienic acid levels while lowering oleic acid levels. Its efficacy against Propionibacterium acnes was also suggested by a decrease in the number of skin surface porphyrins. The investigators concluded that the formulation serves as an effective adjuvant acne treatment by attacking inflammation, dysseborrhea, and proliferation of Propionibacterium acnes.¹⁸
 

Anticancer activity

In 2016, Kim et al. demonstrated that bakuchiol exhibits chemopreventive activity by hindering epidermal growth factor (EGF)–induced neoplastic cell transformation. In what was the first mechanistic study to reveal molecular targets for the anticancer activity of this substance, the investigators found that bakuchiol also reduced the viability and suppressed anchorage-independent growth of A431 human epithelial carcinoma cells. They identified Hck, Blk, and p38 MAPK as the molecular targets of what they identified as a potent anticancer compound.²

Skin-whitening potential

In 2010, Ohno et al. found that bakuchiol, along with other ingredients, isolated from Piper longum demonstrated strong suppressive activity against melanin production in B16 mouse melanoma cells and may have potential to affect melanin synthesis in human skin.¹⁹ Further, with use of a new method for screening tyrosinase, Cheng et al. found in 2017 that four substances used in traditional Chinese medicine (quercetin, kaempferol, bavachinin, and bakuchiol) displayed the potential for inhibiting tyrosinase.²⁰

Conclusion

A compound that acts like a retinoid – yielding antiacne and antiaging effects – without provoking irritation? Most dermatologists and their patients would say, sign me up. Bakuchiol, an active ingredient in various plants, especially Psoralea corylifolia, seems to present that kind of profile. While more research is necessary, experience with this herbal ingredient in traditional medicine and an increasing body of research, including clinical results, provides reasons for optimism that this ingredient may have a versatile role to play in topical skin care, particularly in its retinoid-like functions.

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), as well as 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. Chaudhuri RK et al. Int J Cosmet Sci. 2014 Jun;36(3):221-30.

2. Kim JE et al. Oncotarget. 2016 Mar 22;7(12):14616-27.

3. Kim YJ et al. Molecules. 2016 Aug 17. doi: 10.3390/molecules21081076.

4. Xin Z et al. Pharmacol Res. 2019 Mar;141:208-13.

5. Lev-Tov H. Br J Dermatol. 2019 Feb;180(2):253-4.

6. Shrestha S et al. J Ayurveda Integr Med. 2018 Jul - Sep; 9(3):209-12.

7. Li CC et al. Evid Based Complement Alternat Med. 2016. doi: 10.1155/2016/8108643.

8. Hu C et al. Fitoterapia. 2015 Oct;106:129-34.

9. Yan DM et al. J Ethnopharmacol. 2010 Apr 21;128(3):697-702.

10. Choi SY et al. J Med Food. 2010 Aug;13(4):1019-23.

11. Madrid A et al. J Ethnopharmacol. 2012 Dec 18;144(3):809-11.

12. Dhaliwal S et al. Br J Dermatol. 2019 Feb;180(2):289-96.

13. Yu Q et al. Zhong Yao Cai. 2014 Apr;37(4):632-5.

14. Ma S et al. Clin Exp Dermatol. 2017 Apr;42(3):251-60.

15. Malinauskiene L et al. Contact Dermatitis. 2019 Jun;80(6):398-9.

16. Herndon JH Jr, et al. J Drugs Dermatol. 2016 Apr;15(4):476-82.

17. Poláková K et al. Clin Cosmet Investig Dermatol. 2015 Apr 10;8:187-91.

18. Trompezinski S et al. Clin Cosmet Investig Dermatol. 2016 Aug 31;9:233-9.

19. Ohno O et al. Biosci Biotechnol Biochem. 2010;74(7):1504-6.

20. Cheng M et al. Electrophoresis. 2017 Feb;38(3-4):486-93.

Bakuchiol [(1E,3S)-3-ethenyl-3,7-dimethyl-1,6-octadien-1-yl]phenol, a prenylated phenolic monoterpene found in the seeds and leaves of various plants, particularly Psoralea corylifolia, has been used to treat a broad array of disorders, including skin conditions, in the traditional medical practices of China, Japan, and Korea, as well as Ayurvedic medicine in India.^1-6 Specifically, the seeds of Psoralea corylifolia have also been used in traditional Chinese medicine to treat leukoderma, psoriasis, vitiligo, chronic graft-versus-host disease, and other skin disorders, as well as cardiovascular diseases, nephritis, osteoporosis, and cancer.^7-9

Anna Gorbacheva / iStock / Getty Images Plus

This primary active ingredient is reputed to exert antioxidant, antibacterial, anti-inflammatory, antiaging, and estrogen-like functions, and recent data suggest anticancer activity, including activity against skin cancer. Its antiaging properties manifest via preservation of cutaneous collagen.⁴ The plant itself has displayed a wide range of biological functions, such as antibacterial, anticancer, cytotoxic, cardiac, diaphoretic, diuretic, stimulant, aphrodisiac, and tonifying activities.^8,9 A 2016 quantitative analysis of Psoralea corylifolia and seven of its standard constituents (psoralen, angelicin, neobavaisoflavone, psoralidin, isobavachalcone, bavachinin, and bakuchiol) using high-performance liquid chromatography revealed that bakuchiol is the strongest phytochemical ingredient in the plant, which the investigators found also confers neuroprotective and antineuroinflammatory benefits.³

Other species contain bakuchiol, and its biological activities have been harnessed in other folk medical traditions. The monoterpene is an important constituent found in Ulmus davidiana var. japonica, which is used for its anti-inflammatory properties in traditional Korean medicine.¹⁰ Further, bakuchiol and 3-hydroxy-bakuchiol have been identified as key components isolated from Psoralea glandulosa, which is a shrub used in Chilean folk medicine to treat cutaneous disorders engendered by bacteria and fungus.¹¹ Topical applications of bakuchiol have been demonstrated to confer antiaging benefits.¹² This column briefly identifies some of the various uses emerging for this compelling botanical agent.
 

Antiaging activities

In 2014, Yu et al. found that bakuchiol may impart antiaging benefits by supporting the cellular activity of the expression level of human skin fibroblasts (ESF-1), as well as production of collagen types I and III, while reducing the matrix metalloproteinase-1 mRNA expression.¹³

The same year, Chaudhuri et al. compared the skin care–related activities of retinol and bakuchiol, finding their gene expression profiles very similar. In addition, they observed that bakuchiol up-regulated collagen types I and IV in a DNA microarray study and stimulated type III collagen production in a model of mature fibroblasts. Further, the investigators formulated bakuchiol into a skin care product and tested it clinically, with twice daily applications over 12 weeks yielding significant amelioration in lines and wrinkles, pigmentation, elasticity, and firmness, as well as overall diminished photodamage without provoking redness. They concluded that bakuchiol can act as an antiaging agent through regulation of gene expression comparable to retinol.¹

Retinoids without reactions?

In 2017, Ma et al. set out to synthesize and test in psoriatic cytokine–treated cultures of keratinocytes and organotypic skin substitutes a new substance created by combining two skin-active compounds (bakuchiol and salicylic acid) into bakuchiol salicylate (bakusylan), with the intention of rendering a novel functional retinoid. The researchers reported that the gene expression profile showed elimination of various retinoid-like proinflammatory responses, without a loss of normalizing activity. They concluded that their work may result in a new class of functional retinoids.¹⁴

Early this year, Dhaliwal et al. reported on a randomized, double-blind, 12-week study of 44 patients who applied either bakuchiol 0.5% cream twice daily or retinol 0.5% cream daily. Facial photographs were evaluated at baseline, 4, 8, and 12 weeks, and a blinded dermatologist rated pigmentation and erythema. Side effects were also noted by subjects in tolerability assessment questionnaires. Both compounds significantly reduced wrinkles and hyperpigmentation, with no statistical variance found between the two. More facial skin scaling and stinging was experienced by the retinol group. The investigators concluded that bakuchiol exhibits photoaging activity comparable with retinol and appears to be an emerging alternative to retinol because it is better tolerated.¹² Notably, there is one report to date of an allergic reaction to topical bakuchiol.¹⁵
 

Topical combination therapies for hyperpigmentation, photodamage, and acne

Bakuchiol was a key ingredient incorporated into a 0.5% retinol treatment evaluated in a 12-week, open-label, single-center clinical-usage trial of 44 women with mild to moderate hyperpigmentation and photodamaged facial skin who took a dual product regimen. This 2016 study showed that the retinol and vitamin C facial regimen yielded a statistically significant amelioration in clinical grading of all parameters.¹⁶

A 2015 randomized controlled clinical trial in 111 subjects evaluated the use of adapalene 0.1% gel and a formulation containing bakuchiol, Ginkgo biloba extract, and mannitol in patients with acne. Patients were randomized to the adapalene and botanical formulation or adapalene and vehicle cream for 2 months. Both treatment groups experienced improvements according to all measured outcomes. The botanical formulation was associated with a statistically significant edge over the vehicle combination in reducing inflammatory lesions, investigator global assessment, and intensity of seborrhea. Quality of life was also perceived to be better with the combination of adapalene and the bakuchiol-containing product, which was deemed to be safe with good local tolerability.¹⁷

A subsequent evaluation by a different team also considered the antibacterial, anti-inflammatory, and antioxidative potential of this combination product via in vitro, ex vivo, and clinical studies. The work by Trompezinski et al. revealed that bakuchiol displays nearly twice the antioxidative potential asthat of vitamin E. The bakuchiol-containing cream was shown in acne patients to successfully regulate sebum composition by raising linolenic and sapienic acid levels while lowering oleic acid levels. Its efficacy against Propionibacterium acnes was also suggested by a decrease in the number of skin surface porphyrins. The investigators concluded that the formulation serves as an effective adjuvant acne treatment by attacking inflammation, dysseborrhea, and proliferation of Propionibacterium acnes.¹⁸
 

Anticancer activity

In 2016, Kim et al. demonstrated that bakuchiol exhibits chemopreventive activity by hindering epidermal growth factor (EGF)–induced neoplastic cell transformation. In what was the first mechanistic study to reveal molecular targets for the anticancer activity of this substance, the investigators found that bakuchiol also reduced the viability and suppressed anchorage-independent growth of A431 human epithelial carcinoma cells. They identified Hck, Blk, and p38 MAPK as the molecular targets of what they identified as a potent anticancer compound.²

Skin-whitening potential

In 2010, Ohno et al. found that bakuchiol, along with other ingredients, isolated from Piper longum demonstrated strong suppressive activity against melanin production in B16 mouse melanoma cells and may have potential to affect melanin synthesis in human skin.¹⁹ Further, with use of a new method for screening tyrosinase, Cheng et al. found in 2017 that four substances used in traditional Chinese medicine (quercetin, kaempferol, bavachinin, and bakuchiol) displayed the potential for inhibiting tyrosinase.²⁰

Conclusion

A compound that acts like a retinoid – yielding antiacne and antiaging effects – without provoking irritation? Most dermatologists and their patients would say, sign me up. Bakuchiol, an active ingredient in various plants, especially Psoralea corylifolia, seems to present that kind of profile. While more research is necessary, experience with this herbal ingredient in traditional medicine and an increasing body of research, including clinical results, provides reasons for optimism that this ingredient may have a versatile role to play in topical skin care, particularly in its retinoid-like functions.

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), as well as 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. Chaudhuri RK et al. Int J Cosmet Sci. 2014 Jun;36(3):221-30.

2. Kim JE et al. Oncotarget. 2016 Mar 22;7(12):14616-27.

3. Kim YJ et al. Molecules. 2016 Aug 17. doi: 10.3390/molecules21081076.

4. Xin Z et al. Pharmacol Res. 2019 Mar;141:208-13.

5. Lev-Tov H. Br J Dermatol. 2019 Feb;180(2):253-4.

6. Shrestha S et al. J Ayurveda Integr Med. 2018 Jul - Sep; 9(3):209-12.

7. Li CC et al. Evid Based Complement Alternat Med. 2016. doi: 10.1155/2016/8108643.

8. Hu C et al. Fitoterapia. 2015 Oct;106:129-34.

9. Yan DM et al. J Ethnopharmacol. 2010 Apr 21;128(3):697-702.

10. Choi SY et al. J Med Food. 2010 Aug;13(4):1019-23.

11. Madrid A et al. J Ethnopharmacol. 2012 Dec 18;144(3):809-11.

12. Dhaliwal S et al. Br J Dermatol. 2019 Feb;180(2):289-96.

13. Yu Q et al. Zhong Yao Cai. 2014 Apr;37(4):632-5.

14. Ma S et al. Clin Exp Dermatol. 2017 Apr;42(3):251-60.

15. Malinauskiene L et al. Contact Dermatitis. 2019 Jun;80(6):398-9.

16. Herndon JH Jr, et al. J Drugs Dermatol. 2016 Apr;15(4):476-82.

17. Poláková K et al. Clin Cosmet Investig Dermatol. 2015 Apr 10;8:187-91.

18. Trompezinski S et al. Clin Cosmet Investig Dermatol. 2016 Aug 31;9:233-9.

19. Ohno O et al. Biosci Biotechnol Biochem. 2010;74(7):1504-6.

20. Cheng M et al. Electrophoresis. 2017 Feb;38(3-4):486-93.

Bakuchiol [(1E,3S)-3-ethenyl-3,7-dimethyl-1,6-octadien-1-yl]phenol, a prenylated phenolic monoterpene found in the seeds and leaves of various plants, particularly Psoralea corylifolia, has been used to treat a broad array of disorders, including skin conditions, in the traditional medical practices of China, Japan, and Korea, as well as Ayurvedic medicine in India.^1-6 Specifically, the seeds of Psoralea corylifolia have also been used in traditional Chinese medicine to treat leukoderma, psoriasis, vitiligo, chronic graft-versus-host disease, and other skin disorders, as well as cardiovascular diseases, nephritis, osteoporosis, and cancer.^7-9

Anna Gorbacheva / iStock / Getty Images Plus

This primary active ingredient is reputed to exert antioxidant, antibacterial, anti-inflammatory, antiaging, and estrogen-like functions, and recent data suggest anticancer activity, including activity against skin cancer. Its antiaging properties manifest via preservation of cutaneous collagen.⁴ The plant itself has displayed a wide range of biological functions, such as antibacterial, anticancer, cytotoxic, cardiac, diaphoretic, diuretic, stimulant, aphrodisiac, and tonifying activities.^8,9 A 2016 quantitative analysis of Psoralea corylifolia and seven of its standard constituents (psoralen, angelicin, neobavaisoflavone, psoralidin, isobavachalcone, bavachinin, and bakuchiol) using high-performance liquid chromatography revealed that bakuchiol is the strongest phytochemical ingredient in the plant, which the investigators found also confers neuroprotective and antineuroinflammatory benefits.³

Other species contain bakuchiol, and its biological activities have been harnessed in other folk medical traditions. The monoterpene is an important constituent found in Ulmus davidiana var. japonica, which is used for its anti-inflammatory properties in traditional Korean medicine.¹⁰ Further, bakuchiol and 3-hydroxy-bakuchiol have been identified as key components isolated from Psoralea glandulosa, which is a shrub used in Chilean folk medicine to treat cutaneous disorders engendered by bacteria and fungus.¹¹ Topical applications of bakuchiol have been demonstrated to confer antiaging benefits.¹² This column briefly identifies some of the various uses emerging for this compelling botanical agent.
 

Antiaging activities

In 2014, Yu et al. found that bakuchiol may impart antiaging benefits by supporting the cellular activity of the expression level of human skin fibroblasts (ESF-1), as well as production of collagen types I and III, while reducing the matrix metalloproteinase-1 mRNA expression.¹³

The same year, Chaudhuri et al. compared the skin care–related activities of retinol and bakuchiol, finding their gene expression profiles very similar. In addition, they observed that bakuchiol up-regulated collagen types I and IV in a DNA microarray study and stimulated type III collagen production in a model of mature fibroblasts. Further, the investigators formulated bakuchiol into a skin care product and tested it clinically, with twice daily applications over 12 weeks yielding significant amelioration in lines and wrinkles, pigmentation, elasticity, and firmness, as well as overall diminished photodamage without provoking redness. They concluded that bakuchiol can act as an antiaging agent through regulation of gene expression comparable to retinol.¹

Retinoids without reactions?

In 2017, Ma et al. set out to synthesize and test in psoriatic cytokine–treated cultures of keratinocytes and organotypic skin substitutes a new substance created by combining two skin-active compounds (bakuchiol and salicylic acid) into bakuchiol salicylate (bakusylan), with the intention of rendering a novel functional retinoid. The researchers reported that the gene expression profile showed elimination of various retinoid-like proinflammatory responses, without a loss of normalizing activity. They concluded that their work may result in a new class of functional retinoids.¹⁴

Early this year, Dhaliwal et al. reported on a randomized, double-blind, 12-week study of 44 patients who applied either bakuchiol 0.5% cream twice daily or retinol 0.5% cream daily. Facial photographs were evaluated at baseline, 4, 8, and 12 weeks, and a blinded dermatologist rated pigmentation and erythema. Side effects were also noted by subjects in tolerability assessment questionnaires. Both compounds significantly reduced wrinkles and hyperpigmentation, with no statistical variance found between the two. More facial skin scaling and stinging was experienced by the retinol group. The investigators concluded that bakuchiol exhibits photoaging activity comparable with retinol and appears to be an emerging alternative to retinol because it is better tolerated.¹² Notably, there is one report to date of an allergic reaction to topical bakuchiol.¹⁵
 

Topical combination therapies for hyperpigmentation, photodamage, and acne

Bakuchiol was a key ingredient incorporated into a 0.5% retinol treatment evaluated in a 12-week, open-label, single-center clinical-usage trial of 44 women with mild to moderate hyperpigmentation and photodamaged facial skin who took a dual product regimen. This 2016 study showed that the retinol and vitamin C facial regimen yielded a statistically significant amelioration in clinical grading of all parameters.¹⁶

A 2015 randomized controlled clinical trial in 111 subjects evaluated the use of adapalene 0.1% gel and a formulation containing bakuchiol, Ginkgo biloba extract, and mannitol in patients with acne. Patients were randomized to the adapalene and botanical formulation or adapalene and vehicle cream for 2 months. Both treatment groups experienced improvements according to all measured outcomes. The botanical formulation was associated with a statistically significant edge over the vehicle combination in reducing inflammatory lesions, investigator global assessment, and intensity of seborrhea. Quality of life was also perceived to be better with the combination of adapalene and the bakuchiol-containing product, which was deemed to be safe with good local tolerability.¹⁷

A subsequent evaluation by a different team also considered the antibacterial, anti-inflammatory, and antioxidative potential of this combination product via in vitro, ex vivo, and clinical studies. The work by Trompezinski et al. revealed that bakuchiol displays nearly twice the antioxidative potential asthat of vitamin E. The bakuchiol-containing cream was shown in acne patients to successfully regulate sebum composition by raising linolenic and sapienic acid levels while lowering oleic acid levels. Its efficacy against Propionibacterium acnes was also suggested by a decrease in the number of skin surface porphyrins. The investigators concluded that the formulation serves as an effective adjuvant acne treatment by attacking inflammation, dysseborrhea, and proliferation of Propionibacterium acnes.¹⁸
 

Anticancer activity

In 2016, Kim et al. demonstrated that bakuchiol exhibits chemopreventive activity by hindering epidermal growth factor (EGF)–induced neoplastic cell transformation. In what was the first mechanistic study to reveal molecular targets for the anticancer activity of this substance, the investigators found that bakuchiol also reduced the viability and suppressed anchorage-independent growth of A431 human epithelial carcinoma cells. They identified Hck, Blk, and p38 MAPK as the molecular targets of what they identified as a potent anticancer compound.²

Skin-whitening potential

In 2010, Ohno et al. found that bakuchiol, along with other ingredients, isolated from Piper longum demonstrated strong suppressive activity against melanin production in B16 mouse melanoma cells and may have potential to affect melanin synthesis in human skin.¹⁹ Further, with use of a new method for screening tyrosinase, Cheng et al. found in 2017 that four substances used in traditional Chinese medicine (quercetin, kaempferol, bavachinin, and bakuchiol) displayed the potential for inhibiting tyrosinase.²⁰

Conclusion

A compound that acts like a retinoid – yielding antiacne and antiaging effects – without provoking irritation? Most dermatologists and their patients would say, sign me up. Bakuchiol, an active ingredient in various plants, especially Psoralea corylifolia, seems to present that kind of profile. While more research is necessary, experience with this herbal ingredient in traditional medicine and an increasing body of research, including clinical results, provides reasons for optimism that this ingredient may have a versatile role to play in topical skin care, particularly in its retinoid-like functions.

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), as well as 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. Chaudhuri RK et al. Int J Cosmet Sci. 2014 Jun;36(3):221-30.

2. Kim JE et al. Oncotarget. 2016 Mar 22;7(12):14616-27.

3. Kim YJ et al. Molecules. 2016 Aug 17. doi: 10.3390/molecules21081076.

4. Xin Z et al. Pharmacol Res. 2019 Mar;141:208-13.

5. Lev-Tov H. Br J Dermatol. 2019 Feb;180(2):253-4.

6. Shrestha S et al. J Ayurveda Integr Med. 2018 Jul - Sep; 9(3):209-12.

7. Li CC et al. Evid Based Complement Alternat Med. 2016. doi: 10.1155/2016/8108643.

8. Hu C et al. Fitoterapia. 2015 Oct;106:129-34.

9. Yan DM et al. J Ethnopharmacol. 2010 Apr 21;128(3):697-702.

10. Choi SY et al. J Med Food. 2010 Aug;13(4):1019-23.

11. Madrid A et al. J Ethnopharmacol. 2012 Dec 18;144(3):809-11.

12. Dhaliwal S et al. Br J Dermatol. 2019 Feb;180(2):289-96.

13. Yu Q et al. Zhong Yao Cai. 2014 Apr;37(4):632-5.

14. Ma S et al. Clin Exp Dermatol. 2017 Apr;42(3):251-60.

15. Malinauskiene L et al. Contact Dermatitis. 2019 Jun;80(6):398-9.

16. Herndon JH Jr, et al. J Drugs Dermatol. 2016 Apr;15(4):476-82.

17. Poláková K et al. Clin Cosmet Investig Dermatol. 2015 Apr 10;8:187-91.

18. Trompezinski S et al. Clin Cosmet Investig Dermatol. 2016 Aug 31;9:233-9.

19. Ohno O et al. Biosci Biotechnol Biochem. 2010;74(7):1504-6.

20. Cheng M et al. Electrophoresis. 2017 Feb;38(3-4):486-93.

Minimally invasive cosmetic surgery continued its steady rise in 2018, with a 1.6% increase over the previous year that brought the total to nearly 16 million procedures, according to the American Society of Plastic Surgeons.

The most popular form of minimally invasive cosmetic surgery among the estimated 15.9 million procedures performed in 2018 was, once again, onabotulinumtoxinA injection, which represented almost half of the total for the year with 7.4 million anatomic sites injected (up by 2.9%), the ASPS said in its 2018 Plastic Surgery Statistics Report.

Soft-tissue-filler injections, the next most popular type of surgery, were up 1.7% to almost 2.7 million procedures, while chemical peels rose 0.6% to nearly 1.4 million procedures. Numbers for 2018 were down, however, for the two other top-five surgeries: Laser hair removal slipped 0.9% from 2017 and microdermabrasion fell 4.2%, the ASPS reported.


Going back quite a bit further in time – the year 2000, to be exact – reveals 21st-century growth of 228% for the minimally invasive sector as a whole, but the long-term trend for cosmetic surgery was not quite as rosy – down by 4.7% since 2000. From 2017 to 2018, though, cosmetic surgery procedures were up by 1.2%, with breast augmentation the most popular, followed by liposuction, rhinoplasty, blepharoplasty, and abdominoplasty, according to the ASPS.

The 2018 statistics report was based on analysis of the society’s Tracking Operations and Outcomes for Plastic Surgeons database and an annual survey of board-certified dermatologists, otolaryngologists, and plastic surgeons (final sample = 724).

[email protected]

Minimally invasive cosmetic surgery continued its steady rise in 2018, with a 1.6% increase over the previous year that brought the total to nearly 16 million procedures, according to the American Society of Plastic Surgeons.

The most popular form of minimally invasive cosmetic surgery among the estimated 15.9 million procedures performed in 2018 was, once again, onabotulinumtoxinA injection, which represented almost half of the total for the year with 7.4 million anatomic sites injected (up by 2.9%), the ASPS said in its 2018 Plastic Surgery Statistics Report.

Soft-tissue-filler injections, the next most popular type of surgery, were up 1.7% to almost 2.7 million procedures, while chemical peels rose 0.6% to nearly 1.4 million procedures. Numbers for 2018 were down, however, for the two other top-five surgeries: Laser hair removal slipped 0.9% from 2017 and microdermabrasion fell 4.2%, the ASPS reported.


Going back quite a bit further in time – the year 2000, to be exact – reveals 21st-century growth of 228% for the minimally invasive sector as a whole, but the long-term trend for cosmetic surgery was not quite as rosy – down by 4.7% since 2000. From 2017 to 2018, though, cosmetic surgery procedures were up by 1.2%, with breast augmentation the most popular, followed by liposuction, rhinoplasty, blepharoplasty, and abdominoplasty, according to the ASPS.

The 2018 statistics report was based on analysis of the society’s Tracking Operations and Outcomes for Plastic Surgeons database and an annual survey of board-certified dermatologists, otolaryngologists, and plastic surgeons (final sample = 724).

[email protected]

Minimally invasive cosmetic surgery continued its steady rise in 2018, with a 1.6% increase over the previous year that brought the total to nearly 16 million procedures, according to the American Society of Plastic Surgeons.

The most popular form of minimally invasive cosmetic surgery among the estimated 15.9 million procedures performed in 2018 was, once again, onabotulinumtoxinA injection, which represented almost half of the total for the year with 7.4 million anatomic sites injected (up by 2.9%), the ASPS said in its 2018 Plastic Surgery Statistics Report.

Soft-tissue-filler injections, the next most popular type of surgery, were up 1.7% to almost 2.7 million procedures, while chemical peels rose 0.6% to nearly 1.4 million procedures. Numbers for 2018 were down, however, for the two other top-five surgeries: Laser hair removal slipped 0.9% from 2017 and microdermabrasion fell 4.2%, the ASPS reported.


Going back quite a bit further in time – the year 2000, to be exact – reveals 21st-century growth of 228% for the minimally invasive sector as a whole, but the long-term trend for cosmetic surgery was not quite as rosy – down by 4.7% since 2000. From 2017 to 2018, though, cosmetic surgery procedures were up by 1.2%, with breast augmentation the most popular, followed by liposuction, rhinoplasty, blepharoplasty, and abdominoplasty, according to the ASPS.

The 2018 statistics report was based on analysis of the society’s Tracking Operations and Outcomes for Plastic Surgeons database and an annual survey of board-certified dermatologists, otolaryngologists, and plastic surgeons (final sample = 724).

[email protected]

Use of social media platforms such as Tinder, Snapchat, and Instagram, particularly in conjunction with photo-editing applications, may increase an individual’s acceptance of cosmetic surgery, a new study suggests.

In JAMA Facial Plastic Surgery, researchers report the outcomes of a web-based survey study involving 252 participants, 73.0% of whom were female. The survey asked participants about their use of social media, photo-editing tools such as Photoshop, VSCO, and Snapchat filters, and answered questionnaires to assess their self-esteem, self-worth, and attitudes toward cosmetic surgery.

All participants used at least one social media platform, with a mean of seven, and used a mean of two photo-editing applications; the analysis found that those who used more social media platforms were more likely to consider cosmetic surgery.

People who used Tinder and Snapchat ­– with or without photo filters – showed greater acceptance of cosmetic surgery, while those who used the photography mobile app VSCO and Instagram photo filters showed greater consideration but not acceptance of cosmetic surgery, compared with nonusers.

Participants whose self-worth was more closely tied to their appearance showed greater acceptance of cosmetic surgery. When it came to self-esteem, participants who used YouTube, WhatsApp, VSCO, and Photoshop had lower self-esteem scores, compared with nonusers.

Overall, nearly two-thirds of survey participants said they used photo-editing applications to change the lighting of images, but only 5.16% said they used these applications to make changes to face or body shape. This distinction was also seen in their acceptance of cosmetic surgery scores: Those who said they made changes to face and body shape showed higher acceptance scores than nonusers, but this was not seen in those who only used it for lighting adjustments.

“The rising trend of pursuing cosmetic surgery based on social media inspiration highlights the need to better understand patients’ motivations to seek cosmetic surgery,” wrote Jonlin Chen, a medical student at Johns Hopkins University, Baltimore, and coauthors.

Commenting on the association between YouTube use, lower self-esteem, and higher acceptance of cosmetic surgery, the authors suggested that the platform may generate appearance comparisons between users by allowing them to access beauty-related videos and connect with other users interested in cosmetics.

Michael J. Reilly, MD, department of otolaryngology–head and neck surgery and Keon M. Parsa, MD, from the department of psychiatry at MedStar Georgetown University Hospital in Washington, commented in an accompanying editorial that the findings of this study illustrate an increased trend seen by facial plastic surgeons (JAMA Facial Plast Surg. 2019 June 27. doi: 10.1001/jamafacial.2019.0419). The study “shows the importance of understanding the underlying motives and characteristics of individuals seeking cosmetic surgery.” They noted that facial plastic surgeons can play a role in helping patients to improve their self-esteem, but it is also important to be aware of the clinical signs of depression, anxiety, and social isolation and refer for appropriate nonsurgical support when there are mental health concerns that go beyond the knife and needle.

The authors of the study did note that their choice of a web-based survey meant the demographic was likely to be skewed toward a younger, more social media–savvy demographic, and may not necessarily represent the broader population of individuals seeking cosmetic surgery.

No funding or conflicts of interest were declared.

SOURCE: Chen J et al. JAMA Facial Plast Surg. 2019 Jun 27. doi: 10.1001/jamafacial.2019.0328.

Use of social media platforms such as Tinder, Snapchat, and Instagram, particularly in conjunction with photo-editing applications, may increase an individual’s acceptance of cosmetic surgery, a new study suggests.

In JAMA Facial Plastic Surgery, researchers report the outcomes of a web-based survey study involving 252 participants, 73.0% of whom were female. The survey asked participants about their use of social media, photo-editing tools such as Photoshop, VSCO, and Snapchat filters, and answered questionnaires to assess their self-esteem, self-worth, and attitudes toward cosmetic surgery.

All participants used at least one social media platform, with a mean of seven, and used a mean of two photo-editing applications; the analysis found that those who used more social media platforms were more likely to consider cosmetic surgery.

People who used Tinder and Snapchat ­– with or without photo filters – showed greater acceptance of cosmetic surgery, while those who used the photography mobile app VSCO and Instagram photo filters showed greater consideration but not acceptance of cosmetic surgery, compared with nonusers.

Participants whose self-worth was more closely tied to their appearance showed greater acceptance of cosmetic surgery. When it came to self-esteem, participants who used YouTube, WhatsApp, VSCO, and Photoshop had lower self-esteem scores, compared with nonusers.

Overall, nearly two-thirds of survey participants said they used photo-editing applications to change the lighting of images, but only 5.16% said they used these applications to make changes to face or body shape. This distinction was also seen in their acceptance of cosmetic surgery scores: Those who said they made changes to face and body shape showed higher acceptance scores than nonusers, but this was not seen in those who only used it for lighting adjustments.

“The rising trend of pursuing cosmetic surgery based on social media inspiration highlights the need to better understand patients’ motivations to seek cosmetic surgery,” wrote Jonlin Chen, a medical student at Johns Hopkins University, Baltimore, and coauthors.

Commenting on the association between YouTube use, lower self-esteem, and higher acceptance of cosmetic surgery, the authors suggested that the platform may generate appearance comparisons between users by allowing them to access beauty-related videos and connect with other users interested in cosmetics.

Michael J. Reilly, MD, department of otolaryngology–head and neck surgery and Keon M. Parsa, MD, from the department of psychiatry at MedStar Georgetown University Hospital in Washington, commented in an accompanying editorial that the findings of this study illustrate an increased trend seen by facial plastic surgeons (JAMA Facial Plast Surg. 2019 June 27. doi: 10.1001/jamafacial.2019.0419). The study “shows the importance of understanding the underlying motives and characteristics of individuals seeking cosmetic surgery.” They noted that facial plastic surgeons can play a role in helping patients to improve their self-esteem, but it is also important to be aware of the clinical signs of depression, anxiety, and social isolation and refer for appropriate nonsurgical support when there are mental health concerns that go beyond the knife and needle.

The authors of the study did note that their choice of a web-based survey meant the demographic was likely to be skewed toward a younger, more social media–savvy demographic, and may not necessarily represent the broader population of individuals seeking cosmetic surgery.

No funding or conflicts of interest were declared.

SOURCE: Chen J et al. JAMA Facial Plast Surg. 2019 Jun 27. doi: 10.1001/jamafacial.2019.0328.

Use of social media platforms such as Tinder, Snapchat, and Instagram, particularly in conjunction with photo-editing applications, may increase an individual’s acceptance of cosmetic surgery, a new study suggests.

In JAMA Facial Plastic Surgery, researchers report the outcomes of a web-based survey study involving 252 participants, 73.0% of whom were female. The survey asked participants about their use of social media, photo-editing tools such as Photoshop, VSCO, and Snapchat filters, and answered questionnaires to assess their self-esteem, self-worth, and attitudes toward cosmetic surgery.

All participants used at least one social media platform, with a mean of seven, and used a mean of two photo-editing applications; the analysis found that those who used more social media platforms were more likely to consider cosmetic surgery.

People who used Tinder and Snapchat ­– with or without photo filters – showed greater acceptance of cosmetic surgery, while those who used the photography mobile app VSCO and Instagram photo filters showed greater consideration but not acceptance of cosmetic surgery, compared with nonusers.

Participants whose self-worth was more closely tied to their appearance showed greater acceptance of cosmetic surgery. When it came to self-esteem, participants who used YouTube, WhatsApp, VSCO, and Photoshop had lower self-esteem scores, compared with nonusers.

Overall, nearly two-thirds of survey participants said they used photo-editing applications to change the lighting of images, but only 5.16% said they used these applications to make changes to face or body shape. This distinction was also seen in their acceptance of cosmetic surgery scores: Those who said they made changes to face and body shape showed higher acceptance scores than nonusers, but this was not seen in those who only used it for lighting adjustments.

“The rising trend of pursuing cosmetic surgery based on social media inspiration highlights the need to better understand patients’ motivations to seek cosmetic surgery,” wrote Jonlin Chen, a medical student at Johns Hopkins University, Baltimore, and coauthors.

Commenting on the association between YouTube use, lower self-esteem, and higher acceptance of cosmetic surgery, the authors suggested that the platform may generate appearance comparisons between users by allowing them to access beauty-related videos and connect with other users interested in cosmetics.

Michael J. Reilly, MD, department of otolaryngology–head and neck surgery and Keon M. Parsa, MD, from the department of psychiatry at MedStar Georgetown University Hospital in Washington, commented in an accompanying editorial that the findings of this study illustrate an increased trend seen by facial plastic surgeons (JAMA Facial Plast Surg. 2019 June 27. doi: 10.1001/jamafacial.2019.0419). The study “shows the importance of understanding the underlying motives and characteristics of individuals seeking cosmetic surgery.” They noted that facial plastic surgeons can play a role in helping patients to improve their self-esteem, but it is also important to be aware of the clinical signs of depression, anxiety, and social isolation and refer for appropriate nonsurgical support when there are mental health concerns that go beyond the knife and needle.

The authors of the study did note that their choice of a web-based survey meant the demographic was likely to be skewed toward a younger, more social media–savvy demographic, and may not necessarily represent the broader population of individuals seeking cosmetic surgery.

No funding or conflicts of interest were declared.

SOURCE: Chen J et al. JAMA Facial Plast Surg. 2019 Jun 27. doi: 10.1001/jamafacial.2019.0328.

Female pattern hair loss (FPHL) is an increasingly common and incredibly frustrating disease, affecting about 40% of all women. Although genetics, hormones, age, environment, stress, and nutrition all play a role in the etiology of FPHL, the underlying pathophysiology is poorly understood. The only Food and Drug Administration–approved medication to treat FPHL is topical minoxidil. The armamentarium is limited so alternative treatments such as platelet-rich plasma, topical hair loss preparations, and nutritional supplements are now being used in an effort to slow down progression of this disease.

Hair follicles are metabolically active and thus nutrient deficiency as well as calorie and protein restriction impact the hair growth cycle. Patients often inquire if dietary changes or supplementation can help prevent the loss or increase the growth of the hair. Unfortunately, the quality of evidence on nutritional supplements for this use is poor. Furthermore, it is unclear whether patients with FPHL should be routinely tested for nutritional deficiencies, and which type and concentration of supplementation will be of benefit to patients.

Iron deficiency is one of the most well-known factors for hair loss. Risk factors include heavy bleeding during menses, gastrointestinal blood loss, and malabsorption. Studies have shown that iron supplementation does help increase hair growth in iron-deficient mice. Zinc is also a key mineral in hair follicle development, and zinc deficiency is seen in genetic diseases or malabsorption syndromes and has been linked to hair loss.

Deficiencies in selenium, essential fatty acids, vitamin D, vitamin A, vitamin E, folic acid, and biotin have been documented in relation to hair loss. However, no studies have effectively shown that supplementation of these nutrients helps hair growth in patients without a documented deficiency. Currently, it is difficult to ascertain which nutrients and in what concentrations are both safe and effective to correct hair loss.

In the vast hair supplement market, some of the more popular supplements for FPHL are DeeplyRooted (Hush & Hush), Viviscal, Nutrafol, and Nature’s Bounty and Sugarbearhair products. These supplements contain a combination of micronutrients (such as vitamin D, niacin, zinc, biotin, and selenium) and adaptogens (a natural substance that helps the body heal with stress and increased cortisol production during stress) that may stimulate the growth and health of the hair follicle and minimize the production of stress hormones and dihydrotestosterone.

In my practice, we see over 100 hair loss patients a week; 30%-40% are patients with FPHL who are often suffering from depression, anxiety, and emotional distress. Our combination treatments always include nutritional supplementation and we have had success not only halting subclinical shedding, but also increasing hair growth. Until the complex pathophysiology of FPHL is identified and new therapeutics are developed, practitioners should consider adding nutritional supplements for the treatment of women with FPHL. Monitoring of supplement use is essential given the risk of toxicity from some vitamins and supplements when taken without proper supervision. More research is also needed to help delineate both the guidelines of micronutrient testing and parameters for supplementation.

Dr. Talakoub and Dr. Wesley are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub. Write to them at [email protected]. They had no relevant disclosures.

Sources

Guo EL et al. Dermatol Pract Concept. 2017 Jan 31;7(1):1-10.

Goldberg LJ et al. Clin Dermatol. 2010 Jul-Aug;28(4):412-9.

Finner AM. Dermatol Clin. 2013 Jan;31(1):167-72.

St Pierre SA et al. J Am Acad Dermatol. 2010 Dec;63(6):1070-6.

Rasheed H et al. Skin Pharmacol Physiol. 2013;26(2):101-7.

Rogers NE et al. J Am Acad Dermatol. 2008 Oct;59(4):547-66.

Ablon G et al. J Drugs Dermatol. 2018 May 1;17(5):558-65.

Female pattern hair loss (FPHL) is an increasingly common and incredibly frustrating disease, affecting about 40% of all women. Although genetics, hormones, age, environment, stress, and nutrition all play a role in the etiology of FPHL, the underlying pathophysiology is poorly understood. The only Food and Drug Administration–approved medication to treat FPHL is topical minoxidil. The armamentarium is limited so alternative treatments such as platelet-rich plasma, topical hair loss preparations, and nutritional supplements are now being used in an effort to slow down progression of this disease.

Hair follicles are metabolically active and thus nutrient deficiency as well as calorie and protein restriction impact the hair growth cycle. Patients often inquire if dietary changes or supplementation can help prevent the loss or increase the growth of the hair. Unfortunately, the quality of evidence on nutritional supplements for this use is poor. Furthermore, it is unclear whether patients with FPHL should be routinely tested for nutritional deficiencies, and which type and concentration of supplementation will be of benefit to patients.

Iron deficiency is one of the most well-known factors for hair loss. Risk factors include heavy bleeding during menses, gastrointestinal blood loss, and malabsorption. Studies have shown that iron supplementation does help increase hair growth in iron-deficient mice. Zinc is also a key mineral in hair follicle development, and zinc deficiency is seen in genetic diseases or malabsorption syndromes and has been linked to hair loss.

Deficiencies in selenium, essential fatty acids, vitamin D, vitamin A, vitamin E, folic acid, and biotin have been documented in relation to hair loss. However, no studies have effectively shown that supplementation of these nutrients helps hair growth in patients without a documented deficiency. Currently, it is difficult to ascertain which nutrients and in what concentrations are both safe and effective to correct hair loss.

In the vast hair supplement market, some of the more popular supplements for FPHL are DeeplyRooted (Hush & Hush), Viviscal, Nutrafol, and Nature’s Bounty and Sugarbearhair products. These supplements contain a combination of micronutrients (such as vitamin D, niacin, zinc, biotin, and selenium) and adaptogens (a natural substance that helps the body heal with stress and increased cortisol production during stress) that may stimulate the growth and health of the hair follicle and minimize the production of stress hormones and dihydrotestosterone.

In my practice, we see over 100 hair loss patients a week; 30%-40% are patients with FPHL who are often suffering from depression, anxiety, and emotional distress. Our combination treatments always include nutritional supplementation and we have had success not only halting subclinical shedding, but also increasing hair growth. Until the complex pathophysiology of FPHL is identified and new therapeutics are developed, practitioners should consider adding nutritional supplements for the treatment of women with FPHL. Monitoring of supplement use is essential given the risk of toxicity from some vitamins and supplements when taken without proper supervision. More research is also needed to help delineate both the guidelines of micronutrient testing and parameters for supplementation.

Dr. Talakoub and Dr. Wesley are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub. Write to them at [email protected]. They had no relevant disclosures.

Sources

Guo EL et al. Dermatol Pract Concept. 2017 Jan 31;7(1):1-10.

Goldberg LJ et al. Clin Dermatol. 2010 Jul-Aug;28(4):412-9.

Finner AM. Dermatol Clin. 2013 Jan;31(1):167-72.

St Pierre SA et al. J Am Acad Dermatol. 2010 Dec;63(6):1070-6.

Rasheed H et al. Skin Pharmacol Physiol. 2013;26(2):101-7.

Rogers NE et al. J Am Acad Dermatol. 2008 Oct;59(4):547-66.

Ablon G et al. J Drugs Dermatol. 2018 May 1;17(5):558-65.

Female pattern hair loss (FPHL) is an increasingly common and incredibly frustrating disease, affecting about 40% of all women. Although genetics, hormones, age, environment, stress, and nutrition all play a role in the etiology of FPHL, the underlying pathophysiology is poorly understood. The only Food and Drug Administration–approved medication to treat FPHL is topical minoxidil. The armamentarium is limited so alternative treatments such as platelet-rich plasma, topical hair loss preparations, and nutritional supplements are now being used in an effort to slow down progression of this disease.

Hair follicles are metabolically active and thus nutrient deficiency as well as calorie and protein restriction impact the hair growth cycle. Patients often inquire if dietary changes or supplementation can help prevent the loss or increase the growth of the hair. Unfortunately, the quality of evidence on nutritional supplements for this use is poor. Furthermore, it is unclear whether patients with FPHL should be routinely tested for nutritional deficiencies, and which type and concentration of supplementation will be of benefit to patients.

Iron deficiency is one of the most well-known factors for hair loss. Risk factors include heavy bleeding during menses, gastrointestinal blood loss, and malabsorption. Studies have shown that iron supplementation does help increase hair growth in iron-deficient mice. Zinc is also a key mineral in hair follicle development, and zinc deficiency is seen in genetic diseases or malabsorption syndromes and has been linked to hair loss.

Deficiencies in selenium, essential fatty acids, vitamin D, vitamin A, vitamin E, folic acid, and biotin have been documented in relation to hair loss. However, no studies have effectively shown that supplementation of these nutrients helps hair growth in patients without a documented deficiency. Currently, it is difficult to ascertain which nutrients and in what concentrations are both safe and effective to correct hair loss.

In the vast hair supplement market, some of the more popular supplements for FPHL are DeeplyRooted (Hush & Hush), Viviscal, Nutrafol, and Nature’s Bounty and Sugarbearhair products. These supplements contain a combination of micronutrients (such as vitamin D, niacin, zinc, biotin, and selenium) and adaptogens (a natural substance that helps the body heal with stress and increased cortisol production during stress) that may stimulate the growth and health of the hair follicle and minimize the production of stress hormones and dihydrotestosterone.

In my practice, we see over 100 hair loss patients a week; 30%-40% are patients with FPHL who are often suffering from depression, anxiety, and emotional distress. Our combination treatments always include nutritional supplementation and we have had success not only halting subclinical shedding, but also increasing hair growth. Until the complex pathophysiology of FPHL is identified and new therapeutics are developed, practitioners should consider adding nutritional supplements for the treatment of women with FPHL. Monitoring of supplement use is essential given the risk of toxicity from some vitamins and supplements when taken without proper supervision. More research is also needed to help delineate both the guidelines of micronutrient testing and parameters for supplementation.

Dr. Talakoub and Dr. Wesley are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub. Write to them at [email protected]. They had no relevant disclosures.

Sources

Guo EL et al. Dermatol Pract Concept. 2017 Jan 31;7(1):1-10.

Goldberg LJ et al. Clin Dermatol. 2010 Jul-Aug;28(4):412-9.

Finner AM. Dermatol Clin. 2013 Jan;31(1):167-72.

St Pierre SA et al. J Am Acad Dermatol. 2010 Dec;63(6):1070-6.

Rasheed H et al. Skin Pharmacol Physiol. 2013;26(2):101-7.

Rogers NE et al. J Am Acad Dermatol. 2008 Oct;59(4):547-66.

Ablon G et al. J Drugs Dermatol. 2018 May 1;17(5):558-65.

Practice Gap

Common donor sites for split-thickness skin grafts (STSGs) include the abdomen, buttocks, inner upper arms and forearms, and thighs. Challenges associated with donor site wounds in these areas include slow healing times and poor scar cosmesis. Although the scalp is not commonly considered when selecting a STSG donor site, harvesting from this area yields optimal results to improve these shortcomings.

Tools

A Weck knife facilitates STSG harvesting in an operationally timely, convenient fashion from larger donor sites up to 5.5 cm in width, such as the scalp, using adjustable thickness control guards.

The Technique

The donor site is lubricated with a sterile mineral oil. An assistant provides tension, leading the trajectory of the Weck knife with a guard. Small, gentle, back-and-forth strokes are made with the Weck knife to harvest the graft, which is then meshed with a No. 15 blade by placing the belly of the blade on the tissue and rolling it to-and-fro. The recipient site cartilage is fenestrated with a 2-mm punch biopsy.

A 48-year-old man underwent Mohs micrographic surgery for treatment of a primary basal cell carcinoma of the left helix, resulting in a 2.5×1.3-cm defect after 2 stages. A Weck knife with a 0.012-in guard was used to harvest an STSG from the postauricular scalp (Figure, A), and the graft was inset to the recipient wound bed. Hemostasis at the scalp donor site was achieved through application of pressure and sterile gauze that was saturated with local 1% lidocaine anesthesia containing 1:400,000 epinephrine. Both recipient and donor sites were dressed with tie-over bolsters that were sutured into place. At 2-week follow-up, the donor site was fully reepithelialized and hair regrowth obscured the defect (Figure, B).

Practice Implications

Our case demonstrates the advantages of the scalp as an STSG donor site with prompt healing time and excellent cosmesis. Because grafts are harvested at a depth superficial to the hair follicle, the hair regrows to conceal the donor site scar. Additionally, the robust blood supply of the scalp and hair follicle density optimize healing time. The location of the donor site at the postauricular scalp facilitates accessibility for wound care by the patient. Electrocautery or chemical styptics used for hemostasis may traumatize the hair follicles and risk causing alopecia; therefore, as demonstrated in our case, the preferred method to achieve hemostasis is the use of pressure or application of sterile gauze that has been saturated with local 1% lidocaine anesthesia containing 1:400,000 epinephrine, followed by a pressure dressing provided by a sutured bolster.

Our case also demonstrates the utility of the Weck knife, which was introduced in 1968 as a modification of existing instruments to improve the ease of harvesting STSGs by appending a fixed handle and interchangeable depth gauges to a straight razor.^1,2 The Weck knife can obtain grafts up to 5.5 cm in width (length may be as long as anatomically available), often circumventing the need to overlap grafts of smaller widths for repair of larger defects. Furthermore, grafts are harvested at a depth superficial to the hair follicle, averting donor site alopecia. These characteristics make the technique an ideal option for harvesting grafts from the scalp and other large donor sites.

Limitations of the Weck knife technique include the inability to harvest grafts from small donor sites in difficult-to-access anatomic regions or from areas with notable 3-dimensional structure. For harvesting such grafts, we prefer the DermaBlade (AccuTec Blades). Furthermore, assistance for providing tension along the trajectory of the Weck blade with a guard is optimal when performing the procedure. For practices not already utilizing a Weck knife, the technique necessitates additional training and cost. Nonetheless, for STSGs in which large donor site surface area, adjustable thickness, and convenient and timely operational technique are desired, the Weck knife should be considered as part of the dermatologic surgeon’s armamentarium.

Practice Gap

Common donor sites for split-thickness skin grafts (STSGs) include the abdomen, buttocks, inner upper arms and forearms, and thighs. Challenges associated with donor site wounds in these areas include slow healing times and poor scar cosmesis. Although the scalp is not commonly considered when selecting a STSG donor site, harvesting from this area yields optimal results to improve these shortcomings.

Tools

A Weck knife facilitates STSG harvesting in an operationally timely, convenient fashion from larger donor sites up to 5.5 cm in width, such as the scalp, using adjustable thickness control guards.

The Technique

The donor site is lubricated with a sterile mineral oil. An assistant provides tension, leading the trajectory of the Weck knife with a guard. Small, gentle, back-and-forth strokes are made with the Weck knife to harvest the graft, which is then meshed with a No. 15 blade by placing the belly of the blade on the tissue and rolling it to-and-fro. The recipient site cartilage is fenestrated with a 2-mm punch biopsy.

A 48-year-old man underwent Mohs micrographic surgery for treatment of a primary basal cell carcinoma of the left helix, resulting in a 2.5×1.3-cm defect after 2 stages. A Weck knife with a 0.012-in guard was used to harvest an STSG from the postauricular scalp (Figure, A), and the graft was inset to the recipient wound bed. Hemostasis at the scalp donor site was achieved through application of pressure and sterile gauze that was saturated with local 1% lidocaine anesthesia containing 1:400,000 epinephrine. Both recipient and donor sites were dressed with tie-over bolsters that were sutured into place. At 2-week follow-up, the donor site was fully reepithelialized and hair regrowth obscured the defect (Figure, B).

Practice Implications

Our case demonstrates the advantages of the scalp as an STSG donor site with prompt healing time and excellent cosmesis. Because grafts are harvested at a depth superficial to the hair follicle, the hair regrows to conceal the donor site scar. Additionally, the robust blood supply of the scalp and hair follicle density optimize healing time. The location of the donor site at the postauricular scalp facilitates accessibility for wound care by the patient. Electrocautery or chemical styptics used for hemostasis may traumatize the hair follicles and risk causing alopecia; therefore, as demonstrated in our case, the preferred method to achieve hemostasis is the use of pressure or application of sterile gauze that has been saturated with local 1% lidocaine anesthesia containing 1:400,000 epinephrine, followed by a pressure dressing provided by a sutured bolster.

Our case also demonstrates the utility of the Weck knife, which was introduced in 1968 as a modification of existing instruments to improve the ease of harvesting STSGs by appending a fixed handle and interchangeable depth gauges to a straight razor.^1,2 The Weck knife can obtain grafts up to 5.5 cm in width (length may be as long as anatomically available), often circumventing the need to overlap grafts of smaller widths for repair of larger defects. Furthermore, grafts are harvested at a depth superficial to the hair follicle, averting donor site alopecia. These characteristics make the technique an ideal option for harvesting grafts from the scalp and other large donor sites.

Limitations of the Weck knife technique include the inability to harvest grafts from small donor sites in difficult-to-access anatomic regions or from areas with notable 3-dimensional structure. For harvesting such grafts, we prefer the DermaBlade (AccuTec Blades). Furthermore, assistance for providing tension along the trajectory of the Weck blade with a guard is optimal when performing the procedure. For practices not already utilizing a Weck knife, the technique necessitates additional training and cost. Nonetheless, for STSGs in which large donor site surface area, adjustable thickness, and convenient and timely operational technique are desired, the Weck knife should be considered as part of the dermatologic surgeon’s armamentarium.

Practice Gap

Common donor sites for split-thickness skin grafts (STSGs) include the abdomen, buttocks, inner upper arms and forearms, and thighs. Challenges associated with donor site wounds in these areas include slow healing times and poor scar cosmesis. Although the scalp is not commonly considered when selecting a STSG donor site, harvesting from this area yields optimal results to improve these shortcomings.

Tools

A Weck knife facilitates STSG harvesting in an operationally timely, convenient fashion from larger donor sites up to 5.5 cm in width, such as the scalp, using adjustable thickness control guards.

The Technique

The donor site is lubricated with a sterile mineral oil. An assistant provides tension, leading the trajectory of the Weck knife with a guard. Small, gentle, back-and-forth strokes are made with the Weck knife to harvest the graft, which is then meshed with a No. 15 blade by placing the belly of the blade on the tissue and rolling it to-and-fro. The recipient site cartilage is fenestrated with a 2-mm punch biopsy.

A 48-year-old man underwent Mohs micrographic surgery for treatment of a primary basal cell carcinoma of the left helix, resulting in a 2.5×1.3-cm defect after 2 stages. A Weck knife with a 0.012-in guard was used to harvest an STSG from the postauricular scalp (Figure, A), and the graft was inset to the recipient wound bed. Hemostasis at the scalp donor site was achieved through application of pressure and sterile gauze that was saturated with local 1% lidocaine anesthesia containing 1:400,000 epinephrine. Both recipient and donor sites were dressed with tie-over bolsters that were sutured into place. At 2-week follow-up, the donor site was fully reepithelialized and hair regrowth obscured the defect (Figure, B).

Practice Implications

Our case demonstrates the advantages of the scalp as an STSG donor site with prompt healing time and excellent cosmesis. Because grafts are harvested at a depth superficial to the hair follicle, the hair regrows to conceal the donor site scar. Additionally, the robust blood supply of the scalp and hair follicle density optimize healing time. The location of the donor site at the postauricular scalp facilitates accessibility for wound care by the patient. Electrocautery or chemical styptics used for hemostasis may traumatize the hair follicles and risk causing alopecia; therefore, as demonstrated in our case, the preferred method to achieve hemostasis is the use of pressure or application of sterile gauze that has been saturated with local 1% lidocaine anesthesia containing 1:400,000 epinephrine, followed by a pressure dressing provided by a sutured bolster.

Our case also demonstrates the utility of the Weck knife, which was introduced in 1968 as a modification of existing instruments to improve the ease of harvesting STSGs by appending a fixed handle and interchangeable depth gauges to a straight razor.^1,2 The Weck knife can obtain grafts up to 5.5 cm in width (length may be as long as anatomically available), often circumventing the need to overlap grafts of smaller widths for repair of larger defects. Furthermore, grafts are harvested at a depth superficial to the hair follicle, averting donor site alopecia. These characteristics make the technique an ideal option for harvesting grafts from the scalp and other large donor sites.

Limitations of the Weck knife technique include the inability to harvest grafts from small donor sites in difficult-to-access anatomic regions or from areas with notable 3-dimensional structure. For harvesting such grafts, we prefer the DermaBlade (AccuTec Blades). Furthermore, assistance for providing tension along the trajectory of the Weck blade with a guard is optimal when performing the procedure. For practices not already utilizing a Weck knife, the technique necessitates additional training and cost. Nonetheless, for STSGs in which large donor site surface area, adjustable thickness, and convenient and timely operational technique are desired, the Weck knife should be considered as part of the dermatologic surgeon’s armamentarium.

Many dermatologic procedures are performed on the face, such as skin biopsies, surgical excisions, and cosmetic procedures, which can increase the risk for accidental ocular injuries.^1,2 Ocular chemical burns have been reported to account for approximately 3% to 20% of ocular injuries^3,4 and are one of the few ocular emergencies dermatologists may encounter in practice. Given the potentially severe consequences of permanent vision changes or loss, it is important to take precautionary steps in preventing chemical exposures and know how to appropriately manage ophthalmic emergencies when they occur.^1,5-8 In this article, we describe a patient with a transient ocular chemical injury from exposure to aluminum chloride hexahydrate that completely resolved with immediate care. We also offer practical guidance for the general dermatologist in the acute management of acidic chemical burns to the eye, highlighting immediate copious irrigation as the most important step in preventing severe permanent damage. Given that aluminum chloride hexahydrate is an acidic solution, we focus predominantly on the approach to acidic chemical exposures to the eye.

Case Report

A 61-year-old woman was seen in the dermatology outpatient clinic for a shave biopsy on the left cheek followed by aluminum chloride application for hemostasis. Following the biopsy, the patient stated she felt the sensation that something had dripped into the left eye and she felt a burning pain. There was a 30- to 60-second delay in irrigation of the eye, as it was at first unclear what had occurred. The patient reported an increased burning sensation, and at that point she was instructed to begin flushing the eye with tap water from the examination room sink for 15 to 20 minutes; she wanted to stop irrigation after a few minutes, and convincing her to continue thorough irrigation was somewhat challenging. It was determined that aluminum chloride hexahydrate had dripped from an oversaturated cotton swab in transit from the tray to the biopsy site.

The patient was urgently directed to the ophthalmology clinic and evaluated by an ophthalmologist within 1 to 2 hours of chemical exposure. Visual acuity of the affected left eye was noted to be 20/30 -2 with correctional glasses, and slit lamp examination revealed moderate injection of the conjunctiva and sclera, and at least 3 punctate epithelial erosions and punctate staining of the inferior aspects of the cornea, consistent with a chemical injury. The remaining ocular examination was normal for both eyes. She was diagnosed with keratitis of the left eye from chemical exposure to aluminum chloride and was prescribed loteprednol etabonate ophthalmic suspension 0.5% and tobramycin ophthalmic solution 0.3% to be applied to the left eye 4 times daily, with follow-up 4 days later.

At follow-up, the patient denied any pain, though she was not using the prescribed eye drops consistently. On examination, the patient showed improvement in visual acuity to 20/20 -2 and complete resolution of the keratitis, with slit lamp examination showing clear conjunctiva, sclera, and cornea. Given complete resolution, the eye drops were discontinued.

Comment

Factors Contributing to Ocular Chemical Injuries
Chemical burns to the eyes during cosmetic or surgical procedures are one of the few acute ocular emergencies dermatologists may encounter in practice. If not managed properly, the eye may be permanently damaged. Therefore, dermatologists must be confident in the initial management of ocular chemical burns (Table 1; Figure).

Mechanism of Ocular Chemical Burns
The extent of injury is predominantly determined by 2 factors: (1) the chemical properties of the substance, and (2) the length of exposure.^5,9,10 Potential chemical exposures and their reported ocular effects are listed in Table 2.^11-21 Alkaline chemical burns often have the gravest outcome, as they can rapidly penetrate into the internal ocular structures, potentially leading to cataracts and glaucoma.⁹ Hydroxyl ions, often found in alkaline chemicals, are capable of rapidly denaturing the corneal matrix and triggering release of proteolytic enzymes through a series of inflammatory responses. Conversely, ocular damage from most acidic chemicals often is limited to the more superficial structures, such as the cornea and conjunctiva, given that acids may cause corneal proteins to coagulate, thus forming a barrier that slows further penetration into deeper structures.⁹ Nonetheless, corneal damage can still have a devastating impact on visual acuity, as the cornea provides 65% to 75% of the eye’s total focusing power.²² For both alkaline and acidic chemicals, immediate profuse irrigation is most critical in determining the clinical course.^23-26 To provide perspective, potent alkaline chemicals may penetrate into the anterior chamber of the eye within 15 seconds,⁹ and delayed initiation of irrigation by even 5 to 15 minutes may lead to irreversible intraocular damage.²⁷

Immediate Management
If potential chemical exposure to the eye is suspected either by the health care provider or patient, immediately irrigate the affected eye(s) for at least 15 to 30 minutes (longer for alkaline burns) with at least 1 to 2 L of irrigation fluid until the pH is between 7 and 7.2.^{3-5,9,27,34,35} Irrigation fluids reported to be used include normal saline, Ringer lactate solution, normal saline with sodium bicarbonate, and balanced salt solution.⁵ If no solutions are readily available, immediate irrigation with tap water is sufficient for diluting and washing away the chemical and has been reported to have better clinical outcomes than delaying irrigation.^5,24-26 Studies have shown that prolonged irrigation corresponded with reduced severity, shortened healing time, shorter in-hospital treatment duration, and quicker return to work.^5,26

If an eye wash station is not available, the patient can gently flush the eye under a sink faucet set to a gentle stream of lukewarm water.^6,7 The health care provider also may manually irrigate the eye. Necessary equipment includes a large syringe or clean eyecup, irrigating fluid, local anesthetic drops for comfort, a towel to soak up excessive fluid, and a bowl or kidney dish to collect the irrigated fluid.³⁴ Providers should first wash their hands. If necessary, anesthetic eye drops may be added for comfort. Lay a towel over the patient’s neck and shoulders and position the patient at a comfortable angle. Place a bowl adjacent to the patient’s cheek to collect the irrigating fluid and have the patient tilt his/her head such that the irrigated fluid would flow into the bowl. Pour a steady stream of the irrigating fluid over the eye from a height of no more than 5 cm.^6,7,34

During irrigation, ensure that the patient’s eye(s) is wide open and that all ocular surfaces, including the area underneath the eyelids, are thoroughly washed; everting the eyelids may be beneficial. Ask the patient to move his/her eye(s) in all directions while irrigating. If available, place a litmus strip in the conjunctival fornix to ensure that the goal pH of 7 to 7.2 is reached.⁹ The pH should be rechecked every 15 to 30 minutes to ensure there has been no change, as hidden crystalized chemical particles may continue to elute chemicals, causing further injury.³ Contact lenses, if present, should be removed as soon as practical, as lenses can trap chemicals; however, immediate initiation of irrigation should not be delayed⁸ (Table 1).

Identify and verify the chemical suspected to have been exposed to the patient’s eye. The material safety data sheet, which may often be found online if a hard copy is not available, may provide valuable information for the ophthalmologist.³⁶ After thorough irrigation, refer the patient urgently to ophthalmology or the emergency department for prompt evaluation. The emergency department is frequently equipped with polymethylmethacrylate scleral lenses, also called Morgan Lens, which consist of a plastic lens connected via tubing to a bag of irrigation fluid (eg, Ringer lactate solution), allowing for prolonged continuous irrigation of the conjunctiva and cornea. The ophthalmologist will conduct a visual acuity test and complete a thorough eye examination to assess the extent of ischemic injury to the conjunctiva or sclera and damage to the corneal epithelium and internal ocular structures.⁹

Generally, topical antibiotics, artificial tears, and topical steroids may be provided to patients with mild injury with close follow-up.^9,37 For higher-grade injuries, broad-spectrum topical antibiotics, oral antibiotics, topical corticosteroids, vitamin C, and surgical treatments may be additionally recommended (Table 3). Long-term follow-up may be recommended by the ophthalmologist to monitor for potential late complications, such as glaucoma from damage to the trabecular meshwork, corneal abnormalities and limbal stem cell deficiency, symblepharon formation, or eyelid abnormalities.⁹

Conclusion

We report a case of a transient chemical burn to the eye secondary to exposure to aluminum chloride hexahydrate. Complete resolution of the injury was achieved with prompt irrigation and urgent medical management by ophthalmology. This case emphasizes the potential for ocular emergencies in the dermatology setting and highlights the steps for appropriate management should a chemical burn to the eye occur. We emphasize the importance of immediate profuse irrigation for 15 to 30 minutes and urgent evaluation by an ophthalmologist. Dermatologists should be cognizant of potential hazards to the eye during facial procedures and always take proper precautions to decrease the risk for ocular injuries.

Many dermatologic procedures are performed on the face, such as skin biopsies, surgical excisions, and cosmetic procedures, which can increase the risk for accidental ocular injuries.^1,2 Ocular chemical burns have been reported to account for approximately 3% to 20% of ocular injuries^3,4 and are one of the few ocular emergencies dermatologists may encounter in practice. Given the potentially severe consequences of permanent vision changes or loss, it is important to take precautionary steps in preventing chemical exposures and know how to appropriately manage ophthalmic emergencies when they occur.^1,5-8 In this article, we describe a patient with a transient ocular chemical injury from exposure to aluminum chloride hexahydrate that completely resolved with immediate care. We also offer practical guidance for the general dermatologist in the acute management of acidic chemical burns to the eye, highlighting immediate copious irrigation as the most important step in preventing severe permanent damage. Given that aluminum chloride hexahydrate is an acidic solution, we focus predominantly on the approach to acidic chemical exposures to the eye.

Case Report

A 61-year-old woman was seen in the dermatology outpatient clinic for a shave biopsy on the left cheek followed by aluminum chloride application for hemostasis. Following the biopsy, the patient stated she felt the sensation that something had dripped into the left eye and she felt a burning pain. There was a 30- to 60-second delay in irrigation of the eye, as it was at first unclear what had occurred. The patient reported an increased burning sensation, and at that point she was instructed to begin flushing the eye with tap water from the examination room sink for 15 to 20 minutes; she wanted to stop irrigation after a few minutes, and convincing her to continue thorough irrigation was somewhat challenging. It was determined that aluminum chloride hexahydrate had dripped from an oversaturated cotton swab in transit from the tray to the biopsy site.

The patient was urgently directed to the ophthalmology clinic and evaluated by an ophthalmologist within 1 to 2 hours of chemical exposure. Visual acuity of the affected left eye was noted to be 20/30 -2 with correctional glasses, and slit lamp examination revealed moderate injection of the conjunctiva and sclera, and at least 3 punctate epithelial erosions and punctate staining of the inferior aspects of the cornea, consistent with a chemical injury. The remaining ocular examination was normal for both eyes. She was diagnosed with keratitis of the left eye from chemical exposure to aluminum chloride and was prescribed loteprednol etabonate ophthalmic suspension 0.5% and tobramycin ophthalmic solution 0.3% to be applied to the left eye 4 times daily, with follow-up 4 days later.

At follow-up, the patient denied any pain, though she was not using the prescribed eye drops consistently. On examination, the patient showed improvement in visual acuity to 20/20 -2 and complete resolution of the keratitis, with slit lamp examination showing clear conjunctiva, sclera, and cornea. Given complete resolution, the eye drops were discontinued.

Comment

Factors Contributing to Ocular Chemical Injuries
Chemical burns to the eyes during cosmetic or surgical procedures are one of the few acute ocular emergencies dermatologists may encounter in practice. If not managed properly, the eye may be permanently damaged. Therefore, dermatologists must be confident in the initial management of ocular chemical burns (Table 1; Figure).

Mechanism of Ocular Chemical Burns
The extent of injury is predominantly determined by 2 factors: (1) the chemical properties of the substance, and (2) the length of exposure.^5,9,10 Potential chemical exposures and their reported ocular effects are listed in Table 2.^11-21 Alkaline chemical burns often have the gravest outcome, as they can rapidly penetrate into the internal ocular structures, potentially leading to cataracts and glaucoma.⁹ Hydroxyl ions, often found in alkaline chemicals, are capable of rapidly denaturing the corneal matrix and triggering release of proteolytic enzymes through a series of inflammatory responses. Conversely, ocular damage from most acidic chemicals often is limited to the more superficial structures, such as the cornea and conjunctiva, given that acids may cause corneal proteins to coagulate, thus forming a barrier that slows further penetration into deeper structures.⁹ Nonetheless, corneal damage can still have a devastating impact on visual acuity, as the cornea provides 65% to 75% of the eye’s total focusing power.²² For both alkaline and acidic chemicals, immediate profuse irrigation is most critical in determining the clinical course.^23-26 To provide perspective, potent alkaline chemicals may penetrate into the anterior chamber of the eye within 15 seconds,⁹ and delayed initiation of irrigation by even 5 to 15 minutes may lead to irreversible intraocular damage.²⁷

Immediate Management
If potential chemical exposure to the eye is suspected either by the health care provider or patient, immediately irrigate the affected eye(s) for at least 15 to 30 minutes (longer for alkaline burns) with at least 1 to 2 L of irrigation fluid until the pH is between 7 and 7.2.^{3-5,9,27,34,35} Irrigation fluids reported to be used include normal saline, Ringer lactate solution, normal saline with sodium bicarbonate, and balanced salt solution.⁵ If no solutions are readily available, immediate irrigation with tap water is sufficient for diluting and washing away the chemical and has been reported to have better clinical outcomes than delaying irrigation.^5,24-26 Studies have shown that prolonged irrigation corresponded with reduced severity, shortened healing time, shorter in-hospital treatment duration, and quicker return to work.^5,26

If an eye wash station is not available, the patient can gently flush the eye under a sink faucet set to a gentle stream of lukewarm water.^6,7 The health care provider also may manually irrigate the eye. Necessary equipment includes a large syringe or clean eyecup, irrigating fluid, local anesthetic drops for comfort, a towel to soak up excessive fluid, and a bowl or kidney dish to collect the irrigated fluid.³⁴ Providers should first wash their hands. If necessary, anesthetic eye drops may be added for comfort. Lay a towel over the patient’s neck and shoulders and position the patient at a comfortable angle. Place a bowl adjacent to the patient’s cheek to collect the irrigating fluid and have the patient tilt his/her head such that the irrigated fluid would flow into the bowl. Pour a steady stream of the irrigating fluid over the eye from a height of no more than 5 cm.^6,7,34

During irrigation, ensure that the patient’s eye(s) is wide open and that all ocular surfaces, including the area underneath the eyelids, are thoroughly washed; everting the eyelids may be beneficial. Ask the patient to move his/her eye(s) in all directions while irrigating. If available, place a litmus strip in the conjunctival fornix to ensure that the goal pH of 7 to 7.2 is reached.⁹ The pH should be rechecked every 15 to 30 minutes to ensure there has been no change, as hidden crystalized chemical particles may continue to elute chemicals, causing further injury.³ Contact lenses, if present, should be removed as soon as practical, as lenses can trap chemicals; however, immediate initiation of irrigation should not be delayed⁸ (Table 1).

Identify and verify the chemical suspected to have been exposed to the patient’s eye. The material safety data sheet, which may often be found online if a hard copy is not available, may provide valuable information for the ophthalmologist.³⁶ After thorough irrigation, refer the patient urgently to ophthalmology or the emergency department for prompt evaluation. The emergency department is frequently equipped with polymethylmethacrylate scleral lenses, also called Morgan Lens, which consist of a plastic lens connected via tubing to a bag of irrigation fluid (eg, Ringer lactate solution), allowing for prolonged continuous irrigation of the conjunctiva and cornea. The ophthalmologist will conduct a visual acuity test and complete a thorough eye examination to assess the extent of ischemic injury to the conjunctiva or sclera and damage to the corneal epithelium and internal ocular structures.⁹

Generally, topical antibiotics, artificial tears, and topical steroids may be provided to patients with mild injury with close follow-up.^9,37 For higher-grade injuries, broad-spectrum topical antibiotics, oral antibiotics, topical corticosteroids, vitamin C, and surgical treatments may be additionally recommended (Table 3). Long-term follow-up may be recommended by the ophthalmologist to monitor for potential late complications, such as glaucoma from damage to the trabecular meshwork, corneal abnormalities and limbal stem cell deficiency, symblepharon formation, or eyelid abnormalities.⁹

Conclusion

We report a case of a transient chemical burn to the eye secondary to exposure to aluminum chloride hexahydrate. Complete resolution of the injury was achieved with prompt irrigation and urgent medical management by ophthalmology. This case emphasizes the potential for ocular emergencies in the dermatology setting and highlights the steps for appropriate management should a chemical burn to the eye occur. We emphasize the importance of immediate profuse irrigation for 15 to 30 minutes and urgent evaluation by an ophthalmologist. Dermatologists should be cognizant of potential hazards to the eye during facial procedures and always take proper precautions to decrease the risk for ocular injuries.

Many dermatologic procedures are performed on the face, such as skin biopsies, surgical excisions, and cosmetic procedures, which can increase the risk for accidental ocular injuries.^1,2 Ocular chemical burns have been reported to account for approximately 3% to 20% of ocular injuries^3,4 and are one of the few ocular emergencies dermatologists may encounter in practice. Given the potentially severe consequences of permanent vision changes or loss, it is important to take precautionary steps in preventing chemical exposures and know how to appropriately manage ophthalmic emergencies when they occur.^1,5-8 In this article, we describe a patient with a transient ocular chemical injury from exposure to aluminum chloride hexahydrate that completely resolved with immediate care. We also offer practical guidance for the general dermatologist in the acute management of acidic chemical burns to the eye, highlighting immediate copious irrigation as the most important step in preventing severe permanent damage. Given that aluminum chloride hexahydrate is an acidic solution, we focus predominantly on the approach to acidic chemical exposures to the eye.

Case Report

A 61-year-old woman was seen in the dermatology outpatient clinic for a shave biopsy on the left cheek followed by aluminum chloride application for hemostasis. Following the biopsy, the patient stated she felt the sensation that something had dripped into the left eye and she felt a burning pain. There was a 30- to 60-second delay in irrigation of the eye, as it was at first unclear what had occurred. The patient reported an increased burning sensation, and at that point she was instructed to begin flushing the eye with tap water from the examination room sink for 15 to 20 minutes; she wanted to stop irrigation after a few minutes, and convincing her to continue thorough irrigation was somewhat challenging. It was determined that aluminum chloride hexahydrate had dripped from an oversaturated cotton swab in transit from the tray to the biopsy site.

The patient was urgently directed to the ophthalmology clinic and evaluated by an ophthalmologist within 1 to 2 hours of chemical exposure. Visual acuity of the affected left eye was noted to be 20/30 -2 with correctional glasses, and slit lamp examination revealed moderate injection of the conjunctiva and sclera, and at least 3 punctate epithelial erosions and punctate staining of the inferior aspects of the cornea, consistent with a chemical injury. The remaining ocular examination was normal for both eyes. She was diagnosed with keratitis of the left eye from chemical exposure to aluminum chloride and was prescribed loteprednol etabonate ophthalmic suspension 0.5% and tobramycin ophthalmic solution 0.3% to be applied to the left eye 4 times daily, with follow-up 4 days later.

At follow-up, the patient denied any pain, though she was not using the prescribed eye drops consistently. On examination, the patient showed improvement in visual acuity to 20/20 -2 and complete resolution of the keratitis, with slit lamp examination showing clear conjunctiva, sclera, and cornea. Given complete resolution, the eye drops were discontinued.

Comment

Factors Contributing to Ocular Chemical Injuries
Chemical burns to the eyes during cosmetic or surgical procedures are one of the few acute ocular emergencies dermatologists may encounter in practice. If not managed properly, the eye may be permanently damaged. Therefore, dermatologists must be confident in the initial management of ocular chemical burns (Table 1; Figure).

Mechanism of Ocular Chemical Burns
The extent of injury is predominantly determined by 2 factors: (1) the chemical properties of the substance, and (2) the length of exposure.^5,9,10 Potential chemical exposures and their reported ocular effects are listed in Table 2.^11-21 Alkaline chemical burns often have the gravest outcome, as they can rapidly penetrate into the internal ocular structures, potentially leading to cataracts and glaucoma.⁹ Hydroxyl ions, often found in alkaline chemicals, are capable of rapidly denaturing the corneal matrix and triggering release of proteolytic enzymes through a series of inflammatory responses. Conversely, ocular damage from most acidic chemicals often is limited to the more superficial structures, such as the cornea and conjunctiva, given that acids may cause corneal proteins to coagulate, thus forming a barrier that slows further penetration into deeper structures.⁹ Nonetheless, corneal damage can still have a devastating impact on visual acuity, as the cornea provides 65% to 75% of the eye’s total focusing power.²² For both alkaline and acidic chemicals, immediate profuse irrigation is most critical in determining the clinical course.^23-26 To provide perspective, potent alkaline chemicals may penetrate into the anterior chamber of the eye within 15 seconds,⁹ and delayed initiation of irrigation by even 5 to 15 minutes may lead to irreversible intraocular damage.²⁷

Immediate Management
If potential chemical exposure to the eye is suspected either by the health care provider or patient, immediately irrigate the affected eye(s) for at least 15 to 30 minutes (longer for alkaline burns) with at least 1 to 2 L of irrigation fluid until the pH is between 7 and 7.2.^{3-5,9,27,34,35} Irrigation fluids reported to be used include normal saline, Ringer lactate solution, normal saline with sodium bicarbonate, and balanced salt solution.⁵ If no solutions are readily available, immediate irrigation with tap water is sufficient for diluting and washing away the chemical and has been reported to have better clinical outcomes than delaying irrigation.^5,24-26 Studies have shown that prolonged irrigation corresponded with reduced severity, shortened healing time, shorter in-hospital treatment duration, and quicker return to work.^5,26

If an eye wash station is not available, the patient can gently flush the eye under a sink faucet set to a gentle stream of lukewarm water.^6,7 The health care provider also may manually irrigate the eye. Necessary equipment includes a large syringe or clean eyecup, irrigating fluid, local anesthetic drops for comfort, a towel to soak up excessive fluid, and a bowl or kidney dish to collect the irrigated fluid.³⁴ Providers should first wash their hands. If necessary, anesthetic eye drops may be added for comfort. Lay a towel over the patient’s neck and shoulders and position the patient at a comfortable angle. Place a bowl adjacent to the patient’s cheek to collect the irrigating fluid and have the patient tilt his/her head such that the irrigated fluid would flow into the bowl. Pour a steady stream of the irrigating fluid over the eye from a height of no more than 5 cm.^6,7,34

During irrigation, ensure that the patient’s eye(s) is wide open and that all ocular surfaces, including the area underneath the eyelids, are thoroughly washed; everting the eyelids may be beneficial. Ask the patient to move his/her eye(s) in all directions while irrigating. If available, place a litmus strip in the conjunctival fornix to ensure that the goal pH of 7 to 7.2 is reached.⁹ The pH should be rechecked every 15 to 30 minutes to ensure there has been no change, as hidden crystalized chemical particles may continue to elute chemicals, causing further injury.³ Contact lenses, if present, should be removed as soon as practical, as lenses can trap chemicals; however, immediate initiation of irrigation should not be delayed⁸ (Table 1).

Identify and verify the chemical suspected to have been exposed to the patient’s eye. The material safety data sheet, which may often be found online if a hard copy is not available, may provide valuable information for the ophthalmologist.³⁶ After thorough irrigation, refer the patient urgently to ophthalmology or the emergency department for prompt evaluation. The emergency department is frequently equipped with polymethylmethacrylate scleral lenses, also called Morgan Lens, which consist of a plastic lens connected via tubing to a bag of irrigation fluid (eg, Ringer lactate solution), allowing for prolonged continuous irrigation of the conjunctiva and cornea. The ophthalmologist will conduct a visual acuity test and complete a thorough eye examination to assess the extent of ischemic injury to the conjunctiva or sclera and damage to the corneal epithelium and internal ocular structures.⁹

Generally, topical antibiotics, artificial tears, and topical steroids may be provided to patients with mild injury with close follow-up.^9,37 For higher-grade injuries, broad-spectrum topical antibiotics, oral antibiotics, topical corticosteroids, vitamin C, and surgical treatments may be additionally recommended (Table 3). Long-term follow-up may be recommended by the ophthalmologist to monitor for potential late complications, such as glaucoma from damage to the trabecular meshwork, corneal abnormalities and limbal stem cell deficiency, symblepharon formation, or eyelid abnormalities.⁹

Conclusion

We report a case of a transient chemical burn to the eye secondary to exposure to aluminum chloride hexahydrate. Complete resolution of the injury was achieved with prompt irrigation and urgent medical management by ophthalmology. This case emphasizes the potential for ocular emergencies in the dermatology setting and highlights the steps for appropriate management should a chemical burn to the eye occur. We emphasize the importance of immediate profuse irrigation for 15 to 30 minutes and urgent evaluation by an ophthalmologist. Dermatologists should be cognizant of potential hazards to the eye during facial procedures and always take proper precautions to decrease the risk for ocular injuries.

In a commentary issued on May 6, the Food and Drug Administration stated that “with sunscreens now being used with greater frequency, in larger amounts, and by broader populations, it is more important than ever to ensure that sunscreens are safe and effective for daily, lifelong use.” The statement coincided with the publication of the randomized study, “Effect of sunscreen application under maximal use conditions on plasma concentrations of sunscreen active ingredients,” by Matta et al. of the FDA and others in JAMA (2019 May 6. doi: 10.1001/jama.2019.5586). A maximal usage trial examines the systemic absorption of a topical drug when used according to the guidelines given for the product’s maximum usage. In this study, adult participants were randomized to one of four commercially available sunscreen products: spray 1 (n = 6), spray 2 (n = 6), a lotion (n = 6), and a cream (n = 6). Two mg of sunscreen per 1 cm² was applied to 75% of body surface area four times per day for 4 days, and blood samples were collected from each individual over 7 days.

Plasma concentrations of the four active ingredients tested – avobenzone, oxybenzone, octocrylene, and ecamsule – were above 0.5 ng/mL. The FDA’s guidance for industry and proposed rule on OTC sunscreens state that active ingredients with systemic absorption at 0.5 ng/mL or higher or with possible safety concerns need to undergo further nonclinical toxicology assessment to evaluate risk of systemic carcinogenicity, developmental/reproductive abnormalities, or other adverse effects.

Absorption of some sunscreen ingredients has been detected in other studies. Despite systemic absorption, two active ingredients – zinc oxide and titanium dioxide – have been found by the FDA to be generally recognized as safe and effective. But for 12 other active ingredients (cinoxate, dioxybenzone, ensulizole, homosalate, meradimate, octinoxate, octisalate, octocrylene, padimate O, sulisobenzone, oxybenzone, and avobenzone), there are insufficient data to make a “generally recognized as safe and effective” determination; thus, more data have been requested from the manufacturers. While physical blocking sunscreens have improved in their UV-blocking ability without compromising cosmesis over the past several years, some sunscreens containing chemical blockers are able to achieve higher SPFs with good cosmesis when applied to the skin.

Our skin acts as the ultimate barrier between ourselves and the environment, and it is not uncommon for substances to be blocked, absorbed, or excreted from the skin. Absorption of an ingredient through the skin and into the body does not indicate that the ingredient is unsafe. Rather, findings such as these call for further testing and research to determine the safety of that ingredient with repeated use. Per the FDA, such testing is part of the standard premarket safety evaluation of most chronically administered drugs with appreciable systemic absorption.

In February 2019, the FDA’s proposed rule was issued to “update regulatory requirements for most sunscreen products in the United States,” with the goal of bringing OTC sunscreens “up to date with the latest scientific standards,” according to the FDA May 6 commentary. “As part of this rule, the FDA is asking industry and other interested parties for additional safety data on the 12 active sunscreen ingredients currently available in marketed products” mentioned previously. These rules are being put into place to address the “key data gap” for these 12 ingredients, which is “understanding whether, and to what extent the ingredient is absorbed into the body after topical application.”

More research in this area is needed, but studies have linked these ingredients to harming coral by bleaching, disease, and damage to DNA, and also to decreasing fertility in fish, impairing algae growth, inducing defects in mussel and sea urchin young, and accumulating in the tissues of dolphins. According to NASA, as much as 27% of monitored reef formation have already been lost and over the following 32 years, 32% more are at risk. Reefs cover a mere 0.2% of the ocean’s floor, but it is estimated that reefs are home to and protect nearly 1 million species of fish, invertebrates, and algae.

In early May, Rep. Tulsi Gabbard (D-Hawaii) and Sen. Tim Ryan (D-Ohio) introduced legislation known as the Oxybenzone and Octinoxate Impact Study Act of 2019 (H.R. 2588) to require the Environmental Protection Agency to study the impact of those two chemicals on human health and the environment and to provide findings to Congress and the public within 18 months.

The importance of sun protection and prevention of sunburns is paramount. We know that multiple sunburn events during childhood double a child’s risk of developing skin cancer later in life, and skin cancer is the most common cancer diagnosed in the United States, with 5 million cases treated every year. One in five Americans will develop skin cancer by age 70 years.

As a Mohs and a cosmetic dermatologic surgeon, I appreciate the unquestionable protective effects of sunscreen products with regards to skin cancer, dyspigmentation, solar elastosis, and rhytids associated with photoaging. We can applaud the FDA for improving testing and regulation of OTC ingredients, including those in sunscreen. These types of studies are important and monumental in ensuring that we are utilizing the right type of ingredients to protect our patients, our oceans, and our reefs.

Dr. Wesley and Dr. Talakoub are co-contributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at [email protected]. They had no relevant disclosures.

References

• Matta MK et al. JAMA. 2019 May 6. doi: 10.1001/jama.2019.5586.
• Shedding new light on sunscreen absorption, by Janet Woodcock, MD, director, Center for Drug Evaluation and Research, and Theresa M. Michele, MD, director, CDER’s Division of Nonprescription Drug Products, Office of New Drugs
• Food and Drug Administration. Sunscreen drug products for over-the-counter human use: Proposed rule. Fed Regist. 2019;84(38):6204-75.
• Schlumpf M et al. Chemosphere. 2010 Nov;81(10):1171-83.
• Krause M et al. Int J Androl. 2012 Jun;35(3):424-36.

In a commentary issued on May 6, the Food and Drug Administration stated that “with sunscreens now being used with greater frequency, in larger amounts, and by broader populations, it is more important than ever to ensure that sunscreens are safe and effective for daily, lifelong use.” The statement coincided with the publication of the randomized study, “Effect of sunscreen application under maximal use conditions on plasma concentrations of sunscreen active ingredients,” by Matta et al. of the FDA and others in JAMA (2019 May 6. doi: 10.1001/jama.2019.5586). A maximal usage trial examines the systemic absorption of a topical drug when used according to the guidelines given for the product’s maximum usage. In this study, adult participants were randomized to one of four commercially available sunscreen products: spray 1 (n = 6), spray 2 (n = 6), a lotion (n = 6), and a cream (n = 6). Two mg of sunscreen per 1 cm² was applied to 75% of body surface area four times per day for 4 days, and blood samples were collected from each individual over 7 days.

Plasma concentrations of the four active ingredients tested – avobenzone, oxybenzone, octocrylene, and ecamsule – were above 0.5 ng/mL. The FDA’s guidance for industry and proposed rule on OTC sunscreens state that active ingredients with systemic absorption at 0.5 ng/mL or higher or with possible safety concerns need to undergo further nonclinical toxicology assessment to evaluate risk of systemic carcinogenicity, developmental/reproductive abnormalities, or other adverse effects.

Absorption of some sunscreen ingredients has been detected in other studies. Despite systemic absorption, two active ingredients – zinc oxide and titanium dioxide – have been found by the FDA to be generally recognized as safe and effective. But for 12 other active ingredients (cinoxate, dioxybenzone, ensulizole, homosalate, meradimate, octinoxate, octisalate, octocrylene, padimate O, sulisobenzone, oxybenzone, and avobenzone), there are insufficient data to make a “generally recognized as safe and effective” determination; thus, more data have been requested from the manufacturers. While physical blocking sunscreens have improved in their UV-blocking ability without compromising cosmesis over the past several years, some sunscreens containing chemical blockers are able to achieve higher SPFs with good cosmesis when applied to the skin.

Our skin acts as the ultimate barrier between ourselves and the environment, and it is not uncommon for substances to be blocked, absorbed, or excreted from the skin. Absorption of an ingredient through the skin and into the body does not indicate that the ingredient is unsafe. Rather, findings such as these call for further testing and research to determine the safety of that ingredient with repeated use. Per the FDA, such testing is part of the standard premarket safety evaluation of most chronically administered drugs with appreciable systemic absorption.

In February 2019, the FDA’s proposed rule was issued to “update regulatory requirements for most sunscreen products in the United States,” with the goal of bringing OTC sunscreens “up to date with the latest scientific standards,” according to the FDA May 6 commentary. “As part of this rule, the FDA is asking industry and other interested parties for additional safety data on the 12 active sunscreen ingredients currently available in marketed products” mentioned previously. These rules are being put into place to address the “key data gap” for these 12 ingredients, which is “understanding whether, and to what extent the ingredient is absorbed into the body after topical application.”

More research in this area is needed, but studies have linked these ingredients to harming coral by bleaching, disease, and damage to DNA, and also to decreasing fertility in fish, impairing algae growth, inducing defects in mussel and sea urchin young, and accumulating in the tissues of dolphins. According to NASA, as much as 27% of monitored reef formation have already been lost and over the following 32 years, 32% more are at risk. Reefs cover a mere 0.2% of the ocean’s floor, but it is estimated that reefs are home to and protect nearly 1 million species of fish, invertebrates, and algae.

In early May, Rep. Tulsi Gabbard (D-Hawaii) and Sen. Tim Ryan (D-Ohio) introduced legislation known as the Oxybenzone and Octinoxate Impact Study Act of 2019 (H.R. 2588) to require the Environmental Protection Agency to study the impact of those two chemicals on human health and the environment and to provide findings to Congress and the public within 18 months.

The importance of sun protection and prevention of sunburns is paramount. We know that multiple sunburn events during childhood double a child’s risk of developing skin cancer later in life, and skin cancer is the most common cancer diagnosed in the United States, with 5 million cases treated every year. One in five Americans will develop skin cancer by age 70 years.

As a Mohs and a cosmetic dermatologic surgeon, I appreciate the unquestionable protective effects of sunscreen products with regards to skin cancer, dyspigmentation, solar elastosis, and rhytids associated with photoaging. We can applaud the FDA for improving testing and regulation of OTC ingredients, including those in sunscreen. These types of studies are important and monumental in ensuring that we are utilizing the right type of ingredients to protect our patients, our oceans, and our reefs.

Dr. Wesley and Dr. Talakoub are co-contributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at [email protected]. They had no relevant disclosures.

References

• Matta MK et al. JAMA. 2019 May 6. doi: 10.1001/jama.2019.5586.
• Shedding new light on sunscreen absorption, by Janet Woodcock, MD, director, Center for Drug Evaluation and Research, and Theresa M. Michele, MD, director, CDER’s Division of Nonprescription Drug Products, Office of New Drugs
• Food and Drug Administration. Sunscreen drug products for over-the-counter human use: Proposed rule. Fed Regist. 2019;84(38):6204-75.
• Schlumpf M et al. Chemosphere. 2010 Nov;81(10):1171-83.
• Krause M et al. Int J Androl. 2012 Jun;35(3):424-36.

In a commentary issued on May 6, the Food and Drug Administration stated that “with sunscreens now being used with greater frequency, in larger amounts, and by broader populations, it is more important than ever to ensure that sunscreens are safe and effective for daily, lifelong use.” The statement coincided with the publication of the randomized study, “Effect of sunscreen application under maximal use conditions on plasma concentrations of sunscreen active ingredients,” by Matta et al. of the FDA and others in JAMA (2019 May 6. doi: 10.1001/jama.2019.5586). A maximal usage trial examines the systemic absorption of a topical drug when used according to the guidelines given for the product’s maximum usage. In this study, adult participants were randomized to one of four commercially available sunscreen products: spray 1 (n = 6), spray 2 (n = 6), a lotion (n = 6), and a cream (n = 6). Two mg of sunscreen per 1 cm² was applied to 75% of body surface area four times per day for 4 days, and blood samples were collected from each individual over 7 days.

Plasma concentrations of the four active ingredients tested – avobenzone, oxybenzone, octocrylene, and ecamsule – were above 0.5 ng/mL. The FDA’s guidance for industry and proposed rule on OTC sunscreens state that active ingredients with systemic absorption at 0.5 ng/mL or higher or with possible safety concerns need to undergo further nonclinical toxicology assessment to evaluate risk of systemic carcinogenicity, developmental/reproductive abnormalities, or other adverse effects.

Absorption of some sunscreen ingredients has been detected in other studies. Despite systemic absorption, two active ingredients – zinc oxide and titanium dioxide – have been found by the FDA to be generally recognized as safe and effective. But for 12 other active ingredients (cinoxate, dioxybenzone, ensulizole, homosalate, meradimate, octinoxate, octisalate, octocrylene, padimate O, sulisobenzone, oxybenzone, and avobenzone), there are insufficient data to make a “generally recognized as safe and effective” determination; thus, more data have been requested from the manufacturers. While physical blocking sunscreens have improved in their UV-blocking ability without compromising cosmesis over the past several years, some sunscreens containing chemical blockers are able to achieve higher SPFs with good cosmesis when applied to the skin.

Our skin acts as the ultimate barrier between ourselves and the environment, and it is not uncommon for substances to be blocked, absorbed, or excreted from the skin. Absorption of an ingredient through the skin and into the body does not indicate that the ingredient is unsafe. Rather, findings such as these call for further testing and research to determine the safety of that ingredient with repeated use. Per the FDA, such testing is part of the standard premarket safety evaluation of most chronically administered drugs with appreciable systemic absorption.

In February 2019, the FDA’s proposed rule was issued to “update regulatory requirements for most sunscreen products in the United States,” with the goal of bringing OTC sunscreens “up to date with the latest scientific standards,” according to the FDA May 6 commentary. “As part of this rule, the FDA is asking industry and other interested parties for additional safety data on the 12 active sunscreen ingredients currently available in marketed products” mentioned previously. These rules are being put into place to address the “key data gap” for these 12 ingredients, which is “understanding whether, and to what extent the ingredient is absorbed into the body after topical application.”

More research in this area is needed, but studies have linked these ingredients to harming coral by bleaching, disease, and damage to DNA, and also to decreasing fertility in fish, impairing algae growth, inducing defects in mussel and sea urchin young, and accumulating in the tissues of dolphins. According to NASA, as much as 27% of monitored reef formation have already been lost and over the following 32 years, 32% more are at risk. Reefs cover a mere 0.2% of the ocean’s floor, but it is estimated that reefs are home to and protect nearly 1 million species of fish, invertebrates, and algae.

In early May, Rep. Tulsi Gabbard (D-Hawaii) and Sen. Tim Ryan (D-Ohio) introduced legislation known as the Oxybenzone and Octinoxate Impact Study Act of 2019 (H.R. 2588) to require the Environmental Protection Agency to study the impact of those two chemicals on human health and the environment and to provide findings to Congress and the public within 18 months.

The importance of sun protection and prevention of sunburns is paramount. We know that multiple sunburn events during childhood double a child’s risk of developing skin cancer later in life, and skin cancer is the most common cancer diagnosed in the United States, with 5 million cases treated every year. One in five Americans will develop skin cancer by age 70 years.

As a Mohs and a cosmetic dermatologic surgeon, I appreciate the unquestionable protective effects of sunscreen products with regards to skin cancer, dyspigmentation, solar elastosis, and rhytids associated with photoaging. We can applaud the FDA for improving testing and regulation of OTC ingredients, including those in sunscreen. These types of studies are important and monumental in ensuring that we are utilizing the right type of ingredients to protect our patients, our oceans, and our reefs.

Dr. Wesley and Dr. Talakoub are co-contributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at [email protected]. They had no relevant disclosures.

References

• Matta MK et al. JAMA. 2019 May 6. doi: 10.1001/jama.2019.5586.
• Shedding new light on sunscreen absorption, by Janet Woodcock, MD, director, Center for Drug Evaluation and Research, and Theresa M. Michele, MD, director, CDER’s Division of Nonprescription Drug Products, Office of New Drugs
• Food and Drug Administration. Sunscreen drug products for over-the-counter human use: Proposed rule. Fed Regist. 2019;84(38):6204-75.
• Schlumpf M et al. Chemosphere. 2010 Nov;81(10):1171-83.
• Krause M et al. Int J Androl. 2012 Jun;35(3):424-36.